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A Study of Gene-Activated® Human Glucocerebrosidase (GA-GCB) Enzyme Replacement Therapy in Gaucher Disease

Primary Purpose

Gaucher Disease, Type 1

Status

Completed

Phase

Phase 3

Locations

International

Study Type

Interventional

Intervention

VPRIV ®,

About this trial

This is an interventional treatment trial for Gaucher Disease, Type 1 focused on measuring VPRIV®, 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:

Patient 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 is willing and able to provide written informed consent prior to initiating any study-related procedures
Patient is at least 2 years of age
Patient has Gaucher disease-related anemia and
Patient has at least moderate splenomegaly or
Patient has Gaucher disease-related thrombocytopenia or
Patient has a readily palpable enlarged liver
Patient has not received treatment for Gaucher disease within 30 months prior to study entry
Female patients of child-bearing potential agree to use a medically acceptable method of contraception. Male patients must agree to use a medically acceptable method of birth control.
Patient must be sufficiently cooperative to participate in the study as judged by the Investigator.

Exclusion Criteria:

Includes:

Patient has type 2 or 3 Gaucher disease or is suspected of having type 3 Gaucher disease
Patient is antibody-positive to imiglucerase during screening or has experienced an anaphylactic reaction to imiglucerase
Patient has received treatment with any investigational drug or device within the 30 days prior to study entry
Patient is Human immunodeficiency virus (HIV) positive
Patient is hepatitis positive
Patient presents with iron, folic acid and/or vitamin B12 deficiency sustained anemia during screening
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
Patient has a significant comorbidity(ies)that might affect study data or confound the study results
Patient is a pregnant and/or lactating female
Patient is unable to comply with the protocol or is unlikely to complete the study, as determined by the Investigator

Sites / Locations

Hipolito Yrigoyen
Shaare Zedek Medical Center
Sociedad Espanola de Socorros Mutuos
National Research Center for Haematology
La Rabta Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Arm Label

VPRIV®-45 U/kg, IV, every other week

VPRIV®-60 U/kg, IV, every other week

Arm Description

VPRIV® (velaglucerase alfa, Gene Activated® human glucocerebrosidase, GA-GCB)

VPRIV® (velaglucerase alfa, Gene Activated® human glucocerebrosidase,GA-GCB)

Outcomes

Primary Outcome Measures

Change From Baseline to 12 Months in Hemoglobin Concentration for the 60 U/kg Treatment Group.

Efficacy endpoint

Secondary Outcome Measures

Change From Baseline to 12 Months in Hemoglobin Concentration in 45 U/kg Treatment Group

Change From Baseline to 12 Months in Platelet Counts for Each Treatment Group.

intent to treat (ITT) Population

Change From Baseline to 12 Months in Normalized Liver Volume (Percent Body Weight) for Each Treatment Group (Measured by Magnetic Resonance Imaging (MRI)

Liver Volume has been normalized for percentage of body weight for each treatment arm. Liver size relative to body weight = (Liver volume [cc]/Body weight [kg])*100

Change From Baseline to 12 Months in Normalized Spleen Volume (Percent Body Weight) for Each Treatment Group (Measured by Magnetic Resonance Imaging (MRI))

12 patients in the 60 U/kg group and 13 patients in the 45 U/kg group were analyzed for efficacy in the intent to treat (ITT) population. Spleen Volume has been normalized for percent of body weight for each treatment arm. Spleen size relative to body weight = (Spleen volume [cc]/Body weight [kg])*100

Percent Change From Baseline to 12 Months in Plasma Chitotriosidase for Each Treatment Group

Percent Change from Baseline to Weeks 53 by Randomized velaglucerase alfa Treatment Group - Subset of intent to treat (ITT) Population who were wild type homozygous for chitotriosidase.

Percent Change From Baseline to 12 Months in Chemokine (C-C Motif) Ligand 18 (CCL18)

Full Information

NCT ID

NCT00430625

First Posted

February 1, 2007

Last Updated

June 28, 2021

Sponsor

Shire

1. Study Identification

Unique Protocol Identification Number

NCT00430625

Brief Title

A Study of Gene-Activated® Human Glucocerebrosidase (GA-GCB) Enzyme Replacement Therapy in Gaucher Disease

Official Title

A Multicenter, Randomized, Double-Blind, Parallel Group, Two-Dose Study of Gene-Activated® Human Glucocerebrosidase (GA-GCB) Enzyme Replacement Therapy in Patients With Type 1 Gaucher Disease

Study Type

Interventional

2. Study Status

Record Verification Date

June 2021

Overall Recruitment Status

Completed

Study Start Date

February 15, 2007 (Actual)

Primary Completion Date

April 1, 2009 (Actual)

