A Study Comparing ATB200/AT2221 With Alglucosidase Alfa/Placebo in Adult Subjects With Late-onset Pompe Disease

NCT03729362 | Completed Phase 3 Results DMC FDA Drug

• 1 other identifier: ATB200-03
• Study Type: interventional
• Target: 125
• Locations: 23 countries
• Sites: 72

Brief 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.

Conditions

Pompe Disease (Late-onset)

Keywords

Pompe; rhGAA

Outcome Measures

Primary Outcomes (1)

• Change From Baseline to Week 52 in 6 Minute Walk Distance (6MWD)

  The efficacy of cipaglucosidase alfa/miglustat co-administration on ambulatory function was measured by the 6MWT. The 6MWD, measured in meters, is the distance walked on the 6MWT. A greater distance indicated greater endurance. An increase from baseline indicated improvement.

  Baseline, Week 52

Secondary Outcomes (32)

• Change From Baseline to Week 52 in Sitting Forced Vital Capacity (FVC; % Predicted)

  Baseline, Week 52

• Change From Baseline to Week 52 in the Manual Muscle Test (MMT) Score for the Lower Extremities

  Baseline, Week 52

• Change From Baseline to Week 26 in 6MWD

  Baseline, Week 26

• Change From Baseline to Week 52 in the Total Score for the Patient- Reported Outcomes Measurement Information System (PROMIS®) - Physical Function

  Baseline, Week 52

• Change From Baseline to Week 52 in the Total Score for the PROMIS® - Fatigue

  Baseline, Week 52

Study Arms (2)

Cipaglucosidase Alfa/Miglustat

EXPERIMENTAL

Participants received cipaglucosidase alfa co-administered with miglustat every 2 weeks (Q2W).

Biological: Cipaglucosidase Alfa; Drug: Miglustat

Alglucosidase Alfa/Placebo

ACTIVE COMPARATOR

Participants received alglucosidase alfa co-administered with placebo Q2W.

Biological: Alglucosidase Alfa; Drug: Placebo

Interventions

Cipaglucosidase Alfa BIOLOGICAL

Participants received an intravenous (IV) infusion dose over a 4-hour duration every 2 weeks (Q2W).

Also known as: ATB200

Cipaglucosidase Alfa/Miglustat

Miglustat DRUG

Participants received weight-based doses 1 hour prior to cipaglucosidase alfa infusion Q2W.

Also known as: AT2221

Cipaglucosidase Alfa/Miglustat

Alglucosidase Alfa BIOLOGICAL

Participants received an IV infusion dose over a 4-hour duration Q2W.

Also known as: Myozyme

Alglucosidase Alfa/Placebo

Placebo DRUG

Miglustat matching placebo was administered orally 1 hour prior to alglucosidase alfa infusion Q2W.

Alglucosidase Alfa/Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subject must provide signed informed consent prior to any study-related procedures being performed.
• Male and female subjects are ≥ 18 years old and weigh ≥ 40 kg at screening.
• 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.
• Subject must have a diagnosis of LOPD based on documentation of one of the following:
• deficiency of GAA enzyme
• GAA genotyping
• Subject is classified as one of the following with respect to ERT status:
• 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
• ERT-naïve, defined as never having received investigational or commercially available ERT
• Subject has a sitting FVC ≥ 30% of the predicted value for healthy adults (National Health and Nutrition Examination Survey III) at screening.
• Subject performs two 6MWTs at screening that are valid, as determined by the clinical evaluator, and that meet all of the following criteria:
• both screening values of 6MWD are ≥ 75 meters
• both screening values of 6MWD are ≤ 90% of the predicted value for healthy adults
• the lower value of 6MWD is within 20% of the higher value of 6MWD

You may not qualify if:

• 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.
• Subject has received gene therapy for Pompe disease
• 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.
• Subject requires the use of invasive or noninvasive ventilation support for \> 6 hours per day while awake.
• Subject has a hypersensitivity to any of the excipients in ATB200, alglucosidase alfa, or AT2221.
• 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.
• Subject, if female, is pregnant or breastfeeding at screening.
• Subject, whether male or female, is planning to conceive a child during the study.
• Subject does not have documentation of diagnosis of Pompe disease and refuses to undergo genetic testing.

