High-Dose Ambroxol in Pediatric Type III Gaucher Disease (GD3)

Ambroxol in Type III Gaucher Disease (GD3): A Prospective 6-Month Single-Center Open-Label Study With an Optional 12-month Extension Phase

Type: Prospective, open-label, single center study

Duration: 6 months with an optional 12-month extension phase

Participants: 12 pediatric patients diagnosed with type III Gaucher disease (GD3) aged ≥3 to ≤18 years old treatment naïve or on enzyme replacement therapy (ERT). They will be treated with high-dose Ambroxol (mean 35mg/kg bodyweight).

Location: The Children's Hospital, Lahore, Pakistan.

This single-center, prospective, open-label study investigates the safety, tolerability, and efficacy of high-dose Ambroxol in pediatric patients with genetically confirmed Type III Gaucher Disease (GD3). The study will enroll 12 participants aged 3 to 18 years, either treatment naïve or receiving enzyme replacement therapy (ERT). Participants will receive high-dose Ambroxol orally (mean 35 mg/kg bodyweight) over a 6-month period, with an optional 12-month extension.

Primary Objective:

Evaluate the safety and tolerability of high-dose Ambroxol administered with or without ERT.

Secondary Objective:

Assess efficacy based on at least a 20% improvement in at least 50% of participants using the following measures:

• Assessment and Rating of Ataxia (SARA) for patients with ataxia
• Unified Myoclonus Rating Scale (UMRS) for patients with myoclonic epilepsy
• Lyso-Gb1 levels in peripheral blood after at least 6 months of treatment

Intervention:

High-dose Ambroxol administered orally (mean 35 mg/kg bodyweight)

Study Location:

The Children's Hospital, Lahore, Pakistan

This study aims to provide preliminary safety and efficacy data on Ambroxol as a therapeutic option for pediatric patients with GD3, potentially informing future larger-scale clinical trials.

Inclusion Criteria:

• Pediatric patients aged 3 to 18 years
• Genetically confirmed Type III Gaucher Disease (GD3)
• Treatment naïve or receiving enzyme replacement therapy (ERT)
• SARA score ≥ 8
• Sexually active females must agree to use contraception
• All participants must not be pregnant or breastfeeding

Exclusion Criteria:

• Life-threatening visceral disease (related or unrelated to Gaucher Disease)
• Blood transfusion dependency
• Clinically significant cardiovascular, gastrointestinal, pulmonary, neurologic, endocrine, or psychiatric conditions
• Serious swallowing difficulties
• Renal insufficiency (eGFR < 30 mL/min/1.73 m²)
• Recent chaperone therapy or investigational treatment within the last 6 months
• Pregnancy or lactation
• History of cancer, drug or alcohol abuse, major organ transplant, or inability to adhere to study requirements