Clinical trial NCT00478647: Study of GA-GCB Enzyme Replacement Therapy in Type 1 Gaucher Disease Patients Previously Treated With Imiglucerase
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Gaucher Disease
Keywords: Acid beta-glucocerebrosidase
human
glucocerebrosidase
Gaucher disease
Enzyme Replacement Therapy
D-glucosyl-N-acylsphingosine glucohydrolase
glucosylceramidase
gene activation
beta-glucocerebrosidase
Lead sponsor: Takeda
Sponsor class: INDUSTRY
First posted: 2007-05-25
Enrollment: 40
Sex: ALL
Minimum age (years): 2
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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.

Eligibility 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

Primary outcomes:
measure: Participants Who Experienced at Least One Adverse Event
timeFrame: Week 53
Secondary outcomes:
measure: Change From Baseline to Week 53 in Hemoglobin Concentration
timeFrame: Week 53
measure: Percent Change From Baseline to Week 53 in Platelet Count
timeFrame: Week 53
measure: Percent Change From Baseline to Week 51 in Normalized Liver Volume
timeFrame: Week 51
measure: Percent Change From Baseline to Week 51 in Normalized Spleen Volume
timeFrame: Week 51
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Regional Metabolic Center
state: California
city: Oakland
country: United States
facility: Children's Hospital Oakland
state: California
city: Decatur
country: United States
facility: Emory University
state: Georgia
city: Chicago
country: United States
facility: Feinberg School of Medicine
state: Illinois
city: Minneapolis
country: United States
facility: Children's of Minnesota
state: Minnesota
city: Kansas City
country: United States
facility: Children's Mercy Hospital and Clinic
state: Missouri
city: New York
country: United States
facility: NYU School of Medicine
state: New York
city: Cincinnati
country: United States
facility: Cincinatti Children's Hospital
state: Ohio
city: Houston
country: United States
facility: Texas Children's Hospital
state: Texas
city: Salt Lake City
country: United States
facility: Medical Genetics/Pediatrics
state: Utah
city: Milwaukee
country: United States
facility: Children's Hospital of Wisconsin
state: Wisconsin
city: Jerusalem
country: Israel
facility: Shaare Zedek Medical Center
city: Warszawa
country: Poland
facility: Children's Memorial Health Institute
city: Zaragoza
country: Spain
facility: Hospital Universitario Miguel Servet
city: London
country: United Kingdom
facility: The Royal Free Hospital
Study officials:
affiliation: Takeda
name: Study Director
role: STUDY_DIRECTOR
References:
citation: 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.