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

Gaucher Disease Type 1 Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00319046
• Other study ID #: OGT 918-011
• Status: Completed
• Phase: Phase 3
• Start date: February 1, 2006
• Est. completion date: July 1, 2010

Study information

• Verified date: October 2018
• Source: Actelion
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 42
• Est. completion date: July 1, 2010
• Est. primary completion date: June 1, 2010
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Gaucher Disease
• Gaucher Disease Type 1

Intervention

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

Locations

Country	Name	City	State
Australia	Royal Perth Hospital	Perth
Australia	Royal Brisbane and Women's Hospital	Queensland
Australia	Royal Melbourne Hospital	Victoria
Brazil	Hospital de Clinicas de Porto Alegre	Porto Alegre
Canada	Mount Sinai Hospital	Toronto	Ontario
Czechia	Klinika detskeho a dorostoveho lekarstvi	Prague
France	Hopital Beaujon	Clichy
Germany	Kinderklinik der Universitat Mainz	Mainz
Hungary	University of Debrecen	Debrecen
Italy	Ospedale Burlo Garofolo	Trieste
Netherlands	Academic Medical Center	Amsterdam
Spain	Hospital Universitario Miguel Servet	Zaragoza
Taiwan	National Taiwan University Hospital	Taipei
United Kingdom	University of Cambridge	Cambridge
United States	Emory University	Decatur	Georgia
United States	NYU School of Medicine	New York	New York
United States	Doembecher Children's Hospital, Oregon Health and Sciences University	Portland	Oregon
United States	University of California, San Francisco	San Francisco	California
United States	Children's National Medical Center	Washington	District of Columbia
United States	Medical College of Wisconsin	Wauwatosa	Wisconsin

Sponsors (1)

Lead Sponsor	Collaborator
Actelion

Countries where clinical trial is conducted

United States,  Australia,  Brazil,  Canada,  Czechia,  France,  Germany,  Hungary,  Italy,  Netherlands,  Spain,  Taiwan,  United Kingdom, 

References & 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-inferi — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)
Primary	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	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)
Secondary	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)