Amyotrophic Lateral SclerosisPhase 2AMBALSNCT05959850
A Double-blind Randomised, Placebo-controlled Clinical Trial to Test Ambroxol Treatment in ALS
A Phase 2 study testing Ambroxol in people with Amyotrophic Lateral Sclerosis, run by The Florey Institute of Neuroscience and Mental Health at 5 sites in Australia.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 85 years
- Conditions the study is for
- Amyotrophic Lateral Sclerosis
- What is being tested?
- Ambroxol
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 50 participants
- Where
- 5 sitesAustralia
- Study dates
- 13 Jun 2023to Dec 2024
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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).
Who cannot join
- 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.
Trial locations and contacts
5 sites in 1 country.
5 sites in 1 country
Australia5 sites, 5 recruiting
- Recruiting
Flinders Medical Centre
Adelaide, South Australia, 5042
Edlira Dishnica, +61 8 8204 5168, edlira.dishnica@sa.gov.au
David Schultz
- Recruiting
Launceston General Hospital
Launceston, Tasmania, 7250
Lauren Giles, lauren.giles@ths.tas.gov.au
Lauren Giles
- Recruiting
Calvary Health Care Bethlehem
Melbourne, Victoria, 3162
Emma Windebank, +61 3 9834 9430, Emma.Windebank@calvarycare.org.au
Susan Mathers
- Recruiting
Brain and Mind Centre
Sydney, New South Wales, 2050
Eleanor Ramsey, +61 2 9114 4258, eleanor.ramsey@sydney.edu.au
Matthew Kiernan
- Recruiting
Concord Repatriation General Hospital
Sydney, New South Wales, 2139
Julie Ryder, +61 2 9767 8475, julie.ryder@health.nsw.gov.au
Steve Vucic
About this study
Official title: 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.
Read the 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).
- Conditions
- Amyotrophic Lateral Sclerosis
- Being tested
- Ambroxol, Placebo
- Medical subject headings
- Amyotrophic Lateral Sclerosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AmbroxolDrug
Also called Ambroxol Hydrochloride
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).
PlaceboDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| Experimental: Active | Experimental | Ambroxol taken 3x daily. Variation in doses as follow-up progresses. For detailed information, see Intervention Description. Receives: 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. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Time to event for a maximum of 24 weeks from baseline
Secondary outcomes (10)
ALS functional rating score-revised (ALSFRS-R)
Change in ALSFRS-R Score
Measured: 24 weeks from Baseline
Motor unit number estimation (MUNIX)
Change in MUNIX values
Measured: 24 weeks from Baseline
Split Hand Index (SI)
Change in SI value
Measured: 24 weeks from Baseline
Neurophysiology Index (NPI)
Change in NPI Value
Measured: 24 weeks from Baseline
Kings staging system
Change in Kings stage
Measured: 24 weeks from Baseline
Muscle strength assessment as measured by the Medical Research Council (MRC) Scale for Muscle Strength
Change in Muscle strength, where Grade 0 is no visible contraction and Grade 5 is Normal
Measured: 24 weeks from Baseline
Respiratory function (FVC) as measure by a Spirometer
Change in FVC
Measured: 24 weeks from Baseline
Survival
Overall survival rate
Measured: 24 weeks from Baseline
Serum NFL levels
Change in Serum NFL Levels
Measured: 24 weeks from Baseline
Assessment of Quality of Life (AQoL)
Change in AQoL score
Measured: 24 weeks from Baseline
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Jul 2023
- Study start13 Jun 2023
- Primary completionJun 2024 (estimated)
- Study completionDec 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Amyotrophic Lateral SclerosisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Randomised controlled trial. Participants will be randomised at a 2:1 ratio to the drug solution or placebo respectively.
