Study of Gene-Activated® Human Glucocerebrosidase (GA-GCB) ERT Compared With Imiglucerase in Type I Gaucher Disease

Gaucher Disease, Type 1 Clinical Trial

Official title:

A Multicenter, Randomized, Double-Blind, Parallel-Group Study of Gene-Activated® Human Glucocerebrosidase (GA-GCB) Enzyme Replacement Therapy Compared With Imiglucerase in Patients With Type I Gaucher Disease

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00553631
• Other study ID #: HGT-GCB-039
• Secondary ID: 2007-002840-21
• Status: Completed
• Phase: Phase 3
• Start date: January 29, 2008
• Est. completion date: May 5, 2009

Study information

• Verified date: May 2021
• Source: Takeda
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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 non-inferiority study is to evaluate the efficacy and safety of GA-GCB (velaglucerase alfa) administered every other week in comparison to imiglucerase in treatment naive patients with type 1 Gaucher disease.

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 (velaglucerase alfa) 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 and safety of GA-GCB (velaglucerase alfa) in comparison to imiglucerase in men, women, and children with Type 1 Gaucher disease.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 34
• Est. completion date: May 5, 2009
• Est. primary completion date: May 5, 2009
• Accepts healthy volunteers: No
• Gender: All
• Age group: 2 Years and older

Eligibility

Inclusion Criteria

Includes:

• The patient has a documented diagnosis and clinical manifestation of type 1 Gaucher disease

• The patient is at least 2 years of age.

• The patient has not received treatment for Gaucher disease (investigational products, miglustat, or imiglucerase) within 12 months prior to study entry, as documented in the patient's medical history.

• Female patients of child-bearing potential must agree to use a medically acceptable method of contraception at all times during the study and must have negative results to a pregnancy test performed at the time of enrollment and as required throughout their participation in the study. Male patients must use a medically acceptable method of birth control throughout their participation in the study and must report their partner's pregnancy.

• 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.

Exclusion Criteria

Includes:

• The patient has type 2 or 3 Gaucher disease or is suspected of having type 3 Gaucher disease.

• The patient has received treatment with any non-Gaucher disease-related investigational drug or device within the 30 days prior to study entry; such use during the study is not permitted.

• The patient is known to be positive for human immunodeficiency virus (HIV).

• The patient is known to be positive for hepatitis B and/or C.

• 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.

• The patient has a significant comorbidity(ies) that might affect study data or confound the study results (e.g., malignancies, primary biliary cirrhosis, autoimmune liver disease, etc.).

• The patient is unable to comply with the protocol, e.g., has a clinically relevant medical condition making implementation of the protocol difficult, has an uncooperative attitude, is unable to return for safety evaluations, or is otherwise unlikely to complete the study, as determined by the Investigator.

Related Conditions & MeSH terms

• Gaucher Disease
• Gaucher Disease, Type 1

Intervention

Biological:
• velaglucerase alfa
IV infusion, 60 U/kg every other week for 9 months
• imiglucerase
IV infusion, 60 U/kg every other week for 9 months

Locations

Country	Name	City	State
Argentina	Your Health S.A.	Buenos Aires
India	Malabar Institute of Medical Sciences Ltd.	Calicut	Kerala
India	All India Institute of Medical Sciences	New Delhi
India	KEM Hospital Research Centre	Pune
Israel	Shaare Zedek Medical Center	Jerusalem
Paraguay	Sociedad Espanola de Socorros Mutuos	Asuncion
Russian Federation	National Research Center for Haematology	Moscow
Spain	Hospital Universitario Miguel Servet	Zaragoza
Tunisia	La Rabta Hospital	Tunis
United Kingdom	The Royal Free Hospital	London
United States	Duke Children's Hospital & Health Center	Durham	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Shire

Countries where clinical trial is conducted

United States,  Argentina,  India,  Israel,  Paraguay,  Russian Federation,  Spain,  Tunisia,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Mean Change From Baseline to Month 9 in Hemoglobin (Hgb) Concentration for Each Treatment Group.		Baseline to Month 9
Secondary	Change From Baseline to Month 9 in Platelet Counts for Each Treatment Group.	Values shown are observed change from Baseline to Month 9.	Baseline to Month 9
Secondary	Change From Baseline to Month 9 in Normalized Liver Volume (Percent (%) Body Weight) for Each Treatment Group.	Values shown are observed change from Baseline to Month 9. Measured by Magnetic resonance imaging (MRI). Liver volume has been normalized for percent (%) body weight for each treatment arm. Liver size relative to body weight = (Liver volume [cubic centimeter (cc)]/Body weight [kg]*1000.	Baseline to Month 9
Secondary	Change From Baseline to Month 9 in Normalized Spleen Volume (Percent (%) Body Weight) for Each Treatment Group.	Values shown are observed change from Baseline to month 9. Measured by Magnetic resonance imaging (MRI). Spleen volume was normalized for percent (%) of body weight for each treatment arm. Spleen size relative to body weight=(Spleen volume [cc]/Body weight [kg])*100.	Baseline to Month 9
Secondary	Change From Baseline to Month 9 in Plasma Chitotriosidase for Each Treatment Group.	Values shown are observed change from Baseline to Month 9. Units of measure is defined as nanomole per milliliter per hour.	Baseline to Month 9.
Secondary	Change From Baseline to Month 9 in Plasma Chemokine (C-C Motif) Ligand 18 (CCL18) for Each Treatment Group.	Values shown are observed change from Baseline to Month 9.	Baseline to Month 9
Secondary	Number of Participants Who Developed Antibody for Each Treatment Group.	Measure type is actual number of participants who developed antibodies to treatment; GA-GCB or imiglucerase. Antibody detection was based upon serum samples collected at various time points throughout the study. Serum samples were screened using an enzyme-linked immunosorbent assay (ELISA) and positive antibody confirmation was determined using a radioimmunoprecipitation assay (RIP); positive samples were also tested for enzyme neutralizing activity. Participant samples were compared to internal assay controls (positive/negative), positive samples were determined based upon individual assay criteria.	Baseline to Month 9
Secondary	Time to Response- Comparison of GA-GCB and Imiglucerase on the Earliest Time to Respond as Assessed Via Hemoglobin Concentration	Time to response was defined as a = 1 g/dL improvement in hemoglobin levels relative to Baseline. Units (%) correlates to the percentage of participants who had a change of = 1 g/dL improvement in hemoglobin levels relative to Baseline during their participation in the study.	Response rate at Month 9 compared to Baseline