The University of Pittsburgh School of Medicine announced today that it is operating one of 25 initial sites to test therapies aimed at treating early-stage COVID-19 to keep the illness from becoming severe.
Part of the National Institutes of Health’s Accelerating COVID-19 Therapeutic Interventions and Vaccines (ACTIV) initiative and funded through Operation Warp Speed, the “ACTIV-2 Outpatient Monoclonal Antibodies and Other Therapies Trial” includes both phase 2 and phase 3 clinical evaluation of multiple promising treatments for early COVID-19 in a single trial.
A flurry of ACTIV-ity
In addition to ACTIV-2, this month alone, Pitt announced three other major efforts in the battle against COVID-19. The first, called ACTIV-4, is a trio of National Institutes of Health-sponsored Phase 3 trials that are exploring the role of blood thinners in saving lives and improving care.
Additionally, a study led by Derek Angus, distinguished professor and the Mitchell P. Fink Endowed Chair of Pitt’s Department of Critical Care Medicine, appeared in the Journal of the American Medical Association and informed the World Health Organization’s recommendation to use steroids to treat critically ill COVID-19 patients.
Finally, a study published in Cell showed that a tiny antibody component could be highly effective in treating SARS-CoV-2 infection. Pitt researchers have applied to have this treatment enter the ACTIV-2 trial in the future.
“This study aims to develop a treatment that can prevent people with COVID-19 from progressing to advanced disease that requires hospitalization,” said Madhu Choudhary, associate professor in Pitt’s Division of Infectious Diseases and principal investigator for the Pittsburgh trial site. “While people with COVID-19 may start off with just a few minor symptoms, they can rapidly become very ill, and this is true of both the old and young.”
ACTIV-2 is a randomized, blinded, controlled adaptive platform, meaning that promising drugs can be added and removed over the course of the study, depending on how well they perform. This will allow researchers to efficiently and quickly test a variety of new drugs against a placebo within the same trial. The first drug being studied in this trial is a monoclonal antibody treatment made by pharmaceutical company Lilly that is given intravenously.
Many antibodies are in development for COVID-19 treatment and prevention. These antibodies attach to the coronavirus and prevent it from entering cells in the body. Lilly’s antibody was recently shown to have beneficial effects for people with COVID-19.
In addition to evaluating the performance of the drugs in lessening severity of COVID-19, researchers will assess the correlation between changes in the levels of infectious virus shed by participants and clinical outcome. This will lead to a better understanding of whether medications can reduce or halt the transmission of SARS-CoV-2, the virus that causes COVID-19.
In the phase 2 portion of the trial, underway now, 110 participants will be recruited nationwide to receive a monoclonal antibody infusion. They’ll be compared to 110 participants who will receive a placebo. The participants and their doctors will not know which one they received. If the medication produces positive results without significant safety concerns, it will likely advance to the phase 3 portion.
Phase 3 studies will evaluate the ability of each medication to prevent hospitalization and death in adults with COVID-19. Including participants from the phase 2 trial, 1,000 people will receive the medication and will be compared with an equal number of participants who receive the placebo.
This process will be repeated for multiple medications as they become available. For example, researchers at Pitt have applied to have a monoclonal antibody they’re developing enter the ACTIV-2 platform in the future.
ACTIV-2 is being conducted by the AIDS Clinical Trials Group (ACTG), the world’s largest and longest- running HIV clinical trials network, because of its extensive experience with clinical trials. Pitt has been a member since 1998.
To qualify for the study, participants must have tested positive for SARS-CoV-2 infection as an outpatient and started experiencing symptoms within 10 days of enrolling in the study. Study scientists are particularly interested in enrolling people at high risk for progressing to severe COVID-19, namely those age 55 or older who have one of the following conditions: chronic lung, kidney or liver disease; obesity; hypertension; cardiovascular disease; diabetes or moderate to severe asthma. The ACTG also is committed to enrolling people most impacted by COVID-19 and is working with community partners to make participation in the trial available to those who often are underrepresented in clinical research.
“People living in the Pittsburgh 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,” said Choudhary.
ACTIV-2 is being led nationally by Davey Smith of the University of California, San Diego; along with Kara W. Chew and Eric S. Daar, both of University of California, Los Angeles (UCLA); David Alain Wohl of the University of North Carolina (UNC). It is supported by ACTG chair Judith Currier, UCLA, and ACTG co-chair Joseph J. Eron, UNC.