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

• Register: EUCTR
• Last refreshed on: 8 January 2024
• Main ID: EUCTR2019-000954-67-AT
• Date of registration: 13/03/2020
• Prospective Registration: Yes
• Primary sponsor: Amicus Therapeutics, Inc.
• Public title: 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
• Scientific title: 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
• Date of first enrolment: 19/06/2020
• Target sample size: 110
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2019-000954-67
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no Randomised: no Open: no Single blind: no Double blind: no Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: no Other: no
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Argentina, Australia, Austria, Belgium, Bosnia and Herzegovina, Bulgaria, Canada, Denmark, France, Germany, Greece, Hungary, Italy, Japan, Korea, Republic of, Netherlands, Poland, Romania, Slovakia, Slovenia, Spain, Sweden, Taiwan, United Kingdom, United States

Contacts

• Name: Patient Advocacy
• Affiliation: Amicus Therapeutics, Inc.

• Name: Patient Advocacy
• Affiliation: Amicus Therapeutics, Inc.

Key inclusion & exclusion criteria

Inclusion criteria:
Subjects Who Participated in Study ATB200-03:
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 subjects 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.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 92
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 18

Exclusion criteria:
Subjects Who Participated in Study ATB200-03:
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.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

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

Adult Subjects With Late Onset Pompe Disease (LOPD)
MedDRA version: 24.0 Level: LLT Classification code 10075702 Term: Pompe's disease late onset System Organ Class: 100000004850

Intervention(s)

Product Name: ATB200
Product Code: ATB200
Pharmaceutical Form: Powder for concentrate for solution for injection/infusion
INN or Proposed INN: cipaglucosidase alfa
CAS Number: 420784-05-0
Current Sponsor code: ATB200
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 15-

Product Name: AT2221
Product Code: AT2221
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: MIGLUSTAT
CAS Number: 72599-27-0
Current Sponsor code: AT2221
Other descriptive name: AT2221 65 mg Formulated Capsules
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 65-

Primary Outcome(s)

Secondary Objective: - to 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
- to assess the immunogenicity of ATB200/AT2221 co-administration

Main Objective: The primary objective of this study is to assess the long-term safety and tolerability of ATB200/AT2221 co-administration

Primary end point(s): 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.

Timepoint(s) of evaluation of this end point: Every study visit until regulatory approval or marketing authorization and/or commercialization in the participating subject’s country, or study termination by the sponsor.

Secondary Outcome(s)

Secondary end point(s): - Efficacy:
• change from baseline in 6-minute walk distance (6MWD)
• change from baseline in 6MWD (% predicted)
• change from baseline in sitting FVC (% predicted)
• change from baseline in the manual muscle test score for the lower extremities
• change from baseline in the total score for the PROMIS – physical function
• change from baseline in the total score for the PROMIS – fatigue
• 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
• 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)
• 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
• 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
• actual value of the subject’s functional status (improving, stable, or declining), as measured by the PGIC
• 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)

Pharmacodynamic endpoints are as follows:
• change from baseline in serum CK level
• change from baseline in urinary Hex4 level

Timepoint(s) of evaluation of this end point: - Efficacy: Week 12, 26; after Week 26, every 26 weeks until regulatory approval or marketing authorization and/or commercialization in the participating subject’s country, or study termination by the sponsor.
- Pharmacodynamic: Week 2, 4, 6, 12, 26; after Week 26, every 26 weeks until regulatory approval or marketing authorization and/or commercialization in the participating subject’s country, or study termination by the sponsor.

Secondary ID(s)

2019-000954-67-GB

NCT04138277

ATB200-07

127,387

Source(s) of Monetary Support

Amicus Therapeutics, Inc.

Ethics review

Status: Approved
Approval date: 19/06/2020
Contact: