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

A Phase 2 Study to Assess the Efficacy and Safety of AX-8 in Patients With Chronic Cough

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.

Study Overview

• Status: Completed
• Conditions: Chronic Cough
• Intervention / Treatment: Drug: AX-8, Part 1 of the study; Drug: Placebo, Part 1 of the study; Drug: AX-8, Part 2 of the study; Drug: Placebo, Part 2 of the study

• Study Type: Interventional
• Enrollment (Actual): 108
• Phase: Phase 2

Contacts and Locations

Study Locations

• United Kingdom
  • Belfast, United Kingdom, BT9 7AB
    • Axalbion Study Site 4414
  • Northwood, United Kingdom, HA6 2RN
    • Axalbion Study Site 4415
  • England
    • Birmingham, England, United Kingdom, B9 5SS
      • Axalbion Study Site 4406
    • Broughton, England, United Kingdom, DN20 0HR
      • Axalbion Study Site 4404
    • Chelmsford, England, United Kingdom, CM1 7ET
      • Axalbion Study Site 4409
    • Coventry, England, United Kingdom, CV3 4FJ
      • Axalbion Study Site 4413
    • London, England, United Kingdom, SE5 9RS
      • Axalbion Study Site 4401
    • London, England, United Kingdom, SW3 6HP
      • Axalbion Study Site 4402
    • London, England, United Kingdom, W2 1NY
      • Axalbion Study Site 4410
    • Manchester, England, United Kingdom, M23 9LT
      • Axalbion Study Site 4403
    • North Shields, England, United Kingdom, NE29 8NH
      • Axalbion Study Site 4405
    • Orpington, England, United Kingdom, BR5 3QG
      • Axalbion Study Site 4417
    • Oxford, England, United Kingdom, OX3 9DU
      • Axalbion Study Site 4407
    • Preston, England, United Kingdom, PR2 9HT
      • Axalbion Study Site 4411
    • Shipley, England, United Kingdom, BD18 3SA
      • Axalbion Study Site 4412
  • Wales
    • Newport, Wales, United Kingdom, NP20 2EF
      • Axalbion Study Site 4408

Participation Criteria

Eligibility Criteria

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

Description

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 Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: AX-8 to 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.	Drug: AX-8, Part 1 of the study; orally disintegrating tablets, BID; Drug: Placebo, Part 1 of the study; orally disintegrating tablets, BID
Experimental: Placebo to 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.	Drug: AX-8, Part 1 of the study; orally disintegrating tablets, BID; Drug: Placebo, Part 1 of the study; orally disintegrating tablets, BID
Experimental: AX-8 to 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.	Drug: AX-8, Part 2 of the study; orally disintegrating tablets, TID; Drug: Placebo, Part 2 of the study; orally disintegrating tablets, TID
Experimental: Placebo to 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.	Drug: AX-8, Part 2 of the study; orally disintegrating tablets, TID; Drug: Placebo, Part 2 of the study; orally disintegrating tablets, TID

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	Assessment of number of coughs per hour to be evaluated using a digital recording device	Baseline (i.e., Days -1 and 22) and the 1st day of treatment (i.e., Days 1 and 23) of each study period
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	Assessment of number of coughs per hour to be evaluated using a digital recording device	Baseline (i.e., Days -1 and 22) and the 1st day of treatment (i.e., Days 1 and 23) of each study period

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from Baseline in awake cough frequency	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	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
Change from Baseline in Cough Severity Visual Analog Scale (VAS) score	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").	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
Incidence (percent of participants) of treatment-emergent adverse events (TEAEs)	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).	From first dose of study drug (i.e., Dose 1 on Day 1) to follow-up visit (i.e., Day 50, included)
Incidence (percent of participants) of serious adverse events (SAEs)	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.	From screening visit (i.e., Days -21 to -2) to follow-up visit (i.e., Day 50, included)

Collaborators and Investigators

• Sponsor: Axalbion SA
• Investigators: Study Director: Chief Medical Officer, Axalbion Therapeutics, LTD.

Study record dates

Study Major Dates

• Study Start (Actual): August 11, 2021
• Primary Completion (Actual): June 16, 2025
• Study Completion (Actual): June 16, 2025

Study Registration Dates

• First Submitted: April 23, 2021
• First Submitted That Met QC Criteria: April 26, 2021
• First Posted (Actual): April 30, 2021

Study Record Updates

• Last Update Posted (Estimated): September 8, 2025
• Last Update Submitted That Met QC Criteria: September 1, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Respiration Disorders; Signs and Symptoms, Respiratory; Cough; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Chronic Cough; Substandard Drugs; Pharmaceutical Preparations; Counterfeit Drugs
• Other Study ID Numbers: AX8-003; 2021-000844-23 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No