• ACTG Launches A5383, Clinical Trial Evaluating Potential Immunologic Benefits of Treating Asymptomatic CMV in People Living with HIV

    April 22, 2022 Alexis Sexton Spotlight

    ACTG Launches A5383, Clinical Trial Evaluating Potential Immunologic Benefits of Treating Asymptomatic CMV in People Living with HIV

    The AIDS Clinical Trials Group (ACTG), the largest global HIV research network, today announced the initiation of A5383, a clinical trial evaluating whether the anti- cytomegalovirus (CMV) drug letermovir reduces inflammation when given to people who have well-controlled HIV and CMV without symptoms.

    Approximately 90 percent of people living with HIV also have CMV and there is strong evidence that CMV is associated with chronic inflammation and possibly with end organ disease, including cardiovascular disease, neurological complications, and metabolic disease. Letermovir is a CMV DNA terminase complex inhibitor that is FDA-approved to prevent severe CMV disease in adults with asymptomatic CMV who are receiving allogeneic hematopoietic stem cell transplants (generally for the treatment of blood cancer). Because of letermovir’s utility and safety profile among these individuals, researchers hypothesize that letermovir may also reduce the amount of CMV and consequently decrease inflammation in people living with HIV.

    “Because it is nearly ubiquitous among people living with HIV, CMV remains an important research focus as we seek to improve quality of life among people who are aging with HIV,” said ACTG chair Judith Currier, M.D., M.Sc., University of California, Los Angeles. “This study is particularly important because it will determine whether suppressing asymptomatic CMV replication will decrease systemic inflammation.”

    A5383 is a phase 2, randomized, open-label, controlled, multicenter trial evaluating the anti-inflammatory efficacy of letermovir among adults age 40 and older, whose HIV is virally suppressed while on antiretroviral therapy (ART) and whose CMV is asymptomatic. Half of participants (n=90) will receive 480 mg of letermovir once daily (administered orally as either one or two tablets) and half will not receive any anti-CMV therapy. Participants will be followed for 60 weeks, including 48 weeks taking letermovir for participants in the active group and 12 weeks of post-treatment follow-up. At least one third of participants will be cisgender or transgender women and half will have CD4+ T cell counts <350 cells/mm3.

    “Based on preliminary data, we believe this intervention may be particularly helpful for several groups of people: those who continue to have low CD4 counts despite viral suppression, individuals at highest risk for morbidity and mortality and thus most in need of new interventions, and women, who tend to be underrepresented in most treatment studies,” said protocol co-chair Sara Gianella, M.D., University of California, San Diego. “We are pleased that this study has been designed in a way that features a dedicated effort to recruit these individuals.”

    A5383 is led by Dr. Gianella and Peter Hunt, M.D., University of California at San Francisco (study chair). It is funded by the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health (NIH). Study drugs are supplied by Merck & Co., Inc.

     

    About the ACTG

    Founded in 1987, the AIDS Clinical Trials Group (ACTG) was the world’s first HIV research network. The ACTG conducts groundbreaking studies to improve the treatment of HIV and its complications, including tuberculosis and viral hepatitis; reduce new infections and HIV-related illness; and advance new approaches to prevent, treat, and ultimately cure HIV in adults and children. More recently, The ACTG has expanded its focus to include the evaluation of outpatient treatments for COVID-19. ACTG investigators and research units in 15 countries serve as major resources for HIV/AIDS research, treatment, care, and training/education in their communities. ACTG studies have helped establish current paradigms for managing HIV disease, and have informed HIV treatment guidelines, resulting in dramatic decreases in HIV-related mortality worldwide.

    To read the full press release, click here.

  • Request for Applications Small Clinical Trials Advancing HIV Remission and Cure- Due April 1, 2022

    March 28, 2022 Alexis Sexton Spotlight

    The AIDS Clinical Trials Group (ACTG) Network in collaboration with the NIAID Division of AIDS (DAIDS) has developed a new pathway for the conduct of small experimental trials that aim to advance efforts related to HIV remission and cure utilizing the infrastructure of the ACTG Network. It is anticipated these studies will be small (< 30 participants) and will involve 1-3 clinical research sites experienced at these types of trials. The trials will by nature be intensive and may include specialized assays or procedures, thus making them unsuitable for the ACTG’s larger multi-site studies. Concepts selected for development will be managed by the ACTG’s newly-created Small Clinical Trials Unit (SCTU) with dedicated clinical trial specialists and statistical support. The studies will be conducted at ACTG sites, and the efforts will be coordinated with the ACTG’s Reservoirs, Remission, and Cure Transformative Science Group (Cure TSG). This mechanism is open broadly to investigators with interest in experimental science clinical trials addressing questions important to the HIV cure agenda, and proposing investigators do not need to be affiliated with the ACTG.

    Successful applicants will work with the ACTG SCTU to finalize protocol development and implementation, which will be overseen by the Cure TSG steering committee. The submitting investigator may serve as the study’s chair; additional team members with experience working at ACTG sites will be added to the protocol team. DAIDS will be the sponsor if the study requires an IND/IDE.

    To the extent possible, the ACTG will support all primary endpoint laboratory assays in the currently funded specialty laboratories or through contract laboratories. Secondary, exploratory, and specialized assays can be performed by the applicant but will not be routinely funded by the ACTG. This RFA will not fund assay development. Excess samples will be saved in the ACTG specimen repository and will be available to investigators, both internal and external to the ACTG, for work outside the objectives of the original trial via a standard ACTG request and review process.

    The ACTG Statistical Data Center (SDAC) will lead the analyses of primary endpoint data. Analyses of secondary and exploratory endpoints will be conducted in collaboration with the proposing investigators’ statistical experts and SDAC.

    Applications must demonstrate clear linkage to the DAIDS and ACTG scientific agendas. Examples of areas of particular scientific interest to include but are not limited to:

    • Quantification and characterization of HIV reservoirs and their decay on current antiretroviral therapy or in response to experimental therapies
    • Mechanisms of HIV persistence, immune control and/or immune escape.
    • Therapeutic vaccination to enhance immune clearance of HIV-infected cells
    • Immune-based therapies to clear virus expressing cells and/or control HIV reservoir
    • Novel therapies to induce HIV expression and deplete HIV reservoirs including combination interventions

    Revised Application Procedure

    Applications must use the PHS 398 biosketch form (for the PI and other key personnel) and limit the research plan/proposal to 6 pages (single-spaced, 11 pt Times New Roman font).
    The 6-page research plan/proposal must include the following sections:

    • List of investigators
    • Background
    • Accomplishments
    • Innovation
    • Approach, – should contain the basic design of proposed clinical trial including rationale, hypotheses, objectives and outcomes, study population, intervention and analysis plan
    • Feasibility and accessibility to the investigational product(s) should be specifically addressed. This RFA is not intended to support the development or manufacturing of new products for testing in clinical trials.

    Either the biosketch or the research plan/proposal (limited to 6 pages) must include the information below.

    • Prior and current experience with specific HIV remission and cure studies and a summary of past contributions to the field of HIV remission and cure
    • Proposed scientific contributions to the ACTG and DAIDS agendas in the area of HIV cure and remission
    • Other Support for key personnel

    A schedule of events may be included as the single appendix to the research plan/proposal. Inclusion of a budget is not necessary.

    Criteria for Evaluation

    Proposals will be evaluated on the basis of significance, originality, feasibility, and likely contribution to the HIV remission/cure agenda of the ACTG and DAIDS.

    Specific criteria will include:

    • Investigators: Are the investigators qualified to design, oversee and perform the proposed work, as judged by past accomplishments (publications; independent peer-reviewed support), and/or patient-oriented AIDS research, and experience working in regulated environment? Access to trainees and junior faculty as collaborators in the work should also be described.
    • Institutional Resources: Does the investigator have the resources and environment to conduct assays that will be done outside of the ACTG specialty or contract labs and participate in the statistical analysis? If the applicant proposes to utilize a non-ACTG laboratory, does the team have the capabilities and resources to meet ACTG standards (e.g. QA/QC, data management) and perform any specialized assays required by the concept proposal? Is the host institution committed to providing the necessary space and other infrastructure needed to complete the
      required work for the duration of the award?
    • Innovation: Will the study, if successful, advance efforts to understand HIV reservoirs and/or facilitate HIV remission/cure?
    • Approach: Does the concept propose a study focused on an area of scientific interest to the field of HIV reservoirs and/or HIV remission that is investigational and intensive, uses non-standard experimental endpoints, and/or requires specialized assays or procedures, thus making it unsuitable for the ACTG’s larger multi-site studies? If the study requires experimental interventions or devices, are they available to the investigator?

