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A Study to Evaluate the PK, Safety, Efficacy, and PD With ATB200/AT2221 in LOPD Subjects Aged 12 to <18

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT03911505
Recruitment Status : Recruiting
First Posted : April 11, 2019
Last Update Posted : August 19, 2019
Information provided by (Responsible Party):
Amicus Therapeutics

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.

Condition or disease Intervention/treatment Phase
Pompe Disease (Late-onset) Biological: ATB200 Drug: AT2221 Phase 3

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).

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 14 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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 : August 2019
Estimated Primary Completion Date : February 2021
Estimated Study Completion Date : June 2021

Arm Intervention/treatment
Experimental: ATB200/AT2221
Participants received ATB200 co-administered with AT2221 capsule (Miglustat)
Biological: ATB200
Enzyme Replacement Therapy via intravenous infusion

Drug: AT2221
Participants received ATB200 co-administered with AT2221 (Miglustat)
Other Name: Miglustat

Primary Outcome Measures :
  1. Assessment of pharmacokinetic parameters [ Time Frame: 52 weeks ]
    ATB200 protein and AT2221 concentrations in plasma

  2. 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

Secondary Outcome Measures :
  1. Change from baseline 6-Minute Walk Test [6MWT] [ Time Frame: 52 weeks ]
  2. Change from baseline Gait, Stair, Gower, and Chair maneuver [GSGC] test [ Time Frame: 52 weeks ]
  3. Change from baseline Timed Up and Go [TUG] test) [ Time Frame: 52 weeks ]
  4. Change from baseline manual muscle tests [MMT]) test) [ Time Frame: 52 weeks ]
  5. Change from baseline forced vital capacity [FVC] [ Time Frame: 52 weeks ]
  6. Change from baseline supine and sitting, slow vital capacity [SVC] [ Time Frame: 52 weeks ]
  7. Change from baseline supine and sitting, maximal inspiratory pressure [MIP] [ Time Frame: 52 weeks ]
  8. Change from baseline maximal expiratory pressure [MEP] [ Time Frame: 52 weeks ]
  9. Change from baseline Patient-reported Outcomes Measurement Information System (PROMIS®) [ Time Frame: 52 weeks ]
  10. Change from baseline Gross Motor Function Measure-88 Items (GMFM-88) [ Time Frame: 52 weeks ]
  11. Change from baseline Pompe-pediatric Evaluation of Disability Inventory (PompePedi) [ Time Frame: 52 weeks ]
  12. Change from baseline Subject/Physician Global Impression of Change (SGIC/PGIC) [ Time Frame: 52 weeks ]
  13. Change from baseline Visual Analog Scale (VAS) for pain assessment [ Time Frame: 52 weeks ]
  14. Change from baseline time to initiation of use of assistive device Scale (VAS) for pain assessment [ Time Frame: 52 weeks ]
  15. Biomarkers/Pharmacodynamics of muscle injury and disease substrate [ Time Frame: 52 weeks ]
    Change from baseline in Creatine Kinase and Urinary Hexose Tetrasaccharide

  16. Immunogenicity [ Time Frame: 52 weeks ]
    Change in anti-rhGAA antibodies from baseline over time

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   12 Years to 17 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

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 identifier (NCT number): NCT03911505

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Contact: For Site 609-662-2000
Contact: For Patient 609-662-2000

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United States, Arizona
Neuromuscular Research Center Recruiting
Phoenix, Arizona, United States, 85028
United States, Arkansas
Arkansas Children's Hospital Recruiting
Little Rock, Arkansas, United States, 72202
United States, Virginia
Lysosomal and Rare Disorders Research and Treatment Center, Inc. Recruiting
Fairfax, Virginia, United States, 22030
Sponsors and Collaborators
Amicus Therapeutics

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Responsible Party: Amicus Therapeutics Identifier: NCT03911505     History of Changes
Other Study ID Numbers: ATB200-04
First Posted: April 11, 2019    Key Record Dates
Last Update Posted: August 19, 2019
Last Verified: August 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Amicus Therapeutics:
Additional relevant MeSH terms:
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Glycogen Storage Disease Type II
Lysosomal Storage Diseases, Nervous System
Brain Diseases, Metabolic, Inborn
Brain Diseases, Metabolic
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Genetic Diseases, Inborn
Glycogen Storage Disease
Lysosomal Storage Diseases
Metabolic Diseases
Metabolism, Inborn Errors
Carbohydrate Metabolism, Inborn Errors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Glycoside Hydrolase Inhibitors
Hypoglycemic Agents
Physiological Effects of Drugs