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 Reached Therapeutic Goals with Enzyme Replacement Therapy - ENCORE

• Register: EUCTR
• Last refreshed on: 19 April 2022
• Main ID: EUCTR2008-005223-28-NL
• Date of registration: 01/07/2009
• Prospective Registration: Yes
• Primary sponsor: Genzyme Europe B.V.
• Public title: 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 Reached Therapeutic Goals with Enzyme Replacement Therapy - ENCORE
• Scientific title: 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 Reached Therapeutic Goals with Enzyme Replacement Therapy - ENCORE
• Date of first enrolment: 04/11/2009
• Target sample size: 186
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2008-005223-28
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: yes; Open: yes; Single blind: no; Double blind: no; Parallel group: yes; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: yes; Placebo: no; Other: no
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Czech Republic, France, Germany, Italy, Netherlands, Spain, United Kingdom

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 protocol-required procedures to be performed.
2. The patient is at least 18 years of age at the time of randomization.
3. The patient’s 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 ß-glucosidase activity by enzyme assay.
5. The patient consents to provide a blood sample for genotyping for Gaucher disease, chitotriosidase, and 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. The patient has received treatment with ERT for at least 3 years. Within the 9 months prior to randomization, the patient has received a total monthly dose of 30 to 130 U/kg for at least 6 months.
7. The patient has reached Gaucher disease therapeutic goals prior to randomization. Gaucher disease therapeutic goals are 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 screening.
C. Mean platelet count = 100,000/mm3 at the time of screening.
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. 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 hormonal contraceptive with ethinyl estradiol and
norethindrone or similar active components).
11. The patient is willing to abstain from consumption of grapefruit or grapefruit juice for 72 hours prior to administration of the first dose of study medication (Genz-112638 or Cerezyme) and, if randomized to Genz-112638, for the duration of the primary analysis period.
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
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
Patients will be excluded from participation in this study if they meet any of the following exclusion criteria:
1. The patient received pharmacological chaperone, taliglucerase, or substrate reduction therapies for Gaucher disease 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 within 5 years of randomization, with the exception of basal cell carcinoma.
13. The patient is pregnant or lactating.
14. The patient has received any medication that may cause QTc interval prolongation within 30 days prior to randomization.
15. The patient has received any medication that may induce CYP2D6 or CYP3A4 within 30 days prior to randomization, with the exception of premedications for ERT infusion, which are allowed up to 7 days prior to randomization.
16. The patient is not a CYP2D6 poor metabolizer, and has received any medication that is a strong inhibitor of CYP3A4 or CYP2D6 within 30 days prior to randomization, with the exception of the following:
• premedications for ERT infusion, which are allowed up to 7 days prior to randomization;
• a strong inhibitor of CYP3A4 or a strong inhibitor of CYP2D6 (but not both medications) that has been administered chronically for at least 30 days prior to randomization and will be continued on the same dosing regimen during the primary analysis period.
17. The patient is a CYP2D6 poor metabolizer and has received any medication that is a strong inhibitor of CYP3A4 within 30 days prior to randomization, with th

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

Health Condition(s) or Problem(s) studied

Gaucher Disease type I
MedDRA version: 9.1 Level: PT Classification code 10018048 Term: Gaucher's disease

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: up to
Concentration number: 150-

Trade Name: Cerezyme
Product Name: Cerezyme
Product Code: Imiglucerase
Pharmaceutical Form: Powder for concentrate for solution for infusion
INN or Proposed INN: IMIGLUCERASE
CAS Number: 154248-97-2
Other descriptive name: Recombinant human derived macrophage-targeted ß-Glucocerebrosidase
Concentration unit: U unit(s)
Concentration type: up to
Concentration number: 60 -

Primary Outcome(s)

Primary end point(s): The primary efficacy endpoint will be the percentage (%) of patients who remain stable for 52 weeks (the primary analysis period) assessed for both treatment groups separately along with a difference between the two treatment groups. For a patient to be considered to have demonstrated a clinically meaningful response to treatment with Genz-112638 or Cerezyme, 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]).

Secondary Objective: The secondary objective of this study is to demonstrate that, in patients with Gaucher disease type 1 who have reached therapeutic goals with ERT, the majority of patients who receive Genz-112638 remain stable after 52 weeks of treatment. 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 reached therapeutic goals with ERT.

Main Objective: The primary objective of this study is to assess the efficacy and safety of Genz-112638 compared with Cerezyme after 52 weeks of treatment in patients with Gaucher disease type 1 who have reached therapeutic goals with enzyme replacement therapy (ERT).

Secondary ID(s)

GZGD02607

Ethics review

Status: Approved
Approval date: 04/11/2009
Contact:

Results

• Results available: Yes
• Date Posted: 02/06/2016
• Date Completed: 09/11/2012
• URL: https://www.clinicaltrialsregister.eu/ctr-search/trial/2008-005223-28/results