E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Gaucher disease is the most common of the glycosphingolipid storage diseases and has autosomal recessive inheritance. For a more precise description, please refer to page 16 of the protocol:
1 BACKGROUND AND RATIONALE
1.1 Disease
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MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To evaluate the long-term (i.e. over a 24 month period) effect on liver volume of miglustat (100mg TID) as maintenance therapy in adult patients with stable mild to moderate Type 1 Gaucher disease after a switch from Enzyme Replacement Therapy (ERT) |
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E.2.2 | Secondary objectives of the trial |
To evaluate the long-term (i.e. over a 24 month period) effects of miglustat (100mg TID) on spleen volume and other markers of Type 1 Gaucher disease
To evaluate the long-term safety and tolerability with particular reference to any changes in the neurological assessments (including cognitive function) |
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E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
Eligible patients must meet all of the following inclusion criteria:
1. Patients aged 18 years or older at the study entry with a confirmed diagnosis of type 1 mild to moderate Gaucher disease at the time of enrollment. Diagnosis will be confirmed on glucocerebrosidase assay or molecular analysis of the glucocerebrosidase gene.
2. Patients treated with ERT for at least 3 years and who are receiving their current dose for a minimum of last six months.
3. Clinically and biologically stable for the previous 2 years, i.e. (with at least 3 timepoint assessments available for each parameters) a. Stable organomegaly, defined by <= 10% variation. b. Free of progressive symptomatic bone disease (no proven bone disease progression for the last 2 years) c. Controlled hemoglobin level above 11 g/dl , d. Controlled platelets counts with a mean of at least 100x10 Power 9 /l e. Stable chitotriosidase activity, defined by <= 20% variation.
4. Patients who provide written informed consent to participate in the study |
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E.4 | Principal exclusion criteria |
Eligible patients must meet none of the following exclusion criteria: 1. Patients (males and females) who do not agree to use reliable contraception throughout the study and for three months after cessation of miglustat treatment. 2. Female patients who are pregnant or breast feeding, or will not undergo a pregnancy test prior to enrollment into the study. 3. Patients with a history of significant lactose intolerance. 4. Patients with a confirmed neuropathy. 5. Patients suffering from clinically significant diarrhea (>3 liquid stools per day for >7 days) without definable cause within 6 months of Visit 1, or who have a history of significant gastrointestinal disorders (e.g., Irritable Bowel Syndrome). 6. Patients with history of cataracts or known increased risk of cataract formation. 7. Patients with severe renal impairment i.e., with a creatinine clearance <30 ml/min/1.73mPower2 8. Patients who are not ambulant, or have severe bone disease according to the bone history and symptom list (see appendix 9) 9. Patients splenectomised before 18 years old, because of massive splenomegaly or severe cytopenia. 10. Patients with an intercurrent medical condition that would render them unsuitable for study. 11. Patients currently undergoing therapy with other investigational product, or who have received an investigational product within 3 months prior to study start. 12. Patients with an intercurrent active medical condition such as HIV or Hepatitis B/C that would render them unsuitable for study. 13. Patients who for whatever reason are, in the opinion of the Investigator, thought to be unsuitable for the study. 14. Patients who have previously received treatment with miglustat. 15. Patients with a history of evidence of oculomotor gaze palsies, ataxia or other manifestations typically associated with type 3 (“neuronopatic”) Gaucher disease. 16. Predicted hypersensitivity to miglustat or any excipients. 17. Patients with current alcohol or drug abuse or dependence. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Percent change from baseline to Month 24 in liver volume
For the primary endpoint, the clinically acceptable difference is a mean percentage increase from Baseline to Month 24 of no greater than 10% in liver volume. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | Information not present in EudraCT |
E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
E.7.1.3 | Other | Information not present in EudraCT |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
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E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | Information not present in EudraCT |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | |
E.8.9.1 | In the Member State concerned months | 30 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial months | 30 |