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Study of GA-GCB Enzyme Replacement Therapy in Type 1 Gaucher Disease Patients Previously Treated With Imiglucerase

Primary Purpose

Gaucher Disease

Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
GA-GCB (velaglucerase alfa)
Sponsored by
Shire
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

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

Eligibility Criteria

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

Inclusion Criteria:

Includes:

  • The participant has a documented diagnosis of type 1 Gaucher disease, as determined by deficient glucocerebrosidase (GCB) activity relative to normal as measured in leukocytes or by genotype analysis and the participant/legal guardian is willing and able to provide written informed consent prior to initiating any study-related procedures
  • The participant has received consistent treatment with imiglucerase at a dose ≤ 60 U/kg and ≥ 15 U/kg every other week for a minimum of 30 consecutive months. Participants who are anti-imiglucerase antibody positive will be allowed to enter this study
  • The participant is at least 2 years of age
  • Female participants of child-bearing potential agree to use a medically acceptable method of contraception. Male participants must agree to use a medically acceptable method of birth control
  • Participant must be sufficiently co-operative to participate in the study as judged by the Investigator.

Exclusion Criteria:

Includes:

  • The participant has type 2 or 3 Gaucher disease or is suspected of having type 3 Gaucher disease
  • The participant has received treatment with any investigational drug or device within the 30 days prior to study entry; such use during the study is not permitted
  • Participant is HIV positive
  • Participant is hepatitis B/C positive
  • The participant presents with sustained iron, folic acid and/or vitamin B12 deficiency-related anemia during Screening
  • The participant, participant's parent(s), or participant's legal guardian(s) is/are unable to understand the nature, scope, and possible consequences of the study
  • The participant has a significant comorbidity that might affect study data or confound the study results
  • The participant is unable to comply with the protocol or is otherwise unlikely to complete the study, as determined by the Investigator
  • The participant has experienced an anaphylactic/anaphylactoid reaction during treatment with imiglucerase
  • The participant has received miglustat during the 6 months prior to study enrollment
  • The participant has an active, clinically significant spleen infarction
  • The participant has active, progressive bone necrosis
  • The participant is a pregnant and/or lactating female

Sites / Locations

  • Regional Metabolic Center
  • Children's Hospital Oakland
  • Emory University
  • Feinberg School of Medicine
  • Children's of Minnesota
  • Children's Mercy Hospital and Clinic
  • NYU School of Medicine
  • Cincinatti Children's Hospital
  • Texas Children's Hospital
  • Medical Genetics/Pediatrics
  • Children's Hospital of Wisconsin
  • Shaare Zedek Medical Center
  • Children's Memorial Health Institute
  • Hospital Universitario Miguel Servet
  • The Royal Free Hospital

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

GA-GCB (velaglucerase alfa)

Arm Description

15-60 U/kg, every other week via intravenous infusion

Outcomes

Primary Outcome Measures

Participants Who Experienced at Least One Adverse Event
Safety was assessed throughout the study by assessments including adverse events, concomitant medication use, and vital signs. Additional safety assessments, including 12-lead ECGs, physical examinations, clinical laboratory tests and determination of the presence of anti-velaglucerase alfa antibodies. Refer to Adverse event section for further details.

Secondary Outcome Measures

Change From Baseline to Week 53 in Hemoglobin Concentration
Percent Change From Baseline to Week 53 in Platelet Count
Percent Change From Baseline to Week 51 in Normalized Liver Volume
Liver volume has been normalized for percentage (%) of body weight. Liver size relative to body weight= (Liver volume [cc]/Body weight [kg])*100
Percent Change From Baseline to Week 51 in Normalized Spleen Volume
Spleen volume has been normalized for percentage (%) of body weight. Spleen size relative to body weight= (Spleen volume [cc]/Body weight [kg])*100

Full Information

First Posted
May 23, 2007
Last Updated
May 26, 2021
Sponsor
Shire
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1. Study Identification

Unique Protocol Identification Number
NCT00478647
Brief Title
Study of GA-GCB Enzyme Replacement Therapy in Type 1 Gaucher Disease Patients Previously Treated With Imiglucerase
Official Title
A Multicenter Open-Label Study of Gene-Activated® Human Glucocerebrosidase (GA-GCB) Enzyme Replacement Therapy in Patients With Type 1 Gaucher Disease Previously Treated With Imiglucerase
Study Type
Interventional

2. Study Status

Record Verification Date
May 2021
Overall Recruitment Status
Completed
Study Start Date
July 25, 2007 (Actual)
Primary Completion Date
June 26, 2009 (Actual)
Study Completion Date
June 26, 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 study is to evaluate the safety and efficacy of every other week dosing of GA-GCB (velaglucerase alfa) in participants with type 1 Gaucher disease who were previously treated with imiglucerase.
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 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 safety of GA-GCB in men, women, and children with Type 1 Gaucher disease who were previously treated with imiglucerase. Each participant's duration of treatment will be 12 months.