    Application Timelines

    This RFA has twice-yearly receipt dates on April1st and September 1st.

    A Letter of Intent is strongly encouraged but not required and must be submitted by February 15th and July 15th, respectively and must include the principal investigator, other key investigators, investigator institution, tentative title of the proposal, primary hypotheses and intention to conduct specialized laboratory assays outside of the ACTG and contract laboratories.

    Original release of solicitation: July 12, 2021; Revised August 11, 2021

    First application due date: September 1, 2021

    EXPECTED SUPPORT OF FUNDED APPLICATIONS

    1. The funded applications will generally receive an award of 3 years duration.
    2. The ACTG intends to fund up to 2 small clinical trial awards per year.
    3. The ACTG will provide protocol development support, clinical trials expertise, regulatory support, statistical and data support and the sites, staff and laboratory support need to conduct the trial.
    4. Primary and secondary endpoint assays conducted by the ACTG specialty labs or contract labs will be supported by the ACTG.
    5. Each awardee will receive core support of up to 25% FTE up to the NIH salary cap per year, direct costs. (This funding is to support the effort of the PI and other Key Personnel who will be directly involved in the development and conduct of the clinical trial and will be provided as part of protocol development and implementation as per ACTG standard operating procedures.)
    6. Assay performance work that is deemed essential to the trial and conducted outside of the ACTG or contract labs may be supported by the ACTG using a cost-reimbursement model, depending on the nature of the assays and the volume of work required.
    7. Support for exploratory assays is the responsibility of the proposing investigators.

    Application Submission and Questions
    Completed applications are to be submitted at: https://actgnetwork.org/submit-a-proposal/; an F&Q is posted to the same portal or can be seen here.
    Questions about the RFA can be sent to ACTGLeadershipSupport@DLHCorp.com

  • ACTG and Shionogi Announce Progress on Global Phase 3 Trial of Novel COVID-19 Oral Antiviral Agent S 217622

    March 16, 2022 Alexis Sexton Spotlight

    ACTG and Shionogi Announce Progress on Global Phase 3 Trial of Novel COVID-19 Oral Antiviral Agent S‑217622

    • FDA has cleared the IND for S-217622, a once-daily investigational oral antiviral therapy, enabling the global phase 3 trial to proceed as part of the ACTIV-2 program for COVID-19
    • This NIH-supported study will recruit participants with COVID-19 worldwide who are at risk for progression to severe illness

    Los Angeles, Calif. and Osaka, Japan, March 16, 2022 – The AIDS Clinical Trials Group (ACTG), the largest global HIV research network that expanded its focus to include evaluating outpatient treatments for COVID-19, and Shionogi & Co., Ltd., a global pharmaceutical company headquartered in Osaka, Japan with a long-standing commitment to the research and development of innovative, high-quality infectious disease medicines, today announced progress toward the initiation of ACTIV-2d (also known as SCORPIO-HR), a global, phase 3, multicenter trial to evaluate the safety and efficacy of the COVID-19 antiviral agent S-217622. SCORPIO-HR will evaluate the investigational 3CL protease inhibitor S-217622 as a once-daily oral treatment for high-risk, non-hospitalized adults with COVID-19 within five days of symptom onset. The trial is being conducted by ACTG, sponsored by Shionogi, and funded by the National Institute of Allergy and Infectious Diseases (NIAID) part of the National Institutes of Health (NIH).

    SCORPIO-HR is a phase 3, multicenter, randomized, double‑blind, 48‑week study that will evaluate the safety and efficacy of S-217622 among participants who have tested positive for SARS-CoV-2 in the outpatient setting, started experiencing symptoms within five days of enrolling, and have one or more risk factors that makes them more likely to progress to severe COVID-19. The U.S. Food and Drug Administration (FDA) has cleared the Investigational New Drug (IND) application for S-217622, enabling SCORPIO-HR to proceed. This trial follows supportive, positive results from phase 2a and phase 2b clinical trials (primarily conducted in Japan and used for submission to the Japanese health authority) that demonstrated proof of concept with significant antiviral activity and rapid cessation of infectious virus shedding.

    “While S-217622 is in the same class of treatments as oral medications that are currently available through Emergency Use Authorizations to treat COVID-19, it is administered without a boosting agent and only once daily, which can simplify treatment,” said Annie Luetkemeyer, M.D., University of California, San Francisco and a lead investigator of S-217622. “We need more well-tolerated, highly effective options to treat COVID-19 that reduce the risk of serious complications and the duration of infectiousness. Based on preliminary clinical trial data, we are excited about the potential for S-217622 to be an important addition to our COVID-19 treatment toolkit.”

    SCORPIO-HR will be conducted with trial sites in countries in Europe, South America, North America, Africa, and Asia. Approximately 1,700 participants will be randomized in a 2:1 ratio such that two thirds receive S-217622 and one third receive placebo. Participants may take locally provided COVID-19 treatment after enrollment, as long as it is compatible with S-217622.

    “As more and more people begin to resume their daily lives, there remains a clear need for effective antiviral treatments for COVID-19 that can offer added protection against severe illness and reduce the burden of COVID-19 on our healthcare systems,” said Isao Teshirogi, Ph.D., President and CEO at Shionogi & Co., Ltd. “As a potent antiviral, specifically designed to inhibit SARS-CoV-2’s ability to spread through the body, S-217622 has demonstrated the largest reductions reported to date in infectious virus titer and rapid cessation of infectious virus shedding. We value the collaboration and support of the NIH and ACTG on this investigational antiviral to bring further treatment options to a broad range of COVID-19 patients, and especially to high-risk populations.”

    SCORPIO-HR is led by Kara W. Chew, M.D., M.S., University of California, Los Angeles (UCLA), Dr. Luetkemeyer, and Davey Smith, M.D., University of California, San Diego (protocol co-chairs) and David Alain Wohl, M.D., University of North Carolina (UNC) and Eric S. Daar, M.D., Lundquist Institute at Harbor-UCLA Medical Center (vice-chairs), and is supported by Judith Currier, M.D., M.Sc., UCLA (ACTG Chair) and Joseph J. Eron, M.D., UNC, (ACTG Co-Chair).

    About S-217622

    S-217622, a therapeutic drug for COVID-19, is an 3CL protease inhibitor created through joint research between Hokkaido University and Shionogi. SARS-CoV-2 utilizes an enzyme called 3CL protease that is essential for the replication of the virus. S-217622 suppresses the replication of SARS-CoV-2 by selectively inhibiting 3CL protease. In the phase 2 part of a phase 2/3 clinical trial conducted in Japan and Korea, patients treated with S-217622 showed a significant and rapid decrease in viral titer and/or viral RNA on day 4 (after the 3rd dose), in comparison to the placebo. In the phase 2 part of the phase 2/3 clinical trial, no serious safety concerns were reported. Additionally, in the preliminary in vitro study, S-217622 exhibited similar antiviral activity against the Omicron subvariant BA.2 and other existing variants. Recognizing the urgent global need for more therapies to address COVID-19, Shionogi has already begun to work with worldwide health authorities including those located in Japan and the United States. SCORPIO-HR is a global phase 3 trial of the ACTIV-2 NIH-funded outpatient treatment study for Stopping COVID-19 pRogression with early Protease InhibitOr treatment.

    About ACTIV-2

    ACTIV-2 is sponsored by the NIAID, part of the NIH, which also funds the ACTG. ACTIV-2 is part of NIH’s Accelerating COVID-19 Therapeutic Interventions and Vaccines (ACTIV) initiative, a public-private partnership program set up to create a coordinated research strategy that prioritizes and speeds development of the most promising treatments and vaccines. It also receives support from Federal COVID Response-Therapeutics, the U.S. government’s multi-agency effort to accelerate the development, manufacturing, and distribution of COVID-19 vaccines, therapeutics, and diagnostics.

