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

• ClinicalTrials.gov Identifier: NCT00059280
• Recruitment Status: Completed
• First Posted: April 23, 2003
• Last Update Posted: February 5, 2014
• Sponsor: Genzyme, a Sanofi Company
• Information provided by: Sanofi

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Glycogen Storage Disease Type II	Biological: Myozyme	Phase 2; Phase 3

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 16 participants
• Allocation: Randomized
• Intervention Model: Factorial Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: 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
• Study Start Date: April 2003
• Actual Primary Completion Date: June 2005
• Actual Study Completion Date: September 2005

Arms and Interventions

Arm	Intervention/treatment
Experimental: 1	Biological: Myozyme; 20 mg/kg qow or 40mg/kg qow; Other Name: Alglucosidase alfa

Outcome Measures

Primary Outcome Measures :

1. Evaluate the safety profile of MZ [ Time Frame: 52 weeks ]
2. 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 [ Time Frame: 52 weeks ]
3. Determine PK/PD profile of MZ [ Time Frame: 52 weeks ]
4. Determine effect of different doses of MZ on safety and efficacy [ Time Frame: 52 weeks ]

Eligibility Criteria

• Ages Eligible for Study: up to 26 Weeks (Child)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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.

Contacts and Locations

Locations

United States, Florida

University of Florida College of Medicine

Gainesville, Florida, United States, 32610-00266

United States, North Carolina

Duke University Medical Center

Durham, North Carolina, United States, 27710

United States, Ohio

Children's Hospital Medical Center

Cincinnati, Ohio, United States, 45229

United States, Utah

University of Utah Medical Center

Salt Lake City, Utah, United States, 84132

France

Pediatrique Hopital deBrousse

Lyon, France

Israel

Rambam Medical Center

Haifa, Israel, 31096

Taiwan

National Taiwan University Hospital

Taipei, Taiwan, 100

United Kingdom

Royal Manchester Children's Hospital

Manchester, United Kingdom

Sponsors and Collaborators

Genzyme, a Sanofi Company

Investigators

• Study Director: Medical Monitor; Genzyme, a Sanofi Company

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: Medical Monitor, Genzyme Corporation
• ClinicalTrials.gov Identifier: NCT00059280
• Other Study ID Numbers: AGLU01602
• First Posted: April 23, 2003
• Last Update Posted: February 5, 2014
• Last Verified: July 2006

Keywords provided by Sanofi:

Pompe disease; Glycogen storage disease type II; GSD-II; Acid maltase deficiency disease; Glycogenosis 2

Additional relevant MeSH terms:

Glycogen Storage Disease Type II; Glycogen Storage Disease; Disease; Lysosomal Storage Diseases, Nervous System; Brain Diseases, Metabolic, Inborn; Brain Diseases, Metabolic; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Carbohydrate Metabolism, Inborn Errors; Lysosomal Storage Diseases; Metabolic Diseases; Pathologic Processes