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Trial registered on ANZCTR


Registration number
ACTRN12624001204538
Ethics application status
Approved
Date submitted
18/09/2024
Date registered
1/10/2024
Date last updated
1/10/2024
Date data sharing statement initially provided
1/10/2024
Type of registration
Retrospectively registered

Titles & IDs
Public title
An Open Label Extension of the double-blind randomised, placebo-controlled clinical trial to test the treatment of amyotrophic lateral sclerosis with ambroxol.
Scientific title
Ambroxol therapy for ALS trial: An Open Label Extension of the double-blind, randomised, placebo-controlled Phase 2 clinical trial of ambroxol for ALS
Secondary ID [1] 313002 0
FLO-AMB-01 OLE
Universal Trial Number (UTN)
Trial acronym
AMBALS - OLE
Linked study record
ACTRN12622001380785 is the double blinded randomised placebo-controlled phase of this trial. This registration documents the Open Label Extension phase of the trial, where all participants receive ambroxol for an additional 48 week period.

Health condition
Health condition(s) or problem(s) studied:
Amyotrophic Lateral Sclerosis 335196 0
Condition category
Condition code
Neurological 331684 331684 0 0
Neurodegenerative diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Participants who have successfully completed the randomised phase of the parent AMBALS study, will be invited to participate in the Open Label Extension (OLE). The OLE will involve participants taking 420mg capsules of ambroxol, orally, three times a day (total dose 1260mg per day).
Participants will complete an OLE baseline visit, for consenting and OLE eligibility assessments. They will then start their OLE dosing. This will then be followed 48 weeks of follow-up (4x in clinic follow-up visits - one every 12 weeks). These 48 weeks will be the drug administration period, meaning that the total duration of drug administration is 48 weeks. Following this drug administration and follow-up period, there will be an End of Study safety-follow up visit that will occur 4 weeks after the final follow-up visit (52 weeks from OLE baseline).
Participants will return IP bottles at each of the 4 in-clinic follow-up visits, to monitor IP compliance.
Intervention code [1] 329545 0
Treatment: Drugs
Comparator / control treatment
No control group - Open Label Extension
Control group
Uncontrolled

Outcomes
Primary outcome [1] 339408 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 assessed as a composite outcome
Timepoint [1] 339408 0
12 weeks, 24 weeks, 36 weeks, and 48 weeks from OLE baseline
Secondary outcome [1] 439810 0
ALS functional rating score-revised (ALSFRS-R)
Timepoint [1] 439810 0
48 weeks from OLE baseline
Secondary outcome [2] 439813 0
Split Hand Index (SI) Score for progression of ALS
Timepoint [2] 439813 0
48 weeks from OLE baseline
Secondary outcome [3] 439814 0
Neurophysiology Index (NPI) score for progression of ALS
Timepoint [3] 439814 0
48 weeks from OLE baseline
Secondary outcome [4] 439815 0
Kings staging system score for progression of ALS
Timepoint [4] 439815 0
48 weeks from OLE baseline
Secondary outcome [5] 439816 0
Muscle strength assessment score
Timepoint [5] 439816 0
48 weeks from OLE baseline
Secondary outcome [6] 439817 0
Respiratory function (FVC)
Timepoint [6] 439817 0
48 weeks from OLE baseline
Secondary outcome [7] 439818 0
Survival
Timepoint [7] 439818 0
52 weeks from OLE baseline
Secondary outcome [8] 439819 0
Serum NFL levels
Timepoint [8] 439819 0
48 weeks from OLE baseline
Secondary outcome [9] 439820 0
Assessment of Quality of Life (AQoL)
Timepoint [9] 439820 0
48 weeks from OLE baseline

