A Double-blind Randomised, Placebo-controlled Clinical Trial to Test Ambroxol Treatment in ALS

NCT05959850 | Unknown Phase 2 DMC

• 1 other identifier: FLO-AMB-01
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 5

Brief Summary

Ambroxol is a simple cough medicine that is predicted to slow ALS disease progression. This study aims to investigate if ambroxol in high doses is effective in treating ALS. This study will be carried out across 5 research sites in Australia (2 NSW, 1 VIC, 1 SA and 1 TAS), where newly diagnosed ALS patients will be asked to participate. Participation will be over a 32-week period, where they will come in for a 4-week screening, 24-week treatment, and 4-week end of study safety follow-up period. The participants will receive either the placebo or drug solution that they will take three times a day, up-dosing each week until they reach the maximum dose or highest dose they can tolerate. Throughout the study their disease progression will be assessed using tests, questionnaires, and blood biomarkers.

Conditions

Amyotrophic Lateral Sclerosis

Outcome Measures

Primary Outcomes (1)

• Time to event

  Time to event (death, need for tracheostomy, the need for gastrostomy feeding or non-invasive ventilation (NIV) support (greater than or equal to 12 hours a day in a 24-hour period), or greater than or equal to 6-point progression on the Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS)) This will be measured by patient medical records, and the completion of the ALSFRS by investigators.

  Time to event for a maximum of 24 weeks from baseline

Secondary Outcomes (10)

• ALS functional rating score-revised (ALSFRS-R)

  24 weeks from Baseline

• Motor unit number estimation (MUNIX)

  24 weeks from Baseline

• Split Hand Index (SI)

  24 weeks from Baseline

• Neurophysiology Index (NPI)

  24 weeks from Baseline

• Kings staging system

  24 weeks from Baseline

Study Arms (2)

Experimental: Active

EXPERIMENTAL

Ambroxol taken 3x daily. Variation in doses as follow-up progresses. For detailed information, see Intervention Description.

Drug: Ambroxol

Placebo Comparator: Control

PLACEBO COMPARATOR

Glucose Placebo, taken 3x daily. Variation in doses as follow-up progresses. For detailed information, see Intervention Description.

Drug: Placebo

Interventions

Ambroxol DRUG

Participants in the study will receive varying doses of ambroxol in solution, 3 times per day. Doses will be increased pending a safety review, up to a maximum of 1260mg/day. Blood tests will be conducted weekly to assess tolerance. Compliance will be monitored by returning used bottles. The study will last 32 weeks, including 24 weeks of drug administration and follow-up visits. After the final follow-up, there will be an end of study safety visit occurring 4 weeks later. The total time of participation will be 32 weeks. This includes a screening visit up to 4 weeks prior to Baseline, then a Baseline visit, followed by 24 weeks of follow-up (3x in clinic follow-up visits). These 24 weeks will be the drug administration period, meaning that the total duration of drug administration is 24 weeks. Following this drug administration and follow-up period, there will be an EoS safety-follow up visit that will occur 4 weeks after the final follow-up visit (28 weeks from baseline).

Also known as: Ambroxol Hydrochloride

Experimental: Active

Placebo DRUG

Participants randomised to the control arm will receive a placebo for the duration of the study. The placebo will look and taste like ambroxol, but will have no active ingredient. Participants will not be told which arm they have been randomised to. The placebo will primarily be a glucose solution, however it will also have flavouring (e.g. bitters) and colouring, so as to make it look and taste like ambroxol, to maintain blinding.

