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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Gaucher Disease Type 1

Intervention / Treatment
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* Drug: Miglustat


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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. Exclusion Criteria: 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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

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

What is the study measuring?
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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) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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enzyme replacement therapy, Type 1 Gaucher Disease, miglustat