Purpose

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.

Condition

Eligibility

Eligible Ages
Over 18 Years
Eligible Genders
All
Accepts Healthy Volunteers
No

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:
  5. deficiency of GAA enzyme
  6. GAA genotyping
  7. Subject is classified as one of the following with respect to ERT status:
  8. 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
  9. ERT-naïve, defined as never having received investigational or commercially available ERT
  10. Subject has a sitting FVC ≥ 30% of the predicted value for healthy adults (National Health and Nutrition Examination Survey III) at screening.
  11. Subject performs two 6MWTs at screening that are valid, as determined by the clinical evaluator, and that meet all of the following criteria:
  12. both screening values of 6MWD are ≥ 75 meters
  13. both screening values of 6MWD are ≤ 90% of the predicted value for healthy adults
  14. 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:
  4. miglitol (eg, Glyset)
  5. miglustat (eg, Zavesca)
  6. acarbose (eg, Precose or Glucobay)
  7. 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.

Study Design

Phase
Phase 3
Study Type
Interventional
Allocation
Randomized
Intervention Model
Parallel Assignment
Primary Purpose
Treatment
Masking
Double (Participant, Investigator)
Masking Description
Double-blind masking

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
ATB200/AT2221
Participants received ATB200 co-administered with AT2221 capsule (Miglustat)
  • Drug: AT2221
    Participants received ATB200 co-administered with AT2221 (Miglustat)
    Other names:
    • Miglustat
  • Biological: ATB200
    Enzyme Replacement Therapy via intravenous infusion
Active Comparator
alglucosidase alfa/placebo
Participants received alglucosidase alfa co-administered with placebo capsules.
  • Biological: alglucosidase alfa
    alglucosidase alfa via intravenous infusion as prescribed by the participant's treating physician and in accordance with the approved prescribing information via intravenous infusion as prescribed by the participant's treating physician and in accordance with the approved prescribing information

Recruiting Locations

Neuromuscular Research Center
Phoenix, Arizona 85028

University of Arkansas for Medical Sciences
Little Rock, Arkansas 72205

University of California, Irvine
Irvine, California 92868

UF Helath: University of Florida Clinical Research Center
Gainesville, Florida 32610

University of South Florida Research Center
Tampa, Florida 33612

Emory Clinic
Atlanta, Georgia 30322

University of Kansas Medical Center
Kansas City, Kansas 66205

University of Minnesota Clinical Research Unit
Minneapolis, Minnesota 55455

Washington University School of Medicine
Saint Louis, Missouri 63110

Billings Clinic
Billings, Montana 59101

Hackensack University Medical Center
Hackensack, New Jersey 07601

The Feinstein Institute for Medical Research
Manhasset, New York 11030

NYU School of Medicine
New York, New York 10017

Duke University Medical Center
Durham, North Carolina 27710

University of Cincinnati Neurology
Cincinnati, Ohio 45219

Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio 45229

The Ohio State University Wexner Medical Center
Columbus, Ohio 43210

Oregon Health & Science University
Portland, Oregon 97239

Penn State Health Milton S. Hershey Medical Center
Hershey, Pennsylvania 17033

University of Pennsylvania
Philadelphia, Pennsylvania 19104

University of Pittsburgh
Pittsburgh, Pennsylvania 15213

University of Texas Health Science Center San Antonio
San Antonio, Texas 78229

University of Utah, Center for Clinical and Translational Sciences
Salt Lake City, Utah 84108

Lysosomal and Rare Disorders Research
Fairfax, Virginia 22030

More Details

NCT ID
NCT03729362
Status
Recruiting
Sponsor
Amicus Therapeutics

Study Contact

For Site
609-662-2000
PompeSiteInfo@amicusrx.com

Detailed Description

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.

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.

Enzyme replacement therapy-experienced subjects will continue to take alglucosidase alfa during the screening period; treatment with alglucosidase alfa will then be replaced by study drug (ATB200/AT2221 or alglucosidase alfa/placebo) on the same schedule without interruption (ie, every 2 weeks).

Infusion visits will be scheduled every 2 weeks throughout the study; assessments (eg, clinical laboratory tests) for initial safety monitoring will be performed at these visits for the first 6 weeks of the study. Study visits that include efficacy, safety, and other assessments will be scheduled approximately every 3 months and may occur over 2 days, provided all study assessments and procedures (with the exception of pharmacokinetic [PK] sample collection) are performed before administration of study drug.

Efficacy assessments (ie, functional assessments) include evaluation of ambulatory function (6MWT), motor function tests (Gait, Stair, Gower, and Chair maneuver [GSGC] test and Timed Up and Go [TUG] test), muscle strength (manual muscle testing and quantitative muscle testing), and pulmonary function tests (forced vital capacity [FVC], slow vital capacity [SVC], maximal inspiratory pressure [MIP], maximal expiratory pressure [MEP], and sniff nasal inspiratory pressure [SNIP]). Patient reported outcomes (Rasch-built Pompe-specific Activity [R PAct] Scale, EuroQol 5 Dimensions 5 Levels Instrument [EQ-5D-5L], Patient-Reported Outcomes Measurement Information System [PROMIS®] instruments for physical function, fatigue, dyspnea, and upper extremity, and Subject's Global Impression of Change). The Physician's Global Impression of Change will also be performed.

Pharmacodynamic assessments include measurement of biomarkers of muscle injury (creatine kinase [CK]) and disease substrate (urinary hexose tetrasaccharide [Hex4]). Blood samples will be collected for determination of total GAA protein levels and AT2221 concentrations in plasma for a population PK analysis. Safety assessments include monitoring of adverse events (AEs), including infusion associated reactions (IARs), clinical laboratory tests (chemistry, hematology, and urinalysis), vital signs, physical examinations including weight, electrocardiograms (ECGs), and immunogenicity. Concomitant medications and nondrug therapies will also be recorded.

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.