E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 12.1 |
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 |
The primary objective of this study is to demonstrate that, in patients with Gaucher disease type 1 who have been stabilized with Cerezyme, the majority of patients who receive Genz-112638 remain stable after 39 weeks of treatment. |
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E.2.2 | Secondary objectives of the trial |
The secondary objective is to assess the stability rates and safety of patients treated with Genz-112638 relative to Cerezyme at 39 weeks.The tertiary objective of this study is to evaluate the long-term efficacy, safety, and pharmacokinetics (PK) of Genz-112638 in patients with Gaucher disease type 1 who have been stabilized with Cerezyme. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. The patient is willing and able to provide signed informed consent prior to any study-related procedures to be performed. 2. The patient is 18 to 65 years of age at the time of randomization. 3. The patients Tanner Stage should be ≥ 4 prior to randomization. 4. The patient has a diagnosis of Gaucher disease type 1 confirmed by a documented deficiency of acid β- glucosidase activity by enzyme assay. 5. The patient consents to provide a blood sample for genotyping for Gaucher disease (unless the patients Gaucher genotype is already available), chitotriosidase, and for genotyping of cytochrome P450 2D6 (CYP2D6) to categorize the patients predicted rate of metabolism. 6. The patient has received treatment with Cerezyme for at least 3 years and has received the equivalent of ≥ 20 U/kg to ≤ 60 U/kg (� 5 U/kg) q2w at a stable dose (and in a manner consistent with local labeling) for the last year prior to randomization with Genz-112638. Patients should not have missed more than 4 infusions within the last year prior to randomization. 7. The patient has clinically stable Gaucher disease prior to randomization. Stable Gaucher disease is defined as a patient with all of the following: A. No bone crisis and free of symptomatic bone disease such as bone pain attributable to osteonecrosis and/or pathological fractures within the last year, and no documentation of acute pathological bone involvement by imaging (e.g., osteonecrosis, pathological fractures, etc.) as determined in review with a central bone reviewer. B. Mean hemoglobin level of ≥ 11 g/dL if female and ≥ 12 g/dL if male at the time of randomization and, in the 6 to 12 months prior to randomization, a median hemoglobin level of ≥11 g/dL if female or ≥ 12 g/dL if male that has not varied more than � 1 g/dL. C. Mean platelet count ≥ 100,000/mm3 at the time of randomization and, in the 6 to 12 months prior to randomization, a median platelet count ≥ 100,000/mm3 with no single value < 85,000/mm3. 8. Spleen volume < 10 times Normal or total splenectomy (provided the splenectomy occurred > 3 years prior to randomization). 9. Liver volume < 1.5 times Normal. 10. Male patients agree to use a medically accepted method of contraception throughout the study. 11. Female patients of childbearing potential must have a documented negative pregnancy test prior to randomization. In addition, all female patients of childbearing potential must use a medically accepted form of contraception throughout the study (either a barrier method or contraceptive with norethindrone and ethinyl estradiol). 12. The patient is willing to abstain from consumption of grapefruit or grapefruit juice for 72 hours prior to administration of the first dose of Genz-112638 and throughout the duration of the study. |
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E.4 | Principal exclusion criteria |
The patient received pharmacological chaperones or miglustat within 6 months prior to randomization. 2. The patient has had a partial or total splenectomy within 3 years prior to randomization. 3. The patient has any evidence of neurologic (e.g., peripheral neuropathy, tremor, seizures, Parkinsonism or cognitive impairment) or pulmonary involvement (e.g., pulmonary hypertension) as related to Gaucher disease. 4. The patient is transfusion-dependent. 5. The patient has a documented deficiency of iron, vitamin B-12, or folate that requires treatment not yet initiated or not yet stable under treatment for at least 3 months prior to randomization. 6. The patient has documented prior esophageal varices or liver infarction or current liver enzymes (alanine transaminase [ALT]/aspartate aminotransferase [AST]) or Total Bilirubin > 2 times the upper limit of normal (ULN), unless the patient has a diagnosis of Gilbert Syndrome. 7. The patient has any clinically significant disease, other than Gaucher disease, including cardiovascular, renal, hepatic, gastrointestinal, pulmonary, neurologic, endocrine, metabolic (e.g. hypokalemia, hypomagnesemia), or psychiatric disease, other medical conditions, or serious intercurrent illnesses that, in the opinion of the Investigator, may preclude participation in the study. 8. The patient is known to have any of the following: Clinically significant coronary artery disease including history of myocardial infarction [MI] or ongoing signs or symptoms consistent with cardiac ischemia or heart failure; or clinically significant arrhythmias or conduction defect such as 2nd or 3rd degree atrioventricular (AV) block, complete bundle branch block, prolonged QTc interval, or sustained ventricular tachycardia (VT). 9. The patient has tested positive for the human immunodeficiency virus (HIV) antibody, Hepatitis C antibody, or Hepatitis B surface antigen. 10. The patient has received an investigational product within 30 days prior to randomization. 11. The patient is scheduled for in-patient hospitalization, including elective surgery, during the study. 12. The patient has a history of cancer, with the exception of basal cell carcinoma. 13. The patient is pregnant or lactating. 14. The patient has received any medication within 30 days prior to randomization that may induce or inhibit CYP2D6 or any medication that may cause QTc interval prolongation. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy endpoint will be the percentage (%) of patients who remain stable after treatment with Genz-112638 for 39 weeks (the primary analysis treatment period). For a patient to be considered to have demonstrated a clinically meaningful response to treatment with Genz-112638, patients must remain stable in hematological parameters (hemoglobin levels and platelet counts), and organ volumes (spleen, when applicable, and liver volumes in multiples of normal [MN]). |
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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 | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
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 | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
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 | Yes |
E.8.1.1 | Randomised | Yes |
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 | Yes |
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) | Yes |
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
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
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 | 9 |
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 | Yes |
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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Ultima visita dell`ultimo paziente piu` un periodo di follow-up di sicurezza(dai 30 ai 37 giorni dopo l`ultima dose di trattamento del paziente) |
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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 | 1 |
E.8.9.1 | In the Member State concerned months | 4 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 4 |
E.8.9.2 | In all countries concerned by the trial months | 0 |