A Study of Eliglustat Tartrate (Genz-112638) in Patients With Gaucher Disease to Evaluate Once Daily Versus Twice Daily Dosing (EDGE)

• Register: EUCTR
• Last refreshed on: 21 November 2016
• Main ID: EUCTR2009-015811-42-AT
• Date of registration: 22/11/2010
• Prospective Registration: Yes
• Primary sponsor: Genzyme Europe B.V.
• Public title: A Study of Eliglustat Tartrate (Genz-112638) in Patients With Gaucher Disease to Evaluate Once Daily Versus Twice Daily Dosing (EDGE)
• Scientific title: A Phase 3, Randomized, Multi-Center, Multi-National, Double-Blind Study to Evaluate the Efficacy, Safety, and Pharmacokinetics of Once Daily versus Twice Daily Dosing of Genz-112638 in Patients with Gaucher Disease Type 1 who have Demonstrated Clinical Stability on a Twice Daily Dose of Genz-112638 - EDGE
• Date of first enrolment: 05/01/2011
• Target sample size: 170
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2009-015811-42
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: no Other: yes Other specify the comparator: BID dose versus QD dose of Genz-112638 Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Argentina, Australia, Austria, Brazil, Canada, China, Croatia, France, Greece, India, Japan, Netherlands, Portugal, Romania, Russian Federation, Serbia, Sweden, United States

Contacts

• Name: Medical Information
• Affiliation: Genzyme Europe B.V.

• Name: Medical Information
• Affiliation: Genzyme Europe B.V.

Key inclusion & exclusion criteria

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 ß 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.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 170
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range 0

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

Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Nutritional and Metabolic Diseases [C18]

Gaucher Disease Type I
MedDRA version: 15.0 Level: PT Classification code 10018048 Term: Gaucher's disease System Organ Class: 10010331 - Congenital, familial and genetic disorders

Intervention(s)

Product Name: Genz-112638
Product Code: Genz-112638
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: Eliglustat
CAS Number: NA
Current Sponsor code: Genz-112638
Other descriptive name: not available
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 50-
Pharmaceutical form of the placebo: Capsule, hard
Route of administration of the placebo: Oral use

Product Name: Genz-112638
Product Code: Genz-112638
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: Eliglustat
CAS Number: NA
Current Sponsor code: Genz-112638
Other descriptive name: not available
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 100-
Pharmaceutical form of the placebo: Capsule, hard
Route of administration of the placebo: Oral use

Product Name: Genz-112638
Product Code: Genz-112638
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: Eliglustat
CAS Number: NA
Current Sponsor code: Genz-112638
Other descriptive name: not available
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 150-

Primary Outcome(s)

Secondary Objective: 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.

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.

Main Objective: 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.

Timepoint(s) of evaluation of this end point: 52 weeks

Secondary Outcome(s)

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 (dual-energy X-ray absorptiometry [DXA] and MRI); and Gaucher assessments (mobility, bone crisis, and bone pain).

Timepoint(s) of evaluation of this end point: 52 weeks

Secondary ID(s)

2009-015811-42-SE

NCT01074944

GZGD03109

Source(s) of Monetary Support

Genzyme Europe B.V.