Principal Investigator: Nicola Longo
Keywords: Pompe , Amicus , ATB200 , AT221 Department: Pediatric Genetics
IRB Number: 00117942
Specialty: Pediatric Genetics
Sub Specialties: Medical Genetics
Recruitment Status: Not yet recruiting

Contact Information

Jenny  Billy
jenny.billy@hsc.utah.edu
8015859008

Brief Summary

This is a double-blind, randomized, multicenter, international study of ATB200/AT2221 in adult subjects with late-onset Pompe disease (LOPD) who have received enzyme replacement therapy with alglucosidase alfa (ie, ERT-experienced) or who have never received ERT (ie, ERT-naïve) compared with alglucosidase alfa/placebo. As this study was initially designed to assess the effects of ATB200/AT2221 in ERT-experienced subjects who continued to receive alglucosidase alfa in Study POM-003, subjects from that study who meet the eligibility criteria for this study will make up part of the ERT-experienced study population.


The study will consist of a screening period up to 30 days, a 12-month treatment period, and a 30-day safety follow-up period. Subjects who complete this study will have the option to participate in an open-label extension study to receive ATB200/AT2221 under a separate protocol.

 

Objectives:
Primary
• To assess the efficacy of ATB200/AT2221 co-administration on ambulatory function, as measured by the 6-Minute Walk Test (6MWT), compared with alglucosidase alfa/placebo


Secondary
• To assess the efficacy of ATB200/AT2221 co-administration on pulmonary function, as measured by sitting forced vital capacity (FVC) (% predicted), compared with alglucosidase alfa/placebo

• To assess the efficacy of ATB200/AT2221 co-administration on muscle strength, compared with alglucosidase alfa/placebo
• To assess the efficacy of ATB200/AT2221 co-administration on health-related patient-reported outcomes, compared with alglucosidase alfa/placebo
• To assess the efficacy of ATB200/AT2221 co-administration on motor function, compared with alglucosidase alfa/placebo
• To assess the efficacy of ATB200/AT2221 co-administration on overall clinical impression as assessed by both physician and subject, compared with alglucosidase alfa/placebo
• To assess the safety, tolerability, and immunogenicity of ATB200/AT2221 co-administration compared with alglucosidase alfa/placebo
• To assess the effect of ATB200/AT2221 co-administration on biomarkers of muscle injury and disease substrate compared with alglucosidase alfa/placebo
• To characterize the population pharmacokinetics of ATB200 and alglucosidase alfa using plasma total acid α-glucosidase (GAA) protein level by signature peptide assay and plasma AT2221 concentration.

• To characterize the population pharmacokinetics of ATB200 and alglucosidase alfa in enzyme replacement therapy (ERT)-experienced subjects using plasma total acid α-glucosidase (GAA) protein level by signature peptide assay and plasma AT2221 concentration
• To characterize the pharmacokinetics of ATB200, alglucosidase alfa, and AT2221 in ERT-naïve subjects using noncompartmental analysis

• To explore the exposure-response relationship for ATB200/AT2221 and alglucosidase
alfa/placebo co-administration

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:(Note: None of these medications have a half-life that, when multiplied by 5, is longer than 30 days.)
    1. miglitol (eg, Glyset)
    2. miglustat (eg, Zavesca)
    3. acarbose (eg, Precose or Glucobay)
    4. voglibose (eg, Volix, Vocarb, or Volibo)
  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.