Study Completion Date

April 1, 2009 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Shire

4. Oversight

Data Monitoring Committee

5. Study Description

Brief Summary

Gaucher disease is a rare lysosomal storage disorder caused by the deficiency of the enzyme glucocerebrosidase (GCB). Due to this 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 efficacy of every other week dosing of Gene-Activated® Human Glucocerebrosidase (GA-GCB, velaglucerase alfa) at doses of 45 and 60 U/kg in treatment-naïve 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 Central Nervous System (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. 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, safety and pharmacokinetics of GA-GCB in men, women, and children with Type 1 Gaucher disease. Each patients duration of treatment was 12 months.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Gaucher Disease, Type 1

Keywords

VPRIV®, 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

ParticipantInvestigator

Allocation

Randomized

Enrollment

25 (Actual)

8. Arms, Groups, and Interventions

Arm Title

VPRIV®-45 U/kg, IV, every other week

Arm Type

Experimental

Arm Description

VPRIV® (velaglucerase alfa, Gene Activated® human glucocerebrosidase, GA-GCB)

Arm Title

VPRIV®-60 U/kg, IV, every other week

Arm Type

Experimental

Arm Description

VPRIV® (velaglucerase alfa, Gene Activated® human glucocerebrosidase,GA-GCB)

Intervention Type

Biological

Intervention Name(s)

VPRIV ®,

Other Intervention Name(s)

VPRIV®, velaglucerase alfa, GA-GCB, Gene-activated® human glucocerebrosidase

Intervention Description

Intravenous (IV) infusion, every other week via intravenous infusion for 12 months

Primary Outcome Measure Information:

Title

Change From Baseline to 12 Months in Hemoglobin Concentration for the 60 U/kg Treatment Group.

Description

Efficacy endpoint

Time Frame

Week 53

Secondary Outcome Measure Information:

Title

Change From Baseline to 12 Months in Hemoglobin Concentration in 45 U/kg Treatment Group

Time Frame

Week 53

Title

Change From Baseline to 12 Months in Platelet Counts for Each Treatment Group.

Description

intent to treat (ITT) Population

Time Frame

Week 53

Title

Change From Baseline to 12 Months in Normalized Liver Volume (Percent Body Weight) for Each Treatment Group (Measured by Magnetic Resonance Imaging (MRI)

Description

Liver Volume has been normalized for percentage of body weight for each treatment arm. Liver size relative to body weight = (Liver volume [cc]/Body weight [kg])*100

Time Frame

Week 51

Title

Change From Baseline to 12 Months in Normalized Spleen Volume (Percent Body Weight) for Each Treatment Group (Measured by Magnetic Resonance Imaging (MRI))

Description

Time Frame

Week 51

Title

Percent Change From Baseline to 12 Months in Plasma Chitotriosidase for Each Treatment Group

Description

Percent Change from Baseline to Weeks 53 by Randomized velaglucerase alfa Treatment Group - Subset of intent to treat (ITT) Population who were wild type homozygous for chitotriosidase.

Time Frame

Week 53

Title

Percent Change From Baseline to 12 Months in Chemokine (C-C Motif) Ligand 18 (CCL18)

Time Frame

Week 53

10. Eligibility

Sex

All

Minimum Age & Unit of Time

2 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Patient 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 is willing and able to provide written informed consent prior to initiating any study-related procedures Patient is at least 2 years of age Patient has Gaucher disease-related anemia and Patient has at least moderate splenomegaly or Patient has Gaucher disease-related thrombocytopenia or Patient has a readily palpable enlarged liver Patient has not received treatment for Gaucher disease within 30 months prior to study entry Female patients of child-bearing potential agree to use a medically acceptable method of contraception. Male patients must agree to use a medically acceptable method of birth control. Patient must be sufficiently cooperative to participate in the study as judged by the Investigator. Exclusion Criteria: Includes: Patient has type 2 or 3 Gaucher disease or is suspected of having type 3 Gaucher disease Patient is antibody-positive to imiglucerase during screening or has experienced an anaphylactic reaction to imiglucerase Patient has received treatment with any investigational drug or device within the 30 days prior to study entry Patient is Human immunodeficiency virus (HIV) positive Patient is hepatitis positive Patient presents with iron, folic acid and/or vitamin B12 deficiency sustained anemia during screening 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 Patient has a significant comorbidity(ies)that might affect study data or confound the study results Patient is a pregnant and/or lactating female Patient is unable to comply with the protocol or is 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

Hipolito Yrigoyen

City

Buenos Aires

Country

Argentina

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

La Rabta Hospital

City

Tunis

Country

Tunisia

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

Links:

URL

http://www.vpriv.com/

Description

Shire product Information web site

Learn more about this trial

A Study of Gene-Activated® Human Glucocerebrosidase (GA-GCB) Enzyme Replacement Therapy in Gaucher Disease

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