MND Australia


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.

The primary outcome will be 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)). Secondary outcomes will be ALS functional rating score-revised (ALSFRS-R), Motor unit number estimation (MUNIX), Split Hand Index (SI), Neurophysiology Index (NPI), Kings staging system, Respiratory function (FVC) as measure by a Spirometer, Survival, Serum NFL levels and Assessment of Quality of Life (AQoL).

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).

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.


Concord Hospital

Prof Steve Vucic 

Phone +61 02 9767 8447