    About the ACTG

    Founded in 1987, the AIDS Clinical Trials Group (ACTG) was the world’s first HIV research network. The ACTG conducts groundbreaking studies to improve the treatment of HIV and its complications, including tuberculosis and viral hepatitis; reduce new infections and HIV-related illness; and advance new approaches to prevent, treat, and ultimately cure HIV in adults and children. More recently, the ACTG has expanded its focus to include the evaluation of outpatient treatments for COVID-19. ACTG investigators and research units in 15 countries serve as major resources for HIV/AIDS research, treatment, care, and training/education in their communities. ACTG studies have helped establish current paradigms for managing HIV disease, and have informed HIV treatment guidelines, resulting in dramatic decreases in HIV-related mortality worldwide.

    About Shionogi

    Shionogi & Co., Ltd. is a leading global research-driven pharmaceutical company based in Japan, dedicated to bringing benefits to patients based on its corporate philosophy of “supplying the best possible medicine to protect the health and wellbeing of the patients we serve.” The company has discovered and developed novel medicines for HIV, influenza and antimicrobial resistance, and currently markets products in several therapeutic areas including anti-infectives with the first siderophore cephalosporin, FETROJA® (cefiderocol; known as FETCROJA® in Europe). Other therapeutic areas and the focus of the company’s pipeline include CNS/psychoneurological diseases, oncology and pain. For more information on Shionogi & Co., Ltd., visit https://www.shionogi.com/global/en/. Shionogi Inc. is the U.S. subsidiary of Shionogi & Co., Ltd. based in N.J. For more information on Shionogi Inc., please visit https://www.shionogi.com. Shionogi B.V. is the European headquarters of Shionogi & Co., Ltd. For more information on Shionogi B.V., please visit www.shionogi.eu.

    Shionogi’s Commitment to Fight COVID-19

    With continued social disruption caused by the worldwide spread of the novel coronavirus (SARS-CoV-2), Shionogi continues intensive efforts to deliver pharmaceutical products to patients in need in a reliable and stable manner. As a pharmaceutical company with a major focus on infectious diseases, Shionogi is also working with public institutions, academia, and partner companies to address COVID-19, by pursuing the discovery of novel therapeutics and the development of vaccine and diagnostic products. We will continue to strive to fulfill our social responsibility and to contribute to re-establishing the safety and security of society by bringing forward new tools and technologies for the diagnosis and treatment of COVID-19 to support ending this pandemic. Shionogi will work closely with government, industry, and academia to accelerate our efforts and will keep all stakeholders informed regarding the progress of our efforts.

    Forward Looking Statement

    This announcement contains forward-looking statements. These statements are based on expectations in light of the information currently available, assumptions that are subject to risks and uncertainties which could cause actual results to differ materially from these statements. Risks and uncertainties include general domestic and international economic conditions such as general industry and market conditions, and changes of interest rate and currency exchange rate. These risks and uncertainties particularly apply with respect to product-related forward-looking statements. Product risks and uncertainties include, but are not limited to, completion and discontinuation of clinical trials; obtaining regulatory approvals; claims and concerns about product safety and efficacy; technological advances; adverse outcome of important litigation; domestic and foreign healthcare reforms and changes of laws and regulations. Also, for existing products, there are manufacturing and marketing risks, which include, but are not limited to, inability to build production capacity to meet demand, unavailability of raw materials and entry of competitive products. The company disclaims any intention or obligation to update or revise any forward-looking statements whether as a result of new information, future events or otherwise.

    To read the full press release, click here.

  • ACTG to Make 33 Presentations at CROI 2022

    February 8, 2022 Alexis Sexton Spotlight

    ACTG TO MAKE 33 PRESENTATIONS AT CROI 2022

    Presentations Focus on HIV Cure; COVID-19; Tuberculosis, Hepatitis C, and Other Co-Morbidities; Contraception; HIV Prevention, Persistence, and Resistance

    Los Angeles, Calif. – The AIDS Clinical Trials Group (ACTG), the world’s largest HIV research network whose focus has expanded to include evaluating outpatient treatment for COVID-19, will present six oral and 27 poster sessions at the Conference on Retroviruses and Opportunistic Infections (CROI 2022), which will be held virtually February 12-16, 2022. CROI is the premier global HIV research conference and ACTG’s significant presence at the meeting demonstrates its continued leadership in HIV and related fields.

    “The ACTG has continued to lead high-impact HIV research, including work on tuberculosis, HIV cure, co-morbidities, hepatitis, and now COVID-19, for more than 30 years,” said ACTG Chair Judith Currier, M.D., MSc, of the University of California, Los Angeles. “Highlights of our presentations at CROI this year include findings on COVID-19 among people living with HIV, interactions between emergency contraception and TB treatment, and insights into neurocognitive and functional impairment among people living with HIV. Our presence at this year’s meeting demonstrates our commitment to advancing a broad array of research to support people living with and vulnerable to these conditions.”

    ACTG presentations are listed below by topic.

    COVID-19

    COVID-19 VACCINATION RATES IN A GLOBAL HIV COHORT (ACTG 5332/REPRIEVE; Oral Presentation: Monday, February 14, 2022, 1:09 PM EST) Evelynne S. Fulda, et al.

    This study investigated COVID-19 vaccination rates among participants in ACTG 5332/ REPRIEVE (Randomized Trial to Prevent Vascular Events), a global primary cardiovascular prevention trial among people living with HIV in 12 countries, in order to better understand rates among this immunocompromised population with significant morbidity from COVID-19.

     

    CAMOSTAT IS NOT EFFECTIVE FOR MMILD-MODERATE COVID-19 IN A PHASE II TRIAL OF ACTIV-2 (ACTG 5401/ACTIV-2; Oral Presentation: Tuesday, February 15, 2022, 1:17 PM EST) Nick Jilg, Kara Chew et al.

    This study evaluated the safety, antiviral, and clinical efficacy of orally administered camostat, a serine protease inhibitor, in non-hospitalized adults with mild-moderate COVID-19.

     

    POST-ACUTE SEQUELAE OF SARS-COV-2 IN NON-HOSPITALIZED ACTIV-2 TRIAL PARTICIPANTS (ACTG 5401/ACTIV-2; Poster Presentation: Monday, February 14 2022, 4:00 PM – 5:30 PM EST) Teresa H. Evering, et al.

    ACTG 5401/ACTIV-2 is an ongoing phase 2/3 study evaluating the safety and efficacy of investigational treatments to treat non-hospitalized adults with mild to moderate COVID-19. This analysis reports on symptom diaries completed by participants.

     

    ASYMPTOMATIC SARS-COV-2 INFECTION IS EXTREMELY COMMON AMONG PEOPLE WITH HIV (ACTG 5332/REPRIEVE; Poster Presentation: Tuesday, February 15, 2022, 4:00 PM – 5:30 PM EST) Isabelle R. Weir, et al.

    While asymptomatic COVID-19 is common among the general population, it has not been examined specifically among people living with HIV. This study presents data on asymptomatic COVID-19 among people living with HIV in the REPRIEVE cohort.

     

    PHASE-2 EVALUATION OF SAB-185, A POLYCLONAL ANTIBODY TREATMENT FOR COVID-19 in ACTIV-2 (ACTG 5401/ACTIV-2; Poster Session: Tuesday, February 15, 2022, 4:00 PM – 5:30 PM EST) Babafemi Taiwo, Kara Chew, et al.

    ACTIV-2 evaluated the safety and efficacy of the investigational polyclonal antibody treatment SAB-185 among non-hospitalized adults with mild-moderate COVID-19.

     

    TUBERCULOSIS

    PK OF DOSE-ADJUSTED EMERGENCY CONTRACEPTION WITH RIFAMPICIN THERAPY IN ACTG A5375 (ACTG 5375; Oral Session: Tuesday, February 15, 2022, 1:01 PM EST) Rosie Mngqibisa, et al.

    Expanding access to contraception is essential to prevent pregnancy-related health risks for women with tuberculosis, but drug-drug interactions are a concern, as rifampicin reduces levonorgestrel (for emergency exposure) by 57%. This study evaluates whether an adjusted dose of levonorgestrel during rifampicin therapy would result in similar PK exposure compared to standard dose levonorgestrel in the absence of the drug-drug interaction.

     

    DTG PK IN PEOPLE WITH HIV RECEIVING DAILY 1HP FOR LATENT TB TREATMENT (ACTG A5372; Oral Session: Tuesday, February 15, 2022, 1:09 PM EST) Marjorie Imperial, et al.

