A Study of Efficacy and Safety of AX-8 in Chronic Cough

Phase 2

Recruiting

• Conditions: Chronic Cough
• Interventions: Drug: AX-8, Part 1 of the study; Drug: AX-8, Part 2 of the study; Drug: Placebo, Part 1 of the study; Drug: Placebo, Part 2 of the study

• Registration Number: NCT04866563
• Lead Sponsor: Axalbion SA

Brief Summary

This is a randomized, double-blind, placebo-controlled, crossover, multicenter study of AX-8 in participants with unexplained or refractory chronic cough designed to evaluate the effectiveness of AX-8 in reducing cough frequency.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2021-04-23
• Study First Submitted QC: 2021-04-26
• Study First Posted: 2021-04-30
• Study Start: 2021-08-11
• Status Verified: 2025-01
• Last Update Submitted: 2025-01-27
• Last Update Posted: 2025-01-28
• Primary Completion: 2025-05
• Study Completion: 2025-06

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 100

Inclusion Criteria

• Chest radiograph or computed tomography (CT) of the thorax approximately 12 months before screening not demonstrating any abnormality considered to be significantly contributing to the chronic cough
• Have a diagnosis of refractory chronic cough (RCC) or unexplained chronic cough (UCC) for at least one year
• Women of childbearing potential and their male partners must use 2 acceptable methods of contraception
• Male subjects and their female partners of childbearing potential must use 2 acceptable methods of contraception
• Have provided written informed consent

Exclusion Criteria

• Positive diagnostic nucleic acid test for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)
• Current smoker (including e-cigarettes), individuals who have given up smoking within the past 12 months, or individuals with a smoking history of 20 pack-years
• 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 Baseline Visit
• History of upper or lower respiratory tract infection or recent significant change in pulmonary status within 4 weeks
• History of cystic fibrosis
• Positive test for any drug of abuse
• History of malignancy within 5 years prior to the Baseline Visit
• History of infection or known active infection with human immunodeficiency (HIV), hepatitis B virus (HBV), or hepatitis C virus (HCV)
• History of hypersensitivity or intolerance to AX-8 or other TRPM8 agonists or any of the excipients

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
AX-8 to Placebo, Part 1 of the study	AX-8, Part 1 of the study	AX-8 BID, taken for 2 weeks, followed by a 1-week washout period and then Placebo BID, taken for 2 weeks.
AX-8 to Placebo, Part 1 of the study	Placebo, Part 1 of the study	AX-8 BID, taken for 2 weeks, followed by a 1-week washout period and then Placebo BID, taken for 2 weeks.
AX-8 to Placebo, Part 2 of the study	AX-8, Part 2 of the study	AX-8 TID, taken for 2 weeks, followed by a 1-week washout period and then Placebo BID, taken for 2 weeks.
AX-8 to Placebo, Part 2 of the study	Placebo, Part 2 of the study	AX-8 TID, taken for 2 weeks, followed by a 1-week washout period and then Placebo BID, taken for 2 weeks.
Placebo to AX-8, Part 2 of the study	AX-8, Part 2 of the study	Placebo TID, taken for 2 weeks, followed by a 1-week washout period and then AX-8 BID, taken for 2 weeks.
Placebo to AX-8, Part 2 of the study	Placebo, Part 2 of the study	Placebo TID, taken for 2 weeks, followed by a 1-week washout period and then AX-8 BID, taken for 2 weeks.
Placebo to AX-8, Part 1 of the study	AX-8, Part 1 of the study	Placebo BID, taken for 2 weeks, followed by a 1-week washout period and then AX-8 BID, taken for 2 weeks.
Placebo to AX-8, Part 1 of the study	Placebo, Part 1 of the study	Placebo BID, taken for 2 weeks, followed by a 1-week washout period and then AX-8 BID, taken for 2 weeks.

Primary Outcome Measures

Name	Time	Method
Part 1 of the study: Change from Baseline in objective cough frequency in the 8 hours after the first dose of the day (i.e., Dose 1) on the 1st day of treatment of each study period	Baseline (i.e., Days -1 and 22) and the 1st day of treatment (i.e., Days 1 and 23) of each study period	Assessment of number of coughs per hour to be evaluated using a digital recording device
Part 2 of the study: Change from Baseline in objective cough frequency in the 4 hours after the first dose of the day (i.e., Dose 1) on the 1st day of treatment of each study period	Baseline (i.e., Days -1 and 22) and the 1st day of treatment (i.e., Days 1 and 23) of each study period	Assessment of number of coughs per hour to be evaluated using a digital recording device

Secondary Outcome Measures

Name	Time	Method
Change from Baseline in Cough Severity Visual Analog Scale (VAS) score	Baseline (i.e., Days -1 and 22), the 1st day of treatment (i.e., Days 1 and 23) and the 14th day of treatment (i.e., Days 14 and 36) of each study period	Cough Severity is determined through the use of a 100 mm visual analogue scale (VAS) (ranging between 0 for "no cough" and 100 for "worst cough").
Change from Baseline in awake cough frequency	Baseline (i.e., Days -1 and 22), the 1st day of treatment (i.e., Days 1 and 23) and the 14th day of treatment (i.e., Days 14 and 36) of each study period	Assessment of awake coughs per hour (average hourly cough frequency while the participant is awake based on sound recordings), to be evaluated using a digital recording device
Incidence (percent of participants) of treatment-emergent adverse events (TEAEs)	From first dose of study drug (i.e., Dose 1 on Day 1) to follow-up visit (i.e., Day 50, included)	TEAEs are defined as those AEs (i.e., a new event or an exacerbation of a pre-existing condition) occurring on or after the first study dosing (i.e., Dose 1 on Day 1).
Incidence (percent of participants) of serious adverse events (SAEs)	From screening visit (i.e., Days -21 to -2) to follow-up visit (i.e., Day 50, included)	An SAE is an adverse events occurring during any study phase and that fulfils one or more of the following: results in death, is life-threatening, requires patient hospitalization or results in prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a significant or important medical event, or is a congenital anomaly/birth defect in the offspring of a subject who received study drug.

Trial Locations

Locations (16)

Axalbion Study Site 4417; 🇬🇧 Orpington, England, United Kingdom

Axalbion Study Site 4406; 🇬🇧 Birmingham, England, United Kingdom

Axalbion Study Site 4404; 🇬🇧 Broughton, England, United Kingdom

Axalbion Study Site 4409; 🇬🇧 Chelmsford, England, United Kingdom

Axalbion Study Site 4413; 🇬🇧 Coventry, England, United Kingdom

Axalbion Study Site 4401; 🇬🇧 London, England, United Kingdom

Axalbion Study Site 4402; 🇬🇧 London, England, United Kingdom

Axalbion Study Site 4410; 🇬🇧 London, England, United Kingdom

Axalbion Study Site 4403; 🇬🇧 Manchester, England, United Kingdom

Axalbion Study Site 4405; 🇬🇧 North Shields, England, United Kingdom

Axalbion Study Site 4407; 🇬🇧 Oxford, England, United Kingdom

Axalbion Study Site 4411; 🇬🇧 Preston, England, United Kingdom

Axalbion Study Site 4412; 🇬🇧 Shipley, England, United Kingdom

Axalbion Study Site 4408; 🇬🇧 Newport, Wales, United Kingdom

Axalbion Study Site 4414; 🇬🇧 Belfast, United Kingdom

Axalbion Study Site 4415; 🇬🇧 Northwood, United Kingdom