BLU-5937 for Chronic Cough

(CALM-1 Trial)

Not currently recruiting at 376 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: 12 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new medicine, BLU-5937 (a P2X3 antagonist), to determine its effectiveness for Refractory Chronic Cough (RCC), a cough that persists despite treatment and lasts at least a year. Participants will receive either a low dose, a higher dose of the medicine, or a placebo (a pill with no active medicine) to compare effects. Individuals with a persistent cough for over a year, who haven't found relief with other treatments, might be suitable candidates. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

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.

Is there any evidence suggesting that BLU-5937 is likely to be safe for humans?

Research has shown that BLU-5937, also known as camlipixant, is generally safe for people with a persistent chronic cough. Studies found that those taking camlipixant experienced fewer coughs. Importantly, these studies confirmed the treatment's safety, with no major side effects. Most participants found the treatment acceptable, with no serious health issues linked to the medication. This suggests that BLU-5937 is a promising and safe option for managing chronic cough symptoms. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for chronic cough?

Researchers are excited about BLU-5937 for chronic cough because it targets a different pathway than most current treatments. While standard treatments often focus on suppressing cough reflexes through various means like antihistamines or expectorants, BLU-5937 works by selectively blocking the P2X3 receptor. This receptor is involved in the cough reflex, and by targeting it specifically, BLU-5937 aims to reduce coughing without the side effects commonly associated with other treatments. This novel approach could offer relief for patients who have not found success with existing options.

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

Research has shown that BLU-5937 might help reduce the frequency of coughing in people with refractory chronic cough (RCC). Studies examining its effects over a 24-hour period have found promising results. In this trial, participants will receive either a 25 mg or 50 mg dose of BLU-5937, or a placebo, to evaluate its effectiveness. BLU-5937 targets a specific part of the body related to coughing, which might explain its ability to reduce coughs. Early findings indicate that patients who took BLU-5937 coughed less without experiencing serious side effects. This makes BLU-5937 a potential option for those struggling with RCC, offering hope for better symptom management. ^{1 2 4 6 7}

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 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.

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 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

What Are the Treatments Tested in This Trial?

Interventions

• BLU-5937

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).

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 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]

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]

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]

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]

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]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/nct05600777

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 ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12175956/

Camlipixant: A New Hope for Refractory Chronic Cough? - PMC Gefapixant demonstrated statistically significant results in two phase III studies without serious adverse events, although nearly two-thirds of patients ...

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40043302/

Camlipixant in Refractory Chronic Cough: A Phase 2b, ... Conclusions: Camlipixant treatment reduced cough frequency and improved patient-reported outcomes in patients with refractory chronic cough, with an acceptable ...

4. atsjournals.org atsjournals.org/doi/full/10.1164/rccm.202409-1752OC

Camlipixant in Refractory Chronic Cough: A Phase 2b, ... Camlipixant treatment reduced cough frequency and improved patient-reported outcomes in patients with refractory chronic cough, with an acceptable safety ...

5. mayo.edu mayo.edu/research/clinical-trials/cls-20569103

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.

6. atsjournals.org atsjournals.org/doi/10.1164/rccm.202503-0636ED

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 ...

7. healio.com healio.com/news/pulmonology/20250401/camlipixant-safe-yields-improvements-in-refractory-chronic-cough

Camlipixant safe, yields improvements in refractory chronic ... Adults with refractory chronic cough who received twice-daily camlipixant had decreases in cough frequency and better scores assessing cough severity.