    This study evaluated the effect of 1HP (a 28-day regimen of daily rifapentine+isoniazid) on the pharmacokinetics of dolutegravir to assess a potentially clinical relevant drug interaction.

     

    HIV RESERVOIRS AND CURE STRATEGIES

    POST-TREATMENT CONTROLLERS MAINTAIN A LIMITED INTACT RESERVOIR AFTER ART INTERRUPTION (ACTG 5068; Poster Session: Monday, February 14, 2022, 4:00 PM – 5:30 PM EST) Yijia Li, et al.

    HIV post-treatment controllers (PTCs) are people living with HIV who are able to maintain viral suppression after an analytical treatment interruption (ATI). A5068 evaluated HIV-1 proviral dynamics before and after ATI in PTCs and non-controllers (NCs).

     

    ACTG A5351S: EFFECT OF IMMUNE-MODULATORY INTERVENTIONS ON CMV REPLICATION DURING ART (ACTG 5351s; Poster Session: Monday, February 14, 2022, 4:00 PM – 5:30 PM EST) Elizabeth Hastie, et al.

    This study investigated the impact of different immune modulating interventions on CMV replication.

     

    N-GLYCOSYLATION SITES DIFFERENTIATIONS BETWEEN PTCS AND NCS (NWCS 380; Poster Session: Monday, February 14, 2022, 4:00 PM – 5:30 PM EST) Elmira Esmaeilzadeh, et al.

    Viral evolution is frequently modulated by host immune pressures and comparing viral sequence changes in PTCs and post-treatment NCs may provide insight on mechanisms behind HIV remission. This analysis of NWCS 380 sought to elucidate the link between the N-glycosylation sites in the HIV envelope (which play a critical role in viral evolution and immune escape against humoral immune responses) and post-treatment control.

     

    POST-TREATMENT CONTROLLERS LIMIT COMPLETED AND SPLICED HIV TRANSCRIPTS AFTER ATI (NWCS 380; Poster Session: Monday, February 14, 2022, 4:00 PM – 5:30 PM EST) Adam Wedrychowski, et al.

    The mechanisms that allow PTCs to limit viral replication after ATI remain unclear. This analysis evaluated whether PTCs would show greater blocks to HIV transcriptional completion and splicing following ATI than NCs.

     

    SIZE AND ACTIVITY OF THE HIV RESERVOIR PREDICT REBOUND TIMING AFTER ART INTERRUPTION (ACTG 5345; Poster Session: Tuesday, February 15, 2022, 4:00 PM – 5:30 PM EST) Jonathan Z. Li, et al.

    Identifying biomarker predictors of HIV rebound timing is crucial for accelerating the design and evaluation of effective interventions for HIV remission. ACTG 5345 assessed associations between reservoir measures and the timing of viral rebound.

     

    T CELLS EXPRESSING MULTIPLE INHIBITORY RECEPTORS PERSIST ON LONG-TERM ART (ACTG 5321; Poster Session: Tuesday, February 15, 2022, 4:00 PM – 5:30 PM EST) Bernard JC Macatangay, et al.

    Expression of multiple IRs is associated with T cell exhaustion in chronic viral infections. ACTG 5321 compared frequencies of T cells expressing ≥2 IRs among people living with HIV and in age-matched individuals who were HIV-negative.

     

    INHIBITORY RECEPTOR EXPRESSION CORRELATES WITH HIV PERSISTENCE AND IMMUNE RESPONSES (ACTG 5321; Poster Session: Tuesday, February 15, 2022, 4:00 PM – 5:30 PM EST) Bernard JC Macatangay, et al.

    T cell expression of inhibitory receptors (IR) has been associated with measures of HIV persistence and immune responses to HIV. ACTG 5321 evaluated which combinations of IRs were associated with HIV persistence and HIV-specific immune responses in a cohort of people living with HIV with suppressed plasma viremia.

     

    EARLY ANTIRETROVIRAL THERAPY REDUCES BUT DOES NOT ELIMINATE HIV DNA IN BLOOD (ACTG 5354; Poster Session: Tuesday, February 15, 2022, 4:00 PM – 5:30 PM EST) Trevor A. Crowell, et al.,

    Antiretroviral therapy (ART) initiated during acute or early HIV infection may limit HIV reservoir formation and facilitate HIV remission. ACTG 5354 evaluated HIV DNA levels in blood at and after suppressive ART initiation across acute and early stages of HIV infection and found that ART initiation in earlier stages reduced but did not eliminate the persistence of HIV-infected cells in blood.

     

    HIV-SPECIFIC T CELL FREQUENCIES AND FUNCTION AFTER ART DURING ACUTE OR EARLY HIV (ACTG 5354; Poster Session: Tuesday, February 15, 2022, 4:00 PM – 5:30 PM EST) Scott Sieg, et al.

    The immunologic effects of starting ART during acute or early HIV infection are not well defined. This study evaluated the impact of early ART on antigen exposure and T cell immune responses.

     

    FEASIBILITY AND VIRAL RESPONSE TO TREATING ACUTE/EARLY HIV IN A MULTINATIONAL STUDY (ACTG 5354; Poster Session: Wednesday, February 16, 2022, 4:00 PM – 5:30 PM EST) Eric S. Daar, et al.

    This study reports on the feasibility of rapidly identifying individuals with suspected acute or early HIV infection, starting ART, and achieving viral suppression during acute or early HIV infection.

     

    HIV ENVELOPE DIVERSITY AND SENSITIVITY TO BNABS ACROSS STAGES OF ACUTE AND EARLY HIV (ACTG 5354; Poster Session: Wednesday, February 16, 2022, 4:00 PM – 5:30 PM EST) Laurie VanderVeen, et al.

    Genetic diversity of the HIV envelope complicates use of broadly neutralizing antibodies (bNAbs) for HIV treatment and cure. ART during acute or early HIV infection restricts reservoir size and diversity, increasing the likelihood of bNAb susceptibility. Because successful treatment of ART-suppressed patients with bNAbs requires understanding the evolution of HIV envelope diversity, this study characterized both HIV envelope diversity and bNAb sensitivity at initiation of ART during acute or early HIV infection and after ART suppression.

     

    IMMUNE RESPONSES FOLLOWING ANTI-PD-1 MONOCLONAL ANTIBODY INFUSION IN PERSONS WITH HIV (ACTG 5370; Poster Session: Wednesday, February 16, 2022, 4:00 PM – 5:30 PM EST) Bernard JC Macatangay, et al.

    PD-1 expression on T cells is associated with cellular exhaustion in HIV. ACTG 5370 evaluated multiple immunologic parameters following infusion of an anti-PD1 monoclonal antibody in ARTsuppressed people living with HIV.

     

    HEPATITIS C

    ADHERENCE IN THE ACTG 5360 HCV MINIMAL MONITORING (MINMON) TRIAL (ACTG 5360/MINMON; Poster Presentation: Tuesday, February 15, 2022, 4:00 PM – 5:30 PM EST) Leonard Sowah, et al.

    Understanding of the association between adherence and treatment outcomes and correlates of non-adherence among people receiving direct-acting antivirals for hepatitis C is limited. This analysis of ACTG 5360 (MINMON), a multinational trial to evaluate the safety and efficacy of 12 weeks of sofosbuvir/velpatasvir with reduced in-person visits and laboratory monitoring, evaluated the association of adherence with sustained virologic response and correlates of adherence.

     

    COMORBIDITIES and AGING

    GEOGRAPHICAL DIFFERENCES IN FUNCTIONAL IMPAIRMENT OF PEOPLE WITH HIV (ACTG 5332; Oral Session: Monday, February 14, 2022, 11:50 AM EST) Kristine M. Erlandson, et al.

    Functional impairments occur at a younger age among people living with HIV. ACTG 5332 sought to better understand multinational differences (by Global Burden of Disease regions) in functional status and associated factors in the REPRIEVE cohort.

     

    L-FERRITIN AND TIM-1 ARE ASSOCIATED WITH FRAILTY MEASURES IN PEOPLE WITH HIV (ACTG 5322/HAILO; Poster Session: Monday, February 14, 2022, 4:00 PM – 5:30 PM EST) Asha Kallianpur, et al.