Sponsors & Collaborators

• Amicus Therapeutics: lead

Study Sites (73)

Neuromuscular Research Center

Phoenix, Arizona, 85028, United States

Location

University of Arkansas for Medical Sciences

Little Rock, Arkansas, 72205, United States

Location

University of California, Irvine

Irvine, California, 92868, United States

Location

UF Helath: University of Florida Clinical Research Center

Gainesville, Florida, 32610, United States

Location

University of South Florida Research Center

Tampa, Florida, 33612, United States

Location

Emory Clinic

Atlanta, Georgia, 30322, United States

Location

Indiana University Health Neuroscience Center

Indianapolis, Indiana, 46202, United States

Location

University of Kansas Medical Center

Kansas City, Kansas, 66205, United States

Location

University of Minnesota Clinical Research Unit

Minneapolis, Minnesota, 55455, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Billings Clinic

Billings, Montana, 59101, United States

Location

Hackensack University Medical Center

Hackensack, New Jersey, 07601, United States

Location

The Feinstein Institute for Medical Research

Manhasset, New York, 11030, United States

Location

NYU School of Medicine

New York, New York, 10017, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

University of Cincinnati Neurology

Cincinnati, Ohio, 45219, United States

Location

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229, United States

Location

The Ohio State University Wexner Medical Center

Columbus, Ohio, 43210, United States

Location

Oregon Health & Science University

Portland, Oregon, 97239, United States

Location

Penn State Health Milton S. Hershey Medical Center

Hershey, Pennsylvania, 17033, United States

Location

University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

University of Pittsburgh

Pittsburgh, Pennsylvania, 15213, United States

Location

University of Texas Health Science Center San Antonio

San Antonio, Texas, 78229, United States

Location

University of Utah, Center for Clinical and Translational Sciences

Salt Lake City, Utah, 84108, United States

Location

Lysosomal and Rare Disorders Research

Fairfax, Virginia, 22030, United States

Location

Hospital Universitario Austral

Buenos Aires, B1629ODT, Argentina

Location

Royal Brisbane & Women's Hospital

Herston, Queensland, 4029, Australia

Location

Royal Adelaide Hospital

Adelaide, South Australia, 5000, Australia

Location

Monash Medical Centre

Melbourne, Victoria, 3168, Australia

Location

Westmead Hospital

Westmead, 2145, Australia

Location

Medizinische Universität Innsbruck

Innsbruck, Austria

Location

UZ Leuven

Leuven, 3000, Belgium

Location

University Clinical Centre of the Republic of Srpska

Banja Luka, 78000, Bosnia and Herzegovina

Location

UMHAT Alexandrovska

Sofia, Bulgaria

Location

Heritage Medical Research Clinic, University of Calgary

Calgary, Alberta, T2N 4Z6, Canada

Location

McMaster University Medical Centre

Hamilton, Ontario, L8N 3Z5, Canada

Location

Aarhus Universitets Hospital

Aarhus N, 8200, Denmark

Location

Rigshospitalet Copenhagen Neuromuscular Center

Copenhagen, 2100, Denmark

Location

Hôpital Neurologique Pierre Wertheimer

Bron, 69677, France

Location

Hôpital Raymond Poincaré

Garches, 92380, France

Location

Hôpital Salengro

Lille, 59037, France

Location

Hôpital de la Timone

Marseille, 13385, France

Location

Hôpital Pasteur

Nice, 06001, France

Location

Friedrich-Baur Institut

Munich, Bavaria, 80336, Germany

Location

Universitätsklinikum Bonn

Bonn, North Rhine-Westphalia, 53105, Germany

Location

Universitätsklinikum Münster

Münster, North Rhine-Westphalia, 48149, Germany

Location

Universitätsklinikum Halle (Saale)

Halle, Saxony-Anhalt, 06120, Germany

Location

Eginition Hospital

Athens, Attica, 11528, Greece

Location

Semmelweis University, Institute of Genomic Medicine and Rare Disease

Budapest, 1083, Hungary

Location

University of Pécs

Pécs, 7623, Hungary

Location

University of Szeged

Szeged, 6725, Hungary

Location

UOC di Neurologia e Malattie Neuromuscolari

Messina, NAP, 98125, Italy

Location

UOC Genetica Medica

Napoli, NAP, 80131, Italy

Location

Hokkaido University Hospital

Sapporo, Hokkaido, 060 8648, Japan

Location

Fukuoka University Hospital

Fukuoka, 814-0180, Japan

Location

Kagoshima University Hospital

Kagoshima, Japan

Location

Izumi City General Hospital

Osaka, Japan

Location

The Jikei University Hospital

Tokyo, 105-8471, Japan

Location

National Center of Neurology and Psychiatry

Tokyo, Japan

Location

Erasmus MC

Rotterdam, 3015GD, Netherlands

Location

University of Auckland

Auckland, New Zealand

Location

Szpital Uniwersytecki w Krakowie

Małogoskie, 31-066, Poland

Location

Centrum Medyczne

Rzeszów, 35-326, Poland

Location

University Medical Centre Ljubljana

Ljubljana, 1000, Slovenia

Location

Pusan National University

Yangsan, Gyeongsangnam-do, 50612, South Korea

Location

Seoul National University Hospital

Seoul, 03080, South Korea

Location

Hospital de la Santa Creu I Sant Pau

Barcelona, 08026, Spain

Location

Sahlgrenska University Hospital

Gothenburg, 41345, Sweden

Location

National Taiwan University Hospital

Taipei, 100, Taiwan

Location

Queen Elizabeth Hospital Birmingham

Birmingham, United Kingdom

Location

Cambridge University Hospitals

Cambridge, United Kingdom

Location

Royal Free Hospital NHS

London, NW3 2QG, United Kingdom

Location

Salford Royal NHS Foundation Trust

Salford, M6 8HD, United Kingdom

Location

Related Publications (6)

