BLU-5937 for Chronic Cough

(CALM-1 Trial)

Recruiting at183 trial locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 3

Recruiting

Sponsor: Bellus Health Inc. - a GSK company

Disqualifiers: Smoking, COPD, Asthma, Cancer, others

Pivotal Trial (Near Approval)

Prior Safety Data

Trial Summary

What is the purpose of this trial?

This trial is testing BLU-5937, a medication aimed at reducing cough frequency in adults with persistent coughs that don't improve with other treatments. It works by affecting pathways that trigger the cough reflex.

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

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What data supports the effectiveness of the drug BLU-5937 for chronic cough?

BLU-5937 has shown strong evidence of reducing chronic cough by blocking P2X3 receptors, which are involved in the cough reflex. In animal studies, it significantly reduced coughs without affecting taste, unlike other similar drugs. ^{1 2 3 4 5}

Is BLU-5937 safe for humans?

BLU-5937 has been shown to have a high safety margin in preclinical studies, with good tolerability and no effect on taste perception even at high doses. It is currently in early clinical trials, indicating it has passed initial safety evaluations. ^{3 5 6 7 8}

How is the drug BLU-5937 different from other treatments for chronic cough?

BLU-5937 is unique because it selectively targets P2X3 receptors, which are involved in the cough reflex, without affecting taste perception, a common side effect of similar drugs. This makes it a promising option for treating chronic cough with fewer side effects. ^{2 3 7 8 9}

Research Team

Eligibility Criteria

Adults with a persistent cough lasting over a year that hasn't improved with treatment can join. They must be able to consent and, if they can have children, use effective birth control during the study and for two weeks after. People who've abused substances recently, participated in BLU-5937 trials before, had certain infections or cancers, smoke currently or quit recently, or have specific lung diseases cannot participate.

Inclusion Criteria

Women of child-bearing potential must use a highly effective contraception method during the study and for at least 14 days after the last dose

I am able to understand and sign the consent form.

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

Exclusion Criteria

You have tested positive for the COVID-19 virus in a lab test before the study starts.

I have not had any other cancers in the last 5 years.

I currently smoke or vape, quit within the last 6 months, or have a history of heavy smoking.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive BLU-5937 or placebo for 12 weeks to assess the effect on 24-hour cough frequency

12 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

Long-term

Treatment Details

Interventions

• BLU-5937 (Other)

Trial Overview The trial is testing BLU-5937's effectiveness and safety against a placebo over one year in adults with refractory chronic cough. Participants will randomly receive either the actual drug or a placebo without knowing which one they're getting (double-blind).

Participant Groups

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+

Findings from Research

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]

Gefapixant, a P2X3 receptor antagonist, shows significant efficacy in reducing cough frequency in patients with refractory chronic cough, particularly at doses of 30 mg or higher, based on two randomized, double-blind, placebo-controlled studies.

The studies also indicate that gefapixant is better tolerated at lower doses compared to higher doses, with taste disturbances peaking at doses of 150 mg or more, suggesting a need for further long-term studies to optimize dosing.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gefapixant in two randomised dose-escalation studies in chronic cough. Smith, JA., Kitt, MM., Butera, P., 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]

In a 12-week study involving 253 patients with refractory chronic cough, gefapixant at a dose of 50 mg twice daily significantly reduced cough frequency compared to placebo, demonstrating its efficacy as a treatment option.

The most common side effect observed was dysgeusia (altered taste), which increased with higher doses of gefapixant, indicating a need for monitoring safety alongside its therapeutic benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gefapixant, a P2X3 receptor antagonist, for the treatment of refractory or unexplained chronic cough: a randomised, double-blind, controlled, parallel-group, phase 2b trial. Smith, JA., Kitt, MM., Morice, AH., et al.[2021]

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]

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]

Gefapixant 45 mg taken twice daily significantly reduced 24-hour cough frequency in patients with refractory chronic cough compared to placebo, demonstrating its efficacy in treating this condition in two large phase 3 trials involving a total of 2044 participants.

The most common side effects were taste disturbances, such as ageusia and dysgeusia, but overall, gefapixant showed an acceptable safety profile, making it a promising treatment option for chronic cough.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of gefapixant, a P2X3 receptor antagonist, in refractory chronic cough and unexplained chronic cough (COUGH-1 and COUGH-2): results from two double-blind, randomised, parallel-group, placebo-controlled, phase 3 trials. McGarvey, LP., Birring, SS., Morice, AH., et al.[2023]

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 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]

References

1. United States 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. [2023]

2. England pubmed.ncbi.nlm.nih.gov

Gefapixant in two randomised dose-escalation studies in chronic cough. [2022]

3. England pubmed.ncbi.nlm.nih.gov

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

4. England pubmed.ncbi.nlm.nih.gov

Gefapixant, a P2X3 receptor antagonist, for the treatment of refractory or unexplained chronic cough: a randomised, double-blind, controlled, parallel-group, phase 2b trial. [2021]

5. England 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. [2022]

6. England pubmed.ncbi.nlm.nih.gov

P2X3 receptor antagonist (AF-219) in refractory chronic cough: a randomised, double-blind, placebo-controlled phase 2 study. [2020]

7. England pubmed.ncbi.nlm.nih.gov

Efficacy and safety of gefapixant, a P2X3 receptor antagonist, in refractory chronic cough and unexplained chronic cough (COUGH-1 and COUGH-2): results from two double-blind, randomised, parallel-group, placebo-controlled, phase 3 trials. [2023]

8. Switzerland pubmed.ncbi.nlm.nih.gov

Safety, Pharmacodynamics, and Pharmacokinetics of P2X3 Receptor Antagonist Eliapixant (BAY 1817080) in Healthy Subjects: Double-Blind Randomized Study. [2022]

9. United States 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. [2022]