rhGAA in Patients With Infantile-onset Glycogen Storage Disease-II (Pompe Disease)

An Open-Label, Multicenter, Multinational, Study of the Safety, Efficacy, Pharmacokinetics, and Pharmacodynamics of rhGAA Treatment in Patients Greater Than 6 Months and Less Than or Equal to 36 Months Old With Infantile-Onset GSD-II

Glycogen Storage Disease Type II ("GSD-II"; also known as Pompe disease) is caused by a deficiency of a critical enzyme in the body called acid alpha-glucosidase (GAA). Normally, GAA is used by the body's cells to break down glycogen (a stored form of sugar) within specialized structures called lysosomes. In patients with GSD-II, an excessive amount of glycogen accumulates and is stored in various tissues, especially heart and skeletal muscle, which prevents their normal function. This study is being conducted to evaluate the safety and effectiveness of recombinant human acid alpha-glucosidase (rhGAA) as a potential enzyme replacement therapy for GSD-II. Patients diagnosed with infantile-onset GSD-II who are greater than 6 months old, but less than or equal to 36 months old will be studied.

Study Overview

• Status: Completed
• Conditions: Glycogen Storage Disease Type II; Acid Maltase Deficiency Disease; Glycogenosis 2; Pompe Disease
• Intervention / Treatment: Biological: Myozyme

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• France
  • Lyon, France
    • Pediatrique Hopital de Brousse
• Israel
  • Haifa, Israel, 31096
    • Rambam Medical Center
• United Kingdom
  • Manchester, United Kingdom, M27 4 HA
    • Royal Manchester Children's Hospital
• United States
  • Florida
    • Gainesville, Florida, United States, 32610
      • University of Florida College of Medicine
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University Medical Center
  • Ohio
    • Cincinnati, Ohio, United States, 45229
      • Children's Hospital Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 years to 5 months (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• The patient or the patient's legal guardian(s) must provide written informed consent prior to any study-related procedures being performed
• The patient must have a clinical diagnosis of infantile GSD-II as defined by: (a) the patient has/had documented (in a medical record) onset of symptoms compatible with GSD-II by 12 months of age; (b) the patient has documented GAA deficiency as illustrated by an endogenous GAA activity less than or equal to 2% of the mean of the normal range as assessed in cultured skin fibroblasts; AND (c) the patient has a Left Ventricular Mass Index greater than 2 standard deviations above the mean for age
• The patient is greater than 6 months old and less than or equal to 36 months old at the time of the first dose of rhGAA
• The patient and his/her legal guardian(s) must have the ability to comply with the clinical protocol

Exclusion Criteria:

• Signs and symptoms of cardiac failure and an ejection fraction less than 40%
• Major congenital abnormality
• Clinically significant organic disease (with the exception of symptoms relating to GSD-II), including clinically significant cardiovascular, hepatic, pulmonary, neurologic, or renal disease, or other medical condition, serious intercurrent illness, or extenuating circumstance that, in the opinion of the Investigator, would preclude participation in the trial or potentially decrease survival
• Use of any investigational product within 30 days prior to study enrollment
• Received enzyme replacement therapy with GAA from any source

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1	Biological: Myozyme; 20 mg/kg to 40 mg/kg qow; Other Names: Alglucosidase alfa

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Evaluate the safety of Myozyme	52 weeks
Determine proportion of patients alive over the course of treatment	52 weeks
PK profile of MZ	52 weeks
PD profile of MZ	52 weeks

Collaborators and Investigators

• Sponsor: Genzyme, a Sanofi Company

Publications and helpful links

General Publications

• Kishnani PS, Goldenberg PC, DeArmey SL, Heller J, Benjamin D, Young S, Bali D, Smith SA, Li JS, Mandel H, Koeberl D, Rosenberg A, Chen YT. Cross-reactive immunologic material status affects treatment outcomes in Pompe disease infants. Mol Genet Metab. 2010 Jan;99(1):26-33. doi: 10.1016/j.ymgme.2009.08.003.

Study record dates

Study Major Dates

• Study Start: February 1, 2003
• Primary Completion (Actual): July 1, 2006
• Study Completion (Actual): November 1, 2006

Study Registration Dates

• First Submitted: January 31, 2003
• First Submitted That Met QC Criteria: February 1, 2003
• First Posted (Estimate): February 3, 2003

Study Record Updates

• Last Update Posted (Estimate): February 5, 2014
• Last Update Submitted That Met QC Criteria: February 4, 2014
• Last Verified: February 1, 2014

More Information

Terms related to this study

• Keywords: Glycogen Storage Disease Type II; GSD-II; Pompe Disease
• Additional Relevant MeSH Terms: Pathologic Processes; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Nutrition Disorders; Genetic Diseases, Inborn; Malnutrition; Carbohydrate Metabolism, Inborn Errors; Metabolism, Inborn Errors; Lysosomal Storage Diseases; Brain Diseases, Metabolic; Brain Diseases, Metabolic, Inborn; Lysosomal Storage Diseases, Nervous System; Disease; Metabolic Diseases; Deficiency Diseases; Glycogen Storage Disease Type II; Glycogen Storage Disease
• Other Study ID Numbers: AGLU01702