    ACTG 5322 evaluated whether lower serum levels of the antioxidant iron transporter heavy-chain (H)-ferritin (Fth1) and light-chain (L)-ferritin (Ftl), and higher levels of urine T-cell immunoglobulin and mucin domain (Tim)-1 (Fth1 receptor) were associated with worse frailty among people living with HIV, who are generally at high risk of physical-function impairment and frailty.

     

    H/L-FERRITINS AND TIM-1 ASSOCIATE WITH NEUROCOGNITIVE FUNCTION IN PEOPLE WITH HIV (ACTG 5322/HAILO; Poster Session: Monday, February 14, 2022, 4:00 PM – 5:30 PM EST) Asha Kallianpur, et al.

    ACTG 5322 investigated the association between Fth1, Ftl, and Tim-1 levels and neurocognitive impairment in people living with HIV.

     

    ASSOCIATIONS BETWEEN PLASMA BIOMARKERS AND NEUROCOGNITION IN ART-TREATED PWH (NWCS 447; Poster Session: Monday, February 14, 2022, 4:00 PM – 5:30 PM EST) Robert Kalayjian, et al.

    NWCS 447 examined associations between plasma biomarker concentrations of inflammation and gut integrity with prevalent/incident neurocognitive impairment and cognitive trajectories in aging participants living with HIV receiving ART in the HAILO study.

     

    NAFLD IS COMMON AMONG REPRIEVE PARTICIPANTS AND ASSOCIATED WITH CARDIOVASCULAR RISK (ACTG 5332/REPRIEVE; Poster Session: Monday, February 14, 2022, 4:00 PM – 5:30 PM EST) Carl J. Fichtenbaum, et al.

    Non-alcoholic fatty liver disease (NAFLD) is common among people living with HIV and is associated with elevated cardiovascular disease risk. This study presents baseline data on the prevalence and cardiometabolic characteristics of NAFLD among REPRIEVE participants who underwent computed tomography.

     

    IMMUNE ACTIVATION AND SUBCLINICAL ATHEROSCLEROSIS AMONG US FEMALES VS. MALES WITH HIV (ACTG 5332/REPRIEVE; Poster Session: Monday, February 14, 2022, 4:00 PM – 5:30 PM EST) Markella V. Zanni, Borek Foldyna, et al.

    This analysis characterized sex differences (which may be influenced by underlying differences in immune indices, coronary plaque parameters, or relationships therein) in presentations of atherosclerotic cardiovascular disease among REPRIEVE participants.

     

    PROTEINURIA IS COMMON AMONG PEOPLE WITH HIV WITH CONTROLLED HIV VIREMIA (ACTG 5332/REPRIEVE; Poster Session: Tuesday, February 15, 2022, 4:00 PM – 5:30 PM EST) Edgar T. Overton, et al.

    This study evaluated the prevalence of proteinuria and albuminuria, important markers of chronic kidney disease, among REPRIEVE participants on ART.

     

    ACTG A5324: A randomized trial of ART intensification for cognitive impairment in PWH (ACTG 5324; Oral Session: Wednesday, February 16, 2022, 1:09 PM EST) Scott Letendre, et al.

    Cognitive impairment in people living with HIV on suppressive ART may result from persistence of HIV in the central nervous system. A5324 evaluated whether ART intensification would improve neuropsychological performance among people living with HIV who had neurocognitive impairment on suppressive ART.

     

    IMPACT OF INTEGRASE STRAND TRANSFER INHIBITORS ON COGNITION IN THE HAILO COHORT (ACTG 5322/HAILO; Poster Session: Wednesday, February 16, 2022, 4:00 PM – 5:30 PM EST) Jane A. O’Halloran, et al.

    ACTG A5322 (HAILO, HIV Infection, Aging and Immune Function Long-term Observational Study) evaluated people aging with HIV who had switched to an integrase strand transfer inhibitor (INSTI) in an effort to better understand the impact of ART on neuropsychological outcomes, particularly cognition.

     

    HIV TREATMENT STRATEGIES

    Efficacy OF Tenofovir-Lamivudine-Dolutegravir FOR INITIAL AND FIRST-LINE SWitch ART (ACTG 5381; Poster Session: Wednesday, February 16, 2022, 4:00 PM – 5:30 PM EST) Cissy Kityo, et al.

    The single-tablet tenofovir disoproxil fumarate/lamivudine/dolutegravir (TLD) has been rapidly adopted as first-line ART for adults and adolescents initiating treatment and switching from virally suppressive NNRTI-based first regimens in PEPFAR programs despite limited data on effectiveness and emergence of resistance to TLD in these settings where plasma HIV-1 RNA and drug resistance testing are not widely used. ACTG 5381 assessed therapeutic efficacy and emergence of HIV drug resistance following TLD initiation for first-, second-, or third-line ART.

     

    PHARMACOGENETICS OF WEIGHT GAIN AFTER SWITCH TO INTEGRASE INHIBITOR-BASED REGIMENS (DACS 349; Poster Session: Wednesday, February 16, 2022, 4:00 PM – 5:30 PM EST) David Haas, et al.

    Excessive weight gain affects some people living with HIV after they switch to INSTI-based ART. DACS 349 studied associations between CYP2B6 genotype and weight gain after switching from efavirenz- to INSTI-based ART among participants in ACTG observational cohort studies A5001 and A5322.

     

    EX VIVO ASSAY PREDICTS HIV-1 SUPPRESSION BY BNABS INFUSED IN A PHASE I CLINICAL TRIAL (ACTG 5378; Poster Session: Wednesday, February 16, 2022, 4:00 PM – 5:30 PM EST) Sabrina Helmold Hait, et al.

    This study evaluated whether a newly developed ex vivo assay was able to predict the potential for a bNAb to induce an in vivo virologic response among people living with HIV who were viremic.

     

     HIV PREVENTION

    EXPECTATIONS OF PREVENTIVE BENEFITS AND HIV-RELATED RISK BEHAVIORS IN HPTN069/ACTG 5305 (ACTG 5305/HPTN069; Poster Session: Wednesday, February 16, 2022, 4:00 PM – 5:30 PM EST) Jeremy Sugarman, et al.

    HPTN069/ACTG A5305 evaluated whether participants’ preventive misconceptions (expectations that experimental interventions will confer protection from HIV) increased the likelihood that they would engage in behaviors that could increase their chance of acquiring HIV.

     

    About the ACTG

    Founded in 1987, the AIDS Clinical Trials Group (ACTG), was the world’s first HIV research network. Funded by the National Institute of Allergy and Infectious Diseases, part of the National Institutes of Health, and collaborating NIH institutes, the ACTG conducts groundbreaking studies to improve the treatment of HIV and its complications, including tuberculosis and viral hepatitis; reduce new infections and HIV-related illness; and advance new approaches to prevent, treat, and ultimately cure HIV in adults and children. More recently, The ACTG has expanded its focus to include the evaluation of outpatient treatments for COVID-19. ACTG investigators and research units in 15 countries serve as major resources for HIV/AIDS research, treatment, care, and training/education in their communities. ACTG studies have helped establish current paradigms for managing HIV disease, and have informed HIV treatment guidelines, resulting in dramatic decreases in HIV-related mortality worldwide.

    To read the full press release, click here.

  • ACTG Announces Initiation of A5355, Clinical Trial Studying New CMV Vaccine

    December 16, 2021 Alexis Sexton Spotlight

    The AIDS Clinical Trials Group (ACTG), the largest global HIV research network, today announced the launch of A5355, a clinical trial studying a new cytomegalovirus (CMV) vaccine in adults with both HIV and CMV. The study will evaluate whether the new vaccine Triplex is safe and effective in eliciting a CMV-specific immune response in people living with HIV and is thus able to suppress CMV replication.

    Almost everyone living with HIV is also living with CMV. There is strong evidence that living with both HIV and CMV is associated with chronic inflammation, which may be related to significant co-morbidities, including heart disease, strokes, neurological problems, and diabetes. Triplex is a modified vaccinia ankara (MVA)-based vaccine that encodes three full-length CMV antigens [pp65 (UL83), IE1-exon4 (UL123), and IE2-exon5 (UL122)]. Phase 1 and 2 studies conducted in more than 100 adults with hematologic stem cell transplants have demonstrated that Triplex is safe and can prevent CMV-related disease.

