A study investigating the efficacy and safety of intravenous (IV) ATB200 when Co-administrated with oral AT2221 in adult subjects with Pompe disease compared with Alglucosidase Alfa/Placebo.

• Register: EUCTR
• Last refreshed on: 21 July 2021
• Main ID: EUCTR2018-000755-40-IT
• Date of registration: 25/01/2021
• Prospective Registration: No
• Primary sponsor: AMICUS THERAPEUTICS, INC.
• Public title: A study investigating the efficacy and safety of intravenous (IV) ATB200 when Co-administrated with oral AT2221 in adult subjects with Pompe disease compared with Alglucosidase Alfa/Placebo.
• Scientific title: A Phase 3 Double-blind Randomized Study to Assess 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 - AMICUS ATB200-03
• Date of first enrolment: 17/05/2019
• Target sample size: 110
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2018-000755-40
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: yes; Open: no; Single blind: no; Double blind: yes; Parallel group: no; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: yes; Placebo: yes; Other: no; Number of treatment arms in the trial: 2
• 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, Democratic People's Republic of, 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:
1. Subject must provide signed informed consent prior to any studyrelated procedures being performed.
2. Male and female subjects are = 18 years old and weigh = 40 kg at screening.
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.
4. Subject must have a diagnosis of LOPD based on documentation of one of the following:
a. deficiency of GAA enzyme; b. GAA genotyping;
5. Subject is classified as one of the following with respect to ERT status:
a. ERT-experienced, defined as currently receiving standard of care ERT (alglucosidase alfa) at the recommended dose and regimen (ie, 20 mg/kg dose every 2 weeks) for = 24 months
b. ERT naïve, defined as never having received investigational or commercially available ERT
6. Subject has a sitting FVC = 30% of the predicted value for healthy adults (National Health and Nutrition Examination Survey III) at screening.
7. Subject performs two 6MWTs at screening that are valid, as determined by the clinical evaluator, and that meet all of the following criteria:
a. both screening values of 6MWD are = 75 meters
b. both screening values of 6MWD are = 90% of the predicted value for healthy adults
c. the lower value of 6MWD is within 20% of the higher value of 6MWD
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 90
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 20

Exclusion criteria:
1. Subject has received any investigational therapy or pharmacological treatment for Pompe disease, other than alglucosidase alfa, within 30 days or 5 half lives of the therapy or treatment, whichever is longer, before Day 1 or is anticipated to do so during the study.
2. Subject has received gene therapy for Pompe disease.
3. Subject is taking any of the following prohibited medications within 30 days before Day 1:
• miglitol (eg, Glyset); • miglustat (eg, Zavesca); • acarbose (eg, Precose or Glucobay); • voglibose (eg, Volix, Vocarb, or Volibo)
Note: None of these medications have a half-life that, when multiplied by 5, is longer than 30 days.
4. Subject requires the use of invasive or noninvasive ventilation support for > 6 hours per day while awake.
5. Subject has a hypersensitivity to any of the excipients in ATB200,alglucosidase alfa or AT2221
6. Subject 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.
7. Subject, if female, is pregnant or breastfeeding at screening.
8. Subject, whether male or female, is planning to conceive a child during the study.
9. Subject does not have documentation of diagnosis of Pompe disease and refuses to undergo genetic testing


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: 20.0 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 solution for injection
INN or Proposed INN: non applicabile
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
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 65-
Pharmaceutical form of the placebo: Capsule, hard
Route of administration of the placebo: Oral use

Trade Name: Myozyme
Product Name: Myozyme
Product Code: [Myozyme]
Pharmaceutical Form: Powder for solution for injection
INN or Proposed INN: ALGLUCOSIDASI ALFA UMANA RICOMBINANTE
CAS Number: 420784-05-0
Current Sponsor code: NAP
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 5-

Primary Outcome(s)

Secondary Objective: To assess the efficacy of ATB200/AT2221 co-administration (compared with alglucosidase alfa/placebo) on:
- pulmonary function, as measured by setting forced vital capacity (FVC) - muscle strength; - health-related patient reported outcomes; - motor function; - overall clinical impression as assessed by both physician and subject
To assess the safety, tolerability, and immunogenicity of ATB200/AT2221
To assess the effect of ATB200/AT2221 co-administration on biomarkers of muscle injury and disease substrate
To characterize the population pharmacokinetics of ATB200 and alglucosidase alfa in enzyme replacement therapy using plasma total acid a-glucosidase (GAA) protein level by signature peptide assay and plasma AT2221 concentration.
To characterize the pharmacokinetics of ATB200,alglucosidase alfa, and AT2221 in ERT-naive subjects
To explore the exposure-response relationship for ATB200/AT2221 and alglucosidase alfa/placebo co-administration

Primary end point(s): The primary efficacy endpoint is the change from baseline to Week 52 in 6MWD.

Timepoint(s) of evaluation of this end point: At visits Week 12, 26 and Week 52.

Main Objective: The objective is to assess the efficacy of ATB200/AT2221 coadministration on ambulatory function, as measured by the 6 Minute Walk Test (6MWT), compared with alglucosidase alfa/placebo

Secondary Outcome(s)

Secondary end point(s): • change from baseline to Week 52 in the manual muscle test score for the lower extremities
• change from baseline to Week 52 in the total score for the PROMIS –physical function
• change from baseline to Week 52 in the total score for the PROMIS –fatigue
• change from baseline to Week 52 in GSGC total score
• change from baseline to Week 52 in sitting FVC (% predicted)
• change from baseline to Week 26 in 6MWD
Other secondary efficacy endpoints are as follows:
• change from baseline to Week 52 in the following variables related to motor function:
- 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
- time to complete the TUG test
• change from baseline to Week 52 in the following variables related to muscle strength:
- manual muscle test score for the upper extremities
- manual muscle test total score
- quantitative muscle test value (kg) for the upper extremities
- quantitative muscle test value (kg) for the lower extremities
- quantitative muscle test total value (kg)
• change from baseline to Week 52 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 at Week 52, as measured by the Subject's Global Impression of Change
- overall physical wellbeing; - 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) at Week 52, as measured by the Physician's Global Impression of Change
• change from baseline to Week 52 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 to Week 52 in serum CK level
change from baseline to Week 52 in urinary Hex4 level

Timepoint(s) of evaluation of this end point: Almost all timepoint evaluations happen at visit week 52. Change from baseline for 6MWT is also measured at visit week 26

Secondary ID(s)

2018-000755-40-DE

ATB200-03

Source(s) of Monetary Support

Amicus Therapeutics, Inc.

Ethics review

Status: Approved
Approval date: 21/01/2019
Contact: