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

NCT ID: NCT03729362

Last Updated: 2025-09-11

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 125 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-12-04
• Study Completion Date: 2021-01-15

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.

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, Gowers' maneuver, and Chair [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.

Conditions

Pompe Disease (Late-onset)

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Cipaglucosidase Alfa/Miglustat

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

Group Type: EXPERIMENTAL

Cipaglucosidase Alfa

Intervention Type: BIOLOGICAL

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

Miglustat

Intervention Type: DRUG

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

Alglucosidase Alfa/Placebo

Participants received alglucosidase alfa co-administered with placebo Q2W.

Group Type: ACTIVE_COMPARATOR

Alglucosidase Alfa

Intervention Type: BIOLOGICAL

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

Placebo

Intervention Type: DRUG

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

Interventions

Cipaglucosidase Alfa

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

Intervention Type: BIOLOGICAL

Miglustat

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

Intervention Type: DRUG

Alglucosidase Alfa

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

Intervention Type: BIOLOGICAL

Placebo

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

Intervention Type: DRUG

Other Intervention Names

ATB200; AT2221; Myozyme

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Amicus Therapeutics

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Neuromuscular Research Center

Phoenix, Arizona, United States

University of Arkansas for Medical Sciences

Little Rock, Arkansas, United States

University of California, Irvine

Irvine, California, United States

UF Helath: University of Florida Clinical Research Center

Gainesville, Florida, United States

University of South Florida Research Center

Tampa, Florida, United States

Emory Clinic

Atlanta, Georgia, United States

Indiana University Health Neuroscience Center

Indianapolis, Indiana, United States

University of Kansas Medical Center

Kansas City, Kansas, United States

University of Minnesota Clinical Research Unit

Minneapolis, Minnesota, United States

Washington University School of Medicine

St Louis, Missouri, United States

Billings Clinic

Billings, Montana, United States

Hackensack University Medical Center

Hackensack, New Jersey, United States

The Feinstein Institute for Medical Research

Manhasset, New York, United States

NYU School of Medicine

New York, New York, United States

Duke University Medical Center

Durham, North Carolina, United States

University of Cincinnati Neurology

Cincinnati, Ohio, United States

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, United States

The Ohio State University Wexner Medical Center

Columbus, Ohio, United States

Oregon Health & Science University

Portland, Oregon, United States

Penn State Health Milton S. Hershey Medical Center

Hershey, Pennsylvania, United States

University of Pennsylvania

Philadelphia, Pennsylvania, United States

University of Pittsburgh

Pittsburgh, Pennsylvania, United States

University of Texas Health Science Center San Antonio

San Antonio, Texas, United States

University of Utah, Center for Clinical and Translational Sciences

Salt Lake City, Utah, United States

Lysosomal and Rare Disorders Research

Fairfax, Virginia, United States

Hospital Universitario Austral

Buenos Aires, , Argentina

Royal Brisbane & Women's Hospital

Herston, Queensland, Australia

Royal Adelaide Hospital

Adelaide, South Australia, Australia

Monash Medical Centre

Melbourne, Victoria, Australia

Westmead Hospital

Westmead, , Australia

Medizinische Universität Innsbruck

Innsbruck, , Austria

UZ Leuven

Leuven, , Belgium

University Clinical Centre of the Republic of Srpska

Banja Luka, , Bosnia and Herzegovina

UMHAT Alexandrovska

Sofia, , Bulgaria

Heritage Medical Research Clinic, University of Calgary

Calgary, Alberta, Canada

McMaster University Medical Centre

Hamilton, Ontario, Canada

Aarhus Universitets Hospital

Aarhus N, , Denmark

Rigshospitalet Copenhagen Neuromuscular Center

Copenhagen, , Denmark

Hôpital Neurologique Pierre Wertheimer

Bron, , France

Hôpital Raymond Poincaré

Garches, , France

Hôpital Salengro

Lille, , France

Hôpital de la Timone

Marseille, , France

Hôpital Pasteur

Nice, , France

Friedrich-Baur Institut

Munich, Bavaria, Germany

Universitätsklinikum Bonn

Bonn, North Rhine-Westphalia, Germany

Universitätsklinikum Münster

Münster, North Rhine-Westphalia, Germany

Universitätsklinikum Halle (Saale)

Halle, Saxony-Anhalt, Germany

Eginition Hospital

Athens, Attica, Greece

Semmelweis University, Institute of Genomic Medicine and Rare Disease

Budapest, , Hungary

University of Pécs

Pécs, , Hungary

University of Szeged

Szeged, , Hungary

UOC di Neurologia e Malattie Neuromuscolari

Messina, NAP, Italy

UOC Genetica Medica

Napoli, NAP, Italy

Hokkaido University Hospital

Sapporo, Hokkaido, Japan

Fukuoka University Hospital

Fukuoka, , Japan

Kagoshima University Hospital

Kagoshima, , Japan

Izumi City General Hospital

Osaka, , Japan

The Jikei University Hospital

Tokyo, , Japan

National Center of Neurology and Psychiatry

Tokyo, , Japan

Erasmus MC

Rotterdam, , Netherlands

University of Auckland

Auckland, , New Zealand

Szpital Uniwersytecki w Krakowie

Małogoskie, , Poland

Centrum Medyczne

Rzeszów, , Poland

University Medical Centre Ljubljana

Ljubljana, , Slovenia

Pusan National University

Yangsan, Gyeongsangnam-do, South Korea

Seoul National University Hospital

Seoul, , South Korea

Hospital de la Santa Creu I Sant Pau

Barcelona, , Spain

Sahlgrenska University Hospital

Gothenburg, , Sweden

National Taiwan University Hospital

Taipei, , Taiwan

Queen Elizabeth Hospital Birmingham

Birmingham, , United Kingdom

Cambridge University Hospitals

Cambridge, , United Kingdom

Royal Free Hospital NHS

London, , United Kingdom

Salford Royal NHS Foundation Trust

Salford, , United Kingdom

Countries

United States; Argentina; Australia; Austria; Belgium; Bosnia and Herzegovina; Bulgaria; Canada; Denmark; France; Germany; Greece; Hungary; Italy; Japan; Netherlands; New Zealand; Poland; Slovenia; South Korea; Spain; Sweden; Taiwan; United Kingdom

References

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.

Reference Type: DERIVED

PMID: 40342075 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 39535661 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 39318718 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 38294575 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 34800400 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

ATB200-03

Identifier Type: -

Identifier Source: org_study_id