A Study to Evaluate the PK, Safety, Efficacy, and PD With ATB200/AT2221 in LOPD Subjects Aged 12 to <18
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|ClinicalTrials.gov Identifier: NCT03911505|
Recruitment Status : Not yet recruiting
First Posted : April 11, 2019
Last Update Posted : April 11, 2019
This is a Phase 3, open-label, uncontrolled, multicenter study to evaluate the PK, safety, efficacy, and PD of ATB200/AT2221 treatment in pediatric subjects aged 12 to < 18 years with LOPD.
Enzyme replacement therapy (ERT)-experienced subjects are those who have received at least 1 dose of alglucosidase alfa prior to enrolling in this study.
|Condition or disease||Intervention/treatment||Phase|
|Pompe Disease (Late-onset)||Biological: ATB200 Drug: AT2221||Phase 3|
The study will consist of a 30-day screening period, a 12-month treatment period, and a 30-day safety follow-up period, for a total duration of approximately 14 months. Subjects who complete this study may have an opportunity to enroll in a separate long-term extension study.
Pediatric subjects will be treated every other week with oral AT2221 followed by ATB200 IV. Subjects will undergo PK assessments at Day 1, Week 26, and Week 52. The PK of AT2221 and ATB200 will be assessed to bridge exposures, inform dosing, and validate modeling for future administration of ATB200/AT2221 to younger age groups.
Infusion visits will be scheduled every 2 weeks throughout the study; assessments (eg, clinical laboratory tests) for initial safety monitoring will be performed at these visits for the first 6 weeks of the study. Study visits that include efficacy, additional safety, and other assessments will be scheduled approximately every 3 months. Blood samples will be collected for determination of total human acid α-glucosidase (GAA) protein levels and AT2221 concentrations in plasma for a population PK analysis.
Safety assessments include monitoring of adverse events, clinical laboratory tests, physical examinations, vital signs, echocardiograms, 12-lead electrocardiogram (ECG), and detection of ATB200 antibodies. Efficacy assessments include evaluation of ambulatory function (6-Minute Walk Test [6MWT]); motor function tests; muscle strength; pulmonary function tests; Patient-reported Outcomes Measurement Information System (PROMIS®) for dyspnea, fatigue, physical functioning, and upper extremity; Gross Motor Function Measure-88 Items (GMFM-88); Pompe-pediatric Evaluation of Disability Inventory (PompePedi); Subject/Physician Global Impression of Change (SGIC/PGIC); Visual Analog Scale (VAS) for pain assessment, and time to initiation of use of assistive device. The patient-reported outcomes are to be completed if available. Pharmacodynamic (PD) assessments include measurement of serum creatine kinase (CK) levels and urinary hexose tetrasaccharide (Hex4) levels.
Exploratory efficacy data may also be captured (optional) using wearable devices to monitor physical activity (total and intensity), video capture to report activities of daily living, and smartphone applications for reporting patient-reported outcomes/quality of life (mood, fatigue, appetite, etc).
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||14 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||An Open-label Study of the Pharmacokinetics, Safety, Efficacy, and Pharmacodynamics of ATB200/AT2221 in Pediatric Subjects Aged 12 to < 18 Years With Late-onset Pompe Disease|
|Estimated Study Start Date :||July 2019|
|Estimated Primary Completion Date :||February 2021|
|Estimated Study Completion Date :||June 2021|
Participants received ATB200 co-administered with AT2221 capsule (Miglustat)
Enzyme Replacement Therapy via intravenous infusion
Participants received ATB200 co-administered with AT2221 (Miglustat)
Other Name: Miglustat
- Assessment of pharmacokinetic parameters [ Time Frame: 52 weeks ]ATB200 protein and AT2221 concentrations in plasma
- Number of participants with adverse events [ Time Frame: 52 weeks ]incidence of treatment-emergent AEs, SAEs, infusion-associated reactions, and AEs leading to discontinuation of study drug
- Change from baseline 6-Minute Walk Test [6MWT] [ Time Frame: 52 weeks ]
- Change from baseline Gait, Stair, Gower, and Chair maneuver [GSGC] test [ Time Frame: 52 weeks ]
- Change from baseline Timed Up and Go [TUG] test) [ Time Frame: 52 weeks ]
- Change from baseline manual muscle tests [MMT]) test) [ Time Frame: 52 weeks ]
- Change from baseline forced vital capacity [FVC] [ Time Frame: 52 weeks ]
- Change from baseline supine and sitting, slow vital capacity [SVC] [ Time Frame: 52 weeks ]
- Change from baseline supine and sitting, maximal inspiratory pressure [MIP] [ Time Frame: 52 weeks ]
- Change from baseline maximal expiratory pressure [MEP] [ Time Frame: 52 weeks ]
- Change from baseline Patient-reported Outcomes Measurement Information System (PROMIS®) [ Time Frame: 52 weeks ]
- Change from baseline Gross Motor Function Measure-88 Items (GMFM-88) [ Time Frame: 52 weeks ]
- Change from baseline Pompe-pediatric Evaluation of Disability Inventory (PompePedi) [ Time Frame: 52 weeks ]
- Change from baseline Subject/Physician Global Impression of Change (SGIC/PGIC) [ Time Frame: 52 weeks ]
- Change from baseline Visual Analog Scale (VAS) for pain assessment [ Time Frame: 52 weeks ]
- Change from baseline time to initiation of use of assistive device Scale (VAS) for pain assessment [ Time Frame: 52 weeks ]
- Biomarkers/Pharmacodynamics of muscle injury and disease substrate [ Time Frame: 52 weeks ]Change from baseline in Creatine Kinase and Urinary Hexose Tetrasaccharide
- Immunogenicity [ Time Frame: 52 weeks ]Change in anti-rhGAA antibodies from baseline over time
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03911505
|Contact: For Site||609-662-2000||PompeSiteInfo@amicusrx.com|
|Contact: For Patientfirstname.lastname@example.org|