Advice to the media
Tuesday, December 22, 2020
Experimental monoclonal antibody not effective in phase 3 assay.
Preliminary results of a phase 3 placebo-controlled randomized clinical trial testing the investigated monoclonal antibody LY-CoV555 in hospitalized patients with COVID-19 have been published today. He New England Journal of Medicine. The antibody did not provide any clinical benefit compared with placebo. The trial, which had stopped at new enrollment in late October following a recommendation from the independent Data Control and Safety Board (DSMB), is part of the Accelerating COVID-19 Therapeutic Interventions and Vaccines program ( ACTIVE). The trial is sponsored by the National Institute of Allergy and Infectious Diseases (NIAID), which is part of the National Institutes of Health.
The ACTIV-3 trial used a master protocol designed to allow the study of multiple research agents compared to placebo in adults hospitalized with COVID-19. ACTIV-3 participants are randomly assigned to receive an experimental agent or a matching placebo. All participants also receive standard care for hospitalized patients with COVID-19, including antiviral remdesivir. Five days after enrollment, participants ’clinical status is assessed on an ordinal scale. If the research agent appears safe and effective based on an assessment of the first 300 participants (stage 1), an additional 700 participants are randomized and followed for 90 days to assess sustained recovery, defined as discharged, alive, and house for 14 days (stage 2). Patients with end-stage organ failure are not enrolled in stage 1, but these patients can be enrolled if the process proceeds to phase 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 collaboration with AbCellera.
The trial closed to new entrants on October 26, after DSMB reviewed the data from stage 1 of the trial and recommended that there be no more random participants to receive LY-CoV555 and that investigators not be blinded 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 organic insufficiency. Enrollment in the LY-CoV555 substudy closed with a total of 326 participants, 314 of whom were randomized to receive LY-CoV555 (163 participants) or placebo (151 participants). After five days, 50% of LY-CoV555 receptors and 54% of placebo receptors were in one of the two most favorable outcome categories. The researchers concluded that LY-CoV555 did not accelerate clinical improvement compared to placebo on day 5 using the ordinal scale among hospitalized COVID-19 patients without end-stage organ failure. Similarly, there were no differences in either time to hospital discharge or the main outcome of sustained recovery, back home for 14 days, between LY-CoV555 receptors compared with placebo. .
Although LY-CoV555 did not perform better than placebo in hospitalized patients with COVID-19 studied in this trial, this same research monoclonal antibody received an emergency use authorization (US) from the US. ‘US Food and Drug Administration. The US authorized the use of LY-CoV555 in outpatients and adults with mild to moderate symptoms of COVID-19 who are at high risk of progressing to severe COVID-19 disease.
The ACTIV-3 trial is 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 Testing (INSIGHT), has the support of NIAID. Collaborating clinical trial networks include the Acute Lung Injury Prevention and Treatment Network (PETAL) and the Cardiothoracic Surgical Trials Network (CTSN), with support from the National Heart, Lung, and Blood Institute. of the NIH through the Collaborating Network for the Evaluation of COVID-19 and Therapeutic Strategies Program (CONNECTS) and the U.S. Department of Veterans Affairs.
The principal investigator of ACTIV-3 is Jens Lundgren, MD, of the University of Copenhagen and Rigshospitalet. Participating network leaders 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 U.S. Department of Veterans Affairs. Additional information about ACTIV-3 is available at clinictrials.gov with identifier NCT04501978.
Article
J Lundgren et al. A neutralizing monoclonal antibody for hospitalized 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.
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