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 50 participants (estimated)
Sponsor and investigators
- Lead sponsor
- The Florey Institute of Neuroscience and Mental Health
- Sponsor type
- University, hospital or other
- Collaborators
- Mobius Medical Pty Ltd., The University of Queensland
- Responsible party
- Sponsor
- Investigators
- Bradley Turner, Study chair, The Florey Institute of Neuroscience and Mental HealthSteve Vucic, Principal investigator, Concord Repatriation General HospitalMatthew Kiernan, Principal investigator, Brain and Mind Centre (The University of Sydney)Susan Mathers, Principal investigator, Calvary Health Care BethlehemDavid Schultz, Principal investigator, Flinders Medical CentreLauren Giles, Principal investigator, Launceston General Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05959850
- Sponsor's protocol ID
- FLO-AMB-01
- Acronym
- AMBALS
- Status last verified
- Jul 2023
- First submitted
- 17 Jul 2023
- Last updated
- 7 Sep 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: No plan to have individual participant data available to other researchers
Study at a glance
From the registry record, last updated by the sponsor on 7 Sep 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- AMBroxol Therapy for ALS (AMBALS) Trial: a Double-blind, Randomised, Placebo-controlled Phase 2 Clinical Trial of Ambroxol for ALS
- ClinicalTrials.gov ID
- NCT05959850
- Acronym / sponsor ID
- AMBALS / FLO-AMB-01
- Conditions
- Amyotrophic Lateral Sclerosis
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 50 participants (estimated)
- Lead sponsor
- The Florey Institute of Neuroscience and Mental HealthUniversity, hospital or other
- Collaborators
- Mobius Medical Pty Ltd., The University of Queensland
- Study start
- 13 Jun 2023 (actual)
- Primary completion
- Jun 2024 (estimated)
- Study completion
- Dec 2024 (estimated)
- First posted
- 25 Jul 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- Randomised controlled trial. Participants will be randomised at a 2:1 ratio to the drug solution or placebo respectively.
| Arm | Type | Receives |
|---|---|---|
| Experimental: Active | Experimental | Drug: AmbroxolAmbroxol taken 3x daily. Variation in doses as follow-up progresses. For detailed information, see Intervention Description. |
| Placebo Comparator: Control | Placebo comparator | Drug: PlaceboGlucose Placebo, taken 3x daily. Variation in doses as follow-up progresses. For detailed information, see Intervention Description. |
Who may qualify
- Ages
- 18 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- 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.
Key exclusion criteria (6 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AmbroxolAlso: Ambroxol HydrochlorideParticipants 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). | Drug | Experimental: Active |
| PlaceboParticipants 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. | Drug | Placebo Comparator: Control |
Primary outcome
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.
10 secondary outcomes
ALS functional rating score-revised (ALSFRS-R)
Time frame: 24 weeks from Baseline
Motor unit number estimation (MUNIX)
Time frame: 24 weeks from Baseline
Split Hand Index (SI)
Time frame: 24 weeks from Baseline
Neurophysiology Index (NPI)
Time frame: 24 weeks from Baseline
Kings staging system
Time frame: 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
Respiratory function (FVC) as measure by a Spirometer
Time frame: 24 weeks from Baseline
Survival
Time frame: 24 weeks from Baseline
Serum NFL levels
Time frame: 24 weeks from Baseline
Assessment of Quality of Life (AQoL)
Time frame: 24 weeks from Baseline
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Sep 2023.
- Individual participant dataSharing planned: No. No plan to have individual participant data available to other researchers
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Bradley Turner study chair
The Florey Institute of Neuroscience and Mental Health
Steve Vucic principal investigator
Concord Repatriation General Hospital
Matthew Kiernan principal investigator
Brain and Mind Centre (The University of Sydney)
5 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Ambroxol in people with Amyotrophic Lateral Sclerosis, run by The Florey Institute of Neuroscience and Mental Health at 5 sites in Australia.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 7 Sep 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in Australia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Bradley Turner (+61 3 9035 6521, bradley.turner@florey.edu.au), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Time to event (time frame: Time to event for a maximum of 24 weeks from baseline). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Sep 2023.