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

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.

Timeline

Start

2018-12-04

Primary completion

2020-12-15

Completion

2021-01-15

Outcome

Missed primary endpoint

paper Cipaglucosidase alfa plus miglustat did not achieve statistical superiority to alglucosidase alfa plus placebo for improving 6-min walk distance in our overall population PMID 34800400 ↗

registry p = 0.048; LS Mean Difference 14.21 (95% CI -2.6 to 31.02) NCT03729362 ↗

Publications

• 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.
• 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.
• 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.
• 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.
• 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.
• 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.

Drugs

Evaluation	Drug	Modality	Dose	Route
Subject	Cipaglucosidase alfa	Protein / enzyme biologic	20 mg/kg	Intravenous
Subject	Miglustat	Small molecule	—	Oral
Comparator	alglucosidase alfa	Protein / enzyme biologic	20 mg/kg	Intravenous

Indications