6. Conditions and Keywords

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

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2, Phase 3
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
40 (Actual)

8. Arms, Groups, and Interventions

Arm Title
GA-GCB (velaglucerase alfa)
Arm Type
Experimental
Arm Description
15-60 U/kg, every other week via intravenous infusion
Intervention Type
Biological
Intervention Name(s)
GA-GCB (velaglucerase alfa)
Other Intervention Name(s)
gene-activated® human glucocerebrosidase, VPRIV®, GA-GCB
Intervention Description
15-60 U/kg, every other week via intravenous infusion
Primary Outcome Measure Information:
Title
Participants Who Experienced at Least One Adverse Event
Description
Safety was assessed throughout the study by assessments including adverse events, concomitant medication use, and vital signs. Additional safety assessments, including 12-lead ECGs, physical examinations, clinical laboratory tests and determination of the presence of anti-velaglucerase alfa antibodies. Refer to Adverse event section for further details.
Time Frame
Week 53
Secondary Outcome Measure Information:
Title
Change From Baseline to Week 53 in Hemoglobin Concentration
Time Frame
Week 53
Title
Percent Change From Baseline to Week 53 in Platelet Count
Time Frame
Week 53
Title
Percent Change From Baseline to Week 51 in Normalized Liver Volume
Description
Liver volume has been normalized for percentage (%) of body weight. Liver size relative to body weight= (Liver volume [cc]/Body weight [kg])*100
Time Frame
Week 51
Title
Percent Change From Baseline to Week 51 in Normalized Spleen Volume
Description
Spleen volume has been normalized for percentage (%) of body weight. Spleen size relative to body weight= (Spleen volume [cc]/Body weight [kg])*100
Time Frame
Week 51

10. Eligibility

Sex
All
Minimum Age & Unit of Time
2 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Includes: The participant has a documented diagnosis of type 1 Gaucher disease, as determined by deficient glucocerebrosidase (GCB) activity relative to normal as measured in leukocytes or by genotype analysis and the participant/legal guardian is willing and able to provide written informed consent prior to initiating any study-related procedures The participant has received consistent treatment with imiglucerase at a dose ≤ 60 U/kg and ≥ 15 U/kg every other week for a minimum of 30 consecutive months. Participants who are anti-imiglucerase antibody positive will be allowed to enter this study The participant is at least 2 years of age Female participants of child-bearing potential agree to use a medically acceptable method of contraception. Male participants must agree to use a medically acceptable method of birth control Participant must be sufficiently co-operative to participate in the study as judged by the Investigator. Exclusion Criteria: Includes: The participant has type 2 or 3 Gaucher disease or is suspected of having type 3 Gaucher disease The participant has received treatment with any investigational drug or device within the 30 days prior to study entry; such use during the study is not permitted Participant is HIV positive Participant is hepatitis B/C positive The participant presents with sustained iron, folic acid and/or vitamin B12 deficiency-related anemia during Screening The participant, participant's parent(s), or participant's legal guardian(s) is/are unable to understand the nature, scope, and possible consequences of the study The participant has a significant comorbidity that might affect study data or confound the study results The participant is unable to comply with the protocol or is otherwise unlikely to complete the study, as determined by the Investigator The participant has experienced an anaphylactic/anaphylactoid reaction during treatment with imiglucerase The participant has received miglustat during the 6 months prior to study enrollment The participant has an active, clinically significant spleen infarction The participant has active, progressive bone necrosis The participant is a pregnant and/or lactating female
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Study Director
Organizational Affiliation
Takeda
Official's Role
Study Director
Facility Information:
Facility Name
Regional Metabolic Center
City
Los Angeles
State/Province
California
ZIP/Postal Code
90027
Country
United States
Facility Name
Children's Hospital Oakland
City
Oakland
State/Province
California
ZIP/Postal Code
94609
Country
United States
Facility Name
Emory University
City
Decatur
State/Province
Georgia
ZIP/Postal Code
30033
Country
United States
Facility Name
Feinberg School of Medicine
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60614
Country
United States
Facility Name
Children's of Minnesota
City
Minneapolis
State/Province
Minnesota
ZIP/Postal Code
55404
Country
United States
Facility Name
Children's Mercy Hospital and Clinic
City
Kansas City
State/Province
Missouri
ZIP/Postal Code
64108
Country
United States
Facility Name
NYU School of Medicine
City
New York
State/Province
New York
ZIP/Postal Code
10016
Country
United States
Facility Name
Cincinatti Children's Hospital
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45229
Country
United States
Facility Name
Texas Children's Hospital
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
Medical Genetics/Pediatrics
City
Salt Lake City
State/Province
Utah
ZIP/Postal Code
84132
Country
United States
Facility Name
Children's Hospital of Wisconsin
City
Milwaukee
State/Province
Wisconsin
ZIP/Postal Code
53226
Country
United States
Facility Name
Shaare Zedek Medical Center
City
Jerusalem
Country
Israel
Facility Name
Children's Memorial Health Institute
City
Warszawa
Country
Poland
Facility Name
Hospital Universitario Miguel Servet
City
Zaragoza
ZIP/Postal Code
500009
Country
Spain
Facility Name
The Royal Free Hospital
City
London
Country
United Kingdom

12. IPD Sharing Statement

Citations:
PubMed Identifier
23339116
Citation
Zimran A, Pastores GM, Tylki-Szymanska A, Hughes DA, Elstein D, Mardach R, Eng C, Smith L, Heisel-Kurth M, Charrow J, Harmatz P, Fernhoff P, Rhead W, Longo N, Giraldo P, Ruiz JA, Zahrieh D, Crombez E, Grabowski GA. Safety and efficacy of velaglucerase alfa in Gaucher disease type 1 patients previously treated with imiglucerase. Am J Hematol. 2013 Mar;88(3):172-8. doi: 10.1002/ajh.23383. Epub 2013 Jan 22.
Results Reference
result

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Study of GA-GCB Enzyme Replacement Therapy in Type 1 Gaucher Disease Patients Previously Treated With Imiglucerase

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