Statement—NIH-Sponsored ACTIV-3 Trial Closes LY-CoV555 Sub-Study
October 26, 2020 — The ACTIV-3 clinical trial evaluating the investigational monoclonal antibody LY-CoV555 in hospitalized patients with COVID-19 will not enroll more participants into this sub-study following a recommendation from the independent Data and Safety Monitoring Board (DSMB). The trial is sponsored by the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health.
ACTIV-3 is a master protocol designed to allow for the study of multiple investigational agents compared to placebo in adults hospitalized with COVID-19. Participants in the trial are randomly assigned to receive either an experimental agent or a matched placebo. All participants also receive standard care for patients hospitalized with COVID-19, including the antiviral remdesivir. After five days, participants’ clinical status is assessed based on an ordinal scale. If the investigational agent appears to be safe and effective based on an evaluation of the first 300 participants (stage 1), an additional 700 participants are randomized and followed for 90 days to assess sustained recovery, defined as being discharged, alive and home for 14 days (stage 2).
The first agent evaluated in the Phase 3, randomized, controlled trial was LY-CoV555. The monoclonal antibody was discovered by AbCellera Biologics based in Vancouver, in collaboration with NIAID’s Vaccine Research Center. Subsequently, it was developed and manufactured by Indianapolis-based Lilly Research Laboratories, Eli Lilly and Company, in partnership with AbCellera.
The DSMB reviewed data from the ACTIV-3 trial on Oct. 26, 2020 and recommended no further participants be randomized to receive LY-CoV555 and that the investigators be unblinded to the data. This recommendation was based on a low likelihood that the intervention would be of clinical value in this hospitalized patient population. This follows the Oct. 13, 2020 DSMB recommendation to pause enrollment out of an abundance of caution. While the DSMB noted on Oct. 13 that a pre-defined boundary for safety was reached at day 5, differences in safety outcomes between the groups were not significant in the updated data set and the Oct. 26 decision was driven by lack of clinical benefit for LY-CoV555 in a hospitalized population.
Enrollment into the LY-CoV555 sub-study closed with 326 total participants. Those participants will continue to be followed until day 90. NIAID and trial coordinating investigators are in the process of analyzing the data and will provide more information in a forthcoming report. ACTIV-3 is an adaptive master protocol, and NIAID will provide information on additional investigational agents being planned for evaluation and any potential changes to the trial design as testing of new agents begins.
The DSMB that oversees ACTIV-3 also oversees ACTIV-2, another adaptive trial evaluating LY-CoV555 in the outpatient population. The DSMB does not recommend any changes to ACTIV-2, and this study continues to enroll participants.
Posted: October 2020
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