Clinical trial NCT02675465: First-In-Human Study to Evaluate Safety, Tolerability, and PK of Intravenous ATB200 Alone and When Co-Administered With Oral AT2221
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Pompe Disease
Keywords: Pompe, rhGAA
Lead sponsor: Amicus Therapeutics
Sponsor class: INDUSTRY
First posted: 2016-02-05
Enrollment: 29
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Plasma GAA activity levels as measured by maximum observed plasma concentration (Cmax).
timeFrame: 18 Weeks
measure: Plasma GAA activity levels as measured by time to reach the maximum observed plasma concentration (tmax).
timeFrame: 18 Weeks
measure: Plasma GAA activity levels as measured by area under the plasma-drug concentration time curve.
timeFrame: 18 Weeks
measure: Safety and tolerability as measured by counts of Treatment Emergent Adverse Events (TEAEs), including Infusion Associated Reactions (IARs).
timeFrame: 18 weeks
Secondary outcomes:
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Neuromuscular Research Centre
state: Arizona
city: Orange
country: United States
facility: University of California Irvine
state: California
city: Gainesville
country: United States
facility: University of Florida
state: Florida
city: Decatur
country: United States
facility: Emory University Division of Medical Genetics
state: Georgia
city: Grand Rapids
country: United States
facility: Infusion Associates
state: Michigan
city: Great Falls
country: United States
facility: Great Falls Clinic, LLP
state: Montana
city: Newark
country: United States
facility: Rutgers New Jersey Medical School
state: New Jersey
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Philadelphia
country: United States
facility: Perelman Center for Advanced Medicine
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University of Pittsburgh
state: Pennsylvania
city: West Chester
country: United States
facility: Abramson Cancer Center Chester County Hospital
state: Pennsylvania
city: Fairfax
country: United States
facility: Lysosomal & Rare Disorders Research & Treatment Center (LDRTC)
state: Virginia
city: North Adelaide
country: Australia
facility: Womens & Childrens Hospital, Adelaide
state: South Australia
city: Bochum
country: Germany
facility: University Children's Hospital Department of Neuropediatrics and Inborn Metabolic Disorders, St. Josefs-Hospital
city: Munich
country: Germany
facility: Friedrich-Baur-Institure, Dep of Neurology - University Munich
city: Rotterdam
country: Netherlands
facility: Erasmus Medical Center
city: Auckland
country: New Zealand
facility: School of Medicine, University of Auckland
city: Birmingham
country: United Kingdom
facility: University Hospital Birmingham NHS Foundation Trust, Queen Elizabeth Medical Center
city: Salford
country: United Kingdom
facility: Salford Royal NHS Foundation Trust
Study officials:
References: