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

NCT ID: NCT00430625

Last Updated: 2021-06-29

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 25 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-02-15
• Study Completion Date: 2009-04-01

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.

Conditions

Gaucher Disease, Type 1

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

VPRIV®-45 U/kg, IV, every other week

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

Group Type: EXPERIMENTAL

VPRIV ®,

Intervention Type: BIOLOGICAL

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

VPRIV®-60 U/kg, IV, every other week

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

Group Type: EXPERIMENTAL

VPRIV ®,

Intervention Type: BIOLOGICAL

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

Interventions

VPRIV ®,

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

Intervention Type: BIOLOGICAL

Other Intervention Names

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

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

• Minimum Eligible Age: 2 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Shire

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Study Director

Role: STUDY_DIRECTOR

Takeda

Locations

Hipolito Yrigoyen

Buenos Aires, , Argentina

Shaare Zedek Medical Center

Jerusalem, , Israel

Sociedad Espanola de Socorros Mutuos

Asunción, , Paraguay

National Research Center for Haematology

Moscow, , Russia

La Rabta Hospital

Tunis, , Tunisia

Countries

Argentina; Israel; Paraguay; Russia; Tunisia

References

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.

Reference Type: DERIVED

PMID: 27839979 (View on PubMed)

Related Links

http://www.vpriv.com/

Shire product Information web site

Other Identifiers

TKT032

Identifier Type: -

Identifier Source: org_study_id