NIH/FDA working on standardised language for Covid-19 severity and trial templates

GlobalData Healthcare 30th April 2020 (Last Updated April 30th, 2020 09:28)

NIH/FDA working on standardised language for Covid-19 severity and trial templates

By Jennifer C Smith in London.

The National Institutes of Health (NIH) along with the US Food and Drug Administration (FDA) and medical bioresearchers are in the process of developing standardised Covid-19 severity terminology, as well as clinical trial templates to address, among other issues, biomarkers used in current clinical trials, like IL-6 and oxygen levels, said the FDA’s Center for Drug Evaluation and Research (CDER) Director, Janet Woodcock.

The task force, ACTIV, is trying to reach an agreement and issue recommendations “as fast as humanly possible,” Woodcock told this news service.

The NIH announced 17 April that it and the Foundation for the NIH (FNIH) have joined forces with 16 pharma companies, the Centers for Disease Control and Prevention (CDC), the FDA and the European Medicines Agency (EMA), among others, to develop an international strategy for a coordinated research response to the Covid-19 pandemic. The planned Accelerating Covid-19 Therapeutic Interventions and Vaccines (ACTIV) partnership is intended to develop a collaborative framework for prioritising vaccine and drug candidates, streamlining clinical trials and coordinating regulatory processes, according to an NIH press release.

Among the key issues, the group is discussing is the variety of Covid-19’s clinical manifestations and how they would be classified into disease severity, Woodcock said. There is no one accepted regulatory definition for Covid-19 severity stages or even a standard of care, as that is determined by physicians at hospitals or pharmaceutical companies, she noted.

As data from trials readout, there will be a greater understanding of biomarkers such as oxygen levels and IL-6, which is currently being tested, she noted. In turn, the goal is to establish clinical trial parameters to establish the best body of evidence for Covid-19 drug development, she said.

In terms of oxygen levels, there have been several reports of patients being hypoxic while functioning relatively normally. And regarding IL-6, on 27 April, Sanofi Regeneron Pharmaceuticals announced that their Phase II/III trial (NCT04315298) investigating anti-IL6 monoclonal antibody Kevzara (sarilumab) will continue to enrol only critical patients following early data, rather than including severe patients. On the same day, results from an investigator-led 129-patient controlled Phase II Actemra trial (NCT04331808) showed improved prognosis in moderate or severe Covid-19 patients. The Roche-sponsored Actemra Phase III COVACTA study (NCT04320615) has a primary completion date of August, but the company has indicated early data will be released as soon as they are available. This news service reported 3 April that success with IL-6-targeting antibodies for Covid-19 depends on recruiting less critically ill patients.

Regarding an ideal trial design, considering the variety of trial protocols employed to test Covid-19, Woodcock noted ACTIV aims for master protocols. The numerous case studies of therapeutic candidates for Covid-19 have provided no concrete evidence of efficacy, considering the disease’s variability and lack of randomisation, she said.

A randomised trial is necessary to generate evidence, and a Bayesian adaptive trial design would be best, she said. A single-arm trial for Covid-19 would not be appropriate, because the disease’s natural history is yet unknown, she explained. While open-label studies may be appropriate, such as the University of Oxford RECOVERY trial (EudraCT 2020-001113-21) that tests AbbVie’s Kaletra (lopinavir/ritonavir), interferon-beta1a, the corticosteroid dexamethasone or hydroxychloroquine, the majority may allow for bias, she said.

In terms of the agency’s Coronavirus Treatment Acceleration Program (CTAP), set up to quickly evaluate therapies for Covid-19, the agency’s website indicates interactions “have generally been prioritised based on a product’s scientific merits, stage of development and identification as a possible priority product.” In terms of the benchmarks for merit and development, applications from novel drugs are judged on the extent of in vitro or human data demonstrating efficacy against the virus, Woodcock said. For either novel or repurposed candidates, which don’t need preclinical work, there needs to be a very strong rationale as to how the drug could be effective, she noted. As of 16 April, the FDA had received 950 inquiries and proposals concerning Covid-19 related drug development, according to the CTAP website.

Jennifer C Smith is Senior Editor 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.