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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 : Recruiting
First Posted : April 11, 2019
Last Update Posted : August 19, 2019
Sponsor:
Information provided by (Responsible Party):
Amicus Therapeutics

Tracking Information
First Submitted Date  ICMJE April 9, 2019
First Posted Date  ICMJE April 11, 2019
Last Update Posted Date August 19, 2019
Estimated Study Start Date  ICMJE August 2019
Estimated Primary Completion Date February 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 9, 2019)
  • 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
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT03911505 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: April 9, 2019)
  • 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
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study to Evaluate the PK, Safety, Efficacy, and PD With ATB200/AT2221 in LOPD Subjects Aged 12 to <18
Official Title  ICMJE 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
Brief Summary

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.

Detailed Description

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  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Pompe Disease (Late-onset)
Intervention  ICMJE
  • Biological: ATB200
    Enzyme Replacement Therapy via intravenous infusion
  • Drug: AT2221
    Participants received ATB200 co-administered with AT2221 (Miglustat)
    Other Name: Miglustat
Study Arms  ICMJE Experimental: ATB200/AT2221
Participants received ATB200 co-administered with AT2221 capsule (Miglustat)
Interventions:
  • Biological: ATB200
  • Drug: AT2221
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: April 9, 2019)
14
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE June 2021
Estimated Primary Completion Date February 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Male or female subjects (ERT-naïve [have never received a dose of alglucosidase alfa] or ERT-experienced [have received at least 1 dose of alglucosidase alfa]), diagnosed with late-onset Pompe disease who are aged 12 to < 18 years at screening
  2. Subject's parent or legally authorized representative is willing and able to provide written informed consent and authorization for use and disclosure of personal health information or research-related health information, and subject provides assent, if applicable based on site and local regulations
  3. Subject must have a diagnosis of LOPD based on documentation of one of the following:

    1. deficiency of GAA enzyme
    2. GAA genotyping
  4. If of reproductive potential, both male and female subjects agree to use a highly effective method of contraception throughout the duration of the study and for up to 90 days after their last dose of ATB200/AT2221
  5. Subject has a sitting FVC ≥ 30% of the predicted value for healthy adolescents (Global Lung Function Initiative [GLI]) at screening
  6. Subject performs two 6MWTs at screening that are valid, as determined by the clinical evaluator, and that meet all of the following criteria:

    1. both screening values of 6-Minute Walk Distance (6MWD) are ≥ 75 meters
    2. both screening values of 6MWD are ≤ 90% of the predicted value for healthy adolescents
    3. the lower value of 6MWD is within 20% of the higher value of 6MWD

Exclusion Criteria:

  1. Subject has received any investigational/experimental drug, biologic or device within 30 days or 5 half-lives of the therapy or treatment, whichever is longer, before screening
  2. Subject has received treatment with prohibited medications within 30 days of screening
  3. Subject has received any gene therapy at any time
  4. Subject has any intercurrent illness or condition at screening or baseline that may preclude the subject from fulfilling the protocol requirements or suggests to the investigator and/or the medical monitor that the potential subject may have an unacceptable risk by participating in this study
  5. Subject has a hypersensitivity to any of the excipients in ATB200, alglucosidase alfa, or AT2221
  6. Female subject is pregnant or breast-feeding at screening
  7. Subject requires the use of ventilation support for > 6 hours per day while awake
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 12 Years to 17 Years   (Child)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: For Site 609-662-2000 PompeSiteInfo@amicusrx.com
Contact: For Patient 609-662-2000 patientadvocacy@amicusrx.com
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03911505
Other Study ID Numbers  ICMJE ATB200-04
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Amicus Therapeutics
Study Sponsor  ICMJE Amicus Therapeutics
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Amicus Therapeutics
Verification Date August 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP