BLU-5937 for Chronic Cough

(CALM-2 Trial)

Recruiting at 292 trial locations

Overseen By EU GSK Clinical Trials Call Center

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Bellus Health Inc. - a GSK company

Disqualifiers: Smoking, COPD, Asthma, Cancer, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 24 weeks

975 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new drug, BLU-5937 (a P2X3 antagonist), to determine its effectiveness for people with Refractory Chronic Cough (RCC), a cough lasting over a year that doesn't respond to usual treatments. Participants will receive either BLU-5937 at varying doses or a placebo (a pill with no active medicine) for comparison. This trial is ideal for individuals with a stubborn cough lasting over a year who are non-smokers. The goal is to find a better way to manage this persistent cough and improve daily life for those affected. As a Phase 3 trial, it represents the final step before FDA approval, offering a chance to contribute to a potentially groundbreaking treatment.

Do I need to stop taking my current medications to join the trial?

The trial protocol does not specify whether you need to stop taking your current medications.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that BLU-5937 is generally safe for people with chronic cough. Studies have found that it can reduce cough frequency without causing major side effects. Unlike similar treatments, patients who took BLU-5937 did not report a loss of taste. Some individuals might experience mild side effects, but these are usually not serious. Overall, the research supports that BLU-5937 is safe for humans and could be a promising treatment for chronic cough. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about BLU-5937 for chronic cough because it offers a new approach by targeting the P2X3 receptor, which is different from the mechanisms of current treatments like opioids or cough suppressants. Unlike typical cough medicines that often come with side effects like drowsiness, BLU-5937 aims to reduce coughing without affecting taste perception, a common issue with other P2X3 antagonists. This targeted action not only promises more effective cough relief but also a better quality of life for patients suffering from chronic cough.

What evidence suggests that BLU-5937 might be an effective treatment for chronic cough?

Research has shown that BLU-5937 blocks certain receptors in the body linked to coughing. By targeting these receptors, the treatment aims to reduce excessive coughing in people with chronic cough. Previous studies have found that similar treatments can decrease cough frequency and improve overall patient experience without major side effects. BLU-5937 is specifically designed to avoid taste problems, a common issue with other treatments. Overall, this treatment has shown promise in effectively managing chronic cough symptoms. Participants in this trial will receive either BLU-5937 at varying dosages or a placebo to evaluate its effectiveness and safety. ^{2 6 7 8 9}

Who Is on the Research Team?

GSK Clinical Trials

Principal Investigator

GlaxoSmithKline

Are You a Good Fit for This Trial?

Adults with a persistent cough lasting over a year, not explained by other lung conditions like COPD or asthma, can join this study. They must be non-smokers for at least six months and have no recent infections or history of serious illness like cancer within the past five years.

Inclusion Criteria

I have had a chronic cough for at least one year that hasn't improved with treatment.

I am able to understand and sign the consent form.

I am using effective birth control and will continue for 14 days after my last dose.

Exclusion Criteria

I currently smoke or vape, quit within the last 6 months, or have a 20+ pack-year smoking history.

You have a confirmed case of COVID-19 when you are screened for the study.

I have not had a respiratory infection in the last 4 weeks.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive BLU-5937 or placebo for 24 weeks to assess efficacy and safety in reducing cough frequency

24 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Open-label extension

Participants may opt into continuation of treatment with BLU-5937 long-term

What Are the Treatments Tested in This Trial?

Interventions

• BLU-5937
• Placebo

Trial Overview

The trial is testing BLU-5937, a potential new medication for chronic cough that hasn't responded to other treatments. Participants will either receive BLU-5937 or a placebo (a substance with no active drug) over 24 weeks to compare effectiveness and safety.

How Is the Trial Designed?

Group I: BLU-5937 50 mg Experimental Treatment 1 Intervention

BLU-5937 oral dose 50 mg twice a day.

Group II: BLU-5937 25 mg Experimental Treatment 1 Intervention

BLU-5937 oral dose 25 mg twice a day.

Group III: Placebo Placebo Group 1 Intervention

Matching Placebo for BLU-5937 oral dose twice a day.

Who Is Running the Clinical Trial?

Bellus Health Inc. - a GSK company

Lead Sponsor

Trials

19

Recruited

5,300+

Bellus Health Inc

Lead Sponsor

Trials

16

Recruited

5,300+

Published Research Related to This Trial

In a double-blind, placebo-controlled study involving 24 patients with refractory chronic cough, the P2X3 antagonist AF-219 significantly reduced cough frequency by 75% compared to placebo, demonstrating its efficacy as a potential treatment.

AF-219 treatment led to a decrease in daytime cough frequency from an average of 37 coughs per hour to 11, while the placebo group only saw a minor reduction, indicating that P2X3 receptors play a crucial role in cough hypersensitivity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

P2X3 receptor antagonist (AF-219) in refractory chronic cough: a randomised, double-blind, placebo-controlled phase 2 study. Abdulqawi, R., Dockry, R., Holt, K., et al.[2020]

In a phase 3 study involving 169 Japanese participants with refractory or unexplained chronic cough, gefapixant demonstrated an acceptable safety profile, with no serious treatment-related adverse events reported.

