| CTRI Number |
CTRI/2009/091/000689 [Registered on: 12/10/2009] |
| Last Modified On: |
13/11/2018 |
| Post Graduate Thesis |
No |
| Type of Trial |
Interventional |
Type of Study
Modification(s)
|
Drug |
| Study Design |
Randomized, Parallel Group, Placebo Controlled Trial |
Public Title of Study
Modification(s)
|
A Study of Genz-112638 in Patients With Gaucher Disease (ENGAGE) |
Scientific Title of Study
Modification(s)
|
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 |
| Trial Acronym |
ENGAGE |
Secondary IDs if Any
Modification(s)
|
| Secondary ID |
Identifier |
| 2008-005222-37 |
EudraCT |
| GZGD02507 |
Protocol Number |
| NCT00891202 |
ClinicalTrials.gov |
|
|
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
|
| Name |
|
| Designation |
|
| Affiliation |
|
| Address |
Not Applicable
N/A
India |
| Phone |
|
| Fax |
|
| Email |
|
|
Details of Contact Person
Scientific Query
Modification(s)
|
| Name |
Dr Senthilnathan Mohanasundaram |
| Designation |
Medical Director |
| Affiliation |
Genzyme |
| Address |
1 Genzyme India Pvt. Ltd., 1st Floor, Technopolis
Golf Course Road, Sector-54
Gurgaon
HARYANA
122001
India |
| Phone |
0124-4528307 |
| Fax |
0124-4528400 |
| Email |
senthilnathan.mohanasundaram@genzyme.com |
|
Details of Contact Person
Public Query
Modification(s)
|
| Name |
Dr Senthilnathan Mohanasundaram |
| Designation |
Medical Director |
| Affiliation |
Genzyme |
| Address |
1 Genzyme India Pvt. Ltd., 1st Floor, Technopolis
Golf Course Road, Sector-54
Gurgaon
HARYANA
122001
India |
| Phone |
0124-4528307 |
| Fax |
0124-4528400 |
| Email |
senthilnathan.mohanasundaram@genzyme.com |
|
Source of Monetary or Material Support
Modification(s)
|
| Genzyme Corporation, Primary Sponsor |
|
Primary Sponsor
Modification(s)
|
| Name |
Genzyme Europe BV |
| Address |
Gooimeer 10, 1411 DD Naarden, The Netherlands |
| Type of Sponsor |
Pharmaceutical industry-Global |
|
Details of Secondary Sponsor
Modification(s)
|
|
|
Countries of Recruitment
|
India
Bulgaria
Canada
Chile
Colombia
Israel
Jordan
Lebanon
Mexico
Netherlands
Russian Federation
Saudi Arabia
Tunisia
United Kingdom
United States of America |
Sites of Study
Modification(s)
|
| No of Sites = 4 |
| Name of Principal
Investigator |
Name of Site |
Site Address |
Phone/Fax/Email |
| Dr. Sumita Danda, Proffessor, Clinical Genetics Unit |
Christian Medical College & Hospital |
Department of Gastrointestinal Sciences ,-632 004
Vellore
TAMIL NADU |
sdanda@cmcvellore.ac.in |
| Dr Aabha Nagral consultant Hepatologist |
Jaslok Hospital and Research Centre |
15-Dr. Deshmukh Marg, Peddar Road,-400 026
Mumbai
MAHARASHTRA |
-
aabhanagral@gmail.com |
| Dr. Shubha R. Phadke, Additional Professor |
Sanjay Gandhi Postgraduate Institute of Medical Sciences (SGPGI) |
Department of Medical Genetics,Raebareli Road-226 014
Lucknow
UTTAR PRADESH |
shubharaophadke@gmail.com |
| Dr. I.C. Verma, Sr. Consultant & Chairman |
Sir Gangaram Hospital, Rajinder Nagar |
, Department of Genetic Medicine,-110 060
New Delhi
DELHI |
dr_icverma@yahoo.com |
|
Details of Ethics Committee
Modification(s)
|
| No of Ethics Committees= 4 |
| Name of Committee |
Approval Status |
| Christian Medical College Institutional Review Board, Vellore 632 002, India |
Approved |
| Ethics Committee, Jaslock Hospital & Research Centre, Mumbai 400 026, India |
