While the search for effective treatments for severe COVID-19 illness continues, the month of October continues to provide setbacks and disappointing clinical trial data.
- Last Friday, in BMJ: Clinical Trial On Convalescent Plasma Showed Little Benefit For COVID-19, convalescent plasma was dealt another blow (see last July's Dutch Convalescent Plasma Study For COVID-19 was Halted For Redesign).
- While 10 days ago, in WHO Solidarity Therapeutics Trial: Remdesivir, HCQ, Lopinar/Ritonavir & Interferon Disappoint, we saw that 4 highly touted drug therapies were found to have `. . . had little or no effect on 28-day mortality or in-hospital course of illness.'
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.
Eli Lilly's statement on this decision can be read here.
A second clinical trial - ViralClear's A Phase 2, Randomized, Double-Blind, Placebo-Controlled Study of the Efficacy and Safety of Oral Merimepodib in Combination with Intravenous Remdesivir in Adult Patients with Advanced Coronavirus Disease 2019 (COVID-19) - was halted yesterday as well due to safety concerns.
This press release from ViralClear's parent company BioSig Technologies.
ViralClear halts its Phase 2 Hospitalized COVID-19 Trial
DOWNLOAD AS PDF October 26, 2020
Westport, CT, Oct. 26, 2020 (GLOBE NEWSWIRE) -- BioSig Technologies, Inc. (Nasdaq: BSGM) (“BioSig” or the “Company”) and its majority owned subsidiary, ViralClear Pharmaceuticals, Inc. (ViralClear), announced the halting of its signal finding Phase 2 trial, “A Phase 2, Randomized, Double-Blind, Placebo-Controlled Study of the Efficacy and Safety of Oral Merimepodib in Combination with Intravenous Remdesivir in Adult Patients with Advanced Coronavirus Disease 2019 (COVID-19)”.
After the implementation of a protocol amendment that expanded the size of the trial from 40 to 80 hospitalized COVID-19 patients, and that limited enrollment to seriously ill patients, (NIAID Grade 3, who required high flow, high concentration oxygen to maintain adequate oxygenation) the Safety Monitoring Committee (SMC) was unblinded for safety reasons since these patients are at higher risk for dying from their disease. At the time of the most recent review of the data by the SMC, 44 patients had been enrolled in the trial of whom 42 had received study drug (either merimepodib solution or matching placebo). This most recent review of the data documented all 22 Grade 4 patients were discharged from the hospital and did not relapse during the 37 day follow-up period. However, patients who were NIAID Grade 3 patients (n = 20) at the time of enrollment had markedly different outcomes.
Specifically, the unblinded SMC detected an imbalance in survival rates in these NIAID Grade 3 patients between the placebo and merimepodib making it unlikely that the trial would meet its primary safety endpoints. The company has therefore elected to stop enrollment into the clinical trial. Patients will be followed as per the protocol for safety monitoring; however, no further study drug treatments will be administered.
At this time, the Company does not intend to further develop merimepodib. However, the Company will see if other parties are interested in acquiring or licensing merimepodib.
While Remdesivir has been approved by the FDA (despite its poor showing in the WHO clinical trials), and dexamethasone has been shown to be beneficial for severe COVID (see JAMA study) - the pharmacological options for treating COVID-19 remain quite limited.