High-Dose Ambroxol for Parkinson's Disease Related to GBA1 Mutation

An Open-Label Pilot Study for Assessing the Safety and Efficacy of High-Dose Ambroxol (HDA) in Newly Diagnosed GBA1 Parkinson Disease (PD)

This study is testing if high doses of ambroxol can help people with Parkinson's disease who have a GBA1 gene mutation feel better and manage their symptoms.

Quick facts

• Phase: PHASE1; PHASE2
• Study type: Interventional
• Enrollment: 40 (estimated)
• Ages: 30 Years to 70 Years
• Sex: All
• Sponsor: Agyany Pharma LTD (industry)
• Locations: 1 site (Jerusalem)
• Trial ID: NCT06193421 on ClinicalTrials.gov

What this trial studies

This clinical trial investigates the use of high-dose ambroxol hydrochloride in patients with Parkinson's disease (PD) who carry a GBA1 gene mutation. The study aims to target the misfolded enzyme glucocerebrosidase, which is implicated in both Gaucher disease and GBA1-related PD. By utilizing existing generic medications, the trial seeks to provide a faster pathway to effective treatments for this specific population of PD patients. Participants will be newly diagnosed individuals who meet specific criteria, and the trial will assess the safety and efficacy of ambroxol in managing their condition.

Who should consider this trial

Good fit: Ideal candidates are newly diagnosed Parkinson's disease patients aged 30-70 who carry at least one GBA1 variant and have not experienced motor fluctuations.

Not a fit: Patients with additional genetic variants or those with advanced Parkinson's disease may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could offer a novel therapeutic option for patients with GBA1-related Parkinson's disease.

How similar studies have performed: While there have been attempts to develop treatments for GBA1-related Parkinson's disease, this specific approach using ambroxol is relatively novel and has not been extensively tested in clinical trials.

Eligibility criteria

Inclusion Criteria:

For inclusion into the trial, subjects are required to fulfill all of the following criteria:

Newly diagnosed PD patients:

1. Individuals who exclusively carry at least one single GBA1 variant without any additional genetic variants.
2. Confirmed diagnosis of PD, by a movement disorder specialist, according to MDS PD criteria, within a maximum of three years from the date of diagnosis, coupled with the following conditions:

   iii. Hoehn and Yahr staged between I-II, inclusive.

   iv. No motor fluctuations or L-dopa induced dyskinesia.
3. Stable anti-PD medications for ≥ 4 weeks:

   Subjects can take PD medications including NMDA glutamate antagonists, monoamine oxidase B (MAO-B) inhibitors, dopamine agonists, and L-Dopa.
4. Male or female, age 30-70 years; however, if female:

   * must be using contraception measures if of childbearing potential.
   * must not be lactating.
5. Complying with study protocol.

Exclusion Criteria:

Eligible subjects may not have any of the following exclusion criteria:

1. Presence of any medical, emotional, behavioral, or psychological condition that in the judgment of the Investigator would interfere with the subject's compliance with the requirements of the study (such as clinical depression).
2. Any other disorder that may interfere with the results of the efficacy endpoints.
3. Currently taking another investigational drug for any condition.
4. Use of dopaminergic treatment under these conditions:

   * L-Dopa equivalent daily dose \> 400mg
   * L-Dopa daily dose \> 300mg
   * L-Dopa equivalent and L-Dopa daily dose has been changed in the past 4 weeks prior to screening visit.
5. Medical history of psychosis.
6. Exposure to ambroxol in the last 24 months prior to screening and/or history of adverse events to ambroxol.
7. Exposure to dopamine receptor blocking agents, lithium, cinnarizine, amiodarone or valproic acid in the last 12 months prior to screening.
8. Pregnancy or lactation; female subjects of a childbearing age who are unwilling to use contraceptive measures.

Where this trial is running

Jerusalem

• Shaare Zedek Medical Center — Jerusalem, Israel (RECRUITING)

Study contacts

• Study coordinator: Majdolen Istaiti, MBA

Conditions: Parkinson Disease, GBA Gene Mutation, GBA1-related Parkinson Disease, Glucocerebrosidase, Ambroxol