Phase 3 Randomized Double-Blind Study of Camlipixant (BLU-5937) Versus Placebo in Adults with Refractory or Unexplained Chronic Cough

The primary objective of this Phase 3, 24-week, randomized, double-blind, placebo-controlled study is to assess the effect of **BLU-5937** compared to placebo on 24-hour cough frequency in adults with **Refractory Chronic Cough**, including unexplained chronic cough, at Week 24. Additionally, the study aims to determine the safety profile of BLU-5937 versus placebo in this patient population up to Week 24. This is clinically relevant as it addresses the need for effective treatments in patients with persistent cough that is unresponsive to standard therapies, potentially improving their quality of life.

Secondary objectives include evaluating the effects of BLU-5937 on other measures of cough frequency and patient-reported outcomes (PROs). These assessments will provide a comprehensive understanding of the therapeutic impact of BLU-5937 beyond the primary endpoint, offering insights into its broader clinical benefits.

The clinical trial involves a total of **632 participants** diagnosed with **Refractory Chronic Cough**, including unexplained chronic cough. The study population comprises both male and female adults aged between 18 and 80 years. Participants were selected based on their ability to understand written informed consent and a confirmed diagnosis of refractory chronic cough for at least one year prior to screening. The trial includes individuals who meet specific cough frequency criteria. Female participants are required to be either not of childbearing potential or agree to adhere to contraceptive guidance if they are of childbearing potential. The trial population includes a vulnerable group, although specific lifestyle considerations such as diet or physical activity are not detailed. The selection criteria ensure a diverse and representative sample of individuals affected by this condition, allowing for a comprehensive assessment of the investigational treatment's efficacy and safety.

The clinical trial is a **Phase 3**, 24-week, randomized, double-blind, placebo-controlled, parallel-arm study designed to evaluate the efficacy and safety of **BLU-5937** in adult participants with **refractory chronic cough**, including unexplained chronic cough. The trial includes an open-label extension phase. The primary objective is to assess the effect of BLU-5937 versus placebo on 24-hour cough frequency at Week 24, as well as to determine the safety profile of BLU-5937. The trial is expected to conclude by March 2026, with recruitment having commenced in April 2023.

Participants will be randomly assigned to receive either BLU-5937 or a placebo, administered orally in tablet form. The study will involve several key visits: an initial screening visit to confirm eligibility, regular follow-up visits to monitor safety and efficacy, and an end-of-study visit to assess final outcomes. The inclusion criteria require participants to be between 18 and 80 years of age, capable of understanding informed consent, and diagnosed with refractory chronic cough for at least one year prior to screening. Female participants must adhere to specific contraceptive guidelines if of childbearing potential.

The expected duration of participant involvement is up to 24 weeks, with conditions for early termination including adverse events (AEs) or serious adverse events (SAEs) that necessitate withdrawal. Primary endpoints include the measurement of 24-hour cough frequency and the incidence of AEs and SAEs. Secondary endpoints involve changes in cough severity and quality of life assessments. The trial is not classified as low intervention and is conducted under the sponsorship of Bellus Health Inc., with BLU-5937 being a chemically synthesized drug. Participants will be closely monitored for changes in vital signs, clinical laboratory values, and electrocardiogram (ECG) readings throughout the study period.

The clinical trial involves the administration of **BLU-5937**, a chemically synthesized drug, as the experimental medication. **BLU-5937** is formulated as a tablet and contains the active substance **camlipixant**. The tablets are designed for **oral use** and are manufactured by Bellus Health Inc. The maximum daily dose of **BLU-5937** is 1111 mg, with a total maximum dose of 1111 mg over the treatment period. The treatment duration is set for a maximum of 55 days. Participants will receive the medication in a double-blind manner, ensuring neither the participants nor the investigators know who receives the active drug or the placebo. Compliance with the dosing schedule will be monitored throughout the study to ensure adherence to the protocol.

The study also includes a **placebo** as a comparator treatment. The placebo is designed to mimic the appearance of the **BLU-5937** tablets, being oval, biconvex, plain, and white to off-white in color. The placebo tablets are administered orally, following the same dosing schedule as the active treatment, to maintain the study's double-blind design. The use of a placebo allows for the assessment of the efficacy and safety of **BLU-5937** by providing a baseline for comparison. Participant compliance with the placebo regimen will be similarly monitored to ensure the integrity of the trial data.

The efficacy of BLU-5937 in the treatment of **Refractory Chronic Cough** (RCC), including unexplained chronic cough, will be assessed in a Phase 3, 24-week, randomized, double-blind, placebo-controlled, parallel-arm study with an open-label extension. The primary endpoint for evaluating efficacy is the 24-hour cough frequency at Week 24, measured using a cough monitor. Secondary endpoints include changes from baseline in the Cough Severity Visual Analogue Scale (CS-VAS) and the Leicester Cough Questionnaire (LCQ) total score at Week 24, as well as awake cough frequency and 24-hour cough response from baseline at Week 24.

Data collection will occur at specified timepoints, with primary and secondary endpoints assessed at Week 24. The study will also monitor the incidence of adverse events (AEs) and serious adverse events (SAEs), as well as changes in vital signs, clinical laboratory values, and ECG values from baseline to Week 24. The efficacy assessments will utilize validated tools such as the CS-VAS and LCQ to ensure reliable and consistent measurement of outcomes. The analysis will focus on comparing the effects of BLU-5937 versus placebo in reducing cough frequency and improving patient-reported outcomes related to cough severity and quality of life.