Chronic Refractory CoughPhase 2RELIEFNCT03979638

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

A Phase 2 study testing BLU-5937 in people with Chronic Refractory Cough, run by Bellus Health Inc. - a GSK company at 16 sites in 2 countries.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record

Search all trials

Trial summary

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 Read more about this study

Who is it for?: Ages 18 to 80 years
Conditions the study is for: Chronic Refractory Cough
What is being tested?: BLU-5937
Type of treatment: Pill or oral medicine
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 68 participants
Where: 16 sitesin 2 countries
Study dates: 10 Jul 2019to 23 Apr 2020
Phase: Phase 2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 80 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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

Who cannot join

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

Show all 9Show fewer

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

Trial locations and contacts

16 sites in 2 countries.

Country

City, postcode or hospital

16 sites in 2 countries

United States8 sites

National Allergy & Asthma Research
Charleston, South Carolina, 29420
Clinical Research of Gastonia
Gastonia, North Carolina, 20854
Allergy Asthma & Sinus Center
Greenfield, Wisconsin, 53228
Centre for Cough
Largo, Florida, 33778
Clinical Research Institute
Minneapolis, Minnesota, 55402
Diagnostics Research Group
San Antonio, Texas, 78229
Allergy Associates Medical Group Inc.
San Diego, California, 92108
Allergy & Asthma Associates of Santa Clara Valley
San Jose, California, 95117

Other trials in United States

United Kingdom8 sites

Belfast City Hospital
Belfast, BT9 7BL
Castle Hill Hospital
Cottingham, HU16 5JQ
University Hospitals of Leicester
Leicester, LE3 9QP
Prince Phillip Hospital
Llanelli, SA14 8QF
King's College Hospital
London, SE5 9RS
Royal Brompton Hospital
London, SW3 6HP
Manchester Clinical Research Facility
Manchester, M23 9LT
North Tyneside General Hospital
North Shields, NE29 8NH

Other trials in United Kingdom

About this study

Official title: 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

Read the 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.

Conditions: Chronic Refractory Cough
Being tested: BLU-5937, Placebo
Keywords: Unexplained or refractory chronic cough, P2X3 antagonists
Medical subject headings: Chronic Cough

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

BLU-5937Drug
Four escalating doses of BLU-5937 administered BID over the course of the study
PlaceboDrug
Matching placebo for BLU-5937

Study groups in NCT03979638
Study group	Role	What they receive
BLU-5937 oral tablet BID	Experimental	Randomized crossover design of 4 different doses (25, 50, 100, 200 mg BID) of BLU-5937 tablets to be administered orally BID Receives: Drug: BLU-5937
Placebo oral tablet BID	Placebo comparator	Randomized crossover design of matching placebo tablets to be administered orally BID Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

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
Measured: 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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

10 Jul 201923 Apr 2020

First posted7 Jun 2019
Study start10 Jul 2019
Primary completion23 Apr 2020
Study completion23 Apr 2020

Why it stopped: Trial was terminated due to the impact of the COVID-19 on trial activities. 68 patients with refractory chronic cough were enrolled with 52 completing treatment

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for Chronic Refractory CoughStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Crossover
Model description: Two-arm, Two-Period, crossover assignment
Masking: Quadruple blind
Who is masked: Participant, Care provider, Investigator, Outcomes assessor
Enrolment: 68 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03979638
Sponsor's protocol ID: BUS-P2-01
Other IDs: 2019-000375-16, 2019
Acronym: RELIEF
Status last verified: Apr 2020
First submitted: 6 Jun 2019
Last updated: 3 Aug 2021
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
FDA-regulated drug: Yes
FDA-regulated device: No

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

RecruitingPhase 2
The Effect of Nalbuphine Extended-Release (NAL ER) on Cough in Participants With Refractory Chronic Cough (RCC)
Refractory Chronic Cough
Not yet recruitingPhase 4
A 2x2 Factorial, Randomized, Open-label Trial to Evaluate Neuromodulators and Cough Control Therapy in Patients With Refractory or Unexplained Chronic Cough
Cough, Refractory Chronic Cough
RecruitingPhase 2
A Study to Investigate the Efficacy and Safety of SC0032, a Magnesium Salt Oral Spray, in Adults With Refractory or Unexplained Chronic Cough
Refractory Chronic Cough and Unexplained Chronic Cough
RecruitingPhase 2
Mechanisms of Change in Behavioral Cough Suppression Therapy for Refractory Chronic Cough
Chronic Cough (CC), Refractory Chronic Cough
Active, not recruitingPhase 3
A 24-Week Study of the Efficacy and Safety of BLU-5937 in Adults With Refractory Chronic Cough
Cough, Refractory Chronic Cough

All Chronic Refractory Cough trials

Study at a glance

From the registry record, last updated by the sponsor on 3 Aug 2021. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Randomized, Double-Blind, Placebo-Controlled, Crossover, Dose Escalation Study of BLU-5937 in Subjects With Unexplained or Refractory Chronic Cough (RELIEF)
ClinicalTrials.gov ID: NCT03979638
Acronym / sponsor ID: RELIEF / BUS-P2-01
Conditions: Chronic Refractory Cough
Keywords: Unexplained or refractory chronic cough, P2X3 antagonists
Phase: Phase 2
Study type: Interventional
Recruitment status: TerminatedReason stopped: Trial was terminated due to the impact of the COVID-19 on trial activities. 68 patients with refractory chronic cough were enrolled with 52 completing treatment
Enrolment: 68 participants (actual)
Lead sponsor: Bellus Health Inc. - a GSK companyIndustry (pharma, biotech, devices)
Study start: 10 Jul 2019 (actual)
Primary completion: 23 Apr 2020 (actual)
Study completion: 23 Apr 2020 (actual)
First posted: 7 Jun 2019 (actual)
Results: Posted 3 Aug 2021

