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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Shire
ClinicalTrials.gov Identifier:
NCT01685216
First received: September 10, 2012
Last updated: May 15, 2014
Last verified: May 2014
  Purpose

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.


Condition Intervention Phase
Gaucher Disease, Type 3
Biological: velaglucerase alfa
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Multi-center, Open-label, Efficacy and Safety Study of Velaglucerase Alfa Enzyme Replacement Therapy in Children and Adolescents With Type 3 Gaucher Disease

Resource links provided by NLM:


Further study details as provided by Shire:

Primary Outcome Measures:
  • Change from Baseline to 12 months in hemoglobin concentration [ Time Frame: End of study-12 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Change from Baseline to 12 months in platelet count [ Time Frame: End of study-12 months ] [ Designated as safety issue: No ]
  • Change from Baseline to 12 months in normalized liver volumes measured using magnetic resonance imaging (MRI) [ Time Frame: End of study-12 months ] [ Designated as safety issue: No ]
  • Change from Baseline to 12 months in normalized spleen volumes measured using magnetic resonance imaging (MRI) [ Time Frame: End of study-12 months ] [ Designated as safety issue: No ]
  • Change from Baseline to 12 months in neurological symptoms [ Time Frame: End of study-12 months ] [ Designated as safety issue: No ]
  • Safety Assessments [ Time Frame: Study duration-12 months ] [ Designated as safety issue: Yes ]
    Adverse events (AEs) and infusion-related AEs, serious adverse events (SAEs), clinical laboratory values, urinalysis, vital signs, 12-lead electrocardiogram (ECG) recordings, physical examination, and anti-velaglucerase alfa antibody formation


Estimated Enrollment: 6
Study Start Date: August 2012
Estimated Study Completion Date: April 2015
Estimated Primary Completion Date: March 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: velaglucerase alfa
IV infusion, 60 U/kg, every other week for 1 year
Biological: velaglucerase alfa
lyophilized powder, intravenous infusion, units, Every other week (EOW)
Other Names:
  • VPRIV
  • Gene activated glucocerebrosidase
  • GA-GCB
  • Enzyme replacement therapy

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   2 Years to 17 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01685216

Locations
Egypt
Alexandria University Hospital
Alexandria, Egypt, 21131
Children's Hospital, Ain Shams University Hospital
Cairo, Egypt
Abu El Rich Hospital, Cairo University Hospital
Cairo, Egypt
India
KEM Hospital Research Centre
Pune, Maharashtra, India
Tunisia
Hospital La Rabta
Tuni, Tunisia, 1007
Sponsors and Collaborators
Shire
Investigators
Study Director: Björn Mellgard, MD PhD Shire
  More Information

No publications provided

Responsible Party: Shire
ClinicalTrials.gov Identifier: NCT01685216     History of Changes
Other Study ID Numbers: HGT-GCB-068
Study First Received: September 10, 2012
Last Updated: May 15, 2014
Health Authority: United States: Food and Drug Administration
India: Drugs Controller General of India
Tunisia: Ministry of Public Health
Egypt: Ministry of Health and Population

Keywords provided by Shire:
VPRIV
velaglucerase alfa

Additional relevant MeSH terms:
Gaucher Disease
Sphingolipidoses
Lysosomal Storage Diseases, Nervous System
Brain Diseases, Metabolic, Inborn
Brain Diseases, Metabolic
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Metabolism, Inborn Errors
Genetic Diseases, Inborn
Lipidoses
Lipid Metabolism, Inborn Errors
Lysosomal Storage Diseases
Metabolic Diseases
Lipid Metabolism Disorders

ClinicalTrials.gov processed this record on August 26, 2014