Approved |
| Ethics Committee, Sir Gangaram Hospital, New Delhi 110 060 India |
Approved |
| Institutional Ethics Committee for Human Research, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow 226 014, India |
Approved |
|
Regulatory Clearance Status from DCGI
Modification(s)
|
|
Health Condition / Problems Studied
Modification(s)
|
| Health Type |
Condition |
| Patients |
Gaucher Disease Type 1, (1) ICD-10 Condition: E752||Other sphingolipidosis, |
|
Intervention / Comparator Agent
Modification(s)
|
| Type |
Name |
Details |
| Intervention |
Genz-112638 |
Capsule: 50, 100 or 150 mg BID |
| Comparator Agent |
Placebo |
Capsule |
|
Inclusion Criteria
Modification(s)
|
| Age From |
16.00 Year(s) |
| Age To |
65.00 Year(s) |
| Gender |
Both |
| Details |
The patient (and/or their parent/legal guardian) is willing and able to provide signed informed consent prior to any study-related procedures to be performed. The patient is at least 16 years old at the time of randomization. The patient¡¯s Tanner Stage should be ¡Ý 4 prior to randomization. The patient has a diagnosis of Gaucher disease type 1 confirmed by a documented deficiency of acid ¦Â-glucosidase activity by enzyme assay. The patient has the following symptoms of Gaucher disease during the Screening period:
A. At least one of the following laboratory abnormalities:
1. Hemoglobin level of 8.0 to 11.0 g/dL if female or 8.0 to 12.0 g/dL if male (the mean of 2 measurements from separate blood samples collected at least 24 hours apart during Screening).
2. Platelet count of 50,000 to 130,000/mm3 (the mean of 2 measurements from separate blood samples collected at least 24 hours apart during Screening).
B. Splenomegaly (spleen volume of 6 to 30 MN).
C. If hepatomegaly is present, the liver volume must be 2.5MN.
The patient consents to provide a blood sample to Genzyme for genotyping for Gaucher disease, chitotriosidase, and CYP2D6 (to categorize the patient¡¯s predicted rate of metabolism), unless the patient¡¯s genotypes for Gaucher disease, chitotriosidase, and CYP2D6 are already available. 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). 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 and throughout the duration of the Double-Blind Primary Analysis Period.
|
|
| ExclusionCriteria |
| Details |
The patient has had a partial or total splenectomy. The patient has received pharmacological chaperone or substrate reduction therapies for Gaucher disease within 6 months prior to randomization. The patient has received enzyme replacement therapy for Gaucher disease within 9 months prior to randomization. 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. The patient has current symptomatic bone disease such as bone pain attributable to osteonecrosis and/or pathologic fracture, or has had a bone crisis in the 12 months prior to randomization. The patient is transfusion-dependent.
The patient has the following laboratory abnormalities during the Screening period:
A. Hemoglobin level 8 g/dL (the mean of 2 measurements from separate blood samples collected at least 24 hours apart during Screening).
B. Platelet count of 50,000/mm3 (the mean of 2 measurements from separate blood samples collected at least 24 hours apart during Screening).
