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

• Sponsor: Actelion
• Information provided by (Responsible Party): Actelion

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Gaucher Disease Type 1	Drug: Miglustat	Phase 3

Study Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	42 participants
Intervention Model:	Single Group Assignment
Masking:	None (Open Label)
Primary Purpose:	Treatment
Official Title:	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
Study Start Date :	February 1, 2006
Actual Primary Completion Date :	June 1, 2010
Actual Study Completion Date :	July 1, 2010

Arms and Interventions

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 Name: Zavesca

Outcome Measures

Primary Outcome Measures :

1. Liver Volume at Baseline and at End of Treatment [ Time Frame: Baseline and end of treatment (Month 24) ]
   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.
2. Mean Within-patient Percent Change From Baseline in Liver Volume [ Time Frame: End of treatment (Month 24) ]
   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.

Secondary Outcome Measures :

1. Spleen Volume at Baseline and End of Treatment [ Time Frame: Baseline and end of treatment (Month 24) ]

   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.

2. Mean Percent Change From Baseline in Spleen Volume [ Time Frame: End of treatment (Month 24) ]

   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.

Eligibility Criteria

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Ages Eligible for Study:	18 Years and older (Adult, Older Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

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.

Contacts and Locations

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Sponsors and Collaborators

Actelion

Investigators

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Principal Investigator:	Timothy Cox, Prof	University of Cambridge

More Information

Publications of Results:

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.

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Responsible Party:	Actelion
ClinicalTrials.gov Identifier:	NCT00319046 History of Changes
Other Study ID Numbers:	OGT 918-011
First Posted:	April 27, 2006
Results First Posted:	May 23, 2012
Last Update Posted:	November 21, 2018
Last Verified:	October 2018

Keywords provided by Actelion:

enzyme replacement therapy; Type 1 Gaucher Disease; miglustat

Additional relevant MeSH terms:

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Gaucher Disease; 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; Lipidoses; Lipid Metabolism, Inborn Errors; Lysosomal Storage Diseases	Metabolic Diseases; Lipid Metabolism Disorders; Miglustat; 1-Deoxynojirimycin; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Anti-HIV Agents; Anti-Retroviral Agents; Antiviral Agents; Anti-Infective Agents; Glycoside Hydrolase Inhibitors; Hypoglycemic Agents; Physiological Effects of Drugs