• STOMP: New ACTG monkeypox treatment trial

    September 21, 2022 Alexis Sexton Spotlight

    For more information about a new ACTG monkeypox study, click here.

  • ACTG announces launch of trial evaluating monkeypox treatment

    September 9, 2022 Alexis Sexton Spotlight

    STOMP Will Evaluate Tecovirimat in a Phase 3 Clinical Trial

    Los Angeles, Calif. – The AIDS Clinical Trials Group (ACTG), the largest global HIV research network, which expanded its focus to conduct research into COVID-19, today announced the initiation of STOMP (Study of Tecovirimat for Human Monkeypox Virus), or A5418, a phase 3, randomized, placebo-controlled, double-blind trial evaluating the safety and efficacy of tecovirimat for the treatment of human monkeypox. The study has been designed to learn as much as possible in a broad population of people with monkeypox.

    “There is an urgent need for monkeypox treatments and this study will help us determine whether tecovirimat should be one of them,” said ACTG chair Judith Currier, M.D., M.Sc., University of California, Los Angeles. “The ACTG has designed this study to give us the greatest possible insights into whether and how tecovirimat works against monkeypox, including whether the virus develops resistance to the treatment. An important part of that design is the inclusion of children and pregnant people. The study will also evaluate markers that may tell us that the drug is working so we can identify future promising drugs. Beyond addressing the current outbreak, this study has the potential to profoundly inform the treatment of individuals who acquire monkeypox virus in endemic countries.”

    A global outbreak of monkeypox emerged in the spring of 2022 and has since spread throughout the world, with more than 56,000 cases in 103 countries and more than 21,000 cases in the United States. Monkeypox was first identified in 1958 and has caused an increasing number of infections annually in endemic countries. The current outbreak has been characterized by increased person-to-person transmission. Close contact during sexual activity is believed to play an important role in this outbreak. While most cases thus far have been reported among men who have sex with men, women and children have also been infected. There are currently no therapies approved to treat human monkeypox.

    Tecovirimat (SIGA Technologies, Inc.) is approved by the U.S. Food and Drug Administration (FDA) to treat smallpox, but it is not yet known if it can effectively or safely treat monkeypox.

    This multi-center trial will enroll more than 500 adults with monkeypox virus infection. Importantly, this trial will include people with severe disease and those at high risk of severe disease including pregnant and breastfeeding people, children, and individuals with underlying immune deficiency and active inflammatory skin conditions who will receive open-label tecovirimat. Study participants with symptomatic monkeypox virus infection who do not meet the criteria for the open-label cohort will be randomly assigned in a ratio of two to one to receive either tecovirimat or placebo orally for 14 days. Participants who are randomized in the double-blinded cohort of the study who later progress to severe disease will be offered the option to switch to open-label tecovirimat, as will participants who report persistent severe pain from monkeypox virus infection.

    All participants in STOMP will be followed for at least eight weeks through a combination of virtual and in-person visits and daily self-reports to determine if those receiving tecovirimat heal more quickly compared to those receiving placebo. STOMP will also provide critical data on the optimal dosing and safety of tecovirimat in children and people who are pregnant and breastfeeding.

    “Up until now, there have been no studies of tecovirimat in children or pregnant people, which means we lack any data on the risk and benefits of this treatment in two very important populations,” said STOMP protocol chair Timothy Wilkin, M.D., M.P.H., assistant dean of clinical research compliance and a professor of medicine at Weill Cornell Medicine. “In addition, while the data are limited, they do suggest that monkeypox can be more severe among children and pregnant people, so it will be key to understand how tecovirimat works for them.”

    Individuals who have presumptive or confirmed monkeypox infection (tested positive within seven days) and started experiencing symptoms within 13 days are eligible. Testing will be provided by the study. Participants with presumptive monkeypox virus infection who have not yet been tested are able to enroll as long as their study-provided test is positive. Participants must also have at least one active skin lesion that has not yet scabbed, a mouth lesion, or proctitis (inflammation in the lining of the rectum).

    STOMP 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.  A list of participating sites in the United States can be found here.

    STOMP is led by Dr. Wilkin and William Fischer, M.D., University of North Carolina (UNC) and Jason Zucker, M.D., Columbia University (vice-chairs) and is supported by Dr. Currier and Joseph J. Eron, M.D., UNC, (ACTG Co-Chair).

     

    Read more here.

  • A5418:Study of Tecovirimat for Human Monkeypox Virus (STOMP)

    September 9, 2022 Alexis Sexton Spotlight

    Now open and Enrolling. 

    Study Description

    The study of Tecovirimat for treatment of human Monkeypox (STOMP) is a NIAID-funded clinical trial led by the ACTG to evaluate the effectiveness of the antiviral tecovirimat, also known as TPOXX, for the treatment of human Monkeypox infection.

    Read more here.