Placebo Comparator: Control

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Must have given written informed consent before any study related assessments are performed and must be able to understand purpose of the study, including any possible risks and adverse events.
• ALS as diagnosed according to the recently proposed Gold Coast diagnostic criteria.
• First symptom of ALS less than or equal to 18 months prior to screening. The qualifying first symptoms of ALS are limited to manifestations of weakness in extremity, bulbar, or respiratory muscles. Cramps, fasciculations, or fatigue should not be taken in isolation as a first symptom of ALS.
• Forced vital capacity (FVC) greater than or equal to 60% of predicted value as adjusted for gender, height and age at the Screening Visit.
• Male or female patients aged 18 years or greater (inclusive) and less than 85 years at the time of ALS diagnosis.
• Able to swallow liquid.
• Able to perform reproducible pulmonary function tests
• Female patients must be post-menopausal or sterilized or must not be breastfeeding, have no intention to become pregnant during the study, and use acceptable methods of contraception or abstain from intercourse.
• Male patients who have not had a vasectomy and confirmed zero sperm count must agree after receiving the first dose of study drug either to use acceptable methods of contraception or abstain from intercourse.
• If on riluzole, stable dosing for 30-days prior to screening.
• Pre-study ALSFRS-R progression between disease onset and screening of greater than or equal to 0.5 points/month (calculated by ALSFRS-R total score decline from 48 divided by the months since onset of ALS symptoms).

You may not qualify if:

• Use of non-invasive ventilation (NIV) support for ALS only or gastrostomy tube at time of screening.
• Exposure to investigational drug within 12-weeks prior to screening.
• At screening of any medically significant cardiac, pulmonary, GI, musculoskeletal, or psychiatric illness that might interfere with the patient's ability to comply with study procedures or that might confound the interpretation of clinical safety or data.
• Patient with a history of significant other major medical conditions based on the Investigator's judgment.
• Based on the investigator's judgment, patients who may have difficulty complying with the protocol and/or any study procedures.
• Any person who is an employee or an Investigator or Sponsor, or an immediate relative of an Investigator.

Sponsors & Collaborators

• The Florey Institute of Neuroscience and Mental Health: lead
• Mobius Medical Pty Ltd.: collaborator
• The University of Queensland: collaborator

Study Sites (5)

Brain and Mind Centre

Sydney, New South Wales, 2050, Australia

RECRUITING

Concord Repatriation General Hospital

Sydney, New South Wales, 2139, Australia

RECRUITING

Flinders Medical Centre

Adelaide, South Australia, 5042, Australia

RECRUITING

Launceston General Hospital

Launceston, Tasmania, 7250, Australia

RECRUITING

Calvary Health Care Bethlehem

Melbourne, Victoria, 3162, Australia

RECRUITING

MeSH Terms

Conditions

Amyotrophic Lateral Sclerosis

Interventions

Ambroxol

Condition Hierarchy (Ancestors)

Spinal Cord Diseases; Central Nervous System Diseases; Nervous System Diseases; Motor Neuron Disease; Neurodegenerative Diseases; TDP-43 Proteinopathies; Neuromuscular Diseases; Proteostasis Deficiencies; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Bromhexine; Aniline Compounds; Amines; Organic Chemicals; Cyclohexylamines

Study Officials

• Bradley Turner

  The Florey Institute of Neuroscience and Mental Health

  STUDY CHAIR

• Steve Vucic

  Concord Repatriation General Hospital

  PRINCIPAL INVESTIGATOR

• Matthew Kiernan

  Brain and Mind Centre (The University of Sydney)

  PRINCIPAL INVESTIGATOR

• Susan Mathers

  Calvary Health Care Bethlehem

  PRINCIPAL INVESTIGATOR

• David Schultz

  Flinders Medical Centre

  PRINCIPAL INVESTIGATOR

• Lauren Giles

  Launceston General Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Bradley Turner

CONTACT

+61 3 9035 6521; bradley.turner@florey.edu.au

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Randomised controlled trial. Participants will be randomised at a 2:1 ratio to the drug solution or placebo respectively.

Study Record Dates

• First Submitted: July 17, 2023
• First Posted: July 25, 2023
• Study Start: June 13, 2023
• Primary Completion: June 1, 2024
• Study Completion: December 1, 2024
• Last Updated: September 7, 2023

Record last verified: 2023-07

Data Sharing

• IPD Sharing: Will not share

Locations

AU (5)