A Study of the Efficacy and Safety of Genz-112638 in Type 1 Gaucher Patients

Condition(s) targeted: Gaucher Disease, Type 1; Cerebroside Lipidosis Syndrome; Glucocerebrosidase Deficiency Disease; Glucosylceramide Beta-Glucosidase Deficiency Disease; Gaucher Disease, Non-Neuronopathic Form

Intervention: Genz-112638 (Drug)

Phase: Phase 2

Status: Active, not recruiting

Sponsored by: Genzyme

Official(s) and/or principal investigator(s):
Judith Peterschmitt, M.D. (US Medical Monitor), Study Director, Affiliation: Genzyme
Ana Cristina Scheidt Puga, M.D. Ph.D (EU Medical Monitor), Study Director, Affiliation: Genzyme

Gaucher disease is a genetic disease that results in a deficiency of an enzyme acid β-glucosidase, also known as glucocerebrosidase. This enzyme is needed to digest a substrate (lipid) called glucosylceramide and, to a lesser degree, glucosphingosine. In patients with Gaucher disease, the liver, spleen, bone marrow and brain show increases in lipid concentration, specifically in cells derived from the monocyte/macrophage system.

Genz-112638 is an oral drug that may regulate the Gaucher disease process by decreasing the synthesis of glucosylceramide. This study was designed to determine the efficacy, safety and pharmacokinetics of Genz-112638 in men and women with Type 1 Gaucher disease.

Each patient's duration of participation is expected to be approximately 26 months. After Day 1, each patient is required to return to the study center for 12 additional study visits post-Baseline for efficacy, safety and PK assessments.

Official title: A Phase 2, Open-Label, Multi-Center Study Evaluating the Efficacy, Safety and Pharmacokinetics of Genz-112638 in Gaucher Type 1 Patients

Study design: Treatment, Open Label, Single Group Assignment, Safety/Efficacy Study

Primary outcome: Changes in hemoglobin and platelet levels and spleen volume compared to baseline

Secondary outcome:

Change in liver volume compared to baseline

Levels of biomarkers (ACE; TRAP; CCL18; chitotriosidase; GL-1)

Changes in patient-reported Quality of Life

Changes in mobility, bone pain, bone crisis

Changes in radiographic measures of bone disease

Minimum age: 18 Years. Maximum age: 65 Years. Gender(s): Both.

Criteria:

INCLUSION CRITERIA:

- The patient has a diagnosis of Gaucher Type I disease and a documented deficiency of

glucocerebrosidase activity by enzyme assay and is willing and able to provide written informed consent prior to initiating any study-related procedures.

- The patient is 18 to 65 years old and weighs between 50 and 120 kg at enrollment

- The patient has the following symptoms of Gaucher disease identified within 28 days of

enrollment (at Screening):

- Anemia - indicated by hemoglobin measurements taken during the screening phase

- Thrombocytopenia - indicated by platelet count measurements taken during the

screening phase

- Splenomegaly, as indicated by MRI or spiral computed tomography (CT)

- Female patients of child-bearing potential must have a documented negative serum

pregnancy test prior to dosing. Male and female patients agree to use a reliable method of birth control throughout duration of trial.

EXCLUSION CRITERIA:

- Patient has had a partial or total splenectomy or infarcted areas of the spleen.

- Patient has documented prior bleeding varices or liver infarction.

- Patient received miglustat within 12 months prior to study enrollment

- The patient has received an investigational product within 30 days prior to study

enrollment.

- Patient has neurologic or pulmonary involvement.

- Patient has new pathological bone involvement or bone crisis in the 12 months prior to

enrollment.

- Patient is transfusion-dependent.

- Patient has a documented etiology of anemia due to causes other than Gaucher disease.

- Patient has a clinically significant disease, other than Gaucher disease, including

cardiovascular, renal, hepatic, gastrointestinal, pulmonary, neurologic, endocrine, metabolic, or psychiatric disease, other medical conditions, or serious intercurrent illnesses that, in the opinion of the Investigator, may preclude participation in the study.

Buenos Aires, Argentina

Jerusalem, Israel

Haifa, Israel

Mexico City, Mexico

Moscow, Russian Federation

New York, New York, United States

Starting date: June 2006
Ending date: October 2009
Last updated: December 23, 2007