Clinical trial NCT00319046: 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
Overall status: COMPLETED
Phase: PHASE3
Conditions: Gaucher Disease Type 1
Keywords: enzyme replacement therapy
Type 1 Gaucher Disease
miglustat
Lead sponsor: Actelion
Sponsor class: INDUSTRY
First posted: 2006-04-27
Enrollment: 42
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility 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.

Primary outcomes:
measure: Liver Volume at Baseline and at End of Treatment
timeFrame: Baseline and end of treatment (Month 24)
measure: Mean Within-patient Percent Change From Baseline in Liver Volume
timeFrame: End of treatment (Month 24)
Secondary outcomes:
measure: Spleen Volume at Baseline and End of Treatment
timeFrame: Baseline and end of treatment (Month 24)
measure: Mean Percent Change From Baseline in Spleen Volume
timeFrame: End of treatment (Month 24)
Other outcomes:
Locations:
Study officials:
affiliation: University of Cambridge
name: Timothy Cox, Prof
role: PRINCIPAL_INVESTIGATOR
References:
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.