    “Because almost all individuals living with HIV have also been exposed to CMV and they both persist across the lifetime, CMV is an important research focus as we seek to curtail the impact of other chronic diseases associated with HIV,” said ACTG chair Judith Currier, M.D., M.Sc., University of California, Los Angeles. “The ACTG is eager to gain insights from this first-of-its-kind study into Triplex’s potential ability to reduce systemic inflammation among people living with HIV, which can be linked to a number of health issues that impact their quality of life.”

    A5355 is a phase 2, double-blind, randomized, placebo-controlled study evaluating the safety and immunogenicity of two injections of Triplex in adults aged 18 to 65 living with both HIV and CMV. Participants will be randomized in a 2:1 ratio, such that 60 will receive Triplex and 30 will receive placebo at study entry (day zero) and week four, both through two intramuscular deltoid injections. Participants will be followed for 92 weeks after the last scheduled vaccination at week four, for a total study duration of 96 weeks. At least 25 percent of participants will be cisgender or transgender women, and all must have undetectable HIV RNA on antiretroviral therapy (with current CD4+ cell count >250 cells/μL and nadir CD4+ cell count ≥100 cells/μL).

    “We hope that improved control of asymptomatic CMV replication will decrease systemic markers of inflammation and eventually improve the lives of people with HIV worldwide,” said protocol chair Sara Gianella, M.D., University of California, San Diego (UCSD). “We are particularly excited that this study is making a dedicated effort to enroll cisgender and transgender women, who tend to be underrepresented in most HIV treatment studies.”

    A5355 is led by Dr. Gianella and Davey Smith, M.D., USCD. City of Hope, a National Cancer Institute-designated comprehensive cancer center in southern California, developed Triplex. It is being supplied to study A5355 by City of Hope and Don Diamond, Ph.D., a City of Hope professor. Helocyte, Inc., a partner company of Fortress Biotech, Inc, is the exclusive worldwide licensee of Triplex.

    About the ACTG

    Founded in 1987, the AIDS Clinical Trials Group (ACTG) was the world’s first HIV research network. It is funded by the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health (NIH), and collaborating NIH Institutes. The ACTG conducts groundbreaking studies to improve the treatment of HIV and its complications, including tuberculosis and viral hepatitis; reduce new infections and HIV-related illness; and advance new approaches to prevent, treat, and ultimately cure HIV in adults and children. More recently, The ACTG has expanded its focus to include the evaluation of outpatient treatments for COVID-19. ACTG investigators and research units in 15 countries serve as major resources for HIV/AIDS research, treatment, care, and training/education in their communities. ACTG studies have helped establish current paradigms for managing HIV disease, and have informed HIV treatment guidelines, resulting in dramatic decreases in HIV-related mortality worldwide.

     

    To read full press release, click here.

  • ACTG Announces Initiation of CLO-FAST, Its First Trial Evaluating a Three-month TB Treatment

    November 10, 2021 Alexis Sexton Spotlight

    The AIDS Clinical Trials Group (ACTG), the largest global HIV research network, today announced the launch of A5362 (CLO-FAST), a clinical trial studying a three-month clofazimine- and high-dose rifapentine-containing treatment regimen for people with drug-susceptible tuberculosis (TB). This is the first TB regimen based on preclinical evidence of effectiveness that is less than four-months long to be studied in a clinical trial. A5362 will evaluate the potential efficacy of clofazimine when combined with treatments that have been proven to be effective against TB.

    Clofazimine achieves high tissue concentrations, which may contribute to sustained antimicrobial activity once treatment has ended. While it was first synthesized as an anti-TB drug, it has been primarily used (and well tolerated) in people with lepromatous leprosy over the past 50 years. Preclinical studies suggest that there may be powerful synergies in combining clofazimine with other TB treatments, which could substantively shorten TB treatment.

    “Shortening the duration of TB treatment remains one of the most important goals in global infectious disease research,” said ACTG Chair Judith Currier, M.D., M.Sc., University of California, Los Angeles. “For nearly the last half century, standard TB treatment required people to take medication for six months. The ACTG-sponsored A5349 recently demonstrated the potential of a four-month rifapentine-containing treatment regimen, a paradigm-shifting result. A5362 aims to build upon those findings by helping us better understand the activity of clofazimine and whether it may have the potential to further shorten TB treatment to three months.”

    A5362 is a phase 2c, open label, randomized study that is evaluating the efficacy, safety, and tolerability of adding clofazimine and substituting rifapentine for rifampin, compared to the six-month standard-of-care combination TB therapy. The trial will compare the early efficacy (time needed to convert TB sputum cultures to negative over 12 weeks) of a clofazimine- and rifapentine-containing regimen with the six-month standard TB regimen. It will also identify clinical treatment outcomes that will help determine whether the clofazimine-containing regimen should proceed to be studied in a large phase 3 clinical trial. A5362 will enroll a total of 185 participants and will follow them for 65 weeks. Participants will be randomized to the following groups:

    • Arm 1 (experimental) will begin with a two-week loading dose of 300 mg of clofazimine and rifapentine (1200 mg/day) + isoniazid + pyrazinamide + ethambutol (PHZE) once a day, followed by six weeks of PHZE plus 100 mg of clofazimine once a day, followed by five weeks of rifapentine + isoniazid + pyrazinamide plus 100 mg of clofazimine once a day (for a total of three months of treatment).
    • Arm 2 (standard of care) will begin with eight weeks of rifampin + isoniazid + pyrazinamide + ethambutol (RHZE) for 8 weeks, followed by 18 weeks of rifampin + isoniazid (for a total of six months of treatment).
    • Arm C (subgroup evaluating pharmacokinetics) will replace the first four weeks of standard of care (Arm 2, above) with PHZE plus 100 mg of clofazimine (for a total of six months of treatment).

    “Through the novel trial design of A5362, we aim to shed light on key characteristics of clofazimine treatment that we don’t yet understand, while piloting an early assessment of a potential three-month treatment regimen for drug-susceptible TB,” said protocol chair John Metcalfe, M.D., Ph.D., M.P.H., University of California, San Francisco. “We are hopeful that pairing it with other TB drugs with potent sterilizing activity will allow for a shorter course of treatment, thereby reducing the burden on the millions of people around the world who require TB treatment.”

    A5362 is led by Dr. Metcalfe, Samuel Pierre, M.D. (Les Centres Gheskio CRS, Haiti), and Kimberly Scarsi, PharmD, M.S. (University of Nebraska Medical Center). It is funded by the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health (NIH), and study drugs are supplied by the Global Drug Facility.

    About the ACTG

    Founded in 1987, the AIDS Clinical Trials Group (ACTG) was the world’s first HIV research network. It is funded by NIAID and collaborating NIH Institutes. The ACTG conducts groundbreaking studies to improve the treatment of HIV and its complications, including tuberculosis and viral hepatitis; reduce new infections and HIV-related illness; and advance new approaches to prevent, treat, and ultimately cure HIV in adults and children. ACTG investigators and research units in 15 countries serve as major resources for HIV/AIDS research, treatment, care, and training/education in their communities. ACTG studies have helped establish current paradigms for managing HIV disease, and have informed HIV treatment guidelines, resulting in dramatic decreases in HIV-related mortality worldwide.

    To read the full press release, click here.

  • ACTG Launches Study Evaluating How a History of COVID-19 and Prior Investigational COVID-19 Treatment May Affect COVID-19 Vaccine Response

    November 3, 2021 Alexis Sexton Spotlight

    The AIDS Clinical Trials Group (ACTG), the largest global HIV research network, which recently expanded its focus to include evaluating outpatient treatment for COVID-19, today announced the launch of A5404, a clinical trial studying how prior infection with SARS-CoV-2 and receiving either an investigational COVID-19 therapy or placebo/active comparator affects participants’ immune responses to mRNA COVID-19 vaccines. A5404 is a sub-study of the ACTIV-2 Outpatient Monoclonal Antibodies and Other Therapies Trial (ACTG A5401), which is evaluating multiple investigational agents to treat early, symptomatic COVID-19 in non-hospitalized individuals.

    “A5404 provides us with an important opportunity to gain insights into potentially different responses to mRNA COVID-19 vaccines among participants who have had COVID-19, which will be especially important as we work to optimize the timing of vaccines for those individuals,” said ACTG chair Judith Currier, M.D., M.Sc., University of California, Los Angeles (UCLA).

