A study investigating the long-term safety and efficacy of intravenous (IV) ATB200 when Co-administrated with oral AT2221 in adult subjects with Pompe disease

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Amicus Therapeutics Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16]

Trial duration

15 May 2020 → ongoing

Decision date (initial)

2024-07-17

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Amicus Therapeutics, Inc.

External identifiers

EU CT number

2023-505170-15-00

EudraCT number

2019-000954-67

ClinicalTrials.gov

NCT04138277

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacodynamic, Efficacy, Pharmacokinetic, Safety, Therapy, Others

Assess the long-term safety and tolerability of ATB200/AT2221 co-administration

Secondary objectives 3

1. Assess the long-term efficacy of ATB200/AT2221 co-administration on: • ambulatory function, as measured by the 6-minute walk test (6MWT) • pulmonary function, as measured by sitting forced vital capacity (FVC) (% predicted) • on muscle strength • on health-related patient-reported outcomes • motor function • overall clinical impression, as assessed by both physician and subject • measures of pulmonary function other than FVC (% predicted) • biomarkers of muscle injury and disease substrate
2. Assess the immunogenicity of ATB200/AT2221 co-administration
3. Characterize the pharmacokinetics of ATB200 and AT2221 using plasma total GAA protein level by signature peptide and plasma AT2221 concentration assays in subjects at sites in Japan only

Conditions and MedDRA coding

Adult Subjects With Late Onset Pompe Disease (LOPD)

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 3

1. Subject must provide signed informed consent prior to any study- related procedures being performed. If the subject is under 20 years of age, the subject must provide written informed consent
2. 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 ATB200/AT2221 (eg, hospitalization for a car accident, COVID-19 pandemic, or emergency surgery) and which resulted in several consecutive missed doses may be eligible to participate in this study upon approval by the Amicus medical monitor
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

Exclusion criteria 4

1. Subject plans to receive gene therapy or participate in another interventional study for Pompe disease
2. Subject has a hypersensitivity to any of the excipients in ATB200 or AT2221, or 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
3. Subject, if female, is pregnant or breastfeeding
4. Subject, whether male or female, is planning to conceive a child during the study

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Long-term safety: incidence of treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), and AEs leading to discontinuation of study drug, frequency and severity of immediate and late IARs, and any abnormalities noted in other safety assessments (eg, clinical laboratory tests, ECGs, vital signs). Immunogenicity to ATB200 will also be described

Secondary endpoints 14

1. Change from baseline in 6-minute walk distance (6MWD)
2. Change from baseline in 6MWD (% predicted)
3. Change from baseline in sitting FVC (% predicted)
4. Change from baseline in the manual muscle test score for the lower extremities
5. Change from baseline in the total score for the PROMIS – physical function
6. Change from baseline in the total score for the PROMIS – fatigue
7. Change from baseline in the following variables related to motor function: - GSGC total score, - time to complete the 10-meter walk (ie, assessment of gait) of the GSGC test, - time to complete the 4-stair climb of the GSGC test, - time to complete the Gower's maneuver of the GSGC test, - time to arise from a chair as part of the GSGC test, - change from baseline in the time to complete the TUG test
8. Change from baseline in the following variables related to muscle strength: - manual muscle test score for the upper extremities, - manual muscle test total score (upper and lower extremities combined), - quantitative muscle test value (kg) for the upper extremities, - quantitative muscle test value (kg) for the lower extremities, - quantitative muscle test total value (kg) (upper and lower extremities combined)
9. Change from baseline in the following variables from patient-reported outcome measures: - total score for the PROMIS-dyspnea, - total score for the PROMIS–upper extremity, - R-PAct Scale total score, - EQ-5D-5L health status
10. Actual value of the subject's functional status (improving, stable, or declining) pertaining to the effects of study drug in the following areas of life, as measured by the SGIC: - overall physical well-being, - effort of breathing, - muscle strength, - muscle function, - ability to move around, - activities of daily living, - energy level, - level of muscular pain
11. Actual value of the subject's functional status (improving, stable, or declining), as measured by the PGIC
12. Change from baseline in the following measures of pulmonary function, as follows: - sitting SVC (% predicted), - MIP (cmH2O), - MIP (% predicted), - MEP (cmH2O), - MEP (% predicted), - SNIP (cmH2O)
13. Change from baseline in serum CK level
14. Change from baseline in urinary Hex4 level

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Amicus Therapeutics Inc.

Sponsor organisation

Amicus Therapeutics Inc.

Address

47 Hulfish Street

City

Princeton

Postcode

08542-3713

Country

United States

Scientific contact point

Organisation

Amicus Therapeutics Inc.

Contact name

Amicus Patient Advocacy

Public contact point

Organisation

Amicus Therapeutics Inc.

Contact name

Amicus Patient Advocacy

Third parties 9

Locations

9 EU/EEA countries · 14 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 42 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

5 submissions — initial application plus substantial / non-substantial modifications