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

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

Detailed description

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Crossover
Masking: Quadruple blind (participant, care provider, investigator, outcomes assessor)
Number of arms: 2
Model description: Two-arm, Two-Period, crossover assignment

Arm	Type	Receives
BLU-5937 oral tablet BID	Experimental	Drug: BLU-5937Randomized crossover design of 4 different doses (25, 50, 100, 200 mg BID) of BLU-5937 tablets to be administered orally BID
Placebo oral tablet BID	Placebo comparator	Drug: PlaceboRandomized crossover design of matching placebo tablets to be administered orally BID

Who may qualify

Ages: 18 to 80 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (7 listed)

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

Key exclusion criteria (9 listed)

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

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
BLU-5937Four escalating doses of BLU-5937 administered BID over the course of the study	Drug	BLU-5937 oral tablet BID
PlaceboMatching placebo for BLU-5937	Drug	Placebo oral tablet BID

Primary outcome

Change in Awake Objective Cough Frequency on Log-transformed Scale
Time frame: 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 (average hourly cough frequency while the subject is awake ) evaluated using the VitaloJAK cough monitor with 24-hour sound recordings collected

Results and safety

Results posted to the registry on 3 Aug 2021, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
BLU-5937 > Placebo	33	26
Placebo > BLU-5937	35	28

Primary outcome: Change in Awake Objective Cough Frequency on Log-transformed Scale

Time frame: 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. Least squares mean (95% Confidence Interval). Unit: Log coughs/hour

Measure	BLU-5937 - 25 mg n = 60	Placebo Comparator - 25 mg n = 59	BLU-5937 - 50 mg n = 59	Placebo Comparator - 50 mg n = 58	BLU-5937 - 100 mg n = 56	Placebo Comparator - 100 mg n = 58	BLU-5937 - 200 mg n = 58	Placebo Comparator - 200 mg n = 58
Value	-0.19 (-0.29 to -0.08)	-0.07 (-0.19 to 0.05)	-0.20 (-0.32 to -0.08)	-0.14 (-0.26 to -0.01)	-0.25 (-0.40 to -0.09)	-0.17 (-0.30 to -0.04)	-0.33 (-0.49 to -0.17)	-0.14 (-0.29 to 0.00)

BLU-5937 - 25 mg vs Placebo Comparator - 25 mg: Estimated percent change: -10.8 (95% CI -23.5 to 4.0), p = 0.1424, Mixed Models Analysis
BLU-5937 - 50 mg vs Placebo Comparator - 50 mg: Estimated percent change: -6.1 (95% CI -20.8 to 11.2), p = 0.4602, Mixed Models Analysis
BLU-5937 - 100 mg vs Placebo Comparator - 100 mg: Estimated percent change: -7.8 (95% CI -24.4 to 12.5), p = 0.4181, Mixed Models Analysis

Population analysed: Analysis population consisted of all randomized subjects who took at least one dose of study drug and provided at least one baseline and at least one post-baseline cough frequency measurement

Adverse events

Time frame: All-cause mortality and Adverse Event data collection is up to 11 weeks. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
BLU-5937 - 25 mg	0 of 61 (0%)	10 of 61 (16.4%)	0 of 61
BLU-5937 - 50 mg	0 of 61 (0%)	14 of 61 (23%)	0 of 61
BLU-5937 - 100 mg	0 of 60 (0%)	15 of 60 (25%)	0 of 60
BLU-5937 - 200 mg	0 of 58 (0%)	10 of 58 (17.2%)	0 of 58
Placebo	1 of 61 (1.6%)	19 of 61 (31.1%)	0 of 61

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 3 Aug 2021.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.

Related trials for Chronic Refractory Cough

RecruitingPhase 2
The Effect of Nalbuphine Extended-Release (NAL ER) on Cough in Participants With Refractory Chronic Cough (RCC)
Refractory Chronic Cough
Not yet recruitingPhase 4
A 2x2 Factorial, Randomized, Open-label Trial to Evaluate Neuromodulators and Cough Control Therapy in Patients With Refractory or Unexplained Chronic Cough
Cough, Refractory Chronic Cough
RecruitingPhase 2
A Study to Investigate the Efficacy and Safety of SC0032, a Magnesium Salt Oral Spray, in Adults With Refractory or Unexplained Chronic Cough
Refractory Chronic Cough and Unexplained Chronic Cough
RecruitingPhase 2
Mechanisms of Change in Behavioral Cough Suppression Therapy for Refractory Chronic Cough
Chronic Cough (CC), Refractory Chronic Cough
Active, not recruitingPhase 3
A 24-Week Study of the Efficacy and Safety of BLU-5937 in Adults With Refractory Chronic Cough
Cough, Refractory Chronic Cough

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Jacky Smith, MD, Ph.D. principal investigator

University of Manchester

16 sites in 2 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing BLU-5937 in people with Chronic Refractory Cough, run by Bellus Health Inc. - a GSK company at 16 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 3 Aug 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 16 sites in United States, United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 3 Aug 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change in Awake Objective Cough Frequency on Log-transformed Scale (time frame: 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). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03979638.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Aug 2021.