New Study Evaluating How a History of COVID-19 May Affect mRNA Vaccine Response

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

“A5404 provides us with an important opportunity to understand potentially different responses to mRNA COVID-19 vaccines in 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, MD, M.Sc., University of California, Los Angeles (UCLA).

A5404 is a Phase 4, open-label study that aims to learn more about the difference in neutralizing antibody (NAb) responses to mRNA-based COVID-19 vaccines in participants with previous SARS-CoV-2 infection who enrolled in ACTIV-2 (who received either study treatment with COVID-19 or a placebo or an 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 with no 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 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 study ACTIV-2 treatment. In the second cohort, participants with no prior history of COVID-19 will receive the Moderna COVID-19 vaccine through the study.

All participants will have their blood drawn and immune response measured as close to vaccine administration as feasible and twenty-eight weeks and one and two years after the first vaccine dose.

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

ACTIV-2, the parent study of A5404, is currently evaluating several Phase 3 agents after completing a Phase 2 study of each treatment:

BRII-196 plus BRII-198: two monoclonal antibodies administered as two separate infusions as a single dose (fully enrolled) SAB-185: a polyclonal antibody, which combines many different antibodies in a single infusion SNG001: an nebulized formulation of beta interferon is used 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 in one visit AZD7442: a combination of two monoclonal antibodies (AZD8895 and AZD1061) administered as both a single 15-minute infusion and a one-time intramuscular injection (shot)

A5404 is headed by Dr. Smith (Chairman) and Kara W. Chew, MD, MS, UCLA, David Alain Wohl, MD, University of North Carolina (UNC), and Eric S. There, MD, Lundquist Institute at Harbor-UCLA Medical Center (Vice Chairmen) ). ACTIV-2 is led by Drs. Chew and Smith (protocol chairs) and Drs. Wohl and Daar (Vice Presidents) 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 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 accelerates the development of the most promising treatments and vaccines. It will also receive support from the Federal COVID Response-Therapeutics, the multi-agency effort of the US government to accelerate the development, production and distribution of COVID-19 vaccines, therapies and diagnostics.

About the ACTG

Founded in 1987, the AIDS Clinical Trials Group (ACTG) was the world’s first HIV research network. ACTG conducts groundbreaking studies to improve the treatment of HIV and its complications, including tuberculosis and viral hepatitis; reduction of new infections and HIV-related diseases; and promoting new approaches to prevent, treat and ultimately cure HIV in adults and children. ACTG researchers and research units in 15 countries are important 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 provided guidelines for HIV treatments, leading to a dramatic decline in HIV-related deaths worldwide.