Late Onset Pompe Disease

Primary Objective • To assess the efficacy of ATB200/AT2221 co-administration on ambulatory function, as measured by the 6MWT, compared with alglucosidase alfa/placebo

AT2221/ATB200

MIGLUSTAT
RECOMBINANT HUMAN ACID ALPHA-GLUCOSIDASE

capsule
vial

65
105

Primary Efficacy Endpoint
The primary efficacy endpoint is the change from baseline to Week 52 in 6MWD.
Secondary Efficacy Endpoints
Key secondary efficacy endpoints are as follows:
• change from baseline to Week 52 in the manual muscle test score for the lower
extremities
• change from baseline to Week 52 in the total score for the PROMIS – physical
function
• change from baseline to Week 52 in the total score for the PROMIS – fatigue
• change from baseline to Week 52 in GSGC total score
• change from baseline to Week 52 in sitting FVC (% predicted)
• change from baseline to Week 26 in 6MWD

1. Subject must provide signed informed consent prior to any study-related procedures
being performed.
2. Male and female subjects are ≥ 18 years old and weigh ≥ 50 kg at screening.
3. Female subjects of childbearing potential and male subjects must agree to use medically
accepted methods of contraception during the study and for 90 days after the last dose of
study drug.
4. Subject must have a diagnosis of LOPD based on documentation of one of the following:
a. deficiency of GAA enzyme
b. GAA genotyping
c. muscle biopsy
5. Subject is classified as one of the following with respect to ERT status:
a. ERT-experienced, defined as currently receiving standard of care ERT (alglucosidase
alfa) at the recommended dose and regimen (ie, 20 mg/kg dose every 2 weeks) for
≥ 24 months
b. ERT-naïve, defined as never having received investigational or commercially
available ERT
6. Subject has a sitting FVC ≥ 30% of the predicted value for healthy adults (National
Health and Nutrition Examination Survey III) at screening.
7. Subject performs two 6MWTs at screening that are valid, as determined by the clinical
evaluator, and that meet all of the following criteria:
a. both screening values of 6MWD are ≥ 75 meters
b. both screening values of 6MWD are ≤ 90% of the predicted value for healthy adults
c. the lower value of 6MWD is within 20% of the higher value of 6MWD

1. Subject has received any investigational therapy or pharmacological treatment for Pompe
disease, other than alglucosidase alfa, within 30 days or 5 half-lives of the therapy or
treatment, whichever is longer, before Day 1 or is anticipated to do so during the study.
2. Subject has received gene therapy for Pompe disease.
3. Subject is taking any of the following prohibited medications within 30 days before
Day 1:
• miglitol (eg, Glyset)
• miglustat (eg, Zavesca)
• acarbose (eg, Precose or Glucobay)
• voglibose (eg, Volix, Vocarb, or Volibo)
Note: None of these medications have a half-life that, when multiplied by 5, is longer
than 30 days.
4. Subject requires the use of invasive or noninvasive ventilation support for > 6 hours per
day while awake.
5. Subject has a medical condition or any other extenuating circumstance that may, in the
opinion of the investigator or medical monitor, pose an undue safety risk to the subject or
may compromise his/her ability to comply with or adversely impact protocol
requirements. This includes clinical depression (as diagnosed by a psychiatrist or other
mental health professional) with uncontrolled or poorly controlled symptoms.
6. Subject, if female, is pregnant or breastfeeding at screening.
7. Subject, whether male or female, is planning to conceive a child during the study.