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

• ClinicalTrials.gov Identifier: NCT00553631
• Recruitment Status: Completed
• First Posted: November 4, 2007
• Results First Posted: January 4, 2011
• Last Update Posted: June 8, 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 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.

Condition or disease	Intervention/treatment	Phase
Gaucher Disease, Type 1	Biological: velaglucerase alfa; Biological: imiglucerase	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 (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 and safety of GA-GCB (velaglucerase alfa) in comparison to imiglucerase in men, women, and children with Type 1 Gaucher disease.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 34 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Multicenter, Randomized, Double-Blind, Parallel-Group Study of Gene-Activated® Human Glucocerebrosidase (GA-GCB) Enzyme Replacement Therapy Compared With Imiglucerase in Patients With Type I Gaucher Disease
• Actual Study Start Date: January 29, 2008
• Actual Primary Completion Date: May 5, 2009
• Actual Study Completion Date: May 5, 2009

Arms and Interventions

Arm	Intervention/treatment
Experimental: GA-GCB; VPRIV™ ,velaglucerase alfa	Biological: velaglucerase alfa; IV infusion, 60 U/kg every other week for 9 months; Other Names: VPRIV™; gene-activated human glucocerebrosidase
Active Comparator: imiglucerase	Biological: imiglucerase; IV infusion, 60 U/kg every other week for 9 months; Other Name: Cerezyme®

Outcome Measures

Primary Outcome Measures :

1. Mean Change From Baseline to Month 9 in Hemoglobin (Hgb) Concentration for Each Treatment Group. [ Time Frame: Baseline to Month 9 ]

Secondary Outcome Measures :

1. Change From Baseline to Month 9 in Platelet Counts for Each Treatment Group. [ Time Frame: Baseline to Month 9 ]
   Values shown are observed change from Baseline to Month 9.
2. Change From Baseline to Month 9 in Normalized Liver Volume (Percent (%) Body Weight) for Each Treatment Group. [ Time Frame: Baseline to Month 9 ]
   Values shown are observed change from Baseline to Month 9. Measured by Magnetic resonance imaging (MRI). Liver volume has been normalized for percent (%) body weight for each treatment arm. Liver size relative to body weight = (Liver volume [cubic centimeter (cc)]/Body weight [kg]*1000.
3. Change From Baseline to Month 9 in Normalized Spleen Volume (Percent (%) Body Weight) for Each Treatment Group. [ Time Frame: Baseline to Month 9 ]
   Values shown are observed change from Baseline to month 9. Measured by Magnetic resonance imaging (MRI). Spleen volume was normalized for percent (%) of body weight for each treatment arm. Spleen size relative to body weight=(Spleen volume [cc]/Body weight [kg])*100.
4. Change From Baseline to Month 9 in Plasma Chitotriosidase for Each Treatment Group. [ Time Frame: Baseline to Month 9. ]
   Values shown are observed change from Baseline to Month 9. Units of measure is defined as nanomole per milliliter per hour.
5. Change From Baseline to Month 9 in Plasma Chemokine (C-C Motif) Ligand 18 (CCL18) for Each Treatment Group. [ Time Frame: Baseline to Month 9 ]
   Values shown are observed change from Baseline to Month 9.
6. Number of Participants Who Developed Antibody for Each Treatment Group. [ Time Frame: Baseline to Month 9 ]
   Measure type is actual number of participants who developed antibodies to treatment; GA-GCB or imiglucerase. Antibody detection was based upon serum samples collected at various time points throughout the study. Serum samples were screened using an enzyme-linked immunosorbent assay (ELISA) and positive antibody confirmation was determined using a radioimmunoprecipitation assay (RIP); positive samples were also tested for enzyme neutralizing activity. Participant samples were compared to internal assay controls (positive/negative), positive samples were determined based upon individual assay criteria.
7. Time to Response- Comparison of GA-GCB and Imiglucerase on the Earliest Time to Respond as Assessed Via Hemoglobin Concentration [ Time Frame: Response rate at Month 9 compared to Baseline ]
   Time to response was defined as a ≥ 1 g/dL improvement in hemoglobin levels relative to Baseline. Units (%) correlates to the percentage of participants who had a change of ≥ 1 g/dL improvement in hemoglobin levels relative to Baseline during their participation in the study.

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 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.

Exclusion Criteria

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.

Contacts and Locations

Locations

United States, North Carolina

Duke Children's Hospital & Health Center

Durham, North Carolina, United States, 27710

Argentina

Your Health S.A.

Buenos Aires, Argentina, B1882AQY

India

Malabar Institute of Medical Sciences Ltd.

Calicut, Kerala, India, 673 016

All India Institute of Medical Sciences

New Delhi, India, 110 029

KEM Hospital Research Centre

Pune, India

Israel

Shaare Zedek Medical Center

Jerusalem, Israel

Paraguay

Sociedad Espanola de Socorros Mutuos

Asuncion, Paraguay

Russian Federation

National Research Center for Haematology

Moscow, Russian Federation

Spain

Hospital Universitario Miguel Servet

Zaragoza, Spain

Tunisia

La Rabta Hospital

Tunis, Tunisia

United Kingdom

The Royal Free Hospital

London, United Kingdom

Sponsors and Collaborators

Shire

Investigators

• Study Director: Study Director; Takeda

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: Shire
• ClinicalTrials.gov Identifier: NCT00553631
• Other Study ID Numbers: HGT-GCB-039; 2007-002840-21 ( EudraCT Number )
• First Posted: November 4, 2007
• Results First Posted: January 4, 2011
• Last Update Posted: June 8, 2021
• Last Verified: May 2021

Keywords provided by Takeda ( Shire ):

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

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