Media recommendation
Tuesday, December 22, 2020
The experimental monoclonal antibody is not effective in the phase 3 study.
Preliminary results of a randomized, placebo-controlled phase 3 clinical trial testing the investigative monoclonal antibody LY-CoV555 in patients hospitalized with COVID-19 were published today in New England Journal of Medicine. The antibody did not provide clinical benefits compared to placebo. The process, which was halted for re-enrollment in late October, following a recommendation from the Independent Data Monitoring and Safety Board (DSMB), is part of the Accelerating COVID-19 Therapeutic Interventions and Vaccines (ACTIV) program. The process is sponsored by the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institute of Health.
The ACTIV-3 study used a master protocol designed to allow the study of more investigative agents compared to placebo in adults hospitalized with COVID-19. ACTIV-3 participants are randomly assigned to receive either an experimental agent or an associated placebo. All participants also receive standard of care for patients hospitalized with COVID-19, including antiviral remdesivir. Five days after enrollment, participants’ clinical condition is assessed on an ordinal scale. If the investigator appears to be safe and effective based on an assessment of the first 300 participants (stage 1), another 700 participants are randomized and followed for 90 days to assess sustained recovery, defined as outpatient, in life. and at home for 14 days (stage 2). Patients with end-stage organ failure are not enrolled in stage 1, but these patients are allowed to enroll if the process continues in stage 2.
The first agent evaluated in ACTIV-3 was LY-CoV555. The monoclonal antibody was discovered by Vancouver-based AbCellera Biologics in collaboration with the NIAID Vaccine Research Center. It was later developed and manufactured by Indianapolis-based Lilly Research Laboratories, Eli Lilly and Company, in partnership with AbCellera.
The trial was closed to new entrants on October 26, after the DSMB analyzed data from stage 1 of the trial and recommended that other participants not be randomized to receive LY-CoV555 and that investigators not be linked to the data. This recommendation was based on a low probability that the intervention would have clinical value in this population of hospitalized patients without end-stage organ failure. Enrollment in the LY-CoV555 sub-study ended with a total of 326 participants, of whom 314 were randomized to receive either LY-CoV555 (163 participants) or placebo (151 participants). After five days, 50% of patients with LY-CoV555 and 54% of those receiving placebo were in one of the two most favorable outcome categories. Investigators concluded that LY-CoV555 did not accelerate clinical improvement compared to placebo on day 5, using the ordinal scale among patients hospitalized with COVID-19 without end-stage organ failure. Similarly, there was no difference in time to discharge or in the primary outcome of sustained recovery, back home for 14 days, among LY-CoV555 recipients compared to placebo.
Although LY-CoV555 did not perform better than placebo in hospitalized COVID-19 patients studied in this study, the same investigational monoclonal antibody received an emergency use authorization (EUA) from the US Food and Drug Administration in November. EUA has authorized the use of LY-CoV555 in non-hospitalized adolescents and adults with mild to moderate symptoms of COVID-19 who are at increased risk of progressing to severe COVID-19 disease.
The ACTIV-3 study is being conducted at hospitals around the world that are part of existing clinical trial networks. The core network, the International Network of Strategic Initiatives in Global HIV Studies (INSIGHT), is supported by NIAID. Collaborating clinical trial networks include the Acute Lung Injury Prevention and Treatment Network (PETAL) and the Cardiothoracic Surgical Testing Network (CTSN), supported by the NIH National Heart, Lung, and Blood Institute through the Network Collaboration Network. for the evaluation of COVID-19 and the Therapeutic Strategy Program (CONNECTS) and the US Department of Veterans Affairs Medical Center.
The main investigator of ACTIV-3 is Jens Lundgren, MD, from the University of Copenhagen and Rigshospitalet. Leading network leaders include James Neaton, Ph.D., of the INSIGHT network; Taylor Thompson, MD, of the PETAL network; Annetine Gelijns, PhD, and Alan Moskowitz, MD, CTSN; and Rachel Ramoni, DMD, Sc.D., of the U.S. Department of Veterans Affairs. Additional information about ACTIV-3 is available on clinictrials.gov under the identifier NCT04501978.
Article
J Lundgren et al. A neutralizing monoclonal antibody for patients hospitalized with COVID-19. The New England Journal of Medicine. DOI: 10.1056 / NEJMoa2033130 (2020).
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H. Clifford Lane, MD, Deputy Director of Clinical Research and Special Projects, NIAID, is available for comment.
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