Ambroxol Therapy for Patients With Type 1 Gaucher Disease and Suboptimal Response to Enzyme Replacement Therapy

NCT03950050 | Completed Phase 2

• 1 other identifier: 0005-18-SZMC
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

Ambroxol hydrochloride, an over-the-counter antitussive available in many markets , was identified as an interesting pharmacological chaperone. In addition to a mucolytic action, ambroxol has antioxidant and anti-inflammatory properties. Importantly, ambroxol therapy was found safe when given to pregnant women for prevention of neonatal respiratory distress syndrome . Thus, ambroxol, an oral available drug on the market, may be a safe option for GD patients with potential disease-specific efficacy and should be expanded into a clinical trial using higher doses and placebo-controlled design. The investigators propose to start with a phase II study for patients with type 1 GD and suboptimal response to ERT. In addition the investigators plan to open an international registry of patients with GD currently receiving ambroxol (off study).

Conditions

Gaucher Disease, Type 1

Outcome Measures

Primary Outcomes (3)

• Platelets count

  Increase in platelet count

  12 months.

• bone mineral density evaluated by Dual Energy X-ray Absorptiometry (DEXA)

  Bone Mineral Densitometry (BMD)

  12 months.

• Lyso-GB1 biomarker for Gaucher disease

  decrease in Lyso-GB1.

  12 months

Secondary Outcomes (2)

• Patient-reported outcomes (PRO)

  12 months

• Fatigue Severity Scale (FSS)

  12 months

Study Arms (1)

Ambroxol

EXPERIMENTAL

Ambroxol therapy will be dosed up to 600 mg/day divided to twice a day starting 150 mg for the first month, 300 mg for the following month and 600 mg for the following month. The study was conducted in accordance with the provisions of the Declaration of Helsinki, Good Clinical Practice guidelines, and local laws and regulations.

Drug: Ambroxol

Interventions

Ambroxol DRUG

Ambroxol Hydrochloride therapy will be dosed up to 600 mg/day divided to twice a day starting 150 mg for the first month, 300 mg for the following month and 600 mg for the following month. The study was conducted in accordance with the provisions of the Declaration of Helsinki, Good Clinical Practice guidelines, and local laws and regulations.

Also known as: Ambroxol Hydrochloride

Ambroxol

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \*Adult patients ≥ 18 years with type 1 GD and suboptimal response to ERT defined as one or more than one of the following: platelet count \< 100 x 103/mm3 bone mineral density \< -2 T score Lyso-GB1 \> 200 ng/ml.
• \*No change in dose or preparation of ERT in the last 12 months (Except for Naive patients)

You may not qualify if:

• Patients with comorbidity that may impact on the primary and/or secondary endpoint.
• Pregnant women will be excluded from the study.
• Inability to cooperate with the study procedure
• Hypersensitivity or any other contraindication listed in the local labeling of ambroxol
• Refusal of patients to participate in the study.

Sponsors & Collaborators

• Shaare Zedek Medical Center: lead

Study Sites (1)

Shaare Zedek Medical Center

Jerusalem, Israel

Location

Related Publications (1)

• Ishay Y, Zimran A, Szer J, Dinur T, Ilan Y, Arkadir D. Combined beta-glucosylceramide and ambroxol hydrochloride in patients with Gaucher related Parkinson disease: From clinical observations to drug development. Blood Cells Mol Dis. 2018 Feb;68:117-120. doi: 10.1016/j.bcmd.2016.10.028. Epub 2016 Nov 12.

  PMID: 27866808 RESULT

MeSH Terms

Conditions

Gaucher Disease

Interventions

Ambroxol

Condition Hierarchy (Ancestors)

Sphingolipidoses; Lysosomal Storage Diseases, Nervous System; Brain Diseases, Metabolic, Inborn; Brain Diseases, Metabolic; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Lipidoses; Lipid Metabolism, Inborn Errors; Lysosomal Storage Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases; Lipid Metabolism Disorders

Intervention Hierarchy (Ancestors)

Bromhexine; Aniline Compounds; Amines; Organic Chemicals; Cyclohexylamines

Study Officials

• Ari Zimran

  Ari Zimran - Shaare Zedek

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: The aim of this single arm, phase II study is to evaluate the efficacy and safety of adding ambroxol to patients with type 1 GD and suboptimal response to ERT. HYPOTHESIS The addition of ambroxol will improve the disease related symptoms and disease impact of patients with GD with suboptimal response to ERT.

Study Record Dates

• First Submitted: August 6, 2018
• First Posted: May 15, 2019
• Study Start: March 1, 2019
• Primary Completion: November 30, 2022
• Study Completion: December 30, 2022
• Last Updated: February 14, 2023

Record last verified: 2022-05

Data Sharing

• IPD Sharing: Will not share

Locations

IL (1)