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

Condition(s) targeted: Gaucher Disease, Type 1

Intervention: velaglucerase alfa (Gene-Activated® human glucocerebrosidase) (Biological)

Phase: Phase 2/Phase 3

Status: Recruiting

Sponsored by: Shire Human Genetic Therapies, Inc.

Official(s) and/or principal investigator(s):
Eric Crombez, M.D., Study Director, Affiliation: Shire Human Genetic Therapies, Inc.

Overall contact:
Lisa Gleavy, B.S., Phone: 617-613-4276, Email: lgleavy@shire.com

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 patients with type 1 Gaucher disease who were 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 design: Treatment, Non-Randomized, Open Label, Uncontrolled, Single Group Assignment, Safety/Efficacy Study

Primary outcome: Evaluation of safety assessments

Secondary outcome: Evaluation of hematological parameters and organomegaly

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 patient's duration of treatment will be 12 months.

Minimum age: 2 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

Inclusion Criteria:

Includes:

- The patient 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 patient/legal guardian is willing and able to provide written informed consent prior to initiating any study-related procedures

- The patient has received constant treatment with imiglucerase at a dose ≤ 60 U/kg and

≥ 15 U/kg every other week for a minimum of 30 consecutive months. Patients who are anti-imiglucerase antibody positive will be allowed to enter this study

- The patient is at least 2 years of age

- Female patients of child-bearing potential agree to use a medically acceptable method

of contraception. Male patients must agree to use a medically acceptable method of birth control

- Patient must be sufficiently co-operative to participate in the 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 investigational drug or device within the

30 days prior to study entry; such use during the study is not permitted

- Patient is HIV positive

- Patient is hepatitis B/C positive

- The patient presents with sustained iron, folic acid and/or vitamin B12

deficiency-related anemia during Screening

- 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 that might affect study data or confound the

study results

- The patient is unable to comply with the protocol or is otherwise unlikely to complete

the study, as determined by the Investigator

- The patient has experienced an anaphylactic/anaphylactoid reaction during treatment

with imiglucerase

- The patient has received miglustat during the 6 months prior to study enrollment

- The patient has an active, clinically significant spleen infarction

- The patient has active, progressive bone necrosis

- The patient is a pregnant and/or lactating female

Lisa Gleavy, B.S., Phone: 617-613-4276, Email: lgleavy@shire.com

Shaare Zedek Medical Center, Jerusalem, Israel; Recruiting
Deborah Elstein, Ph.D., Phone: 972-2-6555093, Email: elstein@szmc.org.il
Ari Zimran, MD, Principal Investigator

Children's Memorial Health Institute, Warszawa, Poland; Recruiting
Anna Pohorecka, Phone: +48 501 339 057, Email: m.pohorecka@czd.pl
Anna Tylki-Szmanska, MD, Principal Investigator

Hospital Universitario Miguel Servet, Zaragoza 500009, Spain; Recruiting
Pilar Giraldo, MD, Phone: +34 0 976765561, Ext: 1133, Email: pgiraldo@salud.aragon.es
Pilar Giraldo, M.D., Principal Investigator

The Royal Free Hospital, London, United Kingdom; Recruiting
Alan Milligan, Phone: 44-(0)2074726409, Email: Alan.milligan@royalfree.nhs.uk
Atul Mehta, MD, Principal Investigator

Children's Hospital Oakland, Oakland, California 94609, United States; Recruiting
Jo Ann Johnson, Phone: 510-428-3885, Ext: 5421, Email: jajohnson@mail.cho.org
Paul Harmatz, MD, Principal Investigator

Regional Metabolic Center, Los Angeles, California 90027, United States; Recruiting
Elizabeth Richard, Phone: 310-517-2094, Email: elizabeth.a.richard@kp.org
Rebecca Mardach, MD, Principal Investigator

Northwest Oncology Hematology Association, Coral Springs, Florida 33065, United States; Recruiting
Lisa Constantini, Phone: 954-755-1904, Email: lisa@nwoncology.com
Neal Weinreb, MD, Principal Investigator

Emory University, Decatur, Georgia 30033, United States; Recruiting
Karen A. Grinzaid, MS, CGC, Phone: 404-778-8516, Email: kgrinzaid@genetics.emory.edu
Paul Fernhoff, MD, Principal Investigator

Feinberg School of Medicine, Chicago, Illinois 60614, United States; Recruiting
Dania M. D'Achille, Phone: 773-880-4454, Email: DDAchille@childrensmemorial.org
Joel Charrow, MD, Principal Investigator

Children's Hospital Boston, Boston, Massachusetts 02115, United States; Recruiting
Ellis Neufeld, MD, Principal Investigator

Children's of Minnesota, Minneapolis, Minnesota 55404, United States; Recruiting
Nicole Hart, MS, RN, Phone: 612-813-6751, Email: nicole.hart@childrensmn.org
Margaret Heisel Kurth, MD, Principal Investigator

Children's Mercy Hospital and Clinic, Kansas City, Missouri 64108, United States; Recruiting
Andrea M Atherton, MS, CGC, Phone: 816-234-3290, Email: amatherton@cmh.edu
Laurie Smith, MD, Principal Investigator

NYU School of Medicine, New York, New York 10016, United States; Recruiting
Michelle Ford, RN, Phone: 212-263-8344, Email: michelle.ford@med.nyu.edu
Carol Fisher, RN, Phone: 212-263-8344, Email: carol.fisher@med.nyu.edu
Gregory Pastores, MD, Principal Investigator

Duke Children's Hospital and Health Center, Durham, North Carolina 27710, United States; Recruiting
Stephanie DeArmey, MHS, PA-C, Phone: 919-681-1946, Email: Dearm001@mc.duke.edu
Priya Kishnani, MD, Principal Investigator

Cincinatti Children's Hospital, Cincinnati, Ohio 45229, United States; Recruiting
Greg Grabowski, MD, Principal Investigator

Texas Children's Hospital, Houston, Texas 77030, United States; Recruiting
Claudia R. Soler, R, Phone: 832-822-4261, Email: crsoler@texaschildrens.org
Christine Eng, MD, Principal Investigator

Medical Genetics/Pediatrics, Salt Lake City, Utah 84132, United States; Recruiting
Carrie Ashurst, Phone: 801-587-3605, Email: Carrie.Ashurst@hsc.utah.edu
Nicola Longo, MD, Principal Investigator

Children's Hospital of Wisconsin, Milwaukee, Wisconsin 53226, United States; Recruiting
Patricia D. Chico, Phone: 414-226-3289, Email: pchico@mcw.edu
William J Rhead, MD, Principal Investigator

Starting date: July 2007
Ending date: July 2009
Last updated: May 28, 2008