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

Primary Purpose

Gaucher Disease, Type 1

Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
velaglucerase alfa
imiglucerase
Sponsored by
Shire
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Gaucher Disease, Type 1 focused on measuring Enzyme Replacement Therapy, Gaucher disease, glucocerebrosidase, beta-glucocerebrosidase, Acid beta-glucocerebrosidase, glucosylceramidase, D-glucosyl-N-acylsphingosine glucohydrolase, gene activation, human

Eligibility Criteria

2 Years - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Duke Children's Hospital & Health Center
  • Your Health S.A.
  • Malabar Institute of Medical Sciences Ltd.
  • All India Institute of Medical Sciences
  • KEM Hospital Research Centre
  • Shaare Zedek Medical Center
  • Sociedad Espanola de Socorros Mutuos
  • National Research Center for Haematology
  • Hospital Universitario Miguel Servet
  • La Rabta Hospital
  • The Royal Free Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

GA-GCB

imiglucerase

Arm Description

VPRIV™ ,velaglucerase alfa

Outcomes

Primary Outcome Measures

Mean Change From Baseline to Month 9 in Hemoglobin (Hgb) Concentration for Each Treatment Group.

Secondary Outcome Measures

Change From Baseline to Month 9 in Platelet Counts for Each Treatment Group.
Values shown are observed change from Baseline to Month 9.
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.
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.
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.
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.
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.
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.

Full Information

First Posted
November 1, 2007
Last Updated
May 14, 2021
Sponsor
Shire
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1. Study Identification

Unique Protocol Identification Number
NCT00553631
Brief Title
Study of Gene-Activated® Human Glucocerebrosidase (GA-GCB) ERT Compared With Imiglucerase in Type I Gaucher Disease
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
Study Type
Interventional

2. Study Status

Record Verification Date
May 2021
Overall Recruitment Status
Completed
Study Start Date
January 29, 2008 (Actual)
Primary Completion Date
May 5, 2009 (Actual)
Study Completion Date
May 5, 2009 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Shire

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief 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.
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 (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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Gaucher Disease, Type 1
Keywords
Enzyme Replacement Therapy, Gaucher disease, glucocerebrosidase, beta-glucocerebrosidase, Acid beta-glucocerebrosidase, glucosylceramidase, D-glucosyl-N-acylsphingosine glucohydrolase, gene activation, human

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
34 (Actual)

8. Arms, Groups, and Interventions

Arm Title
GA-GCB
Arm Type
Experimental
Arm Description
VPRIV™ ,velaglucerase alfa
Arm Title
imiglucerase
Arm Type
Active Comparator
Intervention Type
Biological
Intervention Name(s)
velaglucerase alfa
Other Intervention Name(s)
VPRIV™, gene-activated human glucocerebrosidase
Intervention Description
IV infusion, 60 U/kg every other week for 9 months
Intervention Type
Biological
Intervention Name(s)
imiglucerase
Other Intervention Name(s)
Cerezyme®
Intervention Description
IV infusion, 60 U/kg every other week for 9 months
Primary Outcome Measure Information:
Title
Mean Change From Baseline to Month 9 in Hemoglobin (Hgb) Concentration for Each Treatment Group.
Time Frame
Baseline to Month 9
Secondary Outcome Measure Information:
Title
Change From Baseline to Month 9 in Platelet Counts for Each Treatment Group.
Description
Values shown are observed change from Baseline to Month 9.
Time Frame
Baseline to Month 9
Title
Change From Baseline to Month 9 in Normalized Liver Volume (Percent (%) Body Weight) for Each Treatment Group.
Description
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.
Time Frame
Baseline to Month 9
Title
Change From Baseline to Month 9 in Normalized Spleen Volume (Percent (%) Body Weight) for Each Treatment Group.
Description
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.
Time Frame
Baseline to Month 9
Title
Change From Baseline to Month 9 in Plasma Chitotriosidase for Each Treatment Group.
Description
Values shown are observed change from Baseline to Month 9. Units of measure is defined as nanomole per milliliter per hour.
Time Frame
Baseline to Month 9.
Title
Change From Baseline to Month 9 in Plasma Chemokine (C-C Motif) Ligand 18 (CCL18) for Each Treatment Group.
Description
Values shown are observed change from Baseline to Month 9.
Time Frame
Baseline to Month 9
Title
Number of Participants Who Developed Antibody for Each Treatment Group.
Description
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.
Time Frame
Baseline to Month 9
Title
Time to Response- Comparison of GA-GCB and Imiglucerase on the Earliest Time to Respond as Assessed Via Hemoglobin Concentration
Description
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.
Time Frame
Response rate at Month 9 compared to Baseline

10. Eligibility

Sex
All
Minimum Age & Unit of Time
2 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Study Director
Organizational Affiliation
Takeda
Official's Role
Study Director
Facility Information:
Facility Name
Duke Children's Hospital & Health Center
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27710
Country
United States
Facility Name
Your Health S.A.
City
Buenos Aires
ZIP/Postal Code
B1882AQY
Country
Argentina
Facility Name
Malabar Institute of Medical Sciences Ltd.
City
Calicut
State/Province
Kerala
ZIP/Postal Code
673 016
Country
India
Facility Name
All India Institute of Medical Sciences
City
New Delhi
ZIP/Postal Code
110 029
Country
India
Facility Name
KEM Hospital Research Centre
City
Pune
Country
India
Facility Name
Shaare Zedek Medical Center
City
Jerusalem
Country
Israel
Facility Name
Sociedad Espanola de Socorros Mutuos
City
Asuncion
Country
Paraguay
Facility Name
National Research Center for Haematology
City
Moscow
Country
Russian Federation
Facility Name
Hospital Universitario Miguel Servet
City
Zaragoza
Country
Spain
Facility Name
La Rabta Hospital
City
Tunis
Country
Tunisia
Facility Name
The Royal Free Hospital
City
London
Country
United Kingdom

12. IPD Sharing Statement

Citations:
PubMed Identifier
27839979
Citation
Zimran A, Elstein D, Gonzalez DE, Lukina EA, Qin Y, Dinh Q, Turkia HB. Treatment-naive Gaucher disease patients achieve therapeutic goals and normalization with velaglucerase alfa by 4years in phase 3 trials. Blood Cells Mol Dis. 2018 Feb;68:153-159. doi: 10.1016/j.bcmd.2016.10.007. Epub 2016 Oct 21.
Results Reference
derived

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

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