A phase II/III clinical trial (Accelerating COVID-19 Therapeutic Interventions and Vaccines [ACTIV-2]) has been initiated to investigate the efficacy and safety of combination investigational monoclonal antibody therapy (BRII-196 and BRII-198) in individuals suffering from mild or moderate COVID-19.

This program is a public-private partnership to generate a coordinated research approach for accelerating the development of potential therapies and vaccine candidates. It is a master protocol to explore multiple investigational therapeutics in comparison with placebo in individuals with SARS-CoV-2 infection.

This trial will recruit subjects at sites around the world. It was initiated on 4 August 2020 to assess LY-CoV555 (bamlanivimab), an investigational monoclonal antibody. On 10 Nov 2020, the LY-CoV555 received Emergency Use Authorization from Food and Drug Administration to combat mild-to-moderate coronavirus infection in adults and children over 12 years old who are at elevated risk for advancing to severe coronavirus infection and/or hospital admission.

With the start of BRII-198 and BRII-196 investigational antibodies (target SARS-CoV-2 virus), the LY-COV555 sub-trial will close to recruitment. These investigational, neutralizing monoclonal antibodies are the synthetic versions of antibodies naturally generated by humans. The findings on each antibody from the phase I study that are currently ongoing favor the doses being utilized in ACTIV-2.

The trial's blinded design permits investigators to note the efficacy in a few volunteers and then administer it to a larger cohort if the antibodies display safety and effectiveness. This study will primarily recruit 220 individuals with mild/moderate coronavirus disease, who are at elevated risk for disease advancement.

Notably, half of the participants (n=110) will be treated with intravenous infusions of BRII-196 and BRII-198. The remaining half (n=110) will be given placebo infusions. Individuals will be randomly divided into groups. Subjects will be monitored for 72 weeks. The data collected at 28 days will be assessed by Data and Safety Monitoring Board. The data will be monitored to check whether the therapy has safety, can diminish the duration of coronavirus symptoms, and can eradicate the presence of viral RNA in the body.

With no severe safety challenges, if the outcomes seem promising, this analysis will transition to phase III. It will recruit about 622 additional outpatients for a total of 842 trial subjects. These novel individuals will be randomly assigned to receive either the therapeutic or a placebo. The major aim of this phase 3 trial will be to examine if the treatment prevents either hospitalization or mortality by 28 days after trial entry.