Back to resultsClinical Study to Evaluate the Long Term Efficacy, Safety and Tolerability of Miglustat in Patients With Stable Type 1 Gaucher Disease
Primary Purpose
Gaucher Disease Type 1
Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Miglustat
Sponsored by
About this trial
This is an interventional treatment trial for Gaucher Disease Type 1 focused on measuring enzyme replacement therapy, Type 1 Gaucher Disease, miglustat
Eligibility Criteria
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.
Sites / Locations
- University of California, San Francisco
- Children's National Medical Center
- Emory University
- NYU School of Medicine
- Doembecher Children's Hospital, Oregon Health and Sciences University
- Medical College of Wisconsin
- Royal Perth Hospital
- Royal Brisbane and Women's Hospital
- Royal Melbourne Hospital
- Hospital de Clinicas de Porto Alegre
- Mount Sinai Hospital
- Klinika detskeho a dorostoveho lekarstvi
- Hopital Beaujon
- Kinderklinik der Universitat Mainz
- University of Debrecen
- Ospedale Burlo Garofolo
- Academic Medical Center
- Hospital Universitario Miguel Servet
- National Taiwan University Hospital
- University of Cambridge
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Open-label miglustat
Arm Description
Oral administration of miglustat 100 mg t.i.d. for a period of 2 years
Outcomes
Primary Outcome Measures
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.
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.
Secondary Outcome Measures
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.
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.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT00319046
Brief Title
Clinical Study to Evaluate the Long Term Efficacy, Safety and Tolerability of Miglustat in Patients With Stable Type 1 Gaucher Disease
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 Type
Interventional
2. Study Status
Record Verification Date
October 2018
Overall Recruitment Status
Completed
Study Start Date
February 1, 2006 (undefined)
Primary Completion Date
June 1, 2010 (Actual)
Study Completion Date
July 1, 2010 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Actelion
4. Oversight
5. 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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Gaucher Disease Type 1
Keywords
enzyme replacement therapy, Type 1 Gaucher Disease, miglustat
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
42 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Open-label miglustat
Arm Type
Experimental
Arm Description
Oral administration of miglustat 100 mg t.i.d. for a period of 2 years
Intervention Type
Drug
Intervention Name(s)
Miglustat
Other Intervention Name(s)
Zavesca
Intervention Description
Oral capsules containing miglustat 100 mg, administered three times daily (t.i.d.)
Primary Outcome Measure Information:
Title
Liver Volume at Baseline and at End of Treatment
Description
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.
Time Frame
Baseline and end of treatment (Month 24)
Title
Mean Within-patient Percent Change From Baseline in Liver Volume
Description
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.
Time Frame
End of treatment (Month 24)
Secondary Outcome Measure Information:
Title
Spleen Volume at Baseline and End of Treatment
Description
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.
Time Frame
Baseline and end of treatment (Month 24)
Title
Mean Percent Change From Baseline in Spleen Volume
Description
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.
Time Frame
End of treatment (Month 24)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Timothy Cox, Prof
Organizational Affiliation
University of Cambridge
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of California, San Francisco
City
San Francisco
State/Province
California
ZIP/Postal Code
94143
Country
United States
Facility Name
Children's National Medical Center
City
Washington
State/Province
District of Columbia
ZIP/Postal Code
20010
Country
United States
Facility Name
Emory University
City
Decatur
State/Province
Georgia
ZIP/Postal Code
30033
Country
United States
Facility Name
NYU School of Medicine
City
New York
State/Province
New York
ZIP/Postal Code
10016
Country
United States
Facility Name
Doembecher Children's Hospital, Oregon Health and Sciences University
City
Portland
State/Province
Oregon
ZIP/Postal Code
97239
Country
United States
Facility Name
Medical College of Wisconsin
City
Wauwatosa
State/Province
Wisconsin
ZIP/Postal Code
53226
Country
United States
Facility Name
Royal Perth Hospital
City
Perth
Country
Australia
Facility Name
Royal Brisbane and Women's Hospital
City
Queensland
Country
Australia
Facility Name
Royal Melbourne Hospital
City
Victoria
Country
Australia
Facility Name
Hospital de Clinicas de Porto Alegre
City
Porto Alegre
Country
Brazil
Facility Name
Mount Sinai Hospital
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5G 1X5
Country
Canada
Facility Name
Klinika detskeho a dorostoveho lekarstvi
City
Prague
Country
Czechia
Facility Name
Hopital Beaujon
City
Clichy
ZIP/Postal Code
92118
Country
France
Facility Name
Kinderklinik der Universitat Mainz
City
Mainz
ZIP/Postal Code
55131
Country
Germany
Facility Name
University of Debrecen
City
Debrecen
Country
Hungary
Facility Name
Ospedale Burlo Garofolo
City
Trieste
ZIP/Postal Code
34100
Country
Italy
Facility Name
Academic Medical Center
City
Amsterdam
ZIP/Postal Code
1100
Country
Netherlands
Facility Name
Hospital Universitario Miguel Servet
City
Zaragoza
ZIP/Postal Code
50009
Country
Spain
Facility Name
National Taiwan University Hospital
City
Taipei
Country
Taiwan
Facility Name
University of Cambridge
City
Cambridge
ZIP/Postal Code
CB2 2QQ
Country
United Kingdom
12. IPD Sharing Statement
Citations:
PubMed Identifier
23270487
Citation
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.
Results Reference
result
Learn more about this trial
Clinical Study to Evaluate the Long Term Efficacy, Safety and Tolerability of Miglustat in Patients With Stable Type 1 Gaucher Disease
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