First-In-Human Study to Evaluate Safety, Tolerability, and PK of Intravenous ATB200 Alone and When Co-Administered With Oral AT2221

An Open-Label, Fixed-Sequence, Ascending-Dose, First-in-Human Study to Assess the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Efficacy of Intravenous Infusions of ATB200 Co-Administered With Oral AT2221 in Adult Subjects With Pompe Disease

This is an international, multi-center, open-label study designed to evaluate if the co-administration of investigational new drugs ATB200 and AT2221 is safe in adults with Pompe disease.

Study Overview

• Status: Completed
• Conditions: Pompe Disease
• Intervention / Treatment: Drug: AT2221; Drug: ATB200

Detailed Description

This is an open-label, fixed-sequence, ascending-dose, first-in-human study to evaluate the effect of a highly targeted rhGAA (ATB200) co-administered with an enzyme stabilizer (AT2221).

The study aims to evaluate safety, tolerability, pharmacokinetics (PK), efficacy, pharmacodynamics (PD), and immunogenicity of ATB200 co-administered with AT2221.

Stage 1: evaluation of safety, tolerability, and PK following sequential single ascending doses of intravenously infused ATB200

Stage 2: evaluation of safety, tolerability, and PK following single- and multiple-ascending dose combinations of ATB200 and AT2221

Stage 3: evaluation of long term safety, tolerability, and efficacy following 24 month treatment of ATB200 co-administered with AT2221

Stage 4: open-label extension period with functional assessments every 6 months

• Study Type: Interventional
• Enrollment (Actual): 29
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Australia
  • South Australia
    • North Adelaide, South Australia, Australia, 05006
      • Womens & Childrens Hospital, Adelaide
• Germany
  • Bochum, Germany, 44791
    • University Children's Hospital Department of Neuropediatrics and Inborn Metabolic Disorders, St. Josefs-Hospital
  • Munich, Germany, 80336
    • Friedrich-Baur-Institure, Dep of Neurology - University Munich
• Netherlands
  • Rotterdam, Netherlands
    • Erasmus Medical Center
• New Zealand
  • Auckland, New Zealand, 01051
    • School of Medicine, University of Auckland
• United Kingdom
  • Birmingham, United Kingdom, B15 2TH
    • University Hospital Birmingham NHS Foundation Trust, Queen Elizabeth Medical Center
  • Salford, United Kingdom, M6 8HD
    • Salford Royal NHS Foundation Trust
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85028
      • Neuromuscular Research Centre
  • California
    • Orange, California, United States, 92868
      • University of California Irvine
  • Florida
    • Gainesville, Florida, United States, 32610
      • University of Florida
  • Georgia
    • Decatur, Georgia, United States, 30033
      • Emory University Division of Medical Genetics
  • Michigan
    • Grand Rapids, Michigan, United States, 49525
      • Infusion Associates
  • Montana
    • Great Falls, Montana, United States, 59405
      • Great Falls Clinic, LLP
  • New Jersey
    • Newark, New Jersey, United States, 08103
      • Rutgers New Jersey Medical School
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University Medical Center
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Perelman Center for Advanced Medicine
    • Pittsburgh, Pennsylvania, United States, 15213
      • University of Pittsburgh
    • West Chester, Pennsylvania, United States, 19380
      • Abramson Cancer Center Chester County Hospital
  • Virginia
    • Fairfax, Virginia, United States, 22030
      • Lysosomal & Rare Disorders Research & Treatment Center (LDRTC)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 71 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Adults with Diagnosis of Pompe disease

Cohort 1: Enzyme Replacement Therapy (ERT)-experienced subject (ambulatory):

• Male and female subjects between 18 and 65 years of age, inclusive
• Received ERT with alglucosidase alfa (Myozyme/Lumizyme) for the previous 2-6 years, inclusive
• Was receiving alglucosidase alfa at a frequency of once every other week
• Must have been able to walk 200-500 meters on the 6-Minute Walk Test (6MWT)
• Had upright Forced Vial Capacity (FVC) 30-80% of predicted normal value

Cohort 2: ERT-experienced subjects (non-ambulatory):

• Male and female subjects between 18 and 65 years of age, inclusive
• Had been receiving ERT with alglucosidase alfa for ≥2 years at a regular or set frequency
• Was wheelchair-bound

Cohort 3: ERT-naïve subjects (ambulatory):

• Male and female subjects between 18 and 65 years of age, inclusive
• Must have been able to walk 200-500 meters on the 6MWT
• Had upright FVC 30-80% of predicted normal value

Cohort 4: ERT-experienced subject (ambulatory):

• Male and female subjects between 18 and 75 years of age, inclusive
• Had been receiving ERT with alglucosidase alfa for ≥7 years, inclusive
• Was receiving alglucosidase alfa at a frequency of once every other week
• Must have been able to walk 75-600 meters on the 6MWT
• Had upright FVC 30-85% of predicted normal value

Exclusion Criteria:

• Received treatment with prohibited medications within 30 days of Baseline Visit
• Subject, if female, was pregnant or breastfeeding at screening
• Subject, whether male or female, planned to conceive a child during the study
• Had a medical or any other extenuating condition or circumstance that may, in opinion of investigator, pose an undue safety risk to the subject or compromise his/her ability to comply with protocol requirements
• Had a history of allergy or sensitivity to alglucosidase alfa, miglustat or other iminosugars (Cohorts 1, 2, and 4)
• Required invasive ventilatory support, or used noninvasive ventilatory support ≥ 6 hours a day while awake (Cohorts 1, 3, and 4)
• Had active systemic autoimmune disease such as lupus, scleroderma, or rheumatoid arthritis; subjects with autoimmune disease must have been discussed with the Amicus Medical Monitor
• Had active bronchial asthma; subjects with bronchial asthma must have been discussed with the Amicus Medical Monitor

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ATB200; Sequential single ascending doses of intravenously infused ATB200 for 3 dosing periods	Drug: ATB200; Other Names: Cipaglucosidase alfa
Experimental: ATB200 + AT2221; ATB200 co-administered with AT2221 (Miglustat)	Drug: AT2221; Other Names: Miglustat; Drug: ATB200; Other Names: Cipaglucosidase alfa

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 Adverse Events (AEs) Leading to Discontinuation of Study Drug	Number of subjects with TEAE, TESAE, and AE leading to discontinuation during the 2 year treatment period and extension (Stage 3 and 4 combined)	Stage 3 (2 year treatment) and Stage 4 (Extension) combined, (mean = 71 months on treatment)
Plasma Human Acid α-glucosidase (GAA) Activity Levels as Measured by Maximum Observed Plasma Concentration (Cmax).	Plasma GAA levels (Cmax) measured in Cohorts 1 and 3 following 1st and 3rd doses of cipaglucosidase alfa + miglustat	18 Weeks
Plasma GAA Activity Levels as Measured by Time to Reach the Maximum Observed Plasma Concentration (Tmax).	Plasma GAA levels (Tmax) measured in Cohorts 1 and 3 following 1st and 3rd doses of cipaglucosidase alfa + miglustat	18 Weeks
Plasma GAA Activity Levels as Measured by Area Under the Plasma Drug Concentration-time Curve (AUC).	Plasma GAA levels (AUC) measured in Cohorts 1 and 3 following 1st and 3rd doses of cipaglucosidase alfa + miglustat	18 Weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in 6-minute Walk Distance (6MWD)	Motor function was measured in ambulatory subjects using 6MWD (meters).	Baseline, Month 60
Change From Baseline in Pulmonary Function Tests	Pulmonary function was measured by sitting and supine % predicted forced vital capacity (FVC)	Baseline, Month 60
Change From Baseline in Muscle Strength Tests	Muscle strength was measured by total manual muscle test (MMT) score. Total MMT score ranges from 0 to 80 based on all 16 muscle groups, which are right/left shoulder abduction, right/left shoulder adduction, right/left elbow flexion, right/left elbow extension, right/left hip flexion, right/left hip abduction, right/left knee flexion, and right/left knee extension. Higher scores indicate less disease impact on muscle functions.	Baseline, Month 60
Change From Baseline in Fatigue Severity Score (FSS)	The Fatigue Severity Score (FSS) consists of 9 questions, each scored on a scale from 1 ("completely disagree") to 7 ("completely agree"). The total score ranges from 9 to 63, with higher values representing higher level of fatigue due to the disease condition.	Baseline, Month 60
Change From Baseline in Overall Physical Wellbeing (Subject's Global Impression of Change [SGIC], Question1)	The Subject's Global Impression of Change overall physical wellbeing (question 1) is scored on a 7-point rating scale. Improved = response of 5 or higher, No change = response of 4, and Declined = response of 3 or lower.	Baseline, Month 60
Change From Baseline in Overall Physical Wellbeing (Physician's Global Impression of Change [PGIC])	The Physician's Global Impression of Change overall physical wellbeing is scored on a 7-point rating scale. Improved = response of 5 or higher, No change = response of 4, and Declined = response of 3 or lower.	Baseline, Month 60

Collaborators and Investigators

• Sponsor: Amicus Therapeutics

Publications and helpful links

General Publications

• Roberts ME, Proskorovsky I, Guyot P, Shukla P, Thibault N, Hamed A, Pulikottil-Jacob R, O'Callaghan L, Pollissard L. An Indirect Treatment Comparison of Avalglucosidase Alfa versus Cipaglucosidase Alfa Plus Miglustat in Patients with Late-Onset Pompe Disease. Adv Ther. 2025 Sep 8. doi: 10.1007/s12325-025-03301-9. Online ahead of print.
• Byrne BJ, Schoser B, Kishnani PS, Bratkovic D, Clemens PR, Goker-Alpan O, Ming X, Roberts M, Vorgerd M, Sivakumar K, van der Ploeg AT, Goldman M, Wright J, Holdbrook F, Jain V, Benjamin ER, Johnson F, Das SS, Wasfi Y, Mozaffar T. Long-term safety and efficacy of cipaglucosidase alfa plus miglustat in individuals living with Pompe disease: an open-label phase I/II study (ATB200-02). J Neurol. 2024 Apr;271(4):1787-1801. doi: 10.1007/s00415-023-12096-0. Epub 2023 Dec 6.

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2016
• Primary Completion (Actual): August 22, 2024
• Study Completion (Actual): August 22, 2024

Study Registration Dates

• First Submitted: January 26, 2016
• First Submitted That Met QC Criteria: February 3, 2016
• First Posted (Estimated): February 5, 2016

Study Record Updates

• Last Update Posted (Estimated): October 23, 2025
• Last Update Submitted That Met QC Criteria: October 8, 2025
• Last Verified: October 1, 2025

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; Hypoglycemic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Glycoside Hydrolase Inhibitors; miglustat
• Other Study ID Numbers: ATB200-02