The National Institutes of Allergy and Infectious Diseases (NIAID), led by Dr. Anthony Fauci, continues to drive research, full throttle, during the COVID-19 pandemic. Now NIAID will sponsor a Phase 2 clinical trial evaluating the safety and efficacy of a potential new therapeutic for COVID-19, including an investigational therapeutic based on synthetic monoclonal antibodies (mabs) to treat SARS-CoV-2. Known as the ACTIV-2 clinical trial, NIAID, which is part of the National Institutes of Health (NIH), will investigate the use of mabs with patients who have mild to moderate COVID-19. The first investigational therapy under investigation: Eli Lilly’s promising LY-COV555, which was discovered alongside AbCellera Biologics and the NIAID Vaccine Research Center.
NIAID reports in a recent press release that if the investigational mabs show promise, the government-based sponsor would progress the clinical trial from a Phase 2 to a Phase 3 trial to gather additional critical data from a larger pool of participants.
Research Site Network
The study will be led by the NIAID-funded AIDS Clinical Trials Group (ACTG) and include sites (and patients) from around the world.
What is ACTIV-2?
Established as part of NIH’s Accelerating COVID-19 Therapeutic Interventions and Vaccines (ACTIV), the public-private partnership program instituted to speed development of the most promising treatments and vaccines. This particular study is receiving federal (tax payer) funding from the U.S. government’s multi-agency effort to develop, manufacture and distribute medical countermeasures to fight COVID-19 via Operation Warp Speed. TrialSite has written up a profile about ACTIV.
Like a number of studies during the COVID-19 pandemic, this particular study includes “adaptive” qualities to enable maximum flexibility in the shortest time frame reports NIAID in their press release. This means that during the first part of the clinical trial if the results are good then the study team can automatically expand the study to a larger group of participants. Also, the study can morph to accommodate different therapeutics.
NIAID will include as the first mabs LY-COV555, an investigational monoclonal antibody developed by Eli Lilly, in collaboration with AbCellera Biologics, which as TrialSite has reported, is a spinoff of University of British Columbia. TrialSite has showcased the impressive collaboration made possible by AbCellera’s powerful drug discovery technology in combination with the exceptional work of Lilly scientists.
The so-called neutralizing antibodies target specific viruses or other pathogens. The antibody was discovered by AbCellera (and their technology platform) and the NIAID Vaccine Research Center.
Dr. Anthony Fauci suggests the investigational monoclonal antibody product could possibly help researchers accelerate the determination of whether it is “safe and effective.” Fauci, understanding the severity of this pandemic and the need for effective treatments, remains open to “Investigating a variety of different therapeutics, including monoclonal antibodies” to help researchers do all they can to “advance towards an effective treatment for people suffering from COVID-19 disease as quickly as possible.”
This Phase 2 trial starts with 220 volunteers who report recently experiencing symptoms of COVID-19 and who have tested positive for the virus but are not hospitalized. Upon enrollment, the volunteers are randomized into one of two groups including 1) 110 volunteers that receive an intravenous (IV) infusion of Lilly’s LY-CoV555 and 2) 110 volunteers who will receive a placebo infusion, and thereafter the volunteers are observed by study coordinators and investigators.
Tracking During the Study
The NIAID will track the volunteers for the next 28 days as they will attend a series of clinic or at-home visits by clinicians to track their COVID-19 symptoms. Investigators will monitor whether RNA from SARS-CoV-2, can still be detected in participant’s noses and saliva using a standard nasopharyngeal swab. Because people with COVID-19 often have unusually low blood oxygen levels, participants will receive pulse oximetry tests to help determine if the investigational therapeutic has a positive effect on blood oxygen levels. They also will give blood samples to help researchers understand how the experimental therapeutics are functioning in their bodies, as well as whether they are affecting the course of their SARS-CoV-2 infection. Participants will receive additional follow-up for up to 24 weeks.
Goals of the Study
The primary goals of the Phase 2 trial are to evaluate safety, to see if the investigational therapeutic can reduce the duration of symptoms through study day 28, and to see if the investigational therapeutic can increase the proportion of participants with undetectable virus in nasopharyngeal swabs at specific time points. If there are no serious safety concerns and if the investigational therapeutic appears to meet other specific other criteria (such as sufficiently reducing the duration of symptoms or the viral load in the volunteers’ bodies), the trial will transition to Phase 3 and enroll up to 1,780 additional outpatient volunteers, for a total of 2,000 trial participants. The primary goal of the Phase 3 study will be to determine if the investigational therapeutic can prevent either hospitalization or death through study day 28 while also continuing to evaluate its safety. Participants in the Phase 3 portion of the study will not be provided nasopharyngeal swabs, though they will still perform self-collected anterior nasal swabs, and they will attend fewer clinic visits.
Note that the study team has established an independent data and safety monitoring board to oversee the trial and periodically review the accumulating data. Why? NAID sets this up to ensure that the trial is conducted in a safe and effective manner.
Professor Davey Smith, MD, Protocol Chair, University of California, San Diego
David Wohl, MD, University of North Carolina at Chapel Hill
Kara W. Chew, MD, University of California, Los Angeles, protocol vice chair
Eric S. Daar, MD, University of California, Los Angeles, protocol vice chai
Judith Currier, MD, University of California, Los Angeles, ACTG network chair
Joseph Eron, MD, University of North Carolina at Chapel Hill, ACTG network co-chair