ZIP Study - A Study to Evaluate the PK, Safety, Efficacy, and PD With ATB200/AT2221 in LOPD Subjects Aged 12 to <18

This is a Phase 3, open-label, uncontrolled, multicenter study to evaluate the PK, safety, efficacy, and PD of ATB200/AT2221 treatment in pediatric subjects aged 12 to < 18 years with LOPD. Enzyme replacement therapy (ERT)-experienced subjects are those who have received at least 1 dose of alglucosidase alfa prior to enrolling in this study.

The study will consist of a 30-day screening period, a 12-month treatment period, and a 30-day safety follow-up period, for a total duration of approximately 14 months. Subjects who complete this study may have an opportunity to enroll in a separate long-term extension study.

Pediatric subjects will be treated every other week with oral AT2221 followed by ATB200 IV. Subjects will undergo PK assessments at Day 1, Week 26, and Week 52.

Safety assessments include monitoring of adverse events, clinical laboratory tests, physical examinations, vital signs, echocardiograms, 12-lead electrocardiogram (ECG), and detection of ATB200 antibodies. Efficacy assessments include evaluation of ambulatory function (6-Minute Walk Test [6MWT]); motor function tests; muscle strength; pulmonary function tests; Patient-reported Outcomes Measurement Information System (PROMIS®) for dyspnea, fatigue, physical functioning, and upper extremity; Gross Motor Function Measure-88 Items (GMFM-88); Pompe-pediatric Evaluation of Disability Inventory (PompePedi); Subject/Physician Global Impression of Change (SGIC/PGIC); Visual Analog Scale (VAS) for pain assessment, and time to initiation of use of assistive device. The patient-reported outcomes are to be completed if available. Pharmacodynamic (PD) assessments include measurement of serum creatine kinase (CK) levels and urinary hexose tetrasaccharide (Hex4) levels.