A Study of the Safety and Efficacy of rhGAA in Patients With Infantile-onset Pompe Disease

An Open-label, Multicenter, Multinational Study of the Safety, Efficacy, Pharmacokinetics, and Pharmacodynamics of Recombinant Human Acid Alpha-glucosidase Treatment in Patients Less Than 6 Months Old With Infantile-onset Pompe Disease

Pompe disease (also known as glycogen storage disease type II, "GSD-II") 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 Pompe disease, 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 Pompe disease. Patients diagnosed with infantile-onset Pompe disease who are less than or equal to 6 months old will be studied.

Study Overview

• Status: Completed
• Conditions: Glycogen Storage Disease Type II
• Intervention / Treatment: Biological: Myozyme

• Study Type: Interventional
• Enrollment (Actual): 16
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• France
  • Lyon, France
    • Pediatrique Hopital deBrousse
• Israel
  • Haifa, Israel, 31096
    • Rambam Medical Center
• Taiwan
  • Taipei, Taiwan, 100
    • National Taiwan University Hospital
• United Kingdom
  • Manchester, United Kingdom
    • Royal Manchester Children's Hospital
• United States
  • Florida
    • Gainesville, Florida, United States, 32610-00266
      • 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
  • Utah
    • Salt Lake City, Utah, United States, 84132
      • University of Utah Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 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 clinical symptoms (documented in his or her medical record) of infantile-onset Pompe disease. In addition, the patient must have: a. an endogenous GAA activity less than 1% of the mean of the normal range as assessed in cultured skin fibroblasts; AND b. cardiomyopathy (LVMI greater than 65 g/m2) by echocardiography;
• The patient must be no older than 26 weeks and 0 days, when he/she receives 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:

• Symptoms of respiratory insufficiency, including: a. Oxygen saturation less than 90% in room air as measured by pulse oximetry; OR b. venous PCO2 greater than 55 mmHg on room air OR arterial PCO2 greater than 40 mmHg on room air; c. any ventilator use at the time of enrollment;
• Major congenital abnormality;
• Clinically significant organic disease (with the exception of symptoms relating to Pompe disease), 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: RANDOMIZED
• Interventional Model: FACTORIAL
• Masking: NONE

Number of Arms

1

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Evaluate the safety profile of MZ	52 weeks
To estimate the proportion of patients treated w/ MZ who were alive and free of ventilator support at 12 months of age; compared to historical cohort	52 weeks
Determine PK/PD profile of MZ	52 weeks
Determine effect of different doses of MZ on safety and efficacy	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: April 1, 2003
• Primary Completion (ACTUAL): June 1, 2005
• Study Completion (ACTUAL): September 1, 2005

Study Registration Dates

• First Submitted: April 22, 2003
• First Submitted That Met QC Criteria: April 22, 2003
• First Posted (ESTIMATE): April 23, 2003

Study Record Updates

• Last Update Posted (ESTIMATE): February 5, 2014
• Last Update Submitted That Met QC Criteria: February 4, 2014
• Last Verified: July 1, 2006

More Information

Terms related to this study

• Keywords: GSD-II; Glycogenosis 2; Pompe disease; Glycogen storage disease type II; Acid maltase deficiency disease
• Additional Relevant MeSH Terms: Pathologic Processes; Metabolic Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Genetic Diseases, Inborn; Carbohydrate Metabolism, Inborn Errors; Metabolism, Inborn Errors; Lysosomal Storage Diseases; Brain Diseases, Metabolic; Brain Diseases, Metabolic, Inborn; Lysosomal Storage Diseases, Nervous System; Disease; Glycogen Storage Disease Type II; Glycogen Storage Disease
• Other Study ID Numbers: AGLU01602