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

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 an enzyme stabilizer (AT2221).

The study aims to evaluate safety, tolerability, pharmacokinetics (PK), efficacy, pharmacodynamics (PD), and immunogenicity of ATB200 co-administered with AT2221.

Stage 1: evaluation of safety, tolerability, and PK following sequential single ascending doses of intravenously infused ATB200

Stage 2: evaluation of safety, tolerability, and PK following single- and multiple-ascending dose combinations of ATB200 and AT2221

Stage 3: evaluation of long term safety, tolerability, and efficacy following 24 month treatment of ATB200 co-administered with AT2221

Stage 4: open-label extension period with functional assessments every 6 months

Adults with Diagnosis of Pompe disease

Cohort 1: Enzyme Replacement Therapy (ERT)-experienced subject (ambulatory):

• Male and female subjects between 18 and 65 years of age, inclusive
• Received ERT with alglucosidase alfa (Myozyme/Lumizyme) for the previous 2-6 years, inclusive
• Was receiving alglucosidase alfa at a frequency of once every other week
• Must have been able to walk 200-500 meters on the 6-Minute Walk Test (6MWT)
• Had upright Forced Vial Capacity (FVC) 30-80% of predicted normal value

Cohort 2: ERT-experienced subjects (non-ambulatory):

• Male and female subjects between 18 and 65 years of age, inclusive
• Had been receiving ERT with alglucosidase alfa for ≥2 years at a regular or set frequency
• Was wheelchair-bound

Cohort 3: ERT-naïve subjects (ambulatory):

• Male and female subjects between 18 and 65 years of age, inclusive
• Must have been able to walk 200-500 meters on the 6MWT
• Had upright FVC 30-80% of predicted normal value

Cohort 4: ERT-experienced subject (ambulatory