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

NCT00553631 | Completed Phase 3 Results

• 2 other identifiers: HGT-GCB-0392007-002840-21
• Study Type: interventional
• Target: 34
• Locations: 9 countries
• Sites: 11

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.

Conditions

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

Outcome Measures

Primary Outcomes (1)

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

  Baseline to Month 9

Secondary Outcomes (7)

• Change From Baseline to Month 9 in Platelet Counts for Each Treatment Group.

  Baseline to Month 9

• Change From Baseline to Month 9 in Normalized Liver Volume (Percent (%) Body Weight) for Each Treatment Group.

  Baseline to Month 9

• Change From Baseline to Month 9 in Normalized Spleen Volume (Percent (%) Body Weight) for Each Treatment Group.

  Baseline to Month 9

• Change From Baseline to Month 9 in Plasma Chitotriosidase for Each Treatment Group.

  Baseline to Month 9.

• Change From Baseline to Month 9 in Plasma Chemokine (C-C Motif) Ligand 18 (CCL18) for Each Treatment Group.

  Baseline to Month 9

Study Arms (2)

GA-GCB

EXPERIMENTAL

VPRIV™ ,velaglucerase alfa

Biological: velaglucerase alfa

imiglucerase

ACTIVE COMPARATOR

Biological: imiglucerase

Interventions

velaglucerase alfa BIOLOGICAL

IV infusion, 60 U/kg every other week for 9 months

Also known as: VPRIV™, gene-activated human glucocerebrosidase

GA-GCB

imiglucerase BIOLOGICAL

IV infusion, 60 U/kg every other week for 9 months

Also known as: Cerezyme®

imiglucerase

Eligibility Criteria

• Age: 2 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Shire: lead

Study Sites (11)

Duke Children's Hospital & Health Center

Durham, North Carolina, 27710, United States

Location

Your Health S.A.

Buenos Aires, B1882AQY, Argentina

Location

Malabar Institute of Medical Sciences Ltd.

Calicut, Kerala, 673 016, India

Location

All India Institute of Medical Sciences

New Delhi, 110 029, India

Location

KEM Hospital Research Centre

Pune, India

Location

Shaare Zedek Medical Center

Jerusalem, Israel

Location

Sociedad Espanola de Socorros Mutuos

Asunción, Paraguay

Location

National Research Center for Haematology

Moscow, Russia

Location

Hospital Universitario Miguel Servet

Zaragoza, Spain

Location

La Rabta Hospital

Tunis, Tunisia

Location

The Royal Free Hospital

London, United Kingdom

Location

Related Publications (1)

• 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.

  PMID: 27839979 DERIVED

MeSH Terms

Conditions

Gaucher Disease

Interventions

Glucosylceramidase; imiglucerase

Condition Hierarchy (Ancestors)

Sphingolipidoses; Lysosomal Storage Diseases, Nervous System; Brain Diseases, Metabolic, Inborn; Brain Diseases, Metabolic; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Lipidoses; Lipid Metabolism, Inborn Errors; Lysosomal Storage Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases; Lipid Metabolism Disorders

Intervention Hierarchy (Ancestors)

Glucosidases; Glycoside Hydrolases; Hydrolases; Enzymes; Enzymes and Coenzymes

Limitations and Caveats

Participants aged 2-4 years: 4 participants (23.5%) in imiglucerase group and 0 participants in GA-GCB group.

Results Point of Contact

• Title: Study Director
• Organization: Shire

ClinicalTransparency@shire.com

+1 866 842 5335

Study Officials

• Study Director

  Takeda

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 1, 2007
• First Posted: November 5, 2007
• Study Start: January 29, 2008
• Primary Completion: May 5, 2009
• Study Completion: May 5, 2009
• Last Updated: June 8, 2021
• Results First Posted: January 4, 2011

Record last verified: 2021-05

Locations

ES (1); IL (1); AR (1); IN (3); GB (1); US (1); RU (1); PA (1); TU (1)