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

• ClinicalTrials.gov Identifier: NCT03911505
• Recruitment Status: Recruiting
• First Posted: April 11, 2019
• Last Update Posted: May 1, 2020
• Sponsor: Amicus Therapeutics
• Information provided by (Responsible Party): Amicus Therapeutics

Study Description

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.

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 14 participants
• Allocation: N/A
• 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
• Actual Study Start Date: February 13, 2020
• Estimated Primary Completion Date: September 2021
• Estimated Study Completion Date: September 2021

Arms and Interventions

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

Outcome Measures

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 NeuroQOL Lower Extremity Function (Mobility) [ Time Frame: 52 weeks ]
12. Change from baseline Subject/Physician Global Impression of Change (SGIC/PGIC) [ Time Frame: 52 weeks ]
13. Change from baseline time to initiation of use of assistive device Scale (VAS) for pain assessment [ Time Frame: 52 weeks ]
14. Biomarkers/Pharmacodynamics of muscle injury and disease substrate [ Time Frame: 52 weeks ]
    Change from baseline in Creatine Kinase and Urinary Hexose Tetrasaccharide
15. Immunogenicity [ Time Frame: 52 weeks ]
    Change in anti-rhGAA antibodies from baseline over time

Eligibility Criteria

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

Criteria

Inclusion Criteria:

1. Male or female subjects (ERT-naïve or ERT-experienced), diagnosed with late-onset Pompe disease who are aged 12 to < 18 years at screening
2. Subject weighs ≥ 25 kg and ≤ 115 kg
3. 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
4. Subject must have a diagnosis of LOPD
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. 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 any gene therapy at any time
3. Female subject is pregnant or breast-feeding at screening
4. Subject requires the use of ventilation support for > 6 hours per day while awake

Contacts and Locations

Contacts

Contact: For Site; 609-662-2000; PompeSiteInfo@amicusrx.com

Contact: For Patient; 609-662-2000; patientadvocacy@amicusrx.com

Locations

United States, Arizona

Neuromuscular Research Center; Recruiting

Phoenix, Arizona, United States, 85028

United States, California

UCSF Benioff Children's Hospital; Recruiting

Oakland, California, United States, 94609

United States, Florida

University of Florida Clinical Research Center; Recruiting

Gainesville, Florida, United States, 32610

United States, Michigan

Infusion Associates; Recruiting

Grand Rapids, Michigan, United States, 49525

United States, Minnesota

Mayo Clinic; Recruiting

Rochester, Minnesota, United States, 55905

United States, Missouri

St. Louis Children's Hospital; Recruiting

Saint Louis, Missouri, United States, 63110

United States, North Carolina

Duke University Medical Center; Recruiting

Durham, North Carolina, United States, 27710

United States, Virginia

Lysosomal and Rare Disorders Research and Treatment Center, Inc.; Recruiting

Fairfax, Virginia, United States, 22030

Canada, Alberta

University of Calgary; Recruiting

Calgary, Alberta, Canada, T3B 6A8

Taiwan

National Taiwan University Hospital; Recruiting

Taipei, Taiwan, 100

Sponsors and Collaborators

Amicus Therapeutics

More Information

• Responsible Party: Amicus Therapeutics
• ClinicalTrials.gov Identifier: NCT03911505
• Other Study ID Numbers: ATB200-04
• First Posted: April 11, 2019
• Last Update Posted: May 1, 2020
• Last Verified: April 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Amicus Therapeutics:

Pompe; rhGAA

Additional relevant MeSH terms:

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; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Glycogen Storage Disease; Carbohydrate Metabolism, Inborn Errors; Lysosomal Storage Diseases; Metabolic Diseases; Miglustat; 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