A Study to Assess the Long-term Safety and Efficacy of ATB200/AT2221 in Adult Subjects With Late-Onset Pompe Disease (LOPD)

A Phase 3 Open-label Extension Study to Assess the Long-term Safety and Efficacy of Intravenous ATB200 Co-administered With Oral AT2221 in Adult Subjects With Late-onset Pompe Disease (LOPD)

This is a multicenter, international open-label extension study of ATB200/AT2221 in adult subjects with late-onset Pompe disease (LOPD) who completed Study ATB200-03.

Study Overview

• Status: Completed
• Conditions: Pompe Disease (Late-onset)
• Intervention / Treatment: Biological: ATB200; Drug: AT2221

Detailed Description

This is an open-label extension study for subjects who completed the ATB200-03 study. The subjects will stay in this study until regulatory approval or marketing authorization and/or commercialization in the participating subject's country.

• Study Type: Interventional
• Enrollment (Actual): 119
• Phase: Phase 3

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina, B1629ODT
    • Hospital Universitario Austral
• Australia
  • New South Wales
    • Westmead, New South Wales, Australia
      • Westmead Hospital
  • Queensland
    • Brisbane, Queensland, Australia, 4029
      • Royal Brisbane & Women's Hospital
  • South Australia
    • Adelaide, South Australia, Australia, 5000
      • Royal Adelaide Hospital
  • Victoria
    • Clayton, Victoria, Australia, 3168
      • Monash Medical Centre
• Austria
  • Innsbruck, Austria, A-6020
    • Medizinische Universitat Innsbruck
• Belgium
  • Leuven, Belgium, 3000
    • UZ Leuven
• Bosnia and Herzegovina
  • The Republic of Srpska
    • Banja Luka, The Republic of Srpska, Bosnia and Herzegovina, 78000
      • University Clinical Centre of the Republic of Srpska
• Canada
  • Alberta
    • Calgary, Alberta, Canada, T3B 6A8
      • Alberta Children's Hospital, Heritage Medical Research Clinic
  • Ontario
    • Hamilton, Ontario, Canada, L8N 3Z5
      • McMaster University Medical Centre
• Denmark
  • Aarhus, Denmark
    • Aarhus Universitetshospital
• France
  • Bron, France, 69577
    • Hôpital Pierre Wertheimer
  • Garches, France, 92380
    • Hopital Raymond Poincare
  • Lille, France, 59037
    • Hôpital Salengro
  • Marseille, France, 13385
    • Hopital de la Timone
  • Nice, France, 06001
    • Hopital Pasteur 2
• Germany
  • Bonn, Germany, 53127
    • Universitätsklinikum Bonn
  • München, Germany, 80336
    • Friedrich-Baur Institut
  • Münster, Germany, 48149
    • Universitatsklinikum Munster
• Greece
  • Athens, Greece, 11528
    • Eginition Hospital
• Hungary
  • Budapest, Hungary, 1085
    • Semmelweis University
  • Pécs, Hungary, 7623
    • University of Pecs
  • Szeged, Hungary, 6725
    • University of Szeged
• Italy
  • Messina, Italy, 98124
    • UOC di Neurologia e Malattie Neuromuscolari
  • Napoli, Italy, 80131
    • Universitaria Federico II
• Japan
  • Fukuoka, Japan, 814-0180
    • Fukuoka University Hospital
  • Kagashima, Japan, 890-8520
    • Kagoshima University Hospital
  • Osaka, Japan, 594 0073
    • Izumi City General Hospital
  • Sapporo, Japan, 060 8648
    • Hokkaido University Hospital
  • Tokyo, Japan, 105-8471
    • The Jikei University Hospital
• Netherlands
  • Rotterdam, Netherlands, 3015 GD
    • Erasmus MC
• New Zealand
  • Auckland, New Zealand, 1142
    • University of Auckland
• Poland
  • Podkarpackie Voivodeship
    • Rzeszów, Podkarpackie Voivodeship, Poland, 35-326
      • Centrum Medyczne MEDYK
• Slovenia
  • Ljubljana, Slovenia, 1000
    • University Medical Centre Ljubljana
• South Korea
  • Gyeongsangnam-do
    • Yangsan, Gyeongsangnam-do, South Korea, 50612
      • Pusan National University
• Spain
  • Barcelona, Spain
    • Hospital De La Santa Creu I Sant Pau
• Sweden
  • Gothenburg, Sweden, 41345
    • Sahlgrenska University Hospital
• Taiwan
  • Taipei, Taiwan, 100
    • National Taiwan University Hospital
• United Kingdom
  • Birmingham, United Kingdom, B15 2TH
    • Queen Elizabeth Hospital Birmingham
  • Cambridge, United Kingdom, CB2 0QQ
    • Cambridge University Hospitals NHS Foundation Trust
  • London, United Kingdom, NW3 2QG
    • Royal Free Hospital NHS Foundation Trust
  • Salford, United Kingdom, M6 8HD
    • Salford Royal NHS Foundation Trust
• United States
  • Arkansas
    • Little Rock, Arkansas, United States, 72205
      • University of Arkansas for Medical Sciences
  • California
    • Irvine, California, United States, 92868
      • University of California, Irvine
  • Florida
    • Gainesville, Florida, United States, 32610
      • University of Florida Clinical Research Center
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Emory Clinic
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • IU Health Neuroscience Center
  • Missouri
    • St Louis, Missouri, United States, 63110
      • Washington University School of Medicine
  • Montana
    • Billings, Montana, United States, 59101
      • Billings Clinic
  • New Jersey
    • Hackensack, New Jersey, United States, 07061
      • Hackensack University Medical Center
  • New York
    • Great Neck, New York, United States, 11021
      • Northwell Health
    • New York, New York, United States, 10017
      • NYU School of Medicine
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University Medical Center
  • Ohio
    • Cincinnati, Ohio, United States, 45229
      • Cincinnati Children's Hospital
    • Cincinnati, Ohio, United States, 45219
      • University of Cincinnati Gardner Neuroscience Institute
    • Columbus, Ohio, United States, 43210
      • The Ohio State University Wexner Medical Center
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15213
      • UPMC Montefiore Clinical and Translational Research Center
  • Utah
    • Salt Lake City, Utah, United States, 84108
      • University of Utah
  • Virginia
    • Fairfax, Virginia, United States, 22030
      • Lysosomal and Rare Disorders Research and Treatment Center, Inc.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Subject must have completed Study ATB200-03.

