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
Conditions
Interventions
Product Name: ATB200
Product Code: ATB200
Pharmaceutical Form: Powder for concentrate for solution for injection/infusion
INN or Proposed INN: ALGLUCOSIDASE ALFA
CAS Number: 420784-05-0
Current Sponso
Sponsors
Amicus Therapeutics, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Subject must provide signed informed consent prior to any study-related procedures being performed. 2. Male and female subjects are = 18 years old and weigh = 50 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 c. muscle biopsy 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
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 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. 6. Subject, if female, is pregnant or breastfeeding at screening. 7. Subject, whether male or female, is planning to conceive a child during the study.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The objective is to assess the efficacy of ATB200/AT2221 co-administration on ambulatory function, as measured by the 6 Minute Walk Test (6MWT), compared with alglucosidase alfa/placebo;Secondary Objective: To assess the efficacy of ATB200/AT2221 co-administration (compared with alglucosidase alfa/placebo) on: - muscle strength - health-related patient reported outcomes - motor function - pulmonary function - overall clinical impression as assessed by both physician and subject To assess the safety, tolerability, and immunogenicity of ATB200/AT2221 co administration compared with alglucosidase alfa/placebo To assess the effect of ATB200/AT2221 co-administration on biomarkers of muscle injury and disease substrate compared with alglucosidase alfa/placebo To characterize the population pharmacokinetics of ATB200 and alglucosidase alfa using plasma total acid a-glucosidase (GAA) protein level by signature peptide assay and plasma AT2221 concentration. 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. | — |
Secondary
| Measure | Time frame |
|---|---|
| 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 | — |
Countries
Australia, Austria, Belgium, Bosnia and Herzegovina, Brazil, Bulgaria, Canada, Denmark, France, Germany, Greece, Hungary, Israel, Italy, Japan, Korea, Republic of, Netherlands, New Zealand, Poland, Romania, Slovakia, Slovenia, Spain, Sweden, Taiwan, United Kingdom, United States
Contacts
Public ContactPatient advocacy
Amicus Therapeutics, Inc.
Outcome results
None listed