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

NCT00319046 | Completed Phase 3 Results

• 1 other identifier: OGT 918-011
• Study Type: interventional
• Target: 42
• Locations: 0 countries
• Sites: N/A

Brief Summary

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.

Conditions

Gaucher Disease Type 1

Keywords

enzyme replacement therapy; Type 1 Gaucher Disease; miglustat

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (2)

• Spleen Volume at Baseline and End of Treatment

  Baseline and end of treatment (Month 24)

• Mean Percent Change From Baseline in Spleen Volume

  End of treatment (Month 24)

Study Arms (1)

Open-label miglustat

EXPERIMENTAL

Oral administration of miglustat 100 mg t.i.d. for a period of 2 years

Drug: Miglustat

Interventions

Miglustat DRUG

Oral capsules containing miglustat 100 mg, administered three times daily (t.i.d.)

Also known as: Zavesca

Open-label miglustat

Eligibility Criteria

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

You may qualify if:

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

You may not qualify if:

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

Sponsors & Collaborators

• Actelion: lead

Related Publications (1)

• 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.

  PMID: 23270487 RESULT

MeSH Terms

Conditions

Gaucher Disease

Interventions

miglustat

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

Results Point of Contact

• Title: Cécile Luzy, MSc/Clinical Research Scientist
• Organization: Actelion Pharmaceuticals Ltd

+ 41 61 565 6386

Study Officials

• Timothy Cox, Prof

  University of Cambridge

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 26, 2006
• First Posted: April 27, 2006
• Study Start: February 1, 2006
• Primary Completion: June 1, 2010
• Study Completion: July 1, 2010
• Last Updated: February 4, 2025
• Results First Posted: May 23, 2012

Record last verified: 2025-01