Media advice
Tuesday December 22, 2020
Experimental monoclonal antibody ineffective in Phase 3 study.
The preliminary results of a phase 3, randomized, placebo-controlled clinical trial testing the investigational monoclonal antibody LY-CoV555 in hospitalized COVID-19 patients were published today in The New England Journal of Medicine. The antibody did not provide any clinical benefit over placebo. The trial, which was halted for re-enrollment at the end of October on the recommendation of the independent Data and Safety Monitoring Board (DSMB), is part of the Accelerating COVID-19 Therapeutic Interventions and Vaccines (ACTIV) program. The trial is sponsored by the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health.
The ACTIV-3 study used a master’s protocol designed to allow study of multiple study agents compared to placebo in adults hospitalized with COVID-19. Participants in ACTIV-3 are randomly assigned to receive either an experimental agent or a matching placebo. All participants will also receive standard care for patients hospitalized with COVID-19, including the antiviral agent remdesivir. Five days after enrollment, the clinical status of the participants is assessed on an ordinal scale. If the study agent appears safe and effective based on an evaluation of the first 300 participants (Phase 1), an additional 700 participants are randomized and followed for 90 days to assess continued recovery, defined as discharged, alive, and at home for 14 days (Phase 2). Patients with end-stage organ failure are not enrolled in stage 1, but such patients may enroll if the study advances to stage 2.
The first agent to be evaluated in ACTIV-3 was LY-CoV555. The monoclonal antibody was discovered by Vancouver-based AbCellera Biologics in conjunction with NIAID’s Vaccine Research Center. It was then developed and manufactured by Lilly Research Laboratories, Eli Lilly and Company in Indianapolis, in collaboration with AbCellera.
The study was closed to newly enrolled individuals on October 26, after the DSMB reviewed the data from Phase 1 of the study and recommended that no further participants be randomized to receive LY-CoV555 and that the investigators should not be blinded to the data. This recommendation was based on a low likelihood that the intervention would be of clinical value in this population of hospitalized patients without end-stage organ failure. Enrollment in the LY-CoV555 sub-study was completed with 326 participants, of whom 314 were randomized to receive either LY-CoV555 (163 participants) or placebo (151 participants). After five days, 50% of the LY-CoV555 recipients and 54% of the placebo recipients were in one of the two most favorable outcome categories. The researchers concluded that LY-CoV555 did not accelerate clinical improvement compared to placebo at Day 5 using the ordinal scale in hospitalized COVID-19 patients with no end-stage organ failure. Similarly, there was no difference in time to hospital discharge or primary outcome of sustained recovery at home 14 days among recipients of LY-CoV555 compared to placebo.
Although LY-CoV555 did not outperform placebo in the hospitalized COVID-19 patients studied in this study, this same study monoclonal antibody received an Emergency Use Authorization (EUA) from the U.S. Food and Drug Administration in November. The EUA has approved the use of LY-CoV555 in out-of-hospital adolescents and adults with mild to moderate COVID-19 symptoms who are at increased risk of progression to severe COVID-19 disease.
The ACTIV-3 trial is being conducted in hospitals around the world that are part of existing clinical trial networks. The leading network, the International Network of Strategic Initiatives in Global HIV Trials (INSIGHT), is supported by NIAID. Collaborative clinical trial networks include the Prevention and Early Treatment of Acute Lung Injury (PETAL) Network and Cardiothoracic Surgical Trials Network (CTSN), supported by the NIH’s National Heart, Lung and Blood Institute through the Collaborating Network of Networks for Evaluating COVID- 19 and Therapeutic Strategies (CONNECTS) Program and the U.S. Department of Veterans Affairs Medical Centers.
ACTIV-3’s principal investigator is Jens Lundgren, MD, from the University of Copenhagen and Rigshospitalet. Leaders of the participating networks include James Neaton, Ph.D., of the INSIGHT Network; Taylor Thompson, MD, of the PETAL Network; Annetine Gelijns, Ph.D., and Alan Moskowitz, MD, of the CTSN; and Rachel Ramoni, DMD, Sc.D., of the US Department of Veterans Affairs. Additional information about ACTIV-3 is available at clinicaltrials.gov under the identifier NCT04501978.
Article
J Lundgren et al. A neutralizing monoclonal antibody for hospital patients with COVID-19. The New England Journal of Medicine. DOI: 10.1056 / NEJMoa2033130 (2020).
Who
H. Clifford Lane, MD, deputy director of clinical research and special projects, NIAID, is available for comment.
NIAID conducts and supports research – at NIH, in the United States and worldwide – to study the causes of infectious and immune-mediated diseases and to develop better tools to prevent, diagnose and treat these diseases. News releases, fact sheets and other NIAID-related material are available on the NIAID website.
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