Eligibility
Key inclusion criteria
Refer to ACTRN12622001380785 for the inclusion criteria of the randomized placebo-controlled Treatment Period of the AMBALS trial.
1) Participants must have completed the randomized placebo-controlled Treatment Period of the AMBALS trial without compliance issues
2) Able to understand and give written informed consent to participant in the open-label extension.
Minimum age
18 Years
Maximum age
85 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Refer to ACTRN12622001380785 for the exclusion criteria of the randomized placebo-controlled Treatment Period of the AMBALS trial.
1) Lack of treatment compliance during the randomized placebo-controlled Treatment Period.
2) Positive pregnancy test at the Week 24 visit of the AMBALS study randomised phase, or, females who plan to get pregnant during the course of this extension or within 6 months of the end of this extension.
3) Based on the investigator’s judgment, participants who may have difficulty complying with the protocol and/or any study procedures.
4)Participants with any clinically significant medical conditions based on the Investigator’s judgment, which may interfere with continued participation.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
Actual
16/09/2024
Date of last participant enrolment
Anticipated
30/09/2025
Actual
Date of last data collection
Anticipated
30/09/2026
Actual
Sample size
Target
20
Accrual to date
2
Final
Recruitment in Australia
Recruitment state(s)
NSW,SA,TAS,VIC
Recruitment hospital [1] 27113 0
Concord Repatriation Hospital - Concord
Recruitment hospital [2] 27114 0
Neuroscience Research Australia (NeuRA) - Randwick
Recruitment hospital [3] 27115 0
Calvary Health Care Bethlehem Ltd - Caulfield
Recruitment hospital [4] 27116 0
Flinders Medical Centre - Bedford Park
Recruitment hospital [5] 27117 0
Launceston General Hospital - Launceston
Recruitment postcode(s) [1] 43191 0
2139 - Concord
Recruitment postcode(s) [2] 43192 0
2031 - Randwick
Recruitment postcode(s) [3] 43193 0
3162 - Caulfield
Recruitment postcode(s) [4] 43194 0
5042 - Bedford Park
Recruitment postcode(s) [5] 43195 0
7250 - Launceston

Funding & Sponsors
Funding source category [1] 317441 0
Charities/Societies/Foundations
Name [1] 317441 0
FightMND
Country [1] 317441 0
Australia
Primary sponsor type
Other Collaborative groups
Name
The Florey Institute of Neuroscience and Mental Health (part of the University of Melbourne)
Address
Country
Australia
Secondary sponsor category [1] 319733 0
None
Name [1] 319733 0
Address [1] 319733 0
Country [1] 319733 0
Other collaborator category [1] 283204 0
Commercial sector/Industry
Name [1] 283204 0
Mobius Medical Pty Ltd
Address [1] 283204 0
Country [1] 283204 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 316159 0
Sydney Local Health District HREC – Concord Repatriation General Hospital
Ethics committee address [1] 316159 0
http://www.slhd.nsw.gov.au/concord/ethics/
Ethics committee country [1] 316159 0
Australia
Date submitted for ethics approval [1] 316159 0
07/05/2024
Approval date [1] 316159 0
31/05/2024
Ethics approval number [1] 316159 0

Summary
Brief summary
Ambroxol is a simple cough medicine that is predicted to slow ALS disease progression. This study is the open label extension (OLE) of the parent study, which aims to investigate if ambroxol in high doses is effective in treating ALS. This OLE study will be carried out across 5 research sites in Australia (2 NSW, 1 VIC, 1 SA and 1 TAS), where ALS patients whole have successfully completed the randomised phase of the parent study, will be asked to participate in the OLE phase. Participation will be over a 52-week period, where they will come in for a an OLE baseline, followed by 48-week treatment, and 4-week end of study safety follow-up period. All participants will active drug that they will take three times a day, Throughout the study their disease progression will be assessed using tests, questionnaires, and blood biomarkers.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 136978 0
Prof Steve Vucic
Address 136978 0
Building 20, Level 1 Hospital Rd, Concord Hospital Concord, NSW, 2139
Country 136978 0
Australia
Phone 136978 0
+61 02 9767 8447
Fax 136978 0
Email 136978 0
[email protected]
Contact person for public queries
Name 136979 0
Bradley Turner
Address 136979 0
The Florey Institute of Neuroscience and Mental Health 30 Royal Parade, Parkville VIC 3052
Country 136979 0
Australia
Phone 136979 0
+61 3 9035 6521
Fax 136979 0
Email 136979 0
[email protected]
Contact person for scientific queries
Name 136980 0
Bradley Turner
Address 136980 0
The Florey Institute of Neuroscience and Mental Health 30 Royal Parade, Parkville VIC 3052
Country 136980 0
Australia
Phone 136980 0
+61 3 9035 6521
Fax 136980 0
Email 136980 0
[email protected]

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.