Pompe disease, also known as Type II glycogen storage disease or acid maltase deficiency, is an autosomal recessive genetic disorder caused by the deficiency of the glycogen degrading enzyme acid a-glucosidase (GAA). This enzyme deficiency results in lysosomal accumulation of glycogen in skeletal and cardiac muscle, leading to disruption of cellular function. Patients with the most common form of Pompe disease, infantile-onset, exhibit progressive muscle degeneration and hypertrophic cardiomyopathy leading to death usually before 1 year of age. There is currently no therapy for Pompe disease. The overall goal of this study to evaluate the safety and effectiveness of the recombinant acid alpha-glucosidase (rhGAA) in the treatment of infantile-onset Pompe Disease. Specific primary objectives of this study are as follows: 1) To determine the treatment emergent signs and symptoms in infants less than 12 months of age treated for 3 months with a twice weekly intravenous dose of rhGAA anticipated to exceed the minimum effective dose. 2) To determine the clinical effect of rhGAA on skeletal muscle strength, pulmonary function, and heart function. The proposed study consists of a Screening Phase, a 13-week Treatment Phase, and a Follow-On Treatment Phase. During the Screening Phase the general clinical status of the patient will be determined; in addition, GAA and glycogen levels will be determined in skeletal muscle biopsy sample. In the Treatment Phase, patients will receive intravenous infusion of rhGAA twice each week. During this phase of the study patients will be closely monitored for treatment emergent signs and symptoms, and the impact of rhGAA administration on clinical progression of Pompe disease will be evaluated. Weekly monitoring will include assessment of weight gain and muscle strength, and complete urinalysis, hematology, and clinical chemistry analyses. Cardiac function will be closely monitored via echocardiography at weeks 2 through 5, and at weeks 7, 9, 11 and 13. Pulmonary function will be monitored monthly. Determinations of serum immunogenic response to rhGAA infusion will be performed at weeks 2, 4, 8 and 13. Additionally, the serum pharmacokinetic parameters of rhGAA will be evaluated. At the conclusion of this phase, rhGAA in muscle biopsy will again be determined for comparison to baseline. If rhGAA is effectively taken up in skeletal muscle and there is evidence of clinical improvement in the absence of adverse experiences, infants in this trial will continue to receive rhGAA therapy and ultimately be carried over into a Phase 3 study which will escalate or reduce the rhGAA dose based upon evaluation of treatment assessments acquired in the Phase 1/2 study.
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