The AIDS Clinical Trials Group (ACTG), the world’s largest HIV research network, which recently expanded its scope to include the evaluation of outpatient treatment of COVID-19[female[feminine, today announced the launch of A5404, a clinical trial investigating how a previous infection with SARS-CoV-2 and receiving either an investigational COVID-19 treatment or a placebo / active comparator affects the immune responses of participants to COVID-19 mRNA vaccines. A5404 is a substudy of the ACTIV-2 Outpatient Monoclonal Antibodies and Other Therapies Trial (ACTG A5401), which evaluates several investigational agents to treat early and symptomatic COVID-19 in outpatients.
“A5404 provides us with an important opportunity to better understand the potentially different responses to COVID-19 mRNA vaccines among participants who have had COVID-19, which will be particularly important as we work to optimize the vaccine schedule for these individuals.” said ACTG President Judith Currier, MD, M.Sc., University of California, Los Angeles (UCLA).
A5404 is an open-label, phase 4 study that aims to uncover the difference in neutralizing antibody (NAb) responses to COVID-19 mRNA-based vaccines among participants who have previously been infected with SARS-CoV-2 who participated to ACTIV-2 (who received an investigational COVID-19 treatment or a placebo or active comparator) and participants who have no history of COVID-19 and did not participate in ACTIV-2. A5404 will recruit 70 participants each from five different ACTIV-2 therapy groups and up to 70 participants without a history of COVID-19 for each ACTIV-2 therapy group.
- In the first cohort, ACTIV-2 participants will receive either the Moderna COVID-19 vaccine as part of the study, or the Moderna or Pfizer COVID-19 vaccine at a community site. They will receive their vaccine 30 to 240 days after their last day of treatment in the ACTIV-2 study.
- In the second cohort, participants without a history of COVID-19 will receive the Moderna COVID-19 vaccine as part of the study.
All participants will have their blood drawn and their immune responses measured as close as possible to the time the vaccine is given and at eight and 20 weeks and one and two years after the first dose of vaccine.
“The development of COVID-19 vaccines and treatments is advancing rapidly, but we still have a lot to learn,” said Davey Smith, MD, University of California, San Diego, A5404 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 re-infection with COVID-19. As such, this study has the potential to fill 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 completing a phase 2 study of each treatment:
- BRII-196 plus BRII-198: two monoclonal antibodies given as two separate infusions in a single dose (fully recruited)
- SAB-185: a polyclonal antibody, which combines many different antibodies in a single infusion
- SNG001: A nebulized formulation of interferon beta being studied as an inhalant taken daily for 14 days
ACTIV-2 is also currently evaluating several agents in phase 2 (both fully enrolled):
- BMS 986414 and BMS-986413: two monoclonal antibodies given as subcutaneous injections (injections) given in one visit
- AZD7442: a combination of two monoclonal antibodies (AZD8895 and AZD1061) that is studied both as a single 15-minute infusion and as a single intramuscular injection (injection)
A5404 is led by Dr Smith (Chair) and Kara W. Chew, MD, MS, UCLA, David Alain Wohl, MD, University of North Carolina (UNC) and Eric S. Daar, MD, Lundquist Institute at Harbor-UCLA Center medical (vice-presidents). 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, MD, 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 ACTG. ACTIV-2 is part of NIH’s Accelerating COVID-19 Therapeutic Interventions and Vaccines (ACTIV), a public-private partnership program aimed at creating a coordinated research strategy that prioritizes and accelerates the 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, manufacture, and distribution of COVID-19 vaccines, therapeutics, and diagnostics.
Founded in 1987, the AIDS Clinical Trials Group (ACTG) was the world’s first HIV research network. ACTG conducts groundbreaking studies to improve treatment for HIV and its complications, including tuberculosis and viral hepatitis; reduce new infections and HIV-related illnesses; and advancing new approaches to prevent, treat and ultimately cure HIV in adults and children. ACTG investigators and research units in 15 countries are major resources for HIV / AIDS research, treatment, care and training / education in their communities. ACTG studies have helped establish current paradigms for the management of HIV disease and informed HIV treatment guidelines, resulting in dramatic reductions in HIV-related mortality worldwide.