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

Pompe Disease Clinical Trial

Official title:

An Open-Label, Fixed-Sequence, Ascending-Dose, First-in-Human Study to Assess the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Efficacy of Intravenous Infusions of ATB200 Co-Administered With Oral AT2221 in Adult Subjects With Pompe Disease

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02675465
• Other study ID #: ATB200-02
• Status: Active, not recruiting
• Phase: Phase 1/Phase 2
• Start date: January 2016
• Est. completion date: June 2024

Study information

• Verified date: April 2024
• Source: Amicus Therapeutics
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 32
• Est. completion date: June 2024
• Est. primary completion date: June 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Key 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

Related Conditions & MeSH terms

• Glycogen Storage Disease Type II
• Pompe Disease

Intervention

Drug:
• ATB200

• AT2221

Locations

Country	Name	City	State
Australia	Womens & Childrens Hospital, Adelaide	North Adelaide	South Australia
Germany	University Children's Hospital Department of Neuropediatrics and Inborn Metabolic Disorders, St. Josefs-Hospital	Bochum
Germany	Friedrich-Baur-Institure, Dep of Neurology - University Munich	Munich
Netherlands	Erasmus Medical Center	Rotterdam
New Zealand	School of Medicine, University of Auckland	Auckland
United Kingdom	University Hospital Birmingham NHS Foundation Trust, Queen Elizabeth Medical Center	Birmingham
United Kingdom	Salford Royal NHS Foundation Trust	Salford
United States	Emory University Division of Medical Genetics	Decatur	Georgia
United States	Duke University Medical Center	Durham	North Carolina
United States	Lysosomal & Rare Disorders Research & Treatment Center (LDRTC)	Fairfax	Virginia
United States	University of Florida	Gainesville	Florida
United States	Infusion Associates	Grand Rapids	Michigan
United States	Great Falls Clinic, LLP	Great Falls	Montana
United States	Rutgers New Jersey Medical School	Newark	New Jersey
United States	University of California Irvine	Orange	California
United States	Perelman Center for Advanced Medicine	Philadelphia	Pennsylvania
United States	Neuromuscular Research Centre	Phoenix	Arizona
United States	University of Pittsburgh	Pittsburgh	Pennsylvania
United States	Abramson Cancer Center Chester County Hospital	West Chester	Pennsylvania

Sponsors (1)

Lead Sponsor	Collaborator
Amicus Therapeutics

Countries where clinical trial is conducted

United States,  Australia,  Germany,  Netherlands,  New Zealand,  United Kingdom, 

Outcome

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