| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
|
| E.1.1.1 | Medical condition in easily understood language |
| People with Gacher disease have low levels of an enzyme called acid ß-glucosidase, which helps the body control levels of glucosylceramide. In Gaucher disease glucosylceramide levels can get too high |
|
| E.1.1.2 | Therapeutic area | Diseases [C] - Nutritional and Metabolic Diseases [C18] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 14.1 |
| E.1.2 | Level | PT |
| E.1.2 | Classification code | 10018048 |
| E.1.2 | Term | Gaucher's disease |
| E.1.2 | System Organ Class | 10010331 - Congenital, familial and genetic disorders |
|
| 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 evaluate the efficacy and safety of once daily (QD) versus twice daily (BID) dosing of Genz-112638 in patients with Gaucher disease type 1 who have demonstrated clinical stability on BID dosing of Genz-112638. |
|
| E.2.2 | Secondary objectives of the trial |
| The secondary objective is to evaluate the pharmacokinetics (PK) of Genz-99067 when Genz-112638 is administered QD and BID in patients with Gaucher disease type 1 who have demonstrated clinical stability on BID dosing of Genz-112638. |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
Patients must meet all of the following inclusion criteria in order to
participate in this study:
1.The patient is willing and able to provide signed informed consent
prior to any study-related procedures.
2.The patient is ≥18 years of age.
3.The patient has a diagnosis of Gaucher disease type 1 confirmed by a documented deficiency of acid β glucosidase activity by enzyme assay.
The patient may be previously untreated, off prior treatment, or
receiving enzyme replacement therapy for Gaucher disease.
4.The patient meets all of the following criteria at the time of Screening:
•Hemoglobin level ≥9 g/dL (mean of 2 measurements);
•Platelet count ≥70,000/mm3 (mean of 2 measurements);
•Spleen volume ≤25 multiples of normal (MN);
•Liver volume ≤2.0 MN.
5.The patient consents to provide a blood sample for genotyping for Gaucher disease and for cytochrome P450 2D6 (CYP2D6) to categorize the patient's predicted rate of metabolism, if these genotyping results are not already available for the patient.
6.Female patients of childbearing potential must have a documented
negative pregnancy test prior to administration of the first dose of Genz-112638 in this study. In addition, all female patients of childbearing potential must use a medically accepted form of contraception throughout the study, i.e., either a barrier method or hormonal contraceptive with norethindrone and ethinyl estradiol or similar active components.
7.The patient is willing to abstain from consumption of grapefruit,
grapefruit juice, or grapefruit products for 72 hours prior to
administration of the first dose of Genz 112638 and throughout the
duration of the study. |
|
| E.4 | Principal exclusion criteria |
Patients will be excluded from participation in this study if they meet
any of the following exclusion criteria:
1.The patient is participating in GZGD02607 study, "A Phase 3,
Randomized, Multi-Center, Multi-National, Open-Label, Active
Comparator Study to Evaluate the Efficacy and Safety of Genz 112638 in Patients with Gaucher Disease Type 1 who have been Stabilized with Cerezyme," or is eligible for inclusion in GZGD02607 (while enrollment is ongoing) and has access to a physician participating in GZGD02607.
OR
The patient is participating in GZGD02507 study, "A Phase 3,
Randomized, Double-Blind, Placebo-Controlled, Multi-Center Study
Confirming the Efficacy and Safety of Genz 112638 in Patients with
Gaucher Disease Type 1," or is eligible for inclusion in GZGD02507 (while enrollment is ongoing) and has access to a physician participating in GZGD02507.
2.The patient received miglustat within 6 months prior to administration of the first dose of Genz 112638 in this study.
3.The patient has had a partial or total splenectomy within 3 years prior to administration of the first dose of Genz 112638 in this study.
4.The patient has any evidence of neurologic disorder (e.g., peripheral neuropathy, tremor, seizures, Parkinsonism or cognitive impairment) or pulmonary involvement (e.g., pulmonary hypertension) as related to Gaucher disease.
5.The patient is transfusion-dependent.
