BELLUS Health, a clinical-stage biopharmaceutical company, announced the planned trial design for SOOTHE, the company’s phase 2b dose confirmation trial evaluating the efficacy and safety of BLU-5937 in refractory chronic cough (RCC). The phase 2b trial is designed based on the results from the company’s previous phase 2 RELIEF trial including the finding that baseline cough frequency is a key indicator of treatment benefit.
“Building on the results from our RELIEF trial where there was a significant and clinically meaningful improvement observed in patients with baseline cough frequencies =20 coughs per hour when treated with BLU-5937, we believe our plan to recruit patients with baseline cough frequencies >25 coughs per hour for the SOOTHE trial provides the best strategy for success in this patient population,” said Cathy Bonuccelli, chief medical officer at BELLUS Health. “Additional exploratory arms of patients with baseline cough frequencies <25 coughs per hour will allow us to collect additional data to better inform the design of our phase 3 program.”
The SOOTHE phase 2b trial is planned as a multicenter, randomized, double-blind, 4-week, parallel arm study evaluating three doses of BLU-5937 (12.5 mg, 50 mg and 200 mg BID) in 280 patients with refractory chronic cough versus placebo. 240 participants with a baseline cough count of =25 awake coughs per hour are expected to be randomized across four arms (1:1:1:1) evaluating the three active doses and placebo in the main study. Treatment arms will be stratified by baseline awake cough frequency to help balance the baseline cough count across trial arms. The primary efficacy endpoint will be the placebo-adjusted change in the 24-hour cough frequency using a cough recorder in the main study. An additional 40 participants with a baseline cough count <25 awake coughs per hour are expected to be randomized across 2 arms (1:1) evaluating one active dose (200 mg BID) and placebo to further investigate the effect of BLU-5937 in an exploratory analysis.
The trial is expected to enroll participants in approximately 100 sites, including 50 centers in the United States. The first patient is expected to be dosed in Q4 2020.
An interim analysis is expected to be conducted once 50% of patients have completed the main study and is anticipated in mid-2021. Using a predefined probability of efficacy hurdle, results from the interim analysis may be used to help select dose(s) for Phase 3 and initiate phase 3 planning, including health authority interactions. Topline results from SOOTHE are expected in 2H 2021.
The Company has confirmed a meeting with FDA in Q4 2020 and any adjustments to trial design or our expected timeline based on FDA feedback will be disclosed thereafter.
RELIEF was a randomized, placebo-controlled, two-period crossover, dose-escalation study to assess the efficacy, safety and tolerability of BLU-5937, a highly selective P2X3 antagonist, at four doses: 25, 50, 100 and 200 mg, administered orally, twice-daily. RELIEF enrolled a total of 68 refractory chronic cough patients from 16 sites in the United Kingdom and United States.
BLU-5937, a highly selective P2X3 antagonist - (>1500 fold) - is in development for chronic cough, chronic pruritus and other hypersensitization-related disorders.
The P2X3 receptor in the cough reflex pathway, which is implicated in chronic cough, is a rational target for treating chronic cough, and it has been evaluated in multiple clinical trials with different P2X3 antagonists. The Company believes that its highly selective P2X3 antagonist has the potential to reduce coughing in patients with chronic cough while maintaining taste function through targeted inhibition of P2X3 receptors rather than P2X2/3 receptors which play a major role in taste.
In addition to chronic cough and chronic pruritus, BLU-5937 may also have broad applicability across other afferent hypersensitization-related disorders, enabling the Company to consider developing a pipeline of therapies using its P2X3 platform. BELLUS Health is exploring how P2X3 activation can contribute to irritation and pain, and whether inhibition of P2X3 receptors can help treat these afferent hypersensitization-related disorders.