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

• ClinicalTrials.gov Identifier: NCT00478647
• Recruitment Status: Completed
• First Posted: May 25, 2007
• Results First Posted: September 2, 2010
• Last Update Posted: June 10, 2021
• Sponsor: Shire
• Information provided by (Responsible Party): Takeda ( Shire )

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.

Condition or disease	Intervention/treatment	Phase
Gaucher Disease	Biological: GA-GCB (velaglucerase alfa)	Phase 2; Phase 3

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 40 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: July 25, 2007
• Actual Primary Completion Date: June 26, 2009
• Actual Study Completion Date: June 26, 2009

Arms and Interventions

Arm	Intervention/treatment
Experimental: GA-GCB (velaglucerase alfa); 15-60 U/kg, every other week via intravenous infusion	Biological: GA-GCB (velaglucerase alfa); 15-60 U/kg, every other week via intravenous infusion; Other Names: gene-activated® human glucocerebrosidase; VPRIV®; GA-GCB

Outcome Measures

Primary Outcome Measures :

1. Participants Who Experienced at Least One Adverse Event [ Time Frame: Week 53 ]
   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 :

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

Eligibility Criteria

• Ages Eligible for Study: 2 Years and older (Child, Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

United States, California

Regional Metabolic Center

Los Angeles, California, United States, 90027

Children's Hospital Oakland

Oakland, California, United States, 94609

United States, Georgia

Emory University

Decatur, Georgia, United States, 30033

United States, Illinois

Feinberg School of Medicine

Chicago, Illinois, United States, 60614

United States, Minnesota

Children's of Minnesota

Minneapolis, Minnesota, United States, 55404

United States, Missouri

Children's Mercy Hospital and Clinic

Kansas City, Missouri, United States, 64108

United States, New York

NYU School of Medicine

New York, New York, United States, 10016

United States, Ohio

Cincinatti Children's Hospital

Cincinnati, Ohio, United States, 45229

United States, Texas

Texas Children's Hospital

Houston, Texas, United States, 77030

United States, Utah

Medical Genetics/Pediatrics

Salt Lake City, Utah, United States, 84132

United States, Wisconsin

Children's Hospital of Wisconsin

Milwaukee, Wisconsin, United States, 53226

Israel

Shaare Zedek Medical Center

Jerusalem, Israel

Poland

Children's Memorial Health Institute

Warszawa, Poland

Spain

Hospital Universitario Miguel Servet

Zaragoza, Spain, 500009

United Kingdom

The Royal Free Hospital

London, United Kingdom

Sponsors and Collaborators

Shire

Investigators

• Study Director: Study Director; Takeda

More Information

Publications of Results:

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.

• Responsible Party: Shire
• ClinicalTrials.gov Identifier: NCT00478647
• Other Study ID Numbers: TKT034; 2006-006304-11 ( EudraCT Number )
• First Posted: May 25, 2007
• Results First Posted: September 2, 2010
• Last Update Posted: June 10, 2021
• Last Verified: May 2021

Keywords provided by Takeda ( Shire ):

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

Additional relevant MeSH terms:

Gaucher Disease; 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; Lipidoses; Lipid Metabolism, Inborn Errors; Lysosomal Storage Diseases; Metabolic Diseases; Lipid Metabolism Disorders