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

Study Overview
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Brief Summary
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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
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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.

Official Title
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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

Conditions
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Pompe Disease

Intervention / Treatment
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* Drug: ATB200
* Drug: AT2221


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ATB200<br>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<br> <br> |
| Experimental: ATB200 + AT2221<br>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<br> <br> Drug: AT2221<br> <br> * Other names: Miglustat;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 
| Plasma GAA activity levels as measured by area under the plasma-drug concentration time curve. |  | 18 Weeks | 
| Safety and tolerability as measured by counts of Treatment Emergent Adverse Events (TEAEs), including Infusion Associated Reactions (IARs). |  | 18 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pompe, rhGAA