First-In-Human Study to Evaluate Safety, Tolerability, and PK of Intravenous ATB200 Alone and When Co-Administered With Oral AT2221

Phase 1

Completed

• Conditions: Pompe Disease
• Interventions: Drug: ATB200; Drug: AT2221

• Registration Number: NCT02675465
• Lead Sponsor: Amicus Therapeutics

Brief Summary

This study is an international, multi-center, study of Pompe disease patients that are currently receiving enzyme-replacement therapy (ERT). The purpose of this study is to find out if the co-administration of investigational new drugs ATB200 and AT2221 is safe in adults with Pompe disease.

Detailed Description

This is an open-label, fixed-sequence, ascending-dose, first-in-human study to evaluate the effect of a highly targeted rhGAA (ATB200) co-administered with a chaperone (AT2221).

The study aims to evaluate safety, tolerability, pharmacodynamics (PD), and immunogenicity of ATB200 co-administered with AT2221. The study will be conducted in 3 stages.

In Stage 1, safety, tolerability, and PK will be evaluated following sequential single ascending doses of intravenously infused ATB200.

In Stage 2, safety, tolerability, and PK will be evaluated following single- and multiple-ascending dose combinations of ATB200 and AT2221.

In Stage 3, long term safety and efficacy will be assessed following 24 month treatment of ATB200 co-administered with AT2221 (Miglustat)

In Stage 4, treatment period will begin at the end of Stage 3 and will continue as open label extension until commercialization, study discontinuation or subject withdrawal, with functional assessments every 6 months

No Muscle biopsies will be performed in this study.

Study Timeline

• Study First Submitted: 2016-01-26
• Study First Submitted QC: 2016-02-03
• Study First Posted: 2016-02-05
• Study Start: 2016-04
• Primary Completion: 2024-07-15
• Status Verified: 2024-08
• Study Completion: 2024-08-20
• Last Update Submitted: 2024-08-22
• Last Update Posted: 2024-08-23

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 32

Inclusion Criteria

• Male and female subjects between 18 and 75years of age, inclusive
• Diagnosis of Pompe disease

Enzyme Replacement Therapy (ERT)-experienced subject (ambulatory):

• Has received ERT with alglucosidase alfa for the previous 2-6 years, inclusive
• Subject is currently receiving alglucosidase alfa (Myozyme/Lumizyme), at a frequency of once every other week
• Must be able to walk 200-500 meters on the 6-Minute Walk Test (6MWT )
• Has upright Forced Vial Capacity (FVC) 30% to 80% of predicted normal value

ERT-experienced subjects (non-ambulatory):

• Has received ERT with alglucosidase alfa (Myozyme/Lumizyme) for ≥2 years
• Is wheelchair-bound

ERT-naïve subjects (ambulatory):

• Must be able to walk 200-500 meters on the 6MWT
• Has upright FVC must be 30% to 80% of predicted normal value
• Subject has never received alglucosidase alfa

Enzyme Replacement Therapy (ERT)-experienced subject (ambulatory):

• Has received ERT with alglucosidase alfa for >7years, inclusive
• Subject is currently receiving alglucosidase alfa (Myozyme/Lumizyme), at a frequency of once every other week
• Must be able to walk 200-500 meters on the 6-Minute Walk Test (6MWT )
• Has upright Forced Vial Capacity (FVC) 30% to 80% of predicted normal value

Exclusion Criteria

• Subject has received treatment with prohibited medications within 30 days of Baseline Visit
• Subject, if female, is pregnant or breastfeeding at screening
• Subject, whether male or female, planning to conceive a child during the study
• Subject has a medical or any other extenuating condition or circumstance that may, in opinion of investigator, pose an undue safety risk to the subject or compromise his/her ability to comply with protocol requirements
• Subject has a history of allergy or sensitivity to miglustat or other iminosugars
• Subjects with active systemic autoimmune disease such as lupus, scleroderma, or rheumatoid arthritis. All subjects with autoimmune disease must be discussed with the Amicus Medical Monitor
• Subjects with active bronchial asthma. All subjects with bronchial asthma must be discussed with the Amicus Medical Monitor

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
ATB200	ATB200	In Stage 1, safety, tolerability, and PK will be evaluated following sequential single ascending doses of intravenously infused ATB200 for 3 dosing periods.
ATB200 + AT2221	ATB200	In Stage 2, safety, tolerability, and PK will be evaluated following single- and multiple-ascending dose combinations of ATB200 co-administered with AT2221 (Miglustat) In Stage 3, long term safety and efficacy will be assessed following 24 month treatment of ATB200 co-administered with AT2221 (Miglustat)
ATB200 + AT2221	AT2221	In Stage 2, safety, tolerability, and PK will be evaluated following single- and multiple-ascending dose combinations of ATB200 co-administered with AT2221 (Miglustat) In Stage 3, long term safety and efficacy will be assessed following 24 month treatment of ATB200 co-administered with AT2221 (Miglustat)

Primary Outcome Measures

Name	Time	Method
Plasma GAA activity levels as measured by area under the plasma-drug concentration time curve.	18 Weeks
Plasma GAA activity levels as measured by maximum observed plasma concentration (Cmax).	18 Weeks
Plasma GAA activity levels as measured by time to reach the maximum observed plasma concentration (tmax).	18 Weeks
Safety and tolerability as measured by counts of Treatment Emergent Adverse Events (TEAEs), including Infusion Associated Reactions (IARs).	18 weeks

Trial Locations

Locations (19)

Lysosomal & Rare Disorders Research & Treatment Center (LDRTC); 🇺🇸 Fairfax, Virginia, United States

Emory University Division of Medical Genetics; 🇺🇸 Decatur, Georgia, United States

University Hospital Birmingham NHS Foundation Trust, Queen Elizabeth Medical Center; 🇬🇧 Birmingham, United Kingdom

Infusion Associates; 🇺🇸 Grand Rapids, Michigan, United States

Rutgers New Jersey Medical School; 🇺🇸 Newark, New Jersey, United States

Friedrich-Baur-Institure, Dep of Neurology - University Munich; 🇩🇪 Munich, Germany

University of California Irvine; 🇺🇸 Orange, California, United States

Abramson Cancer Center Chester County Hospital; 🇺🇸 West Chester, Pennsylvania, United States

Womens & Childrens Hospital, Adelaide; 🇦🇺 North Adelaide, South Australia, Australia

Salford Royal NHS Foundation Trust; 🇬🇧 Salford, United Kingdom

University Children's Hospital Department of Neuropediatrics and Inborn Metabolic Disorders, St. Josefs-Hospital; 🇩🇪 Bochum, Germany

School of Medicine, University of Auckland; 🇳🇿 Auckland, New Zealand

Erasmus Medical Center; 🇳🇱 Rotterdam, Netherlands

Duke University Medical Center; 🇺🇸 Durham, North Carolina, United States

Perelman Center for Advanced Medicine; 🇺🇸 Philadelphia, Pennsylvania, United States

University of Pittsburgh; 🇺🇸 Pittsburgh, Pennsylvania, United States

Great Falls Clinic, LLP; 🇺🇸 Great Falls, Montana, United States

Neuromuscular Research Centre; 🇺🇸 Phoenix, Arizona, United States

University of Florida; 🇺🇸 Gainesville, Florida, United States