Clinical trial NCT00954460: Treatment Protocol of Velaglucerase Alfa for Patients With Type 1 Gaucher Disease
Official title: Multicenter Open-Label Treatment Protocol to Observe the Safety of Gene-Activated™ Human Glucocerebrosidase (GA-GCB, Velaglucerase Alfa) ERT in Newly Diagnosed or Previously Treated (With Imiglucerase) Patients With Type 1 Gaucher Disease
Study type: EXPANDED_ACCESS
Overall status: APPROVED_FOR_MARKETING
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: 2009-08-07
Sex: ALL
Minimum age (years): 3
Standard ages: CHILD
ADULT
OLDER_ADULT

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 treatment protocol is to observe the safety of velaglucerase alfa in patients with type 1 Gaucher disease who are either treatment naive (newly diagnosed) or who are currently being treated with the Enzyme Replacement Therapy (ERT) imiglucerase.

Detailed description: Type 1 Gaucher disease, the most common form, accounts for more than 90% of all cases of Gaucher disease 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. Velaglucerase alfa (Gene-Activated™ human glucocerebrosidase;GA-GCB) 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. Velaglucerase alfa contains terminal mannose residues that target the enzyme to the macrophages-the primary target cells in Gaucher disease. This treatment protocol will observe the safety of velaglucerase alfa in patients with type 1 Gaucher disease who are either treatment naive (newly diagnosed) or who are currently being treated with the Enzyme Replacement Therapy (ERT) imiglucerase. Patients currently being treated with ERT for their Gaucher disease will receive the same number of units of velaglucerase alfa per month as their imiglucerase dose for doses between 30-120 U/kg/month. For patients who experienced dose reductions in their imiglucerase treatment due to supply constraints the pre-reduction monthly dose may be used to determine the monthly dose of velaglucerase alfa.

Eligibility criteria: Inclusion Criteria:

1. The patient has a documented diagnosis of type 1 Gaucher disease
2. The patient is \> 2 years of age
3. The patient has NOT previously experienced an anaphylactic or anaphylactoid reaction to another ERT including imiglucerase
4. Women of child-bearing potential must agree to use a medically acceptable method of contraception at all times during the study; and must have a negative result to a pregnancy test 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.
5. The patient is sufficiently cooperative to participate in this treatment plan as judged by the Investigator
6. If the patient is naïve or new to treatment, the patient has one or more of the following (in absence of the following criteria, please call the sponsor for treatment justification):

   * Gaucher disease-related anemia
   * Moderate splenomegaly (2 to 3 cm below the left costal margin), by palpation
   * Gaucher disease-related thrombocytopenia
   * Gaucher disease-related palpable enlarged liver

Exclusion Criteria: None

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: St Joseph's Hospital & Medical Center
state: Arizona
city: Beverly Hills
country: United States
facility: Tower Hematology Oncology
state: California
city: La Jolla
country: United States
facility: Rady's Children's Hospital of San Diego
state: California
city: Los Angeles
country: United States
facility: Southern California Permanente Medical Group
state: California
city: Sacramento
country: United States
facility: The Permanente Medical Group
state: California
city: Stanford
country: United States
facility: Stanford University Medical Genetics
state: California
city: Denver
country: United States
facility: Rocky Mountain Cancer Centers
state: Colorado
city: New Haven
country: United States
facility: Yale University
state: Connecticut
city: Coral Springs
country: United States
facility: University Research Foundation for Lysosomal Storage Diseases
state: Florida
city: Gainesville
country: United States
facility: Gainesville Hematology Oncology Associates
state: Florida
city: Orlando
country: United States
facility: Adventis Healthcare System dba Florida Hospital
state: Florida
city: Palm Harbor
country: United States
facility: East Lake Oncology
state: Florida
city: Decatur
country: United States
facility: Emory Genetics
state: Georgia
city: Chicago
country: United States
facility: Children's Memorial Hospital
state: Illinois
city: Iowa City
country: United States
facility: University of Iowa Hospitals and Clinics
state: Iowa
city: Annapolis
country: United States
facility: Annapolis Oncology Center
state: Maryland
city: Baltimore
country: United States
facility: Sinai Hospital of Baltimore
state: Maryland
city: Shrewsbury
country: United States
facility: University of Massachusetts
state: Massachusetts
city: Minneapolis
country: United States
facility: Children's Hospitals and Clinics of Minnesota
state: Minnesota
city: Kansas City
country: United States
facility: The University Research Foundation for Lysosomal Storage Diseases
state: Missouri
city: Paterson
country: United States
facility: St. Joseph's
state: New Jersey
city: Buffalo
country: United States
facility: Hemophilia Center of Western New York Incorporated
state: New York
city: Manhasset
country: United States
facility: North Shore Hematology/Oncology - Manhasset
state: New York
city: New York
country: United States
facility: New York University School of Medicine
state: New York
city: New York
country: United States
facility: Mount Sinai School of Medicine
state: New York
city: Asheville
country: United States
facility: Fullerton Genetic
state: North Carolina
city: Durham
country: United States
facility: Duke Medical Center
state: North Carolina
city: Akron
country: United States
facility: Akron Children's Hospital
state: Ohio
city: Cincinnati
country: United States
facility: Cincinnati Children's Hospital Medical Center
state: Ohio
city: Philadelphia
country: United States
facility: Children's Hospital of Philadelphia
state: Pennsylvania
city: Charlottesville
country: United States
facility: University of Virginia Health Systems
state: Virginia
city: Springfield
country: United States
facility: O & O Alpan, LLC
state: Virginia
Study officials:
affiliation: Takeda
name: Study Director
role: STUDY_DIRECTOR
References:
citation: Pastores GM, Rosenbloom B, Weinreb N, Goker-Alpan O, Grabowski G, Cohn GM, Zahrieh D. A multicenter open-label treatment protocol (HGT-GCB-058) of velaglucerase alfa enzyme replacement therapy in patients with Gaucher disease type 1: safety and tolerability. Genet Med. 2014 May;16(5):359-66. doi: 10.1038/gim.2013.154. Epub 2013 Nov 21.