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Trial registered on ANZCTR


Registration number
ACTRN12622001380785
Ethics application status
Approved
Date submitted
20/10/2022
Date registered
27/10/2022
Date last updated
3/08/2024
Date data sharing statement initially provided
27/10/2022
Type of registration
Prospectively registered

Titles & IDs
Public title
A double-blind randomised, placebo-controlled clinical trial to test the treatment of amyotrophic lateral sclerosis with ambroxol.
Scientific title
Ambroxol therapy for ALS trial: a double-blind,
randomised, placebo-controlled Phase 2 clinical trial of ambroxol for
ALS
Secondary ID [1] 308208 0
FLO-AMB-01
Universal Trial Number (UTN)
Trial acronym
AMBALS
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Amyotrophic Lateral Sclerosis 327959 0
Condition category
Condition code
Neurological 325024 325024 0 0
Neurodegenerative diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
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. If the bloods indicate no safety issues, the dose will be increased. If there are any safety issues, dosing will remain the same for another week, before another safety blood review. These safety bloods will continue weekly until the participant is at their highest tolerated does (up to 1260mg per day max). Once at their tolerated dose, participants will remain on this daily dose for a period of up to 19 weeks (possibly less depending on up individual dosing schedule). To monitor drug compliance, participants will return used IP bottles to clinic for reconciliation.
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 a End of Study safety-follow up visit that will occur 4 weeks after the final follow-up visit (28 weeks from baseline).
Intervention code [1] 324666 0
Treatment: Drugs
Comparator / control treatment
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.
Control group
Placebo

Outcomes
Primary outcome [1] 332880 0
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,
Timepoint [1] 332880 0
Time to event for a maximum of 24 weeks from baseline
Secondary outcome [1] 414947 0
ALS functional rating score-revised (ALSFRS-R)
Timepoint [1] 414947 0
24 weeks from Baseline
Secondary outcome [2] 414948 0
Motor unit number estimation (MUNIX)
Timepoint [2] 414948 0
24 weeks from Baseline
Secondary outcome [3] 414949 0
Split Hand Index (SI)
Timepoint [3] 414949 0
24 weeks from Baseline
Secondary outcome [4] 414950 0
Neurophysiology Index (NPI)
Timepoint [4] 414950 0
24 weeks from Baseline
Secondary outcome [5] 414951 0
Kings staging system
Timepoint [5] 414951 0
24 weeks from Baseline
Secondary outcome [6] 414952 0
Muscle strength assessment as measured by the Medical Research Council (MRC) Scale for Muscle Strength
Timepoint [6] 414952 0
24 weeks from Baseline
Secondary outcome [7] 414953 0
Respiratory function (FVC) as measure by a Spirometer
Timepoint [7] 414953 0
24 weeks from Baseline
Secondary outcome [8] 414954 0
Survival
Timepoint [8] 414954 0
24 weeks from Baseline
Secondary outcome [9] 414955 0
Serum NFL levels
Timepoint [9] 414955 0
24 weeks from Baseline
Secondary outcome [10] 414956 0
Assessment of Quality of Life (AQoL)
Timepoint [10] 414956 0
24 weeks from Baseline

Eligibility
Key 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).
Minimum age
18 Years
Maximum age
85 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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 design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
IWRS system will provide blinded dispensing codes. IP will be labelled with these codes by unblinded IP distributer, and all site staff will be blinded.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Permuted block randomisation scheme will be used as generated by the IWRS.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
1/12/2022
Actual
14/06/2023
Date of last participant enrolment
Anticipated
30/06/2025
Actual
Date of last data collection
Anticipated
31/12/2025
Actual
Sample size
Target
50
Accrual to date
18
Final
Recruitment in Australia
Recruitment state(s)
NSW,SA,TAS,VIC
Recruitment hospital [1] 23417 0
Concord Repatriation Hospital - Concord
Recruitment hospital [2] 23418 0
Brain and Mind Centre - University of Sydney - Camperdown
Recruitment hospital [3] 23419 0
Calvary Health Care Bethlehem Ltd - Caulfield
Recruitment hospital [4] 23420 0
Flinders Medical Centre - Bedford Park
Recruitment hospital [5] 23421 0
Launceston General Hospital - Launceston
Recruitment postcode(s) [1] 38818 0
2139 - Concord
Recruitment postcode(s) [2] 38819 0
2050 - Camperdown
Recruitment postcode(s) [3] 38820 0
3162 - Caulfield
Recruitment postcode(s) [4] 38821 0
5042 - Bedford Park
Recruitment postcode(s) [5] 38822 0
7250 - Launceston

Funding & Sponsors
Funding source category [1] 312465 0
Charities/Societies/Foundations
Name [1] 312465 0
FightMND
Country [1] 312465 0
Australia
Primary sponsor type
Other Collaborative groups
Name
The Florey Institute of Neuroscience and Mental Health (part of the University of Melbourne)
Address
30 Royal Parade, Parkville VIC 3052
Country
Australia
Secondary sponsor category [1] 314079 0
None
Name [1] 314079 0
Address [1] 314079 0
Country [1] 314079 0
Other collaborator category [1] 282463 0
Commercial sector/Industry
Name [1] 282463 0
Mobius Medical Pty Ltd
Address [1] 282463 0
Suite 1043 275 Alfred Street N, North Sydney, NSW, 2060.
Country [1] 282463 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 311810 0
Sydney Local Health District Human Research Ethics Committee
Ethics committee address [1] 311810 0
Ethics committee country [1] 311810 0
Australia
Date submitted for ethics approval [1] 311810 0
28/07/2022
Approval date [1] 311810 0
14/10/2022
Ethics approval number [1] 311810 0

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 122442 0
Prof Steve Vucic
Address 122442 0
Building 20, Level 1
Hospital Rd, Concord Hospital
Concord, NSW, 2139
Country 122442 0
Australia
Phone 122442 0
+61 02 9767 8447
Fax 122442 0
Email 122442 0
steve.vucic@sydney.edu.au
Contact person for public queries
Name 122443 0
Bradley Turner
Address 122443 0
The Florey Institute of Neuroscience and Mental Health
30 Royal Parade, Parkville VIC 3052
Country 122443 0
Australia
Phone 122443 0
+61 3 9035 6521
Fax 122443 0
Email 122443 0
bradley.turner@florey.edu.au
Contact person for scientific queries
Name 122444 0
Bradley Turner
Address 122444 0
The Florey Institute of Neuroscience and Mental Health
30 Royal Parade, Parkville VIC 3052
Country 122444 0
Australia
Phone 122444 0
+61 3 9035 6521
Fax 122444 0
Email 122444 0
bradley.turner@florey.edu.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

No Supporting Document Provided


Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.