    A5404 is a phase 4, open-label study that aims to learn about the difference in neutralizing antibody (NAb) responses to mRNA-based COVID-19 vaccines among participants with prior SARS-CoV-2 infection who participated in ACTIV-2 (who either received an investigational COVID-19 treatment or placebo or active comparator) and participants who have no history of COVID-19 and did not participate in ACTIV-2. A5404 will enroll 70 participants each from five different ACTIV-2 therapy groups and up to 70 participants without prior history of COVID-19 for each ACTIV-2 therapy group.

    • In the first cohort, ACTIV-2 participants will either receive the Moderna COVID-19 vaccine through the study or the Moderna or Pfizer COVID-19 vaccine at a community site. They will receive their vaccine 30-240 days after their last day of ACTIV-2 study treatment.
    • In the second cohort, participants without history of prior COVID-19 will receive the Moderna COVID-19 vaccine through the study.

    All participants will have their blood collected and their immune responses measured as close to when the vaccine is administered as feasible and at eight and 20 weeks and one and two years after the first vaccine dose.

    “The development of COVID-19 vaccines and treatments is moving fast, but we still have a lot to learn,” said Davey Smith, M.D., University of California, San Diego, A5404 study chair. “A5404 aims to help us better understand how people who have had COVID-19 and may have been treated for it respond to vaccination to prevent reinfection with COVID-19. As such, this study has the potential to fill in a major gap in our knowledge about the relationship between COVID-19 treatment and vaccination.”

    ACTIV-2, the parent study of A5404, is currently evaluating several agents in phase 3 after having completed a phase 2 study of each treatment:

    • BRII-196 plus BRII-198: two monoclonal antibodies administered as two separate infusions as a one-time dose (fully enrolled)
    • SAB-185: a polyclonal antibody, which combines many different antibodies in a single infusion
    • SNG001: a nebulized formulation of beta interferon being studied as an inhalant taken every day for 14 days

    ACTIV-2 is also currently evaluating several agents in phase 2 (both are fully enrolled):

    • BMS 986414 and BMS-986413: two monoclonal antibodies administered as subcutaneous injections (shots) given at one visit
    • AZD7442: a combination of two monoclonal antibodies (AZD8895 and AZD1061) that is being studied both as a single 15-minute infusion and a one-time intramuscular injection (shot)

    A5404 is led by Dr. Smith (chair) and Kara W. Chew, M.D., M.S., UCLA, David Alain Wohl, M.D., University of North Carolina (UNC), and Eric S. Daar, M.D., Lundquist Institute at Harbor-UCLA Medical Center (vice-chairs). ACTIV-2 is led by Drs. Chew and Smith (protocol chairs) and Drs. Wohl and Daar (vice-chairs) and supported by Dr. Currier and ACTG Co-Chair Joseph J. Eron, M.D., UNC.

    ACTIV-2 is sponsored by the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health (NIH), which also funds the ACTG. ACTIV-2 is part of NIH’s Accelerating COVID-19 Therapeutic Interventions and Vaccines (ACTIV), a public-private partnership program to create a coordinated research strategy that prioritizes and speeds development of the most promising treatments and vaccines. It also receives support from the Federal COVID Response-Therapeutics, the U.S. government’s multi-agency effort to accelerate the development, manufacturing, and distribution of COVID-19 vaccines, therapeutics, and diagnostics.

    For more information please visit www.actgnetwork.org or clinicaltrials.gov.

    About the ACTG

    Founded in 1987, the AIDS Clinical Trials Group (ACTG) was the world’s first HIV research network. The ACTG conducts groundbreaking studies to improve the treatment of HIV and its complications, including tuberculosis and viral hepatitis; reduce new infections and HIV-related illness; and advance new approaches to prevent, treat, and ultimately cure HIV in adults and children. ACTG investigators and research units in 15 countries serve as major resources for HIV/AIDS research, treatment, care, and training/education in their communities. ACTG studies have helped establish current paradigms for managing HIV disease, and have informed HIV treatment guidelines, resulting in dramatic decreases in HIV-related mortality worldwide.

    To read the full press release, click here.

  • ACTG Announces Graduation of Investigational Inhaled COVID-19 Treatment to Phase 3 Study in ACTIV-2

    October 21, 2021 Alexis Sexton Spotlight

    The AIDS Clinical Trials Group (ACTG), the largest global HIV research   network, which recently expanded its focus to include evaluating outpatient treatment for COVID-19, today announced that the external data and safety monitoring board (DSMB) has recommended that SNG001, an inhaled formulation of interferon beta, advance to phase 3 in the ACTIV-2 Outpatient Monoclonal Antibodies and Other Therapies Trial (ACTG A5401). SNG001 is the third agent to graduate to phase 3 in ACTIV-2, which is evaluating multiple investigational agents to treat early, symptomatic COVID-19 in non-hospitalized individuals. For more information about the trial, please visit the study website.

    ACTIV-2 is the first U.S. study to evaluate SNG001 (developed by Synairgen) among non-hospitalized people with COVID-19. SNG001 is self-administered as a nebulized dose (15.6 MIU) that participants inhale once daily for 14 days. Participants are trained to use the nebulizer device by study staff and take all doses at home. BRII-196/BRII-198 (a combination monoclonal antibody treatment) and SAB-185 (a novel polyclonal antibody therapy) are both currently also in phase 3 study in ACTIV-2.

    “ACTIV-2 is currently evaluating treatment options that can be delivered in different ways, which is important as we aim to identify solutions that work for people who have a variety of needs,” said ACTG Chair Judith Currier, M.D., M.Sc., University of California, Los Angeles (UCLA). “In addition to a combination monoclonal antibody infusion and polyclonal antibody infusion, this nebulized, inhaled version of interferon beta broadens potential treatment options for people who have COVID-19 but are not hospitalized, which we believe could significantly simplify care for some people with COVID-19.”

    The ACTIV-2 DSMB recommended that SNG001 advance into a phase 3 study among participants with mild to moderate COVID-19. The planned phase 3 study will evaluate the safety and efficacy of SNG001 in reducing the risk of hospitalization and death among non-hospitalized adults with COVID-19.

    ACTIV-2 is a randomized, blinded, controlled adaptive platform that allows promising therapies to be added and removed over the course of the study to efficiently test a variety of new agents within the same trial infrastructure. The SNG001 study is being led by William Fischer, M.D., University of North Carolina (UNC) and Upinder Singh, M.D., and Prasanna Jagannathan, M.D., both of Stanford University. ACTIV-2 is led by Kara W. Chew, M.D., M.S., UCLA and Davey Smith, M.D., University of California, San Diego (protocol chairs) and David Alain Wohl, M.D., UNC and Eric S. Daar, M.D., Lundquist Institute at Harbor-UCLA Medical Center (vice-chairs) and supported by Dr. Currier and ACTG Co-Chair Joseph J. Eron, M.D., UNC.

    ACTIV-2 is sponsored by the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health (NIH), which also funds the ACTG. ACTIV-2 is part of NIH’s Accelerating COVID-19 Therapeutic Interventions and Vaccines (ACTIV), a public-private partnership program to create a coordinated research strategy that prioritizes and speeds development of the most promising treatments and vaccines. It also receives support from the Federal COVID Response-Therapeutics, the U.S. government’s multi-agency effort to accelerate the development, manufacturing, and distribution of COVID-19 vaccines, therapeutics, and diagnostics.

    For more information about ACTIV-2, please visit www.riseabovecovid.org, www.actgnetwork.org, or clinicaltrials.gov.

    About the ACTG

    Founded in 1987, the AIDS Clinical Trials Group (ACTG) was the world’s first HIV research network. The ACTG conducts groundbreaking studies to improve the treatment of HIV and its complications, including tuberculosis and viral hepatitis; reduce new infections and HIV-related illness; and advance new approaches to prevent, treat, and ultimately cure HIV in adults and children. ACTG investigators and research units in 15 countries serve as major resources for HIV/AIDS research, treatment, care, and training/education in their communities. ACTG studies have helped establish current paradigms for managing HIV disease, and have informed HIV treatment guidelines, resulting in dramatic decreases in HIV-related mortality worldwide.

     

    To read the full press release, click here.

