Clinical trial NCT00635427: An Open-Label Extension Study of GA-GCB ERT in Patients With Type 1 Gaucher Disease
Official title: An Open-Label Extension Study of Gene-Activated® Human Glucocerebrosidase (GA-GCB) Enzyme Replacement Therapy in Patients With Type 1 Gaucher Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Gaucher Disease, Type 1
Keywords: VPRIV
Enzyme Replacement Therapy
Gaucher disease
glucocerebrosidase
beta-glucocerebrosidase
Acid beta-glucocerebrosidase
glucosylceramidase
D-glucosyl-N-acylsphingosine glucohydrolase
gene activation
human
Lead sponsor: Takeda
Sponsor class: INDUSTRY
First posted: 2008-03-13
Enrollment: 95
Sex: ALL
Minimum age (years): 2
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to evaluate the long-term safety of every other week dosing of Gene-Activated® human glucocerebrosidase (GA-GCB, velaglucerase alfa) intravenously in patients with type 1 Gaucher disease.

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 long-term safety of GA-GCB in men, women, and children with Type 1 Gaucher disease.

Eligibility criteria: Inclusion Criteria:

1. The patient has completed study TKT032 or TKT034, or study HGT-GCB-039.
2. 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.
3. Male patients must agree to use a medically acceptable method of contraception at all times during the study and report a partner's pregnancy to the investigator.
4. 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).
5. The patient must be sufficiently cooperative to participate in this clinical study as judged by the Investigator

Exclusion Criteria:

1. 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.
2. The patient is pregnant or lactating.
3. 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.
4. 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.).
5. 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

Primary outcomes:
measure: Overall Summary of Treatment Emergent Adverse Events
timeFrame: Baseline to termination of study
Secondary outcomes:
measure: Change From Baseline to 24 Months in Hemoglobin Concentration for Each Treatment Group
timeFrame: Baseline to 24 months
measure: Change From Baseline to 24 Months in Platelet Counts for Each Treatment Group
timeFrame: Baseline to 24 months
measure: Change From Baseline to 24 Months in Normalized Liver Volume for Each Treatment Group
timeFrame: Baseline to 24 months
measure: Percentage Change From Baseline to 24 Months in Normalized Spleen Volume for Each Treatment Group
timeFrame: Baseline to 24 months
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Los Angeles Medical Center
state: California
city: Oakland
country: United States
facility: Children's Hospital Oakland
state: California
city: Atlanta
country: United States
facility: Emory University School of Medicine
state: Georgia
city: Chicago
country: United States
facility: Children's Memorial Hospital
state: Illinois
city: Minneapolis
country: United States
facility: Children's Hospitals and Clinics of Minnesota
state: Minnesota
city: Kansas City
country: United States
facility: Children's Mercy Hospitals & Clinics
state: Missouri
city: New York
country: United States
facility: NYU Medical Center
state: New York
city: Cincinnati
country: United States
facility: Cincinnati Children's Hospital Medical Center
state: Ohio
city: Salt Lake City
country: United States
facility: University of Utah Medical Center
state: Utah
city: Milwaukee
country: United States
facility: Children's Hospital of Wisconsin
state: Wisconsin
city: Buenos Aires
country: Argentina
facility: Your Health S.A.
city: New Delhi
country: India
facility: All India Institute of Medical Sciences
city: Pune
country: India
facility: KEM Hospital
city: Jerusalem
country: Israel
facility: Shaare Zedek Medical Center
city: Jinju
country: Korea, Republic of
facility: Gyeongsang National University Hospital
state: Gyeongsangnam-do
city: Asuncion
country: Paraguay
facility: Sociedad Espanola de Socorros Mutuos
city: Warszawa
country: Poland
facility: Instytut "Pomnik-Centrum Zdrowia Dziecka"
city: Moscow
country: Russian Federation
facility: State Institution "Hematology Research Centre RAMS"
city: Zaragoza
country: Spain
facility: Hospital Universitario Miguel Servet
city: Tunis
country: Tunisia
facility: Hospital de La Rabta
state: Jebbari
city: London
country: United Kingdom
facility: Royal Free Hospital
Study officials:
affiliation: Takeda
name: Study Director
role: STUDY_DIRECTOR
References:
citation: 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.
citation: Smith L, Rhead W, Charrow J, Shankar SP, Bavdekar A, Longo N, Mardach R, Harmatz P, Hangartner T, Lee HM, Crombez E, Pastores GM. Long-term velaglucerase alfa treatment in children with Gaucher disease type 1 naive to enzyme replacement therapy or previously treated with imiglucerase. Mol Genet Metab. 2016 Feb;117(2):164-71. doi: 10.1016/j.ymgme.2015.05.012. Epub 2015 Jun 1.
citation: Hughes DA, Gonzalez DE, Lukina EA, Mehta A, Kabra M, Elstein D, Kisinovsky I, Giraldo P, Bavdekar A, Hangartner TN, Wang N, Crombez E, Zimran A. Velaglucerase alfa (VPRIV) enzyme replacement therapy in patients with Gaucher disease: Long-term data from phase III clinical trials. Am J Hematol. 2015 Jul;90(7):584-91. doi: 10.1002/ajh.24012.