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

NCT04866563 | Completed Phase 2

• 2 other identifiers: AX8-0032021-000844-23
• Study Type: interventional
• Target: 108
• Locations: 1 country
• Sites: 16

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.

Conditions

Chronic Cough

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (4)

• 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

• 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

• 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)

• 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)

Study Arms (4)

AX-8 to Placebo, Part 1 of the study

EXPERIMENTAL

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; Drug: Placebo, Part 1 of the study

Placebo to AX-8, Part 1 of the study

EXPERIMENTAL

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; Drug: Placebo, Part 1 of the study

AX-8 to Placebo, Part 2 of the study

EXPERIMENTAL

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; Drug: Placebo, Part 2 of the study

Placebo to AX-8, Part 2 of the study

EXPERIMENTAL

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; Drug: Placebo, Part 2 of the study

Interventions

AX-8, Part 1 of the study DRUG

orally disintegrating tablets, BID

AX-8 to Placebo, Part 1 of the study; Placebo to AX-8, Part 1 of the study

Placebo, Part 1 of the study DRUG

orally disintegrating tablets, BID

AX-8 to Placebo, Part 1 of the study; Placebo to AX-8, Part 1 of the study

AX-8, Part 2 of the study DRUG

orally disintegrating tablets, TID

AX-8 to Placebo, Part 2 of the study; Placebo to AX-8, Part 2 of the study

Placebo, Part 2 of the study DRUG

orally disintegrating tablets, TID

AX-8 to Placebo, Part 2 of the study; Placebo to AX-8, Part 2 of the study

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Axalbion SA: lead

Study Sites (16)

Axalbion Study Site 4406

Birmingham, England, B9 5SS, United Kingdom

Location

Axalbion Study Site 4404

Broughton, England, DN20 0HR, United Kingdom

Location

Axalbion Study Site 4409

Chelmsford, England, CM1 7ET, United Kingdom

Location

Axalbion Study Site 4413

Coventry, England, CV3 4FJ, United Kingdom

Location

Axalbion Study Site 4401

London, England, SE5 9RS, United Kingdom

Location

Axalbion Study Site 4402

London, England, SW3 6HP, United Kingdom

Location

Axalbion Study Site 4410

London, England, W2 1NY, United Kingdom

Location

Axalbion Study Site 4403

Manchester, England, M23 9LT, United Kingdom

Location

Axalbion Study Site 4405

North Shields, England, NE29 8NH, United Kingdom

Location

Axalbion Study Site 4417

Orpington, England, BR5 3QG, United Kingdom

Location

Axalbion Study Site 4407

Oxford, England, OX3 9DU, United Kingdom

Location

Axalbion Study Site 4411

Preston, England, PR2 9HT, United Kingdom

Location

Axalbion Study Site 4412

Shipley, England, BD18 3SA, United Kingdom

Location

Axalbion Study Site 4408

Newport, Wales, NP20 2EF, United Kingdom

Location

Axalbion Study Site 4414

Belfast, BT9 7AB, United Kingdom

Location

Axalbion Study Site 4415

Northwood, HA6 2RN, United Kingdom

Location

MeSH Terms

Conditions

Chronic Cough

Condition Hierarchy (Ancestors)

Cough; Respiration Disorders; Respiratory Tract Diseases; Signs and Symptoms, Respiratory; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• Chief Medical Officer

  Axalbion Therapeutics, LTD.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 23, 2021
• First Posted: April 30, 2021
• Study Start: August 11, 2021
• Primary Completion: June 16, 2025
• Study Completion: June 16, 2025
• Last Updated: September 8, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

GB (16)