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.

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.