Note: Subjects who were forced to withdraw from Study ATB200-03 for a logistical reason not related to the efficacy or safety of cipaglucosidase alfa/miglustat (eg, hospitalization for a car accident, COVID-19 pandemic, or emergency surgery) that resulted in several consecutive missed doses may have been eligible to participate in this study upon approval by the Amicus medical monitor.

Exclusion Criteria

1. Subject plans to receive gene therapy or participate in another interventional study for Pompe disease.
2. Subject, if female, is pregnant or breastfeeding.
3. Subject, whether male or female, is planning to conceive a child during the study.
4. Subject had a hypersensitivity to any of the excipients in cipaglucosidase alfa or miglustat, or had a medical condition or any other extenuating circumstance that may have, in the opinion of the investigator or medical monitor, posed an undue safety risk to the subject or may have compromised his/her ability to comply with or adversely impacted protocol requirements.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ATB200/AT2221; Participants received ATB200 (cipaglucosidase alfa) co-administered with AT2221 capsule (miglustat)	Biological: ATB200; Enzyme Replacement Therapy via intravenous infusion; Other Names: cipaglucosidase alfa; Drug: AT2221; Participants received ATB200 co-administered with AT2221 (miglustat); Other Names: miglustat

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Treatment-emergent Adverse Events (TEAEs), Treatment-emergent Serious Adverse Events (TESAEs), and TEAEs Leading to Discontinuation of Study Drug	Number of subjects with TEAE, TESAE, and TEAE leading to discontinuation during this long-term extension study	Entire extension study (mean = 40.5 months on treatment)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in 6-Minute Walk Distance (6MWD)	Motor function was measured using the 6-minute walk distance (meters)	baseline, Week 208
Change From Baseline in Sitting % Predicted Forced Vital Capacity (FVC)	Pulmonary function was measured by sitting % predicted forced vital capacity (FVC)	baseline, Week 208
Change From Baseline in Manual Muscle Testing (MMT) Lower Extremity Score	Strength was measured by manual muscle testing (MMT) using the Medical Research Council grading scale (0 to 5 points, with 5 indicating normal function). Change from baseline values >0 represent improvement.	baseline, Week 208
Change From Baseline in the Total Score for Patient-reported Outcomes Measurement Information System (PROMIS®) - Physical Function	Physical Function Short Form 20a (v2.0) consisted of 20 questions. The first 14 questions were each scored on a scale from 1 to 5 as follows: 1 = unable to do; 2 = with much difficulty; 3 = with some difficulty; 4 = with a little difficulty; 5 = without any difficulty; the next 6 questions were each scored on a scale from 1 to 5 as follows: 1 = cannot do; 2 = quite a lot; 3 = somewhat; 4 = very little; 5 = not at all. The total score was calculated by summing up scores (1 to 5) across all items. Total scores range from 20 to 100. A higher score represented a better outcome.	baseline, Week 208
Change From Baseline in Gait, Stairs, Gower, Chair (GSGC) Test	The GSGC consisted of a 10-meter walk for evaluation of gait, a 4-stair climb, Gowers' maneuver, and arising from a chair. Results of the GSGC included the time required to complete the individual tests, individual scores for each of the tests (1 to 7 points for each of gait, 4-stair climb, and Gowers' maneuver, and 1 to 6 points for arising from a chair), and a total score. GSGC total score was the sum of the component scores from the 4 functional tests. The total score ranged from a minimum of 4 points (normal performance) to a maximum of 27 points (worst performance).	baseline, Week 208
Change From Baseline in Overall Physical Well-being (Subject's Global Impression of Change [SGIC], Question 1)	The Subject's Global Impression of Change overall physical well-being (question 1) is scored on a 7-point rating scale ranging from "very much worse" to "very much improved."	baseline, Week 208
Change From Baseline in Physician's Global Impression of Change (PGIC) Overall Status	The Physician's Global Impression of Change (PGIC) is designed to record the physician's assessment of the subject's status, taking into account the subject's signs and symptoms and other neuromuscular symptoms, and signs relative to their status at the Baseline Visit. The PGIC is based on a single item that is scored on a 7-point rating scale ranging from 1 "very much worse" to 7 "very much improved."	baseline, Week 208
Percent Change From Baseline in Creatine Kinase (U/L)	Percent change from baseline to Week 208 in the levels of biomarker creatine kinase (CK)	baseline, Week 208
Percent Change From Baseline in Urine Hex4 (mmol/Mol Creatinine)	Percent change from baseline to Week 208 in the levels of biomarker urine Hex4.	baseline, Week 208
Proportion of Subjects With Positive Anti-drug Antibodies at Baseline and Week 208	Immunogenicity was assessed by the number (%) of subjects with positive specific anti-cipaglucosidase antibodies at baseline and at Week 208	baseline, Week 208
Change From Baseline in the Total Score for PROMIS® - Fatigue	Fatigue Short Form 8a consisted of 6 questions, each scored on a scale from 1 to 5 as follows: 1 = not at all; 2 = a little bit; 3 = somewhat; 4 = quite a bit; 5 = very much; and 2 questions, each scored on a scale from 1 to 5 as follows: 1 = never; 2 = rarely; 3 = sometimes; 4 = often; 5 = always. The total score was calculated by summing up scores (1 to 5) across all items resulting in a total score range from 6 (minimum) to 30 (maximum). A lower score represented lower fatigue symptoms.	baseline, Week 208
Change From Baseline in EuroQol 5 Dimensions 5 Levels (EQ-5D-5L) Responses	The EuroQol 5 Dimensions 5 Levels (EQ-5D-5L) questionnaire comprises 5 dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension has 5 levels: Level 1=no problems, Level 2=slight problems, Level 3=moderate problems, Level 4=severe problems, and Level 5=extreme problems. In this categorical assessment, subjects were asked to indicate their health state by ticking the box next to the most appropriate statement in each of the 5 dimensions. Outcomes for change from baseline at Week 208 include 'no change', 'worsening' relative to baseline category, or 'improvement' relative to baseline category. Changes (worsening or improvement) are shown by magnitude of change (how many Levels) in each categorical assessment.	baseline, Week 208

Collaborators and Investigators

• Sponsor: Amicus Therapeutics

Publications and helpful links

General Publications

• Schoser B, Kishnani PS, Bratkovic D, Byrne BJ, Claeys KG, Diaz-Manera J, Laforet P, Roberts M, Toscano A, van der Ploeg AT, Castelli J, Goldman M, Holdbrook F, Sitaraman Das S, Wasfi Y, Mozaffar T; ATB200-07 Study Group. 104-week efficacy and safety of cipaglucosidase alfa plus miglustat in adults with late-onset Pompe disease: a phase III open-label extension study (ATB200-07). J Neurol. 2024 May;271(5):2810-2823. doi: 10.1007/s00415-024-12236-0. Epub 2024 Feb 28.
• Hopkin RJ, Byrne BJ, Dimachkie MM, Kishnani PS, Mozaffar T, Roberts M, Schoser B, van der Beek NAME, van der Ploeg AT, Wenninger S, Brudvig J, Fox B, Holdbrook F, Jain V, Johnson F, Zhang J, Parenti G. Miglustat: a first-in-class enzyme stabilizer for cipaglucosidase alfa for the treatment of late-onset Pompe disease. Ther Adv Rare Dis. 2026 Feb 26;7:26330040261425686. doi: 10.1177/26330040261425686. eCollection 2026 Jan-Dec.
• 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.

Study record dates

Study Major Dates

• Study Start (Actual): December 18, 2019
• Primary Completion (Actual): December 31, 2024
• Study Completion (Actual): December 31, 2024

Study Registration Dates

• First Submitted: October 18, 2019
• First Submitted That Met QC Criteria: October 22, 2019
• First Posted (Actual): October 24, 2019

Study Record Updates

• Last Update Posted (Actual): March 5, 2026
• Last Update Submitted That Met QC Criteria: March 2, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: Pompe; rhGAA
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Metabolic Diseases; Carbohydrate Metabolism, Inborn Errors; Lysosomal Storage Diseases; Brain Diseases, Metabolic, Inborn; Brain Diseases, Metabolic; Lysosomal Storage Diseases, Nervous System; Glycogen Storage Disease; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Nutritional and Metabolic Diseases; Glycogen Storage Disease Type II; Anti-Infective Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Hypoglycemic Agents; Enzyme Inhibitors; Antiviral Agents; Anti-HIV Agents; Anti-Retroviral Agents; Glycoside Hydrolase Inhibitors; miglustat
• Other Study ID Numbers: ATB200-07

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No