Back to resultsFirst-In-Human Study to Evaluate Safety, Tolerability, and PK of Intravenous ATB200 Alone and When Co-Administered With Oral AT2221
Primary Purpose
Pompe Disease
Status
Active
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
ATB200
AT2221
Sponsored by
About this trial
This is an interventional treatment trial for Pompe Disease focused on measuring Pompe, rhGAA
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
Sites / Locations
- Neuromuscular Research Centre
- University of California Irvine
- University of Florida
- Emory University Division of Medical Genetics
- Infusion Associates
- Great Falls Clinic, LLP
- Rutgers New Jersey Medical School
- Duke University Medical Center
- Perelman Center for Advanced Medicine
- University of Pittsburgh
- Abramson Cancer Center Chester County Hospital
- Lysosomal & Rare Disorders Research & Treatment Center (LDRTC)
- Womens & Childrens Hospital, Adelaide
- University Children's Hospital Department of Neuropediatrics and Inborn Metabolic Disorders, St. Josefs-Hospital
- Friedrich-Baur-Institure, Dep of Neurology - University Munich
- Erasmus Medical Center
- School of Medicine, University of Auckland
- University Hospital Birmingham NHS Foundation Trust, Queen Elizabeth Medical Center
- Salford Royal NHS Foundation Trust
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
ATB200
ATB200 + AT2221
Arm Description
In Stage 1, safety, tolerability, and PK will be evaluated following sequential single ascending doses of intravenously infused ATB200 for 3 dosing periods.
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)
Outcomes
Primary Outcome Measures
Plasma GAA activity levels as measured by maximum observed plasma concentration (Cmax).
Plasma GAA activity levels as measured by time to reach the maximum observed plasma concentration (tmax).
Plasma GAA activity levels as measured by area under the plasma-drug concentration time curve.
Safety and tolerability as measured by counts of Treatment Emergent Adverse Events (TEAEs), including Infusion Associated Reactions (IARs).
Secondary Outcome Measures
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02675465
Brief Title
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
2. Study Status
Record Verification Date
August 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
January 2016 (undefined)
Primary Completion Date
December 2023 (Anticipated)
Study Completion Date
December 2023 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Amicus Therapeutics
4. Oversight
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Pompe Disease
Keywords
Pompe, rhGAA
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
32 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
ATB200
Arm Type
Experimental
Arm Description
In Stage 1, safety, tolerability, and PK will be evaluated following sequential single ascending doses of intravenously infused ATB200 for 3 dosing periods.
Arm Title
ATB200 + AT2221
Arm Type
Experimental
Arm Description
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)
Intervention Type
Drug
Intervention Name(s)
ATB200
Intervention Type
Drug
Intervention Name(s)
AT2221
Other Intervention Name(s)
Miglustat
Primary Outcome Measure Information:
Title
Plasma GAA activity levels as measured by maximum observed plasma concentration (Cmax).
Time Frame
18 Weeks
Title
Plasma GAA activity levels as measured by time to reach the maximum observed plasma concentration (tmax).
Time Frame
18 Weeks
Title
Plasma GAA activity levels as measured by area under the plasma-drug concentration time curve.
Time Frame
18 Weeks
Title
Safety and tolerability as measured by counts of Treatment Emergent Adverse Events (TEAEs), including Infusion Associated Reactions (IARs).
Time Frame
18 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
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
Facility Information:
Facility Name
Neuromuscular Research Centre
City
Phoenix
State/Province
Arizona
ZIP/Postal Code
85028
Country
United States
Facility Name
University of California Irvine
City
Orange
State/Province
California
ZIP/Postal Code
92868
Country
United States
Facility Name
University of Florida
City
Gainesville
State/Province
Florida
ZIP/Postal Code
32610
Country
United States
Facility Name
Emory University Division of Medical Genetics
City
Decatur
State/Province
Georgia
ZIP/Postal Code
30033
Country
United States
Facility Name
Infusion Associates
City
Grand Rapids
State/Province
Michigan
ZIP/Postal Code
49525
Country
United States
Facility Name
Great Falls Clinic, LLP
City
Great Falls
State/Province
Montana
ZIP/Postal Code
59405
Country
United States
Facility Name
Rutgers New Jersey Medical School
City
Newark
State/Province
New Jersey
ZIP/Postal Code
08103
Country
United States
Facility Name
Duke University Medical Center
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27710
Country
United States
Facility Name
Perelman Center for Advanced Medicine
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
Facility Name
University of Pittsburgh
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15213
Country
United States
Facility Name
Abramson Cancer Center Chester County Hospital
City
West Chester
State/Province
Pennsylvania
ZIP/Postal Code
19380
Country
United States
Facility Name
Lysosomal & Rare Disorders Research & Treatment Center (LDRTC)
City
Fairfax
State/Province
Virginia
ZIP/Postal Code
22030
Country
United States
Facility Name
Womens & Childrens Hospital, Adelaide
City
North Adelaide
State/Province
South Australia
ZIP/Postal Code
05006
Country
Australia
Facility Name
University Children's Hospital Department of Neuropediatrics and Inborn Metabolic Disorders, St. Josefs-Hospital
City
Bochum
ZIP/Postal Code
44791
Country
Germany
Facility Name
Friedrich-Baur-Institure, Dep of Neurology - University Munich
City
Munich
ZIP/Postal Code
80336
Country
Germany
Facility Name
Erasmus Medical Center
City
Rotterdam
Country
Netherlands
Facility Name
School of Medicine, University of Auckland
City
Auckland
ZIP/Postal Code
01051
Country
New Zealand
Facility Name
University Hospital Birmingham NHS Foundation Trust, Queen Elizabeth Medical Center
City
Birmingham
ZIP/Postal Code
B15 2TH
Country
United Kingdom
Facility Name
Salford Royal NHS Foundation Trust
City
Salford
ZIP/Postal Code
M6 8HD
Country
United Kingdom
12. IPD Sharing Statement
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First-In-Human Study to Evaluate Safety, Tolerability, and PK of Intravenous ATB200 Alone and When Co-Administered With Oral AT2221
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