     

  • Solicitation for ACTG Science Committee Membership Positions DUE September 21st

    August 26, 2022 Alexis Sexton Spotlight

    DEADLINE: Wednesday, September 21, 2022

    The AIDS Clinical Trials Group (ACTG) Network is currently soliciting for member nominations to the ACTG’s scientific committees. The ACTG is seeking qualified clinical and laboratory investigators with expertise relevant to the area of research who are willing to commit the time necessary to serve on the Transformative Science Groups (TSGs) and Collaborative Science Groups (CSGs). Interested investigators with appropriate expertise need not be affiliated with a funded ACTG Clinical Trials Unit (CTU) or Clinical Research Site (CRS) and/or have previous involvement with ACTG studies.

    • International investigators and junior investigators are strongly encouraged to submit their names in nomination to science committees appropriate to their interests.
    • International site personnel are strongly encouraged to submit their names in nomination to committees appropriate to their interests and experience.

    Current members of committees for whom a second term is permitted and who are interested in serving a second term must submit a nomination packet.

    VACANCIES:

    The detailed listing of position vacancies for the different committees is available on the ACTG Committee Nomination web site at https://nomination.mis.s-3.net/. The listing also specifies who is eligible for the positions, term duration, number of conference calls per month and meetings per year, and a brief description of duties and responsibilities of the positions.

    NOMINATION PROCESS:

    Nominations and required accompanying materials must be submitted online at https://nomination.mis.s-3.net/ by Wednesday, September 21.

    The individual position descriptions for the vacancies specify who may submit a nomination and when self-nominations are acceptable with the appropriate documentation.

    Nominees must submit all required documents and acknowledge their willingness to serve. The list of required documents, also available on the website, is as follows:

    1. Nomination letter outlining the candidate’s qualifications, relevant expertise, experience, and accomplishments pertinent to the position
    2. NIH biosketch (template available at http://grants.nih.gov/grants/forms/biosketch.htm and on the ACTG member web site)

    SELECTION PROCESS:
    Nominations for science committees will be distributed to the relevant committee for review and selection. The AEC will review and determine whether to endorse the selections made by the respective committees. Following the AEC review, the nominees will be notified of the election outcome. Once the committees have advised nominees of the outcome, the AEC will broadly announce the selections and post the results to the ACTG web site. 

    INQUIRIES

    Questions regarding the nomination process should be directed to the ACTG Network Coordinating Center at ACTGCommitteeNominations@dlhcorp.com.

  • Upcoming Monkeypox Study

    From NIAID

    In September 2022, NIAID will start a clinical trial of tecovirimat in the U.S. in collaboration with the AIDS Clinical Trials Group (ACTG). People with monkeypox infection, including people living with HIV, would be eligible and encouraged to enroll. More than 500 volunteer participants will be randomly assigned to receive either tecovirimat or a placebo at a ratio of two to one. Investigators will be evaluating if those taking tecovirimat heal more quickly than those taking placebo, among other data points. There is an additional segment of the study open to pregnant and breastfeeding people and children and all will receive tecovirimat and will be closely monitored for safety. If a positive signal is seen in the study, it will provide the necessary data to make this medicine readily available for treatment of monkeypox disease.

     

  • ACTG Announces Launch of ACTIV-2d, a Global Phase 3 Trial of the Novel Investigational COVID-19 Oral Antiviral Agent S‑217622

    August 15, 2022 Alexis Sexton Spotlight

    Los Angeles, Calif. – The AIDS Clinical Trials Group (ACTG), the largest global HIV research network, which expanded its focus to conduct research into COVID-19, today announced the initiation of ACTIV-2d, a global, phase 3, multicenter trial to evaluate the impact of S-217622, an investigational oral COVID-19 antiviral agent. ACTIV-2d will evaluate the safety and efficacy of S-217622 as a once-daily treatment to reduce the duration of COVID-19 symptoms in non-hospitalized adults with early COVID-19.

    S-217622, a selective inhibitor of the 3CL protease (an enzyme essential for the replication of SARS-CoV-2) was created through joint research between Hokkaido University and Shionogi & Co. Ltd. Recent results from a trial conducted in Japan and Korea demonstrated that patients treated with S-217622 showed a significant and rapid decrease in viral level and culturability after the third dose of S-217622 compared to placebo. Previous clinical trials also showed that S-217622 was well-tolerated, with few treatment-related discontinuations, and no serious adverse events or death. The most common adverse events were mild headache and transient reduction in HDL cholesterol. Additionally, S-217622 has recently demonstrated high in vitro antiviral activity against the Omicron subvariants (BA.4 and BA.5), with antiviral potency against other existing variants

    ACTIV-2d is a global phase 3, multicenter, randomized, double‑blind, 24‑week study evaluating whether S-217622 is able to reduce the time it takes for COVID-19 symptoms to resolve among participants who have tested positive for SARS-CoV-2 in the outpatient setting and started experiencing symptoms within five days of enrolling. The study will include people at lower and higher risk of progression to severe COVID-19.

    “S-217622 has the potential to simplify COVID-19 treatment, as it is administered once a day without a boosting agent,” said Annie Luetkemeyer, M.D., University of California, San Francisco and a lead investigator of S-217622. “As COVID-19 remains a major global concern, we need to increase our treatment options. We are hopeful that S-217622 will be an important addition to the COVID-19 treatment toolkit.”

    ACTIV-2d is being conducted with trial sites in countries in Europe, South America, North America, Africa, and Asia. Approximately 1,490 participants will be randomized in a 1:1 ratio receiving either S-217622 or placebo. Participants may take locally provided COVID-19 treatment after enrollment, as long as it is compatible with S-217622.

    ACTIV-2d is funded by the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health (NIH), which also funds the ACTG, and is sponsored by Shionogi. ACTIV-2d 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.

    ACTIV-2d 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).

    Read more here.

     

     

     

     

  • ACTG announces publication of #ACTIV-2 study in Cell Reports Medicine demonstrating rapid clearance of culturable SARS-COV-2 following monoclonal antibody treatment

    The AIDS Clinical Trials Group (ACTG), the largest global HIV research   network, which expanded to conduct research into COVID-19, today announced the publication of “Monoclonal Antibody Treatment Drives Rapid Culture Conversion in SARS-CoV-2 Infection,” in the journal Cell Reports Medicine. The publication reports on findings from the ACTIV-2/A5401 study of Outpatient Monoclonal Antibodies and Other Therapies and found that treatment with the monoclonal antibody bamlanivimab led to a rapid clearance in culturable virus from the nose that was far faster than the decline in viral RNA levels. While bamlanivimab is not currently in clinical use, the identical mechanisms of action of all clinically used SARS-CoV-2-targeting monoclonal antibodies make it likely that these findings will translate to other monoclonal antibodies.

    Bamlanivimab is a neutralizing monoclonal antibody that received an Emergency Use Authorization (EUA) as a treatment for people with mild to moderate COVID-19 in November 2020. Lilly voluntarily asked the Food and Drug Administration to revoke the EUA for bamlanivimab 700 mg alone in April 2021 due to reduced activity against circulating variants (there were no new safety concerns).

    This publication reports on a study that included viral culture analysis of participants enrolled in the ACTIV-2 randomized placebo-controlled trial of bamlanivimab monotherapy for adults with mild to moderate COVID-19 who were not hospitalized, to understand how monoclonal antibody treatment impacts the dynamics of shedding culturable SARS-CoV-2, a potential marker of SARS-CoV-2 infectivity.

    “These findings may provide important insights into the impact of monoclonal antibodies on SARS-CoV-2 transmission,” said ACTG Chair Judith Currier, M.D., M.Sc., University of California, Los Angeles. “Within 24 hours of monoclonal antibody treatment, culture-positive virus could not be detected in any of the treated participants. This suggests that viral culture could be a more sensitive marker of monoclonal antibody activity than viral RNA levels.”

    This publication reports on 69 participants, 39 in the placebo arm and 30 in the bamlanivimab arm. Baseline participant characteristics, including age, race, comorbidities, days of symptoms before enrollment, and serostatus, were similar between groups. Participants received either placebo or bamlanivimab on day zero of the study. Anterior nasal sample SARS CoV-2 RNA levels were assessed prior to treatment and one, two, three, and seven days after treatment. Shedding of culturable virus was assessed at the same timepoints for all samples with viral loads greater than 2 log10.

    One day after treatment, while the anterior nasal sample viral RNA levels were similar between participants receiving bamlanvimab or placebo, a significant difference in culture positivity was observed: the culture positivity rate in the placebo arm was 41 percent compared to zero in the bamlanivimab arm. Two days after treatment, 18 percent of participants in the placebo arm were still culture positive; three days after treatment, 22 percent of placebo participants remained culture positive; and seven days after treatment one placebo participant remained culture positive. All bamlanivimab-treated participants without bamlanivimab-resistant virus remained culture negative from day one onward.

    The study also found that individuals with emerging drug resistance to bamlanivimab had rebound of culturable virus, highlighting the fact that individuals with symptom rebound after monoclonal antibody treatment should re-isolate, as they may be infectious again, and possibly with virus containing new monoclonal antibody-resistant mutations, although the association between symptom rebound and return of culturable virus was not assessed in this study.

    “These data suggest that monoclonal antibodies may have an additional role beyond treatment of the individual, to include reducing the risk of secondary transmission,” said Jonathan Z. Li, M.D., Brigham and Women’s Hospital and Harvard Medical School, Co-Chair of this sub-study.

    His Co-Chair Amy K. Barczak, M.D., Massachusetts General Hospital and Harvard Medical School, continued, “as such, the findings raise the question of whether we should consider reduced forward transmission as a goal of monoclonal antibody treatment and if so, what endpoints might be useful in determining how therapies impact the duration of infectiousness.”

    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. 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.

    This substudy was led by Dr. Li and Dr. Barczak. 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 Joseph J. Eron, M.D., UNC (ACTG Co-Chair).

    Read more here.

  • 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.

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