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.
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.