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 18 of the protocol:
1 BACKGROUND AND RATIONALE
1.1 Disease
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10018048 |
E.1.2 | Term | Gaucher's disease |
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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 effect on liver volume of miglustat 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 effects on spleen volume, and other markers of type 1 Gaucher disease, of miglustat as maintenance therapy. · To evaluate the long-term safety and tolerability of miglustat, in particular on peripheral neuropathies and cognitive functions in this patient population. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Male or female patients 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 at least the previous 2 years, with at least two time point 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 documented symptomatic bone disease. · Mean hemoglobin level > 11g/dl. · Mean platelet count > 100x109 /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., ACE, TRAP and ferritin) could be considered. 5. Written informed consent. |
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E.4 | Principal 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 documented symptomatic bone disease. 3. Splenectomy before 18 years of age for splenomegaly and/or thrombocytopenia. 4. Peripheral polyneuropathy (not mononeuropathy) documented both by compatible clinical signs and/or symptoms, and electrodiagnosis (EDX). 5. Patients (males and females) who do not agree to use reliable contraception throughout the study and for 3 months after study drug discontinuation.6. Female patients who are pregnant or breast feeding, or without a 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 with a creatinine clearance <30 ml/min/1.73mP2P 11. Concomitant active medical condition such as HIV or hepatitis B/C that would render patients unsuitable for study. 12. Previous treatment with miglustat. 13. Known hypersensitivity to miglustat or any excipients. 14. Patients with current alcohol or drug abuse or dependence. 15. Current treatment with another investigational drug, or within 3 months prior to Day 1. |
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E.5 End points |
E.5.1 | Primary end point(s) |
· Mean percentage change from baseline to Month 24 in liver volume (assessed by MRI). The acceptable clinically relevant difference in liver volume is a mean percentage increase from baseline to Month 24 < 10%. |
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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 | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
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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) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | No |
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 | No |
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.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 7 |
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 | No |
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 |