A Dose Escalation Study of BLU-5937 in Unexplained or Refractory Chronic Cough (RELIEF)

A Randomized, Double-Blind, Placebo-Controlled, Crossover, Dose Escalation Study of BLU-5937 in Subjects With Unexplained or Refractory Chronic Cough (RELIEF)

This is a multi-center, randomized, double-blind, placebo-controlled, crossover, dose escalation study of BLU-5937 in subjects with unexplained or refractory chronic cough

Study Overview

• Status: Terminated
• Conditions: Chronic Refractory Cough
• Intervention / Treatment: Drug: BLU-5937; Drug: Placebo

Detailed Description

This study will have two 16-day treatment periods (four escalating doses or matching placebo at four days interval) separated by a 10 to 14-day washout period. There will be a 14-day follow-up period.

• Study Type: Interventional
• Enrollment (Actual): 68
• Phase: Phase 2

Contacts and Locations

Study Locations

• United Kingdom
  • Belfast, United Kingdom, BT9 7BL
    • Belfast City Hospital
  • Cottingham, United Kingdom, HU16 5JQ
    • Castle Hill Hospital
  • Leicester, United Kingdom, LE3 9QP
    • University Hospitals of Leicester
  • Llanelli, United Kingdom, SA14 8QF
    • Prince Phillip Hospital
  • London, United Kingdom, SE5 9RS
    • King's College Hospital
  • London, United Kingdom, SW3 6HP
    • Royal Brompton Hospital
  • Manchester, United Kingdom, M23 9LT
    • Manchester Clinical Research Facility
  • North Shields, United Kingdom, NE29 8NH
    • North Tyneside General Hospital
• United States
  • California
    • San Diego, California, United States, 92108
      • Allergy Associates Medical Group Inc.
    • San Jose, California, United States, 95117
      • Allergy & Asthma Associates of Santa Clara Valley
  • Florida
    • Largo, Florida, United States, 33778
      • Centre for Cough
  • Minnesota
    • Minneapolis, Minnesota, United States, 55402
      • Clinical Research Institute
  • North Carolina
    • Gastonia, North Carolina, United States, 20854
      • Clinical Research of Gastonia
  • South Carolina
    • Charleston, South Carolina, United States, 29420
      • National Allergy & Asthma Research
  • Texas
    • San Antonio, Texas, United States, 78229
      • Diagnostics Research Group
  • Wisconsin
    • Greenfield, Wisconsin, United States, 53228
      • Allergy Asthma & Sinus Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Unexplained or refractory chronic cough for at least one year
• Chest radiograph or CT thorax within the last 60 months not demonstrating any abnormality considered to be significantly contributing to the chronic cough
• Cough count of ≥ 10 per hour (Awake Cough Count) at Screening
• Score of ≥ 40mm on the Cough Severity VAS at Screening
• Women of child-bearing potential must have a negative serum pregnancy test at Screening
• Women of child-bearing potential must use a highly effective contraception method from Screening through the Follow-Up Visit
• Male subjects and their partners of child-bearing potential must use 2 methods of acceptable birth control

Exclusion Criteria:

• Current smoker or individuals who have given up smoking within the past 6 months, or those with >20 pack-year smoking history
• Diagnosis of COPD, bronchiectasis, idiopathic pulmonary fibrosis
• Treatment with an ACE-inhibitor as the potential cause of a subject's cough, or requiring treatment with an ACE-inhibitor during the study, or within 12 weeks prior to the Screening Visit
• FEV1/FVC < 60%
• History of upper respiratory tract infection or recent significant change in pulmonary status within 4 weeks of the Baseline Visit
• History of concurrent malignancy or recurrence of malignancy within 2 years prior to Screening
• History of a diagnosis of drug or alcohol dependency or abuse within the last 3 years
• Clinically significant abnormal electrocardiogram (ECG) or laboratory tests at Screening
• Other severe, acute, or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with trial participation or investigational product administration or may interfere with the interpretation of trial results

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: BLU-5937 oral tablet BID; Randomized crossover design of 4 different doses (25, 50, 100, 200 mg BID) of BLU-5937 tablets to be administered orally BID	Drug: BLU-5937; Four escalating doses of BLU-5937 administered BID over the course of the study
Placebo Comparator: Placebo oral tablet BID; Randomized crossover design of matching placebo tablets to be administered orally BID	Drug: Placebo; Matching placebo for BLU-5937

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Awake Objective Cough Frequency on Log-transformed Scale	Change in awake cough frequency (average hourly cough frequency while the subject is awake ) evaluated using the VitaloJAK cough monitor with 24-hour sound recordings collected	Period 1: baseline (Day 0) and 24 hours after Day 4, 8, 12, 16 doses ; Period 2: baseline (Day 30) and 24 hours after Day 34, 38, 42, 46 doses

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Awake Cough Frequency on Log-transformed Scale in the Subgroup of Participants With Awake Cough Frequency > or = 20 Coughs/Hour at Baseline	Change in awake cough frequency (average hourly cough frequency while the subject is awake) in the a pre-specified subgroup of participants with awake cough frequency > or = 20 coughs/hour at baseline evaluated using the VitaloJAK cough monitor with 24-hour sound recordings collected	Period 1: baseline (Day 0) and 24 hours after Day 4, 8, 12, 16 doses ; Period 2: baseline (Day 30) and 24 hours after Day 34, 38, 42, 46 doses
Change in Awake Cough Frequency on Log-transformed Scale in the Subgroup of Participants With Awake Cough Frequency > or = Median (32.4 Coughs/Hour) at Baseline	Change in awake cough frequency (average hourly cough frequency while the subject is awake) in the a pre-specified subgroup of participants with awake cough frequency > or = median (32.4 coughs/hour) at baseline evaluated using the VitaloJAK cough monitor with 24-hour sound recordings collected	Period 1: baseline (Day 0) and 24 hours after Day 4, 8, 12,16 doses ; Period 2: baseline (Day 30) and 24 hours after Day 34, 38, 42, 46 doses

Collaborators and Investigators

• Sponsor: Bellus Health Inc
• Investigators: Principal Investigator: Jacky Smith, MD, Ph.D., University of Manchester

Study record dates

Study Major Dates

• Study Start (Actual): July 10, 2019
• Primary Completion (Actual): April 23, 2020
• Study Completion (Actual): April 23, 2020

Study Registration Dates

• First Submitted: June 6, 2019
• First Submitted That Met QC Criteria: June 6, 2019
• First Posted (Actual): June 7, 2019

Study Record Updates

• Last Update Posted (Actual): August 3, 2021
• Last Update Submitted That Met QC Criteria: July 31, 2021
• Last Verified: April 1, 2020

More Information

Terms related to this study

• Keywords: Unexplained or refractory chronic cough, P2X3 antagonists
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Respiration Disorders; Signs and Symptoms, Respiratory; Cough
• Other Study ID Numbers: BUS-P2-01; 2019-000375-16 (EudraCT Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No