6.The patient has a documented deficiency of iron, vitamin B-12, or
folate that requires treatment not yet initiated or, if initiated, the patient has not been stable under treatment for at least 3 months prior to administration of the first dose of Genz 112638 in this study.
7.The patient has documented prior esophageal varices or clinically
significant 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.
8.The patient has any clinically significant disease, other than Gaucher disease, including cardiovascular, renal, hepatic, gastrointestinal, pulmonary, neurologic, endocrine, metabolic (including hypokalaemia or hypomagnesemia), or psychiatric disease, other medical conditions, or serious intercurrent illnesses that may preclude participation in the study.
9.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).
10.The patient is known to have tested positive for the human
immunodeficiency virus (HIV) antibody, Hepatitis C antibody, or
Hepatitis B surface antigen.
11.The patient has received an investigational product (other than Genz-112638) within 30 days prior to administration of the first dose of Genz-112638 in this study.
12.The patient is scheduled for in-patient hospitalization, including
elective surgery, during the study.
13.The patient has a history of cancer, with the exception of basal cell carcinoma, within 5 years prior to administration of the first dose of Genz 112638 in this study.
14.The patient is pregnant or lactating.
15.The patient has received any medication that may cause QTc interval prolongation within 30 days prior to the first dose of Genz 112638.
Exception: Diphenhydramine (Benadryl) or other medications used as premedication for ERT infusions are allowed up to 7 days prior to the first dose of Genz-112638.
16.The patient has received for the first time (i.e., the patient is not
already chronically using) any of the following medications within 30
days prior to the first dose of Genz-112638:
•Strong inhibitors of CYP2D6 or CYP3A4
•Inducers of CYP3A4
Exception: premedications for ERT infusions are allowed up to 7 days prior to the first dose of Genz-112638.
17.The patient is a CYP2D6 non-poor metabolizer or an indeterminate metabolizer with one allele identified as active who is chronically receiving both a strong competitive inhibitor of CYP2D6 and a strong competitive inhibitor of CYP3A4 and for whom no reasonable alternative medication exists.
OR
The patient is a CYP2D6 poor metabolizer or an indeterminate
metabolizer with neither allele known to be active who is chronically
receiving a strong competitive inhibitor of CYP3A4 and for whom no
reasonable alternative medication exists.
Exception for both cases: Premedications for ERT infusions are allowed up to 7 days prior to the first dose of Genz-112638. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| The primary efficacy endpoint will be the percentage (%) of randomized patients who remain stable after treatment with Genz-112638 through R-Week 52 (the Primary Analysis Period) assessed for both dosing regimens (BID full dose, QD full dose) separately along with a difference between the two dosing regimens. |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
| E.5.2 | Secondary end point(s) |
The secondary efficacy endpoints include the following: Hemoglobin
level, platelet count, and spleen and liver volumes (in MN) (assessed by magnetic resonance imaging [MRI]); biomarkers (chemokine CC motif ligand 18 [CCL18] and chitotriosidase); bone disease assessments (dualenergy X-ray absorptiometry [DXA] and MRI); and Gaucher assessments (mobility, bone crisis, and bone pain). |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
|
| 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 | Yes |
| 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 | No |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | Yes |
| 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) | No |
| E.8.2.2 | Placebo | No |
| E.8.2.3 | Other | Yes |
| E.8.2.3.1 | Comparator description |
| BID dose versus QD dose of Genz-112638 |
|
| E.8.2.4 | Number of treatment arms in the trial | 2 |
| 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 | 2 |
| 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 | No |
| 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 |
| Argentina |
| Australia |
| Austria |
| Brazil |
| Canada |
| China |
| Croatia |
| France |
| Greece |
| India |
| Japan |
| Netherlands |
| Portugal |
| Romania |
| Russian Federation |
| Serbia |
| Sweden |
| United States |
|
| 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
|
| last patient last visit plus a safety follow-up period (30 to 37 days after the patient's last dose of treatment) |
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 5 |
| E.8.9.1 | In the Member State concerned months | 0 |
| E.8.9.1 | In the Member State concerned days | 0 |
| E.8.9.2 | In all countries concerned by the trial years | 5 |
| E.8.9.2 | In all countries concerned by the trial months | 0 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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