- Double-blind, 4-week placebo controlled, parallel arm trial will evaluate the efficacy and safety of 3 doses of BLU-5937 in 280 patients with refractory chronic cough –
- Trial to recruit patients with baseline cough count ≥25 coughs per hour -- RELIEF Phase 2 trial results demonstrated significant reductions in cough frequency in pre-specified analyses with patients ≥32 coughs/hour (50% of trial participants) and ≥20 coughs/hour (80% of trial participants) at baseline -
- Phase 2b trial expected to initiate in Q4 2020 with interim analysis in mid-2021 and topline data in 2H 2021 -
“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
SOOTHE Phase 2b Trial Design
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
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.
Learnings from RELIEF Phase 2 Data
The previous Phase 2 RELIEF trial indicated a significant interaction between baseline cough frequency and the response to BLU-5937. Pre-specified analyses regarding the impact of baseline cough frequency on treatment effect, including subgroup analyses in participants with baseline awake cough frequency of ≥20 coughs/hour and ≥32 coughs/hour (median), revealed statistically significant and clinically meaningful reductions in cough frequency relative to placebo:
- Patients with ≥20 coughs/hour (80% of trial patients) saw placebo adjusted reduction in awake cough frequency of 20% (p=0.001), 18% (p=0.02), 19% (p=0.03) and 27% (p=0.003) at doses of 25, 50, 100 and 200 mg BID respectively.
- Patients above the median with ≥32 coughs/hour at baseline (50% of trial patients) saw placebo adjusted reduction in awake cough frequency of 28%, 28%, 30% and 32% (all p< 0.0015) at doses of 25, 50, 100 and 200 mg BID respectively.
- A statistically significant relationship (p=0.0258) was observed between average awake cough frequency at baseline and treatment effect, linking increased baseline cough frequency with improved treatment benefit.
“The SOOTHE Phase 2b trial represents a significant milestone for BELLUS and patients suffering from refractory chronic cough,” said
About the Phase 2 RELIEF Trial
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
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.
Chronic cough, the lead indication for BLU-5937, is a cough lasting more than eight weeks and is associated with significant adverse physical, social and psychosocial effects on health and quality of life. It is estimated that approximately 26 million adults in
Chronic pruritus, commonly known as chronic itch, is an irritating sensation that leads to scratching, and persists for longer than six weeks, which can be debilitating and has a significant impact on quality-of-life. It is a hallmark of many conditions, including atopic dermatitis (AD). It is estimated that chronic pruritus associated with AD affects more than 16.9 million adults in
Certain statements contained in this news release, other than statements of fact that are independently verifiable at the date hereof, may constitute "forward-looking statements" within the meaning of Canadian securities legislation and regulations, the
Director, Investor Relations and Communications