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

NCT00478647 | Completed Phase 2 Results

• 2 other identifiers: TKT0342006-006304-11
• Study Type: interventional
• Target: 40
• Locations: 5 countries
• Sites: 15

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.

Conditions

Gaucher Disease

Keywords

Acid beta-glucocerebrosidase; human; glucocerebrosidase; Gaucher disease; Enzyme Replacement Therapy; D-glucosyl-N-acylsphingosine glucohydrolase; glucosylceramidase; gene activation; beta-glucocerebrosidase

Outcome Measures

Primary Outcomes (1)

• 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.

  Week 53

Secondary Outcomes (4)

• Change From Baseline to Week 53 in Hemoglobin Concentration

  Week 53

• Percent Change From Baseline to Week 53 in Platelet Count

  Week 53

• Percent Change From Baseline to Week 51 in Normalized Liver Volume

  Week 51

• Percent Change From Baseline to Week 51 in Normalized Spleen Volume

  Week 51

Study Arms (1)

GA-GCB (velaglucerase alfa)

EXPERIMENTAL

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

Biological: GA-GCB (velaglucerase alfa)

Interventions

GA-GCB (velaglucerase alfa) BIOLOGICAL

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

Also known as: gene-activated® human glucocerebrosidase, VPRIV®, GA-GCB

GA-GCB (velaglucerase alfa)

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 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Shire: lead

Study Sites (15)

Regional Metabolic Center

Los Angeles, California, 90027, United States

Location

Children's Hospital Oakland

Oakland, California, 94609, United States

Location

Emory University

Decatur, Georgia, 30033, United States

Location

Feinberg School of Medicine

Chicago, Illinois, 60614, United States

Location

Children's of Minnesota

Minneapolis, Minnesota, 55404, United States

Location

Children's Mercy Hospital and Clinic

Kansas City, Missouri, 64108, United States

Location

NYU School of Medicine

New York, New York, 10016, United States

Location

Cincinatti Children's Hospital

Cincinnati, Ohio, 45229, United States

Location

Texas Children's Hospital

Houston, Texas, 77030, United States

Location

Medical Genetics/Pediatrics

Salt Lake City, Utah, 84132, United States

Location

Children's Hospital of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

Shaare Zedek Medical Center

Jerusalem, Israel

Location

Children's Memorial Health Institute

Warsaw, Poland

Location

Hospital Universitario Miguel Servet

Zaragoza, 500009, Spain

Location

The Royal Free Hospital

London, United Kingdom

Location

Related Publications (1)

• 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.

  PMID: 23339116 RESULT

MeSH Terms

Conditions

Gaucher Disease

Interventions

Glucosylceramidase

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

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 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 23, 2007
• First Posted: May 25, 2007
• Study Start: July 25, 2007
• Primary Completion: June 26, 2009
• Study Completion: June 26, 2009
• Last Updated: June 10, 2021
• Results First Posted: September 2, 2010

Record last verified: 2021-05

Locations

PL (1); GB (1); IL (1); US (11); ES (1)