The National Institutes of Health’s (NIH’s) Phase III ACTIV-3 trial will add another monoclonal antibody (mAb) therapy to its Covid-19 treatment platform in the next few weeks, said a source familiar with the study and a trial investigator. Considering accrual rates, data from ongoing cohorts evaluating GlaxoSmithKline and Vir Biotechnology’s VIR-7831 as well as Brii Biosciences’ BRII-196/BRII-198 should be sent to the Data and Safety Monitoring Board (DSMB) for a futility analysis sometime in February, the source added.
The Phase III trial is currently evaluating VIR-7831 and the Durham, North Carolina-headquartered Brii’s BRII-196/BRII-198 as a treatment on top of Gilead Sciences’ Veklury (remdesivir) in hospitalised Covid-19 patients. The study’s ClinicalTrials.gov entry was modified on 29 December with an amendment to add GSK/Vir’s and Brii’s mAbs in the trial design.
Previously, the platform trial—estimated to enrol 10,000 patients—was evaluating Eli Lilly’s LY-CoV555 (bamlanivimab), but enrolment to this cohort was stopped following a 26 October announcement. Bamlanivimab is currently authorised for use in mild-to-moderate Covid-19 at high risk of progressing to severe disease or hospitalisation.
Both sources declined to name the mAb candidate, but the investigator said an announcement will be made after the first patient is dosed with the new mAb. Apart from the aforementioned mAbs, those in development for treatment or prevention of Covid-19 in Phase II or more advanced trials include Celltrion’s CTP-59 (regdanvimab), AstraZeneca’s AZD7442 and Singapore-headquartered Hummingbird Biosciences’ HMBD-115. Regeneron Pharmaceuticals’ REGN-COV2 (casirivimab/imdevimab) has also received an FDA emergency use authorisation for use in individuals with mild-to-moderate Covid-19 at high risk for progressing to severe disease.
The ACTIV-3 trial’s current focus is to enrol approximately 150 patients each on treatment arms for VIR-7831, BRII-196/BRII-198 or placebo onto the first stratum, as defined by the trial protocol, said the source. If the DSMB decides to continue the study, it will expand and move to the second stratum and have 500 patients on each arm, including the ones enrolled on the first stratum, the source added. Two ordinal outcomes—assessing oxygen requirements and extrapulmonary complications and respiratory dysfunction—at day 5 will be used to assess futility, as per ClinicalTrials.gov.
As per the 26 October announcement, the bamlanivimab cohort stopped enrolling patients following a futility analysis showing a low likelihood of the intervention being of clinical value in that population. The published interim data indicated the percentage of patients with the primary safety outcome (a composite of death, serious adverse events, or clinical grade 3 or 4 adverse events through day 5) was 19% on bamlanivimab and 14% on placebo group (odds ratio, 1.56; 95% CI, 0.78 to 3.10; P=0.20) (December 22, 2020, DOI: 10.1056/NEJMoa2033130). The final follow-up data from this cohort will be published soon, said the source.
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The ACTIV-3 trial is being sponsored by the National Institute of Allergy and Infectious Diseases, a division of the NIH. The NIH did not respond to a request for comment before press time.
Manasi Vaidya is a Senior Reporter for Clinical Trials Arena parent company GlobalData’s investigative journalism team. A version of this article originally appeared on the Insights module of GlobalData’s Pharmaceutical Intelligence Center. To access more articles like this, visit GlobalData.