A Study Comparing ATB200/AT2221 With Alglucosidase Alfa/Placebo in Adult Subjects With Late-onset Pompe Disease
Condition: Pompe Disease (Late-onset)
MeSH terms: Glycogen Storage Disease Type II
Intervention: Cipaglucosidase Alfa; Miglustat; Alglucosidase Alfa; Placebo
Intervention description: Participants received an intravenous (IV) infusion dose over a 4-hour duration every 2 weeks (Q2W).; Participants received weight-based doses 1 hour prior to cipaglucosidase alfa infusion Q2W.; Participants received an IV infusion dose over a 4-hour duration Q2W.; Miglustat matching placebo was administered orally 1 hour prior to alglucosidase alfa infusion Q2W.
Intervention MeSH terms: Miglustat
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 125.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Pompe; rhGAA

Summary:

      This is a phase 3 double-blind randomized study to study the efficacy and safety of
      intravenous ATB200 Co-administered with oral AT2221 in adult subjects with Late Onset Pompe
      Disease compared with Alglucosidase Alfa/placebo.
    

Eligibility criteria:

        Inclusion Criteria:

          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 ≥ 40 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:

               1. deficiency of GAA enzyme

               2. GAA genotyping

          5. Subject is classified as one of the following with respect to ERT status:

               1. 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

               2. 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:

               1. both screening values of 6MWD are ≥ 75 meters

               2. both screening values of 6MWD are ≤ 90% of the predicted value for healthy adults

               3. the lower value of 6MWD is within 20% of the higher value of 6MWD

        Exclusion Criteria

          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 hypersensitivity to any of the excipients in ATB200, alglucosidase alfa,
             or AT2221.

          6. 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.

          7. Subject, if female, is pregnant or breastfeeding at screening.

          8. Subject, whether male or female, is planning to conceive a child during the study.

          9. Subject does not have documentation of diagnosis of Pompe disease and refuses to
             undergo genetic testing.