Clinical Study to Evaluate the Long Term Efficacy, Safety and Tolerability of Miglustat in Patients With Stable Type 1 Gaucher Disease
Condition: Gaucher Disease Type 1
MeSH terms: Gaucher Disease
Intervention: Miglustat
Intervention description: Oral capsules containing miglustat 100 mg, administered three times daily (t.i.d.)
Intervention MeSH terms: Miglustat
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 42.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: enzyme replacement therapy; Type 1 Gaucher Disease; miglustat

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.