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

Phase 3

Completed

• Conditions: Gaucher Disease Type 1
• Interventions: Drug: Miglustat

• Registration Number: NCT00319046
• Lead Sponsor: Actelion

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2006-02-01
• Study First Submitted: 2006-04-26
• Study First Submitted QC: 2006-04-27
• Study First Posted: 2006-04-27
• Primary Completion: 2010-06-01
• Study Completion: 2010-07-01
• Results First Submitted: 2012-04-24
• Results First Submitted QC: 2012-04-24
• Results First Posted: 2012-05-23
• Status Verified: 2025-01
• Last Update Submitted: 2025-01-31
• Last Update Posted: 2025-03-25

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 42

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Open-label miglustat	Miglustat	Oral administration of miglustat 100 mg t.i.d. for a period of 2 years

Primary Outcome Measures

Name	Time	Method
Liver Volume at Baseline and at End of Treatment	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.
Mean Within-patient Percent Change From Baseline in Liver Volume	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

Name	Time	Method
Spleen Volume at Baseline and End of Treatment	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.
Mean Percent Change From Baseline in Spleen Volume	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.

Trial Locations

Locations (20)

NYU School of Medicine; 🇺🇸 New York, New York, United States

Royal Melbourne Hospital; 🇦🇺 Victoria, Australia

Royal Brisbane and Women's Hospital; 🇦🇺 Queensland, Australia

Royal Perth Hospital; 🇦🇺 Perth, Australia

Klinika detskeho a dorostoveho lekarstvi; 🇨🇿 Prague, Czechia

Academic Medical Center; 🇳🇱 Amsterdam, Netherlands

Hospital Universitario Miguel Servet; 🇪🇸 Zaragoza, Spain

Ospedale Burlo Garofolo; 🇮🇹 Trieste, Italy

University of Cambridge; 🇬🇧 Cambridge, United Kingdom

Hospital de Clinicas de Porto Alegre; 🇧🇷 Porto Alegre, Brazil

Medical College of Wisconsin; 🇺🇸 Wauwatosa, Wisconsin, United States

Children's National Medical Center; 🇺🇸 Washington, District of Columbia, United States

Hopital Beaujon; 🇫🇷 Clichy, France

Kinderklinik der Universitat Mainz; 🇩🇪 Mainz, Germany

University of Debrecen; 🇭🇺 Debrecen, Hungary

National Taiwan University Hospital; 🇨🇳 Taipei, Taiwan

University of California, San Francisco; 🇺🇸 San Francisco, California, United States

Mount Sinai Hospital; 🇨🇦 Toronto, Ontario, Canada

Emory University; 🇺🇸 Decatur, Georgia, United States

Doembecher Children's Hospital, Oregon Health and Sciences University; 🇺🇸 Portland, Oregon, United States