TORONTO—Revive Therapeutics Ltd. just reported that the company has filed its Clinical Trial Application (Pre-CTA) with Health Canada. Revive has also provided an update on the filing of its Investigational New Drug (IND) package to the U.S. Food and Drug Administration (FDA) for a proposed Phase 3 confirmatory clinical trial to evaluate Bucillamine in the treatment of patients with mild to moderate COVID-19 due to SARS-CoV-2 infection.
“We are very pleased with the progress that has been made with our clinical strategy for Bucillamine in the potential treatment of COVID-19, specifically with our focus on a Phase 3 confirmatory study to be conducted in the U.S. and our expansion into Canada,” said Michael Frank, chief executive officer of Revive Therapeutics.
Revive will have its Pre-CTA meeting with Health Canada this week. A complete briefing package accompanied the meeting request to discuss Bucillamine’s chemistry, manufacturing and controls; non-clinical and clinical safety information; clinical trial design; and Health Canada’s guidance regarding the possibility of including an additional exploratory arm in the proposed trial in a subset of pediatric patients. Results from the Pre-CTA meeting with Health Canada will be made available, and Revive Therapeutics expects to initiate a clinical study as soon as possible, following receipt of regulatory clearance from Health Canada.
Revive is also finalizing its IND with the FDA for the company’s proposed Phase 3 confirmatory clinical trial to evaluate Bucillamine in the treatment of patients with mild to moderate COVID-19 due to SARS-CoV-2. The company will file the IND later this month, and expects final approval to proceed to the Phase 3 study shortly thereafter.
The Phase 3 study, entitled “A Multi-Center, Randomized, Double-Blind, Placebo-Controlled Study of Bucillamine or Placebo in Patients with Mild-Moderate COVID-19,” will have an adaptive design trial. Symptomatic patients will initially be randomized 1:1:1 to receive Bucillamine 300 mg/day, Bucillamine 600 mg/day or placebo. The study will enroll a minimum of 210 patients, and then select a single Bucillamine dose. Patients will be randomized 2:1 to the selected Bucillamine dose and placebo. Interim analyses will occur every 100 subjects, up to the maximum sample size of 800 people. An independent data safety monitoring board will actively monitor interim data for the ongoing safety of patients.
The primary objective of the Phase 3 study is to study the frequency of hospitalization and mortality in patients with mild to moderate COVID-19 receiving Bucillamine therapy, compared to those receiving placebo. The primary endpoint is a 3-level ordinal scale of a patient’s worst outcome between randomization and day 28. The levels of the ordinal outcome are 1) death, 2) alive and hospitalized, and 3) alive and not hospitalized.
Secondary objectives include: evaluating the safety of Bucillamine therapy at low and high dose levels when administered up to 14 days; comparing disease course in patients with mild to moderate COVID-19 receiving Bucillamine therapy with those receiving placebo; evaluating time to clinical improvement in patients with COVID- 19 receiving low- and high-dose Bucillamine compared with placebo; and assessing impact of Bucillamine therapy on supplemental oxygen needs of patients with COVID-19. The study additionally has an exploratory objective, which is to evaluate the effects of Bucillamine on viral clearance from nasal swabs in patients with COVID-19.
Revive Therapeutics Ltd. stated back in April that the company had received positive feedback from the FDA in response to the company’s pre-IND meeting. The FDA recommendation was that Revive proceed directly into a Phase 3 confirmatory clinical trial for Bucillamine, in order to ensure expeditious safety and efficacy evaluation.
The FDA has provided guidance on study design and outcome measures for the Phase 3 study. The organization also agreed that Revive could rely on the data included in the company’s previous IND with Bucillamine for gout to support the COVID-19 study. Therefore, no Phase 1 or Phase 2 clinical studies were required before the Phase 3 confirmatory trial.
“[The] FDA’s support in advising Revive to move directly into a Phase 3 confirmatory trial provides an acknowledgment for the potential of Bucillamine in the treatment of COVID-19,” Frank noted in a press release. “Entering into a Phase 3 study is a major milestone for the Company, and we are excited to unlock the full potential of Bucillamine not only for this virus but also for other infectious diseases that we will investigate in the future.”