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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

Sponsor
Amicus Therapeutics (Industry)
Overall Status
Active, not recruiting
CT.gov ID
NCT02675465
Collaborator
(none)
32
Enrollment
19
Locations
2
Arms
95
Duration (Months)
1.7
Patients Per Site
0
Patients Per Site Per Month

Study Details

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.

Condition or Disease Intervention/Treatment Phase
Phase 1/Phase 2

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 Design

Study Type:
Interventional
Anticipated Enrollment :
32 participants
Allocation:
Non-Randomized
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
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 Start Date :
Jan 1, 2016
Anticipated Primary Completion Date :
Dec 1, 2023
Anticipated Study Completion Date :
Dec 1, 2023

Arms and Interventions

Arm Intervention/Treatment
Experimental: ATB200

In Stage 1, safety, tolerability, and PK will be evaluated following sequential single ascending doses of intravenously infused ATB200 for 3 dosing periods.

Drug: ATB200
Experimental: ATB200 + 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)

Drug: ATB200

Drug: AT2221
Other Names:
  • Miglustat

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Plasma GAA activity levels as measured by maximum observed plasma concentration (Cmax). [18 Weeks]

    2. Plasma GAA activity levels as measured by time to reach the maximum observed plasma concentration (tmax). [18 Weeks]

    3. Plasma GAA activity levels as measured by area under the plasma-drug concentration time curve. [18 Weeks]

    4. Safety and tolerability as measured by counts of Treatment Emergent Adverse Events (TEAEs), including Infusion Associated Reactions (IARs). [18 weeks]

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 75 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Neuromuscular Research Centre Phoenix Arizona United States 85028
    2 University of California Irvine Orange California United States 92868
    3 University of Florida Gainesville Florida United States 32610
    4 Emory University Division of Medical Genetics Decatur Georgia United States 30033
    5 Infusion Associates Grand Rapids Michigan United States 49525
    6 Great Falls Clinic, LLP Great Falls Montana United States 59405
    7 Rutgers New Jersey Medical School Newark New Jersey United States 08103
    8 Duke University Medical Center Durham North Carolina United States 27710
    9 Perelman Center for Advanced Medicine Philadelphia Pennsylvania United States 19104
    10 University of Pittsburgh Pittsburgh Pennsylvania United States 15213
    11 Abramson Cancer Center Chester County Hospital West Chester Pennsylvania United States 19380
    12 Lysosomal & Rare Disorders Research & Treatment Center (LDRTC) Fairfax Virginia United States 22030
    13 Womens & Childrens Hospital, Adelaide North Adelaide South Australia Australia 05006
    14 University Children's Hospital Department of Neuropediatrics and Inborn Metabolic Disorders, St. Josefs-Hospital Bochum Germany 44791
    15 Friedrich-Baur-Institure, Dep of Neurology - University Munich Munich Germany 80336
    16 Erasmus Medical Center Rotterdam Netherlands
    17 School of Medicine, University of Auckland Auckland New Zealand 01051
    18 University Hospital Birmingham NHS Foundation Trust, Queen Elizabeth Medical Center Birmingham United Kingdom B15 2TH
    19 Salford Royal NHS Foundation Trust Salford United Kingdom M6 8HD

    Sponsors and Collaborators

    • Amicus Therapeutics

    Investigators

    None specified.

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Amicus Therapeutics
    ClinicalTrials.gov Identifier:
    NCT02675465
    Other Study ID Numbers:
    • ATB200-02
    First Posted:
    Feb 5, 2016
    Last Update Posted:
    Jun 13, 2022
    Last Verified:
    Jun 1, 2022
    Keywords provided by Amicus Therapeutics
    Pompe, rhGAA
    Additional relevant MeSH terms:
    Glycogen Storage Disease Type II
    Miglustat

    Study Results

    No Results Posted as of Jun 13, 2022