Efficacy and Safety Study of Velaglucerase Alfa in Children and Adolescents With Type 3 Gaucher Disease

A Multi-center, Open-label, Efficacy and Safety Study of Velaglucerase Alfa Enzyme Replacement Therapy in Children and Adolescents With Type 3 Gaucher Disease

Gaucher disease is a rare lysosomal storage disorder caused by the deficiency of the enzyme glucocerebrosidase (GCB). Gaucher disease has been classified into 3 clinical subtypes based on the presence or absence of neurological symptoms and the severity of these neurological symptoms. Patients with type 2 Gaucher disease present with acute neurological deterioration, and those with type 3 disease typically display a more sub acute neurological course. Type 1 Gaucher disease, the most common form accounting for more than 90% of all Gaucher disease cases, does not involve the central nervous system.

The purpose of this clinical research study is to investigate the safety and effectiveness of velaglucerase alfa in patients with type 3 Gaucher disease.

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 the macrophages leading to cellular engorgement, organomegaly, and organ system dysfunction. Gaucher disease has been classified into 3 clinical subtypes based on the presence or absence of neurological symptoms and severity of neurological symptoms. Patients with type 2 Gaucher disease present with acute neurological deterioration, and those with type 3 Gaucher disease typically display a more sub acute neurological course; type 1 Gaucher disease, the most common form accounting for more than 90% of all cases, does not involve the central nervous system.

Velaglucerase alfa is an approved enzyme replacement therapy (ERT) for pediatric and adult patients with type 1 Gaucher disease. ERTs have been proven to reduce organomegaly, improve hematological parameters and positively impact health-related quality of life; ERTs have not been shown to cross the blood brain barrier and as a result have shown limited ability to improve the neurological (Central Nervous System; CNS) manifestations associated with Gaucher disease.

This study will provide a basis for exploring the efficacy and safety of velaglucerase alfa in patients with type 3 Gaucher disease.

Inclusion Criteria: Each patient must meet the following criteria to be enrolled in this study.

1. The patient has a confirmed diagnosis of type 3 Gaucher disease.

2. The patient is ≥ 2 and < 18 years of age at the time of enrollment.

3. The patient is either näive to treatment or has not received treatment (investigational or approved) for Gaucher disease within 12 months prior to study entry.

4. The patient has Gaucher disease-related anemia, defined as hemoglobin concentration below the lower limit of normal for age and sex.

   AND ONE OR MORE OF THE FOLLOWING THREE CRITERIA

   • The patient has at least moderate splenomegaly (2 to 3 cm below the left costal margin) by palpation.
   • The patient has Gaucher disease-related thrombocytopenia, defined as platelet count < 120 x 10,000 platelets/cubic mm.
   • The patient has a Gaucher disease-related readily palpable enlarged liver.

5. Patients who have undergone splenectomy may still be eligible to participate in the study.

6. Female patients of child-bearing potential must agree to use a medically acceptable method of contraception at all times during the study. Pregnancy testing will be performed at the time of enrollment and as required throughout participation in the study. Male patients must agree to use a medically acceptable method of contraception at all times during the study and report a partner's pregnancy to the Investigator.

7. The patient's parent(s) or the patient's legally authorized representative(s) has provided written informed consent that has been approved by the Institutional Review Board/Independent Ethics Committee (IRB/IEC).

Exclusion Criteria: Patients who meet any of the following criteria will be excluded from this study.

1. The patient is suspected of having type 2 or type 1 Gaucher disease.
2. The patient is < 2 years of age.
3. The patient has experienced a severe (Grade 3 or higher) infusion-related hypersensitivity reaction (anaphylactic or anaphylactoid reaction) to any enzyme replacement therapy for Gaucher disease (approved or investigational).
4. The patient has received any non-Gaucher disease-related treatment with an investigational drug within 30 days prior to study entry.
5. The patient is a pregnant and/or lactating female.