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

September 4, 2023 updated by: The Florey Institute of Neuroscience and Mental Health

AMBroxol Therapy for ALS (AMBALS) Trial: a Double-blind, Randomised, Placebo-controlled Phase 2 Clinical Trial of Ambroxol for ALS

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

This study is a double-blind, randomised, placebo-controlled phase 2 clinical trial, to assess the safety, tolerability and efficacy of ambroxol therapy in ALS patients by using electrophysiological and functional measures to detect preservation of motor units. The study design will have participants be randomised to either ambroxol or placebo at a 2:1 ratio (ambroxol (n=34) and placebo (n=16)). Participants randomised to the active arm will receive various doses of ambroxol in solution, taken orally, three times a day. Doses will be increased pending a safety review for each participant. The doses will be 180mg per day, 260mg per day, 540mg per day, 900mg per day, and 1260 mg per day. Each week safety bloods will be performed to assess tolerance to the dose. Participants randomised to the control arm will receive a placebo for the duration of the study. Disease progression will be assessed by the following, time to event (death, need for tracheostomy, the need for gastrostomy feeding or non-invasive ventilation support (≥12 hours a day in a 24-hour period), or ≥6-point progression (ALS functional rating score-revised).

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
50

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Locations

  • Australia
    • New South Wales
      • Sydney, New South Wales, Australia, 2139
        • Recruiting
        • Concord Repatriation General Hospital
        • Contact:
        • Principal Investigator:
          • Steve Vucic
      • Sydney, New South Wales, Australia, 2050
        • Recruiting
        • Brain and Mind Centre
        • Contact:
        • Principal Investigator:
          • Matthew Kiernan
    • South Australia
      • Adelaide, South Australia, Australia, 5042
        • Recruiting
        • Flinders Medical Centre
        • Principal Investigator:
          • David Schultz
        • Contact:
    • Tasmania
      • Launceston, Tasmania, Australia, 7250
    • Victoria
      • Melbourne, Victoria, Australia, 3162
        • Recruiting
        • Calvary Health Care Bethlehem
        • Principal Investigator:
          • Susan Mathers
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. 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.
  2. ALS as diagnosed according to the recently proposed Gold Coast diagnostic criteria.
  3. 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.
  4. Forced vital capacity (FVC) greater than or equal to 60% of predicted value as adjusted for gender, height and age at the Screening Visit.
  5. Male or female patients aged 18 years or greater (inclusive) and less than 85 years at the time of ALS diagnosis.
  6. Able to swallow liquid.
  7. Able to perform reproducible pulmonary function tests
  8. 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.
  9. 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.
  10. If on riluzole, stable dosing for 30-days prior to screening.
  11. 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).

Exclusion Criteria:

  1. Use of non-invasive ventilation (NIV) support for ALS only or gastrostomy tube at time of screening.
  2. Exposure to investigational drug within 12-weeks prior to screening.
  3. 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.
  4. Patient with a history of significant other major medical conditions based on the Investigator's judgment.
  5. Based on the investigator's judgment, patients who may have difficulty complying with the protocol and/or any study procedures.
  6. Any person who is an employee or an Investigator or Sponsor, or an immediate relative of an Investigator.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Experimental: Active
Ambroxol taken 3x daily. Variation in doses as follow-up progresses. For detailed information, see Intervention Description.
Drug: Ambroxol
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).
Other Names:
  • Ambroxol Hydrochloride
Placebo Comparator: Placebo Comparator: Control
Glucose Placebo, taken 3x daily. Variation in doses as follow-up progresses. For detailed information, see Intervention Description.
Drug: Placebo
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.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Time to event
Time Frame: Time to event for a maximum of 24 weeks from baseline
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 Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
ALS functional rating score-revised (ALSFRS-R)
Time Frame: 24 weeks from Baseline
Change in ALSFRS-R Score
24 weeks from Baseline
Motor unit number estimation (MUNIX)
Time Frame: 24 weeks from Baseline
Change in MUNIX values
24 weeks from Baseline
Split Hand Index (SI)
Time Frame: 24 weeks from Baseline
Change in SI value
24 weeks from Baseline
Neurophysiology Index (NPI)
Time Frame: 24 weeks from Baseline
Change in NPI Value
24 weeks from Baseline
Kings staging system
Time Frame: 24 weeks from Baseline
Change in Kings stage
24 weeks from Baseline
Respiratory function (FVC) as measure by a Spirometer
Time Frame: 24 weeks from Baseline
Change in FVC
24 weeks from Baseline
Survival
Time Frame: 24 weeks from Baseline
Overall survival rate
24 weeks from Baseline
Serum NFL levels
Time Frame: 24 weeks from Baseline
Change in Serum NFL Levels
24 weeks from Baseline
Assessment of Quality of Life (AQoL)
Time Frame: 24 weeks from Baseline
Change in AQoL score
24 weeks from Baseline
Muscle strength assessment as measured by the Medical Research Council (MRC) Scale for Muscle Strength
Time Frame: 24 weeks from Baseline
Change in Muscle strength, where Grade 0 is no visible contraction and Grade 5 is Normal
24 weeks from Baseline

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
The Florey Institute of Neuroscience and Mental Health

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
The University of Queensland
Mobius Medical Pty Ltd.

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Chair: Bradley Turner, The Florey Institute of Neuroscience and Mental Health
  • Principal Investigator: 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

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
June 13, 2023

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
June 1, 2024

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 1, 2024

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
July 17, 2023

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
July 17, 2023

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
July 25, 2023

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
September 7, 2023

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
September 4, 2023

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
July 1, 2023

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • FLO-AMB-01

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

No plan to have individual participant data available to other researchers

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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