None listed
Conditions
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 till 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.
Interventions
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
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).
Sponsors
The Florey Institute of Neuroscience and Mental Health (part of the University of Melbourne)
Study design
Allocation
Randomised controlled trial
Intervention model
Parallel
Primary purpose
Treatment
Masking
Blinded (masking used) (Subject, Caregiver, Outcomes Assessor)
Eligibility
Sex/Gender
All
Age
18 Years to 85 Years
Healthy volunteers
No
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 24 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.
Outcome results
None listed