Two studies will investigate monoclonal antibody-based treatments in both patients with mild disease and those who are hospitalized.
The National Institutes of Health (NIH) announced today it is moving forward with 2 clinical trials to evaluate therapeutics against coronavirus 2019 (COVID-19), including 2 monoclonal antibody-based treatments, as part of the Accelerating COVID-19 Therapeutic Interventions and Vaccines (ACTIV) program.
ACTIV-2 and ACTIV-3 are being conducted with funding from a variety of public and private agencies, and Operation Warp Speed.
ACTIV-3 is a phase 3 study and will allow patients at various clinical sites to enroll. The trial is intended to be adaptive to emerging information, so patients can be enrolled mid-study and the protocol can be used to evaluate the safety and efficacy of several different monoclonal antibody treatments.
The initial stage of the ACTIV-3 clinical trial aims to enroll approximately 300 volunteers who have been hospitalized with mild to moderate COVID-19 with fewer than 13 days of symptoms.
The ACTIV-3 will start with the investigational monoclonal antibody LY-CoV555, developed by Eli Lilly and Company in partnership with AbCellera, and based on a blood sample in a recovered COVID-19 patient early in the pandemic.
Participants will be randomly assigned to receive either an intravenous (IV) infusion of LY-CoV555 or a saline placebo infusion. Participants also will receive standard care for COVID-19, including the antiviral remdesivir.
After 5 days, participants’ symptoms will be assessed, as will their need for supplemental oxygen, mechanical ventilation, or other supportive care.
Data collected on the fifth day of the volunteers’ participation will determine whether the investigational therapeutic will be administered to a larger group of volunteers. If LY-CoV555 appears to be safe and appears to be effective, the trial will enroll an additional 700 participants.
Volunteers will be followed for 90 days after enrollment and will receive regular examinations and have blood samples taken periodically during this time to analyze their response to the investigational therapeutic.
While ACTIV-3 will study patients who are being cared for at the hospital, ACTIV-2 will focus on patients with mild to moderate disease.
“Studying the impact of this investigational therapeutic on multiple patient populations at the same time is critical to determining whether it can help COVID-19 patients with differing levels of disease severity,” said NIAID Director Anthony S. Fauci, MD “These concurrent trials have the potential to yield significant and comprehensive clinical data.”
ACTIV-2 will run concurrently to ACTIV-3, and the study’s participants will also take either LY-CoV555 or placebo in this randomized clinical trial. The initial stage of the trial is designed to enroll approximately 220 volunteers who report recently experiencing symptoms of COVID-19 but not requiring hospitalization.
The primary goals of the ACTIV-2 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.
The design of the study is adaptive to enable maximum flexibility in the shortest time frame. If the experimental treatment appears effective in the first stage, the treatment can be advanced rapidly to testing in larger groups of volunteers.
“We have seen encouraging, rapid results from other adaptive treatment trials for COVID-19,” NIH Director Francis S. Collins, MD, PhD, said. “Under ACTIV, specific therapeutics are being prioritized based on their likelihood for success. Prioritized therapeutics under ACTIV will use a master protocol that emphasizes flexibility, which enables these critical trials to be conducted without incurring delays when a treatment shows promise.”
The trial may investigate other experimental therapeutics later under the same trial protocol.