The Infectious Disease Clinical Research Unit at Washington University School of Medicine has launched the ACTIV-2 Outpatient Monoclonal Antibodies and Other Therapies Trial, which will be conducted by the AIDS Clinical Trials Group. The school’s Infectious Disease Clinical Research Unit is one of 25 initial sites conducting ACTIV-2, which includes both phase 2 and phase 3 evaluations of multiple promising investigational agents for treating early COVID-19 in a single trial. There is currently no approved vaccine or therapeutic to prevent or treat COVID-19. For information about enrolling in the trial at Washington University, please email firstname.lastname@example.org or call 314-454-0058.
ACTIV-2 will evaluate the safety and efficacy of investigational agents to treat adults who have COVID-19 illness but do not require hospitalization. The study will also enable researchers to assess the correlation between changes in viral shedding and clinical outcomes, leading to a better understanding of whether effective medications can reduce or halt the transmission to others of SARS-CoV-2 (the virus that causes COVID-19). ACTIV-2 is a randomized, blinded, controlled adaptive platform that allows promising investigational agents to be added and removed over the course of the study, in order to efficiently test a variety of new agents against placebo within the same trial infrastructure.
“This study aims to evaluate treatments that can be given in the outpatient setting to prevent people with COVID-19 from developing advanced disease that requires hospitalization,” said Rachel Presti, MD, PhD, associate professor of medicine and director for the school’s Infectious Diseases Clinical Research Unit. “Many people with COVID-19 may start off with just a few minor symptoms, but they can rapidly become very ill. They may also transmit the virus to other people when they have only mild symptoms. Limiting the severity and spread of COVID-19 will be critically important to controlling the pandemic. People living in the St. Louis area who have recently been diagnosed with COVID-19 and are not hospitalized have the opportunity to make a huge contribution by participating in this study.”
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 AIDS Clinical Trials Group. 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 is also receiving support from Operation Warp Speed, the U.S. government’s multi-agency effort to accelerate the development, manufacturing, and distribution of COVID-19 vaccines, therapeutics, and diagnostics.
The first investigational agent to be evaluated by ACTIV-2 is LY3819253, an experimental monoclonal antibody treatment made by Lilly Research Laboratories in partnership with AbCellera Biologics. AbCellera and the Vaccine Research Center at NIAID identified the antibody from a blood sample of one of the first people in the United States to recover from COVID-19.
In phase 2 of ACTIV-2, investigational agents will be studied to determine their safety, antiviral activity, and ability to reduce the duration of COVID-19 symptoms over 28 days. These agents will be selected based on the presence of in vitro data demonstrating activity against SARS-CoV-2 and phase 1 pharmacokinetics and safety data. In phase 2, 110 participants will receive the investigational agent and be compared to 110 participants randomized to receive placebo. If an agent demonstrates positive results and meets study-defined criteria for further evaluation, it will advance from phase 2 to phase 3. The phase 3 studies will evaluate the ability of each investigational agent to prevent hospitalization and death in non-hospitalized adults with COVID-19; 1,000 participants will receive the investigational agent (inclusive of the 110 participants from phase 2) and be compared to 1,000 participants randomized to placebo.
To qualify for the study, participants must have tested positive for SARS-CoV-2 infection in the outpatient setting within seven days and started experiencing symptoms within 10 days of enrolling into the study. At least half of participants will have factors that put them at “high risk” of progressing to severe COVID-19, including being age 55 or older and having one of the following conditions: chronic lung, kidney, or liver disease; obesity; hypertension; cardiovascular disease; diabetes; or moderate to severe asthma. The ACTG is committed to enrolling individuals most impacted by COVID-19 and will work closely with community partners to make participation in the trial available to those who are often underrepresented in clinical research.
The trial is being led by protocol chair Davey Smith, M.D., University of California, San Diego, along with Kara W. Chew M.D., M.S., University of California, Los Angeles (UCLA), David Alain Wohl, M.D., University of North Carolina (UNC), and Eric S. Daar, M.D., UCLA. It is supported by ACTG Chair Judith Currier, M.D., M.Sc., UCLA and ACTG Co-Chair Joseph J. Eron, M.D., UNC.
“Early treatment of COVID-19 will be vital to help us prevent advanced illness, hospitalization, and transmission of SARS-CoV-2,” said Dr. Currier. “ACTIV-2 is designed to help us rapidly identify treatments that have the potential to radically alter the current pandemic landscape and make a profound difference in the lives of people with and at risk for the disease.”