A Phase II trial launched yesterday by the NIH’s National Institute of Allergy and Infectious Diseases (NIAID) will compare two late-stage antibody treatment candidates in combination with Gilead Sciences’ Veklury® (remdesivir) to assess if they show enough promise against COVID-19 to be advanced into larger clinical trials.

NIAID’s fifth trial conducted through the public-private partnership Accelerating COVID-19 Therapeutic Innovations and Vaccines program (ACTIV-5)—also known as the Big Effect Trial (BET)—is an adaptive, randomized, double-blind, placebo-controlled study designed to compare two combination therapies to a common control arm, with the goal of determining which experimental treatments show the greatest effect.

ACTIV-5/BET (NCT04583969) will evaluate Skyrizi® (risankizumab-rzaa), the Boehringer Ingelheim/AbbVie monoclonal antibody now marketed for moderate to severe plaque psoriasis, with remdesivir—one of several treatments that President Donald Trump took for COVID-19—compared to a placebo plus remdesivir.

The ACTIV-5/BET trial will also test Humanigen’s monoclonal antibody candidate lenzilumab with remdesivir, compared to placebo and remdesivir.

Lenzilumab is an engineered (Humaneered®) anti-human granulocyte macrophage-colony stimulating factor (GM-CSF) monoclonal antibody designed to prevent and treat cytokine storm. In addition to the ACTIV-5/BET trial, Lenzilumab is currently being tested separately in a Phase III trial (NCT04351152) in hospitalized adults with severe or critical COVID, and in a Phase Ib/II study as sequenced therapy with CAR-T treatments.

Lenzilumab is among 19 “front runners” among the more than 300 drug and vaccine candidates tracked on GEN’s COVID-19 Drug & Vaccine Candidate Tracker.”

ACTIV-5/BET will enroll adult volunteers hospitalized with COVID-19 at as many as 40 U.S sites, twice as many as originally planned. Approximately 100 hospitalized volunteers will be assigned to each study arm—200 participants total—with each of the study sites testing no more than three investigational treatments at once.

“The NIH study is going to look at patients who are ventilated, as well as critical, as well as severe, as well as less severe or moderate. That means patients are in the hospital and they are breathing room air; they’re not on supplemental oxygen,” Humaniger chairman and CEO Cameron Durrant, MD, told GEN.

“Could be game-changing”

“Lenzilumab could be a game-changing treatment with frontline potential for many categories of hospitalized COVID patients.”

The study is set to start on October 30, with an estimated primary completion date of January 8, 2021, and an estimated completion date for the full study of July 1, 2021.

Durrant said Humanigen need not wait for results from ACTIV-5/BET to come out before pursuing an emergency use authorization (EUA) submission for lenzilumab.

“We have had a very successful type B meeting with the FDA,” Durrant said, referring to agency meetings with drug sponsors held before submission of EUAs or BLAs, “in which we received clear written guidance on our regulatory strategy. We are all-guns-blazing, and hopeful that we will get an EUA.”

Humanigen has said it expects to have topline data from the Phase III trial later this year.

“We would like to be able to submit an EUA this year,” Durrant said. “Obviously it’s up to FDA as to when they would want to consider issuing an EUA, if they do at all. And that means we’d likely be commercializing immediately thereafter.”

Volunteers assigned to receive risankizumab will be administered a single intravenous dose on day 1 of the study. Study participants assigned to receive lenzilumab will be given a 600 mg intravenous infusion every eight hours for a total of three doses.

“The goal here is to identify as quickly as possible the experimental therapeutics that demonstrate the most clinical promise as COVID-19 treatments and move them into larger-scale testing,” NIAID director Anthony S. Fauci, MD, said in a statement. “This study design is both an efficient way of finding those promising treatments and eliminating those that are not.”

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