The study showed significant improvements in cough-specific quality of life, as measured by the Leicester Cough Questionnaire, indicating gefapixant's efficacy in reducing chronic cough symptoms over 52 weeks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase 3, randomized, double-blind, clinical study to evaluate the long-term safety and efficacy of gefapixant in Japanese adult participants with refractory or unexplained chronic cough. Niimi, A., Sagara, H., Kikuchi, M., et al.[2022]

BLU-5937 is a highly selective and potent antagonist of the P2X3 receptor, which plays a key role in the hypersensitization of the cough reflex, making it a promising treatment for chronic cough.

In preclinical studies, BLU-5937 demonstrated significant anti-cough effects in guinea pigs without affecting taste perception, indicating its safety and tolerability, and it is currently in phase I clinical development.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

BLU-5937: A selective P2X3 antagonist with potent anti-tussive effect and no taste alteration. Garceau, D., Chauret, N.[2020]

Eliapixant, a selective P2X3 receptor antagonist, was found to be well tolerated in a study of 47 healthy male volunteers, with low incidence of adverse effects, including taste disturbances, after repeated doses over 2 weeks.

The study demonstrated that eliapixant achieved plasma concentrations sufficient to occupy P2X3 receptors effectively at doses of 200 mg and 750 mg, supporting its potential efficacy for treating refractory chronic cough.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety, Pharmacodynamics, and Pharmacokinetics of P2X3 Receptor Antagonist Eliapixant (BAY 1817080) in Healthy Subjects: Double-Blind Randomized Study. Friedrich, C., Francke, K., Gashaw, I., et al.[2022]

In a phase 2b trial involving 406 patients with refractory or unexplained chronic cough, sivopixant did not show a statistically significant improvement in 24-hour cough frequency compared to placebo, although the 300 mg dose showed the most promise for reducing cough severity and improving patient-reported outcomes.

The treatment was generally well-tolerated, with mild to moderate adverse effects, particularly taste disturbances, reported in a dose-dependent manner, suggesting that while sivopixant may be effective, further studies are necessary to confirm its benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Phase 2b Trial of P2X3 Receptor Antagonist Sivopixant for Refractory or Unexplained Chronic Cough. McGarvey, L., Smith, JA., Morice, A., et al.[2023]

In a Phase 1 study involving 36 healthy participants, gefapixant, a P2X3-receptor antagonist for chronic cough, was found to have a safety profile consistent with previous studies, with taste-related adverse events being the most common.

The study highlighted that older adults and females had different pharmacokinetic responses to gefapixant compared to younger males, suggesting that age and sex may influence drug exposure and effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Randomized, Placebo-Controlled Study to Investigate the Safety, Tolerability, and Pharmacokinetics of 3 Weeks of Orally Administered Gefapixant in Healthy Younger and Older Adults. Nussbaum, J., Hussain, A., Ford, A., et al.[2022]

In a study involving 23 patients with refractory chronic cough, the P2X3 receptor antagonist filapixant significantly reduced cough frequency and severity, with reductions ranging from 17% to 37% compared to placebo, depending on the dosage.

Filapixant was found to be safe and well-tolerated, with no serious adverse events reported, although taste-related side effects increased with higher doses, affecting up to 57% of patients at the highest dosage.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The P2X3 receptor antagonist filapixant in patients with refractory chronic cough: a randomized controlled trial. Friedrich, C., Francke, K., Birring, SS., et al.[2023]

Citations

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By inhibiting P2X3 receptors on the primary sensory neurons, BLU-5937 would inhibit the hypersensitization of the cough reflex and, hence, the exaggerated cough ...

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Benefit-risk profile of P2X3 receptor antagonists for treatment ...

Primary outcomes were a reduction rate in 24-hour cough frequency and incidence of taste disturbance. Dose-response curves and median effective ...

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A 24-Week Study of the Efficacy and Safety of BLU-5937 in ...

The primary efficacy objective is to assess the effect of BLU-5937 on 24-hour cough frequency in adults with refractory chronic cough (including unexplained ...

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Camlipixant: A New Hope for Refractory Chronic Cough?

SOOTHE demonstrated a 34% reduction in 24-hour cough frequency at both 50- and 200-mg doses compared with placebo. However, patient-reported outcomes showed ...

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A 24-Week Study of the Efficacy and Safety of BLU-5937 in ...

The purpose of this study is to assess the effect of BLU-5937 on 24-hour cough frequency in an enriched population of adults with refractory chronic cough.

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Camlipixant in Refractory Chronic Cough: A Phase 2a ...

Camlipixant, another P2X3 antagonist, was well tolerated in healthy volunteers, with an acceptable safety profile and no complete taste loss (ageusia) at any ...