Clinical Study to Evaluate the Long Term Efficacy, Safety and Tolerability of Miglustat in Patients With Stable Type 1 Gaucher Disease

Open-label, Non Comparative, Multi-center Study to Evaluate the Long Term Efficacy, Safety and Tolerability of Oral Miglustat as a Maintenance Therapy After a Switch From Enzyme Replacement Therapy in Adult Patients With Stable Type 1 Gaucher Disease

Although miglustat has been approved as a treatment for mild to moderate type 1 Gaucher disease in patients who are unsuitable for enzyme replacement therapy (ERT), more data are required to establish the long term efficacy, safety and tolerability of miglustat in maintaining diseases stability after a switch from ERT.

Study Overview

• Status: Completed
• Conditions: Gaucher Disease Type 1
• Intervention / Treatment: Drug: Miglustat

• Study Type: Interventional
• Enrollment (Actual): 42
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • Perth, Australia
    • Royal Perth Hospital
  • Queensland, Australia
    • Royal Brisbane and Women's Hospital
  • Victoria, Australia
    • Royal Melbourne Hospital
• Brazil
  • Porto Alegre, Brazil
    • Hospital de Clínicas de Porto Alegre
• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5G 1X5
      • Mount Sinai Hospital
• Czechia
  • Prague, Czechia
    • Klinika Dětského a Dorostového Lékařstvi
• France
  • Clichy, France, 92118
    • Hôpital Beaujon
• Germany
  • Mainz, Germany, 55131
    • Kinderklinik der Universitat Mainz
• Hungary
  • Debrecen, Hungary
    • University of Debrecen
• Italy
  • Trieste, Italy, 34100
    • Ospedale Burlo Garofolo
• Netherlands
  • Amsterdam, Netherlands, 1100
    • Academic Medical Center
• Spain
  • Zaragoza, Spain, 50009
    • Hospital Universitario Miguel Servet
• Taiwan
  • Taipei, Taiwan
    • National Taiwan University Hospital
• United Kingdom
  • Cambridge, United Kingdom, CB2 2QQ
    • University of Cambridge
• United States
  • California
    • San Francisco, California, United States, 94143
      • University of California, San Francisco
  • District of Columbia
    • Washington, District of Columbia, United States, 20010
      • Children's National Medical Center
  • Georgia
    • Decatur, Georgia, United States, 30033
      • Emory University
  • New York
    • New York, New York, United States, 10016
      • NYU School of Medicine
  • Oregon
    • Portland, Oregon, United States, 97239
      • Doembecher Children's Hospital, Oregon Health and Sciences University
  • Wisconsin
    • Wauwatosa, Wisconsin, United States, 53226
      • Medical College of Wisconsin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Males or females aged 18 years or older
2. Type 1 Gaucher disease, diagnosed by glucocerebrosidase assay or molecular analysis of the glucocerebrosidase gene.
3. Treatment with ERT for at least 3 years, with a stable dose regimen for at least the last 6 months.

4. Clinically and biologically stable disease for the previous 2 years, with at least 2 time points assessments (including baseline as one potential time point), defined as:

   • Stable organomegaly (assessed by magnetic resonance imaging (MRI) or computed tomography (CT)):

     • Liver volume within 10% of the mean.
     • Spleen volume within 10% of the mean.
   • Free of progressive symptomatic documented bone disease.
   • Hemoglobin levels > 11g/dl
   • Mean platelet count > 100x10^9 /l.

   • Chitotriosidase activity within 20% of the mean.

     • If chitotriosidase is not available (in the case of chitotriosidase deficiency, or if it was not determined), other relevant biomarkers (e.g., angiotensin converting enzyme (ACE), tartrate resistant acid phosphatase (TRAP) and ferritin) could be considered.
5. Written informed consent.

Exclusion Criteria:

