A Study of GA-GCB Enzyme Replacement Therapy in Gaucher Disease

Condition(s) targeted: Gaucher Disease, Type 1

Intervention: velaglucerase alfa (Biological); velaglucerase alfa (Biological)

Phase: Phase 3

Status: Active, not recruiting

Sponsored by: Shire Human Genetic Therapies, Inc.

Official(s) and/or principal investigator(s):
Kiran Bhirangi, M.D., FRCS, Study Director, Affiliation: Shire Human Genetic Therapies, Inc.

Gaucher disease is a rare lysosomal storage disorder caused by the deficiency of the enzyme glucocerebrosidase (GCB). Due to the deficiency of functional GCB, glucocerebroside accumulates within macrophages leading to cellular engorgement, organomegaly, and organ system dysfunction. The purpose of this study is to evaluate the efficacy of every other week dosing of GA-GCB (velaglucerase alfa) at doses of 45 and 60 U/kg in treatment-naïve patients with type 1 Gaucher disease.

Official title: A Multicenter, Randomized, Double-Blind, Parallel Group, Two-Dose Study of Gene-Activated® Human Glucocerebrosidase (GA-GCB) Enzyme Replacement Therapy in Patients With Type 1 Gaucher Disease

Study design: Treatment, Randomized, Double Blind (Subject, Investigator), Dose Comparison, Parallel Assignment, Safety/Efficacy Study

Primary outcome: To evaluate a change in hemoglobin concentration

Secondary outcome: To evaluate safety and efficacy through changes in hemoglobin concentration, platelet counts, spleen and liver volumes, biomarkers (CCL18 and chitotriosidase) and patient-reported quality of life as well as pharmacokinetics.

Detailed description: Type 1 Gaucher disease, the most common form,accounts for more than 90% of all cases and does not involve the CNS. Typical manifestations of type 1 Gaucher disease include hepatomegaly, splenomegaly, thrombocytopenia, bleeding tendencies, anemia, hypermetabolism, skeletal pathology, growth retardation, pulmonary disease, and decreased quality of life. Gene-Activated® human glucocerebrosidase (GA-GCB; velaglucerase alfa) is produced in a continuous human cell line using proprietary gene-activation technology and has an identical amino acid sequence to the naturally occurring human enzyme. GA-GCB contains terminal mannose residues that target the enzyme to the macrophages-the primary target cells in Gaucher disease. This study was designed to determine the efficacy, safety and pharmacokinetics of GA-GCB in men, women, and children with Type 1 Gaucher disease. Each patients duration of treatment will be 12 months.

Minimum age: 2 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

Inclusion Criteria:

- Patient has a documented diagnosis of type 1 Gaucher disease, as determined by

deficient glucocerebrosidase (GCB) activity relative to normal as measured in leukocytes or by genotype analysis and is willing and able to provide written informed consent prior to initiating any study-related procedures

- Patient is at least 2 years of age

- Patient has Gaucher disease-related anemia and

- Patient has at least moderate splenomegaly or

- Patient has Gaucher disease-related thrombocytopenia or

- Patient has a readily palpable enlarged liver

- Patient has not received treatment for Gaucher disease within 30 months prior to study

entry

- Female patients of child-bearing potential agree to use a medically acceptable method

of contraception. Male patients must agree to use a medically acceptable method of birth control.

- Patient must be sufficiently cooperative to participate in the study as judged by the

Investigator.

Exclusion Criteria:

Includes:

- Patient has type 2 or 3 Gaucher disease or is suspected of having type 3 Gaucher

disease

- Patient is antibody-positive to imiglucerase during screening or has experienced an

anaphylactic reaction to imiglucerase

- Patient has received treatment with any investigational drug or device within the 30

days prior to study entry

- Patient is HIV positive

- Patient is hepatitis positive

- Patient presents with iron, folic acid and/or vitamin B12 deficiency sustained anemia

during screening

- Patient, patient's parent(s), or patient's legal guardian(s) is/are unable to

understand the nature, scope, and possible consequences of the study

- Patient has a significant comorbidity(ies)that might affect study data or confound the

study results

- Patient is pregnant and/or lactating female

- Patient is unable to comply with the protocol or is unlikely to complete the study, as

determined by the Investigator

Hipolito Yrigoyen, Buenos Aires, Argentina

Shaare Zedek, Medical Center, Jerusalem, Israel

Sociedad Espanola de Socorros Mutuos, Asuncion, Paraguay

National Research Center for Haematology, Moscow, Russian Federation

La Rabta Hospital, Tunis, Tunisia

Starting date: January 2007
Ending date: April 2009
Last updated: April 25, 2008