• Andersen H, Diaz-Manera J, Goker-Alpan O, Mozaffar T, Sitaraman Das S, Fox B, Amon F, O'Brien-Prince K, Goldman M, Holdbrook F, Jain V, Byrne BJ. Safety of home administration of cipaglucosidase alfa plus miglustat in late-onset Pompe disease: results from multiple clinical trials. Ther Adv Rare Dis. 2026 Jan 31;7:26330040261416943. doi: 10.1177/26330040261416943. eCollection 2026 Jan-Dec.

  PMID: 41631150 DERIVED

• Kushlaf H, Diaz-Manera J, Bratkovic D, Byrne BJ, Claeys KG, Clemens PR, Dimachkie MM, Kishnani PS, Laforet P, Roberts M, Schoser B, Toscano A, Castelli J, Holdbrook F, Sitaraman Das S, Goldman M, Mozaffar T; PROPEL Study Group. Switching Enzyme Replacement Therapy for Late-Onset Pompe Disease From Alglucosidase Alfa to Cipaglucosidase Alfa Plus Miglustat: Post Hoc Effect Size Analysis of PROPEL. Muscle Nerve. 2025 Aug;72(2):230-239. doi: 10.1002/mus.28420. Epub 2025 May 7.

  PMID: 40342075 DERIVED

• Kishnani PS, Byrne BJ, Claeys KG, Diaz-Manera J, Dimachkie MM, Kushlaf H, Mozaffar T, Roberts M, Schoser B, Hummel N, Kopiec A, Holdbrook F, Shohet S, Toscano A; PROPEL Study Group. Switching treatment to cipaglucosidase alfa plus miglustat positively affects patient-reported outcome measures in patients with late-onset Pompe disease. J Patient Rep Outcomes. 2024 Nov 13;8(1):132. doi: 10.1186/s41687-024-00805-w.

  PMID: 39535661 DERIVED

• MacCulloch A, Griffiths A, Johnson N, Shohet S. Health-Related Quality-of-Life Utility Values in Adults With Late-Onset Pompe Disease: Analyses of EQ-5D Data From the PROPEL Clinical Trial. J Health Econ Outcomes Res. 2024 Sep 18;11(2):80-85. doi: 10.36469/001c.121928. eCollection 2024.

  PMID: 39318718 DERIVED

• Kishnani PS, Shohet S, Raza S, Hummel N, Castelli JP, Sitaraman Das S, Jiang H, Kopiec A, Keyzor I, Hahn A. Validation of the Patient-Reported Outcomes Measurement Information System (PROMIS(R)) physical function questionnaire in late-onset Pompe disease using PROPEL phase 3 data. J Patient Rep Outcomes. 2024 Jan 31;8(1):13. doi: 10.1186/s41687-024-00686-z.

  PMID: 38294575 DERIVED

• Schoser B, Roberts M, Byrne BJ, Sitaraman S, Jiang H, Laforet P, Toscano A, Castelli J, Diaz-Manera J, Goldman M, van der Ploeg AT, Bratkovic D, Kuchipudi S, Mozaffar T, Kishnani PS; PROPEL Study Group. Safety and efficacy of cipaglucosidase alfa plus miglustat versus alglucosidase alfa plus placebo in late-onset Pompe disease (PROPEL): an international, randomised, double-blind, parallel-group, phase 3 trial. Lancet Neurol. 2021 Dec;20(12):1027-1037. doi: 10.1016/S1474-4422(21)00331-8.

  PMID: 34800400 DERIVED

MeSH Terms

Conditions

Glycogen Storage Disease Type II

Interventions

miglustat; GAA protein, human

Condition Hierarchy (Ancestors)

Lysosomal Storage Diseases, Nervous System; Brain Diseases, Metabolic, Inborn; Brain Diseases, Metabolic; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Glycogen Storage Disease; Carbohydrate Metabolism, Inborn Errors; Lysosomal Storage Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases

Results Point of Contact

• Title: Patient advocacy
• Organization: Amicus Therapeutics, Inc.

clinicaltrials@amicusrx.com

001 6096622000

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 10, 2018
• First Posted: November 2, 2018
• Study Start: December 4, 2018
• Primary Completion: December 15, 2020
• Study Completion: January 15, 2021
• Last Updated: September 11, 2025
• Results First Posted: September 11, 2023

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

GR (1); TW (1); NZ (1); BE (1); BO (1); DE (4); US (25); HU (3); JP (6); BU (1); FR (5); AU (4); DK (2); PL (2); KR (2); IT (2); SE (1); AR (1); GB (4); ES (1); SL (1); CA (2); NL (1)