• 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.

  • Assessing the Relationship Between Greater Muscle Fat and Lower Muscle Area and Inflammation and Immune Activation after Starting ART

    JAIDS, August 5, 2021.

    Research has demonstrated that starting antiretroviral therapy (ART) is associated with an increase in skeletal muscle, though it tends to be quite fatty. A5260s explored whether the gains in skeletal muscle area or the amount of fattiness were associated with markers of inflammation and immune activation. Individuals living with HIV were randomized to start treatment with raltegravir, ritonavir-boosted atazanavir, or darunavir, in combination with tenofovir disoproxil fumarate/emtricitabine. This substudy included 222 participants and analyzed abdominal computed tomography (CT) scans at baseline and week 96 for muscle amount and fattiness and used previously measured markers of inflammation and immune activation. At baseline, greater muscle fat and lower muscle area were associated with higher inflammation and immune activation. From baseline to week 96, a greater increase in muscle fat and decrease in muscle area were associated with greater increases in inflammation and immune activation. Whether these muscle characteristics are the cause or the consequence of inflammation cannot be determined within this study. Future studies will need to explore the impact of these changes in muscle and inflammation on physical function and other complications, including cardiometabolic risk.

    To read the full manuscript 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.

  • ACTG announces data from ACTIV-2 study, demonstrating benefit of BRII-196 and BRII-198 in non-hospitalized participants with COVID-19

    August 26, 2021 Alexis Sexton Spotlight

    The AIDS Clinical Trials Group (ACTG), the largest global HIV research network, which has expanded its focus to include evaluating outpatient treatment for COVID-19, today announced positive data for the monoclonal antibody combination therapy BRII-196/BRII-198 from the ACTIV-2 study of Outpatient Monoclonal Antibodies and Other Therapies. In an interim analysis of the phase 3 evaluation of BRII-196/BRII-198, the combination demonstrated a 78 percent reduction in the combined endpoint of hospitalization and death compared with placebo in more than 800 non-hospitalized COVID-19 participants who were at high risk of clinical progression.

     

    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 (the virus that causes COVID-19). In the ACTIV-2 group receiving BRII-196/BRII-198, there were 12 hospitalizations and one death, compared to 45 hospitalizations and nine deaths among the group receiving placebo. There were no safety concerns.

     

    This interim analysis of this fully enrolled study included 837 participants who were at high risk of progressing to severe COVID-19, including being age 60 or older, being a current smoker, or having one of the following conditions: chronic lung, kidney, or liver disease; obesity; hypertension; cardiovascular disease; diabetes; or current cancer or immunosuppression. Participants were enrolled within 10 days of COVID-19 symptom onset across six countries (United States, Argentina, South Africa, Brazil, Philippines, and Mexico). Nearly two-thirds of participants had follow-up through 28 days following treatment.

     

    “The ACTG is very excited to announce such positive data from the ACTIV-2 study, particularly as we continue to see cases of COVID-19 skyrocket as a result of the Delta variant,” said ACTG Chair Judith Currier, M.D., M.Sc., University of California, Los Angeles (UCLA). “These data offer very convincing evidence of the clinical benefit of the combination of BRII-196/BRII-198 among people at high risk of progressing to severe COVID-19.”

     

    Today’s data were revealed by the ACTIV-2 Data Safety Monitoring Board (DSMB) based on an interim analysis of the trial. The DSMB recommended that the study continue in a blinded manner for longer term follow-up, and all participants continue to be followed.

     

    The study will ultimately evaluate the clinical efficacy of BRII-196/BRII-198 by SARS-CoV-2 variants. Participants were enrolled during a period when a number of variants of concern were circulating, including Alpha, Beta, Gamma, and Delta. Current in vitro pseudovirus testing data suggest that BRII-196/BRII-198 is active against all major SARS-CoV-2 variants, including the Delta variant. In addition, ACTIV-2 will conduct analyses to better understand the clinical benefits of BRII-196/BRII-198 treatment among participants who received it within five days compared to within six to 10 days of symptom onset.

     

    “The recent surge in COVID-19 hospitalizations and deaths serves as a stark reminder of the importance of early treatment for this devastating illness,” said Teresa H. Evering, M.D., M.S., Weill Cornell Medicine, co-lead investigator of BRII-196/BRII-198 in ACTIV-2.

     

    “These data suggest that BRII-196/BRII-198 will be a potent new treatment option for COVID-19,” said Eric S. Daar, M.D., Lundquist Institute at Harbor-UCLA Medical Center, co-lead investigator of BRII-196/BRII-198 in ACTIV-2. “ACTIV-2 will provide us with vital insights that will help clinicians make real-world treatment decisions for the many people who continue to be affected by 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 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 was 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 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 Dr. Daar (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.