The patient has documented anemia due to causes other than Gaucher disease that requires treatment not yet initiated or not yet stable under treatment for at least 3 months (e.g., iron, vitamin B-12, and/or folate deficiency) prior to randomization. The patient has documented thalassemia minor or sickle cell trait with a platelet count of 50,000 or 130,000/mm3. The patient has ever had any radiation treatment in the abdominal region. The patient has documented prior esophageal varices or liver infarction or current liver enzymes (alanine aminotransferase [ALT]/ aspartate aminotransferase [AST]) or total bilirubin 2 times the upper limit of normal (ULN), unless the patient has a diagnosis of Gilbert Syndrome. The patient has any clinically significant disease, other than Gaucher disease, including cardiovascular, renal, hepatic, GI, 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. 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 AV block, complete bundle branch block, prolonged QTc interval, or sustained ventricular tachycardia (VT). The patient has tested positive for the human immunodeficiency virus (HIV) antibody, Hepatitis C antibody, or Hepatitis B surface antigen. The patient has received an investigational product within 30 days prior to randomization. The patient is scheduled for in-patient hospitalization, including elective surgery, during the study. The patient has a history of cancer within 5 years of randomization, with the exception of basal cell carcinoma. The patient is pregnant or lactating. The patient has received any medication that may cause QTc interval prolongation within 30 days prior to randomization. The patient has received (acute or chronic) treatment with a CYP3A4 or CYP2D6 inducer within 30 days prior to randomization. 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, except where a patient has been receiving chronic treatment with either a strong inhibitor of CYP3A4 or a strong inhibitor of CYP2D6 (but not both medications) for at least 30 days prior to randomization and plans to continue on the same dosing regimen during the Double-Blind Primary Analysis Period. The patient is a CYP2D6 poor metabolizer and has received (acute or chronic) treatment with a strong inhibitor of CYP3A4 within 30 days prior to randomization. |
|
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Method of Generating Random Sequence
|
|
Method of Concealment
Modification(s)
|
Centralized |
Blinding/Masking
Modification(s)
|
Participant, Investigator and Outcome Assessor Blinded |
Primary Outcome
Modification(s)
|
| Outcome |
TimePoints |
The Primary objective is to compare the effects of Genz-112638 as compared to placebo in patients with Type 1 Gaucher Disease
|
Time Frame: 39 weeks |
|
Secondary Outcome
Modification(s)
|
| Outcome |
TimePoints |
| The secondary objectives for this study include an evaluation of safety and the effects on disease manifestations and disease specific bio-markers |
Time Frame: 39 weeks |
|
Target Sample Size
Modification(s)
|
Total Sample Size="28"
Sample Size from India="12"
Final Enrollment numbers achieved (Total)= ""
Final Enrollment numbers achieved (India)="" |
Phase of Trial
Modification(s)
|
Phase 3 |
Date of First Enrollment (India)
Modification(s)
|
14/02/2010 |
| Date of Study Completion (India) |
Date Missing |
| Date of First Enrollment (Global) |
13/10/2009 |
| Date of Study Completion (Global) |
Date Missing |
Estimated Duration of Trial
Modification(s)
|
Years="4"
Months="5"
Days="0" |
Recruitment Status of Trial (Global)
Modification(s)
|
Completed |
| Recruitment Status of Trial (India) |
Completed |
Publication Details
Modification(s)
|
Not yet available
|
|
Individual Participant Data (IPD) Sharing Statement
|
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
|
Brief Summary
Modification(s)
|
This Phase 3, Study was designed to confirm the Efficacy and Safety of Genz-112638 in Patients with Gaucher Disease Type 1. Gaucher disease is characterised by lysosomal accumulation of glucosylceramide due to impaired glucosylceramide hydrolysis. Gaucher Disease Type 1, the most common form accounts for > 90% of cases and does not involve the CNS. Typical manifestations of Gaucher Disease type 1 include splenomegaly, hepatomegaly, thrombocytopenia, anemia, skeletal pathology and decreased quality of life. The disease manifestations are caused by accumulation of glucosylceramide (storage material) in Gaucher cells which infiltrate the spleen and liver as well as other tissue. Genz-112638 is a small molecule developed as an oral therapy which acts to specifically inhibit production of this storage material. This study is designed to determine the efficacy, safety, and pharmacokinetics (PK) of Genz-112638 in adult patients (¡Ý 16 years) with Gaucher Disease type 1 Target Sample Size for India - 12 patients. We anticipate to enroll first patient from India, ,and globally, on 13 Oct 2009. |