  • ACTG to Present Data on Investigational New COVID-19 Treatment at IDWeek 2021

    September 29, 2021 Alexis Sexton Spotlight

    The AIDS Clinical Trials Group (ACTG), the largest global HIV research network, which recently expanded its focus to include evaluating outpatient treatment for COVID-19, today announced that Teresa H. Evering, M.D., M.S., a co-lead investigator (with Eric S. Daar, M.D.) for BRII-196/BRII-198 in the ACTIV-2 study of Outpatient Monoclonal Antibodies and Other Therapies, will present data for the monoclonal antibody combination at the virtual IDWeek 2021 conference, taking place September 29 – October 3, 2021.

    As SARS-CoV-2, the virus that causes COVID-19, continues to spread, there remains a significant need to develop safe and effective therapeutics that prevent severe disease,” said ACTG Chair Judith Currier, M.D., M.Sc., University of California, Los Angeles (UCLA). “This presentation demonstrates that BRII-196/BRII-198 was safe, well-tolerated, and demonstrated a significant reduction in the risk of hospitalization and death among adults with mild to moderate COVID-19 who were high risk of progressing to severe disease. We are excited to present data highlighting a new therapeutic with the potential to help attenuate the impact of this pandemic.”

    BRII-196 and BRII-198 (developed by Brii Biosciences) were derived from antibodies isolated from people who had recovered from COVID-19. Administered as two separate infusions as a one-time dose, they target two different parts of SARS-CoV-2. In an interim analysis, the combination demonstrated a 78 percent reduction in the combined endpoint of hospitalization and death compared with placebo in 837 non-hospitalized participants with COVID-19 who were at high risk of clinical progression. In the ACTIV-2 arm receiving BRII-196/BRII-198, there were 12 hospitalizations and one death, compared to 45 hospitalizations and nine deaths in the arm receiving placebo [2.4 vs. 11.1 percent, relative risk 0.22 (95% CI: 0.05, 0.86), P=0.00001]. Grade 3 or higher adverse events (AEs) were observed less frequently among BRII-196/BRII-198 participants than placebo (3.8 percent vs. 13.4 percent), with no severe infusion reactions or drug-related serious AEs. Notably, the clinical benefit was similar among participants who entered the study after having five or fewer days of symptoms and those who had experieinced symptoms for more than five days.

    Between January and July 2021, ACTIV-2 enrolled participants from sites in the United States, Brazil, South Africa, Mexico, Argentina, and the Philippines who were randomized to receive either BRII-196/BRII-198 or placebo. The median participant age was 49 years; 51 percent of participants were female, 17 percent were Black, and 49 percent were Hispanic. In this interim analysis, 71 percent of participants had a day 28 visit and 97 percent had a day seven visit.

    ACTIV-2 is a randomized, blinded, controlled adaptive platform that allows promising therapies to be added and removed over the course of the study to efficiently test a variety of new agents against placebo within the same trial infrastructure. In addition to studying the safety and efficacy of investigational therapies, ACTIV-2 also aims to determine whether they can decrease viral shedding, thereby potentially preventing transmission of SARS-CoV-2.

    ACTIV-2 is sponsored by the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health (NIH), which also funds the ACTG. ACTIV-2 is part of NIH’s Accelerating COVID-19 Therapeutic Interventions and Vaccines (ACTIV), a public-private partnership program to create a coordinated research strategy that prioritizes and speeds development of the most promising treatments and vaccines. It also receives support from the Federal COVID Response – Therapeutics, the U.S. government’s multi-agency effort to accelerate the development, manufacturing, and distribution of COVID-19 vaccines, therapeutics, and diagnostics. The phase 3 trial is a continuation of the phase 2 trial in which BRII-196/BRII-198 met study-defined safety and efficacy criteria.

    ACTIV-2 is led by Kara Chew, M.D., M.S., UCLA and Davey Smith, M.D., University of California San Diego (protocol chairs) and David Alain Wohl, M.D., University of North Carolina (UNC) and Dr. Daar, Lundquist Institute at Harbor-UCLA Medical Center (vice-chairs), and supported by Dr. Currier and Joseph J. Eron, M.D., UNC (ACTG Co-Chair).

    For more information about ACTIV-2, please visit www.riseabovecovid.orgwww.actgnetwork.org, or clinicaltrials.gov.

    To read the full press release click here.

  • ACTG Announces Graduation of Novel Polyclonal Antibody Therapy SAB-185 to Phase 3 Study in ACTIV-2

    September 27, 2021 Alexis Sexton Spotlight

    The AIDS Clinical Trials Group (ACTG), the largest global HIV research   network, which recently expanded its focus to include evaluating outpatient treatment for COVID-19, today announced that SAB-185, a novel polyclonal antibody therapy, has demonstrated safety and efficacy in phase 2 that meet the criteria for graduation to phase 3 in the ACTIV-2 Outpatient Monoclonal Antibodies and Other Therapies Trial (ACTG A5401). SAB-185 is the second agent to graduate to phase 3 in ACTIV-2, which is evaluating multiple investigational agents to treat early, symptomatic COVID-19 in non-hospitalized individuals. The combination monoclonal antibody treatment BRII-196/BRII-198 graduated to phase 3 in May 2021 and recently reported positive data. For more information about the trial, please visit the study website.

    SAB-185 (developed by SAB Biotherapeutics), is the first polyclonal antibody (a treatment containing a variety of targeted, highly potent antibodies) to be evaluated in ACTIV-2. SAB-185 is made by Tc Bovines™ that have been genetically engineered to make fully human antibodies. Once the bovines develop an immune response and generate antibodies against the spike protein on the surface of SARS-CoV-2 (the virus that causes COVID-19), their plasma is collected, and the antibodies are separated out and purified.

    “The graduation of SAB-185 from phase 2 to phase 3 in ACTIV-2 is an important milestone as we evaluate a variety of potential treatments for people who have COVID-19 but aren’t sick enough to be hospitalized, “said ACTG Chair Judith Currier, M.D., M.Sc., University of California, Los Angeles (UCLA). “We are thrilled that, per the study protocol, the interim analysis of phase 2 data from participants receiving SAB-185 demonstrated sufficient safety and efficacy to justify advancement to phase 3.”

    The phase 2 study of SAB-185 evaluated two doses, both of which met pre-defined criteria for graduation to phase 3. Evaluations are ongoing to determine which of these doses will advance to phase 3. The planned phase 3 study will evaluate the safety and efficacy of SAB-185 to prevent hospitalization and death in non-hospitalized adults with COVID-19. The study will enroll 1,200 participants at high risk of progressing to severe COVID-19. Half of the participants will receive SAB-185 and half will receive casirivimab and imdevimab, Regeneron’s combination monoclonal antibody treatment. Both will be administered as an intravenous infusion.

    ACTIV-2 is a randomized, blinded, controlled adaptive platform that allows promising therapies to be added and removed over the course of the study to efficiently test a variety of new agents within the same trial infrastructure.

    “We are pleased to advance a second agent to phase 3 in the ACTIV-2 study,” said Babafemi Taiwo, M.B.B.S., Professor of Medicine and Chief of Infectious Diseases at Northwestern University and lead investigator of SAB-185 in ACTIV-2. “We are especially enthusiastic about the first polyclonal antibody therapy being evaluated in ACTIV-2. Because it contains a diverse mix of antibodies, SAB-185 can simultaneously attack SARS-CoV-2 at different points, rendering it a very promising treatment option.”

    ACTIV-2 is led by Kara W. Chew, M.D., M.S., UCLA and Davey Smith, M.D., University of California, San Diego (protocol chairs) and David Alain Wohl, M.D., University of North Carolina (UNC) and Eric S. Daar, M.D., Lundquist Institute at Harbor-UCLA Medical Center (vice-chairs) and supported by Dr. Currier and ACTG Co-Chair Joseph J. Eron, M.D., UNC.

    ACTIV-2 is sponsored by the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health (NIH), which also funds the ACTG. ACTIV-2 is part of NIH’s Accelerating COVID-19 Therapeutic Interventions and Vaccines (ACTIV), a public-private partnership program to create a coordinated research strategy that prioritizes and speeds development of the most promising treatments and vaccines. It also receives support from the Federal COVID Response-Therapeutics, the U.S. government’s multi-agency effort to accelerate the development, manufacturing, and distribution of COVID-19 vaccines, therapeutics, and diagnostics.

    For more information about ACTIV-2, please visit www.riseabovecovid.orgwww.actgnetwork.org, or clinicaltrials.gov.

    To read the full press release click here.