Study of Velaglucerase Alfa Enzyme Replacement Therapy in Japanese Patients With Gaucher Disease

A Multicenter, Open-Label Study of Velaglucerase Alfa Enzyme Replacement Therapy in Japanese Patients With Gaucher Disease

Gaucher disease is an inherited deficiency of the lysosomal enzyme glucocerebrosidase (GCB) that leads to progressive accumulation of glucocerebroside within macrophages and subsequent tissue and organ damage; typically of the liver, spleen, bone marrow, and brain. The disease has been classified into 3 clinical subtypes based on the presence or absence of neurological symptoms and severity of neurological disease. Type 1 Gaucher disease affects an estimated 30,000 persons worldwide and is the most common. Type 1 Gaucher disease does not involve the central nervous system. Patients with type 2 Gaucher disease present with acute neurological deterioration, which leads to early death. Those with type 3 disease typically display a more sub-acute neurological course, with later onset and slower progression.

The primary objective of this study is to evaluate the safety of every other week dosing of velaglucerase alfa in Japanese patients with Gaucher disease.

Velaglucerase alfa has been developed and approved as an enzyme replacement therapy for Type 1 Gaucher disease.

Gaucher disease is an inherited deficiency of the lysosomal enzyme glucocerebrosidase (GCB) that leads to progressive accumulation of glucocerebroside within macrophages and subsequent tissue and organ damage; typically of the liver, spleen, bone marrow, and brain.

Gaucher disease has been designated in the list of Specified Rare and Intractable Diseases by Specified Disease Treatment Research Program of Ministry of Health, Labor and Welfare (MHLW) as one of "lysosomal storage diseases" since 2001. Gaucher disease is also designated in the Medical Aid Program for Specified Categories of Chronic Pediatric Diseases.

The prevalence of mutations and the phenotype of patients with Gaucher disease in Japan differs from that in non-Japanese populations. Some patients with type 1 Gaucher disease in Japan have more severe and progressive disease compared to non-Japanese patients and the disease is characterized by an earlier onset of symptoms.

Velaglucerase alfa, a highly-purified form of the naturally occurring enzyme glucocerebrosidase, has been developed as an enzyme replacement therapy for Gaucher disease for the symptoms (anemia, thrombocytopenia, hepatomegaly, splenomegaly, and bone manifestation).

The primary objective of this study is to evaluate the safety of every other week dosing of velaglucerase alfa in Japanese patients (naive or previously treated with imiglucerase) 2 years of age and older with Gaucher disease.

Inclusion Criteria:

• The patient has a documented diagnosis of Gaucher disease
• The patient is at least 2 years of age
• Female patients of child bearing potential must agree to use a medically acceptable method of contraception at all times during the study
• The patient, the patient's parent(s) or legal guardian(s) has provided written informed consent that has been approved by the Institutional Review Board/Independent Ethics Committee (IRB/IEC)
• The patient must be sufficiently cooperative to participate in this clinical study as judged by the Investigator

Patients who are switched from imiglucerase ERT must meet the following additional criteria:

• Received treatment with imiglucerase for a minimum of 12 consecutive months
• Meet predefined limits for hemoglobin concentration and platelet counts

Patients naïve to treatment for Gaucher disease must meet the following additional criteria:

• Not received treatment for Gaucher disease (investigational or approved products) within 12 months prior to study entry
• Have Gaucher disease related anemia and at least one of the following: moderate splenomegaly or, Gaucher disease-related thrombocytopenia or Gaucher disease-related enlarged liver

Exclusion Criteria:

• Treatment with any investigational drug or device within the 30 days prior to study entry (time of informed consent); such use during the study is not permitted
• Positive for hepatitis B or hepatitis C.
• Non-Gaucher disease related anemia
• The 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
• Significant comorbidity, as determined by the Investigator that might affect study data or confound the study results
• The patient is unable to comply with the protocol or is unlikely to complete the study, as determined by the Investigator
• The patient has experienced a severe (grade 3 or higher) infusion-related hypersensitivity reaction (anaphylactic or anaphylactoid reaction) to any ERT (approved or investigational)
• Currently receiving red blood cell growth factor, (eg, erythropoietin) or chronic systemic corticosteroids in the last 6 months
• Patient has had a splenectomy or the patient has an active, clinically significant spleen infarction within 12 months of screening
• Patient has worsening bone necrosis within 12 months of screening
• The patient is pregnant or lactating.