1. History or evidence of oculomotor gaze palsy, ataxia or other clinical manifestations typically associated with neuronopathic type 3 Gaucher disease.
2. Not ambulant patients, or with progressive symptomatic documented bone disease.
3. Splenectomy before 18 years of age for splenomegaly and/or thrombocytopenia.
4. Peripheral polyneuropathy (not mononeuropathy) documented with both clinical signs and symptoms, and electrodiagnostic (EDX).
5. Patients (males and females) who do not agree to use reliable contraception throughout the study and for 3 months after cessation of miglustat treatment.
6. Female patients who are pregnant or breast feeding, or without pregnancy test prior to Day 1.
7. History of significant lactose intolerance.
8. Clinically significant diarrhea (>3 liquid stools per day for >7 days) without definable cause within 6 months prior to Day 1, or a history of clinically relevant gastrointestinal disorders.
9. History of cataracts or known increased risk of cataract formation.
10. Severe renal impairment i.e., with a creatinine clearance <30 ml/min/1.73m^2
11. Concomitant active medical condition such as human immunodeficiency virus (HIV) or hepatitis B/C that would render patients unsuitable for study.
12. Previous treatment with miglustat.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Open-label miglustat; Oral administration of miglustat 100 mg t.i.d. for a period of 2 years	Drug: Miglustat; Oral capsules containing miglustat 100 mg, administered three times daily (t.i.d.); Other Names: Zavesca

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Liver Volume at Baseline and at End of Treatment	Liver volume was assessed at baseline and end of treatment by magnetic resonance imaging. Imputation methods for patients with missing values at Month 24 were applied as follows: if a patient had at least 640 days of treatment with the study drug, the last observation that was not more than 2 days after the end of treatment was carried forward. If a patient had discontinued study drug before Day 640, the 'worst' within-patient value not more than 2 days after the end of treatment was used to impute the missing value.	Baseline and end of treatment (Month 24)
Mean Within-patient Percent Change From Baseline in Liver Volume	Liver volume was assessed at baseline and end of treatment by magnetic resonance imaging. Imputation methods for patients with missing values at Month 24 were applied as follows: if a patient had at least 640 days of treatment with the study drug, the last observation that was not more than 2 days after the end of treatment was carried forward. If a patient had discontinued study drug before Day 640, the 'worst' within-patient value not more than 2 days after the end of treatment was used to impute the missing value.	End of treatment (Month 24)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Spleen Volume at Baseline and End of Treatment	Spleen volume was assessed at baseline and end of treatment by magnetic resonance imaging. Imputation methods for patients with missing values at Month 24 were applied as follows: if a patient had at least 640 days of treatment with the study drug, the last observation that was not more than 2 days after the end of treatment was carried forward. If a patient had discontinued study drug before Day 640, the 'worst' within-patient value not more than 2 days after the end of treatment was used to impute the missing value.	Baseline and end of treatment (Month 24)
Mean Percent Change From Baseline in Spleen Volume	Spleen volume was assessed at baseline and end of treatment by magnetic resonance imaging. Imputation methods for patients with missing values at Month 24 were applied as follows: if a patient had at least 640 days of treatment with the study drug, the last observation that was not more than 2 days after the end of treatment was carried forward. If a patient had discontinued study drug before Day 640, the 'worst' within-patient value not more than 2 days after the end of treatment was used to impute the missing value.	End of treatment (Month 24)

Collaborators and Investigators

• Sponsor: Actelion
• Investigators: Principal Investigator: Timothy Cox, Prof, University of Cambridge

Publications and helpful links

General Publications

• Cox TM, Amato D, Hollak CE, Luzy C, Silkey M, Giorgino R, Steiner RD; Miglustat Maintenance Study Group. Evaluation of miglustat as maintenance therapy after enzyme therapy in adults with stable type 1 Gaucher disease: a prospective, open-label non-inferiority study. Orphanet J Rare Dis. 2012 Dec 27;7:102. doi: 10.1186/1750-1172-7-102.

Study record dates

Study Major Dates

• Study Start: February 1, 2006
• Primary Completion (Actual): June 1, 2010
• Study Completion (Actual): July 1, 2010

Study Registration Dates

• First Submitted: April 26, 2006
• First Submitted That Met QC Criteria: April 27, 2006
• First Posted (Estimated): April 27, 2006

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: January 31, 2025
• Last Verified: January 1, 2025

More Information

Terms related to this study

• Keywords: enzyme replacement therapy; miglustat; Type 1 Gaucher Disease
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Metabolic Diseases; Lipid Metabolism Disorders; Lysosomal Storage Diseases; Brain Diseases, Metabolic, Inborn; Brain Diseases, Metabolic; Lipid Metabolism, Inborn Errors; Lysosomal Storage Diseases, Nervous System; Sphingolipidoses; Lipidoses; Gaucher Disease; Anti-Infective Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Hypoglycemic Agents; Enzyme Inhibitors; Antiviral Agents; Anti-HIV Agents; Anti-Retroviral Agents; Glycoside Hydrolase Inhibitors; Miglustat
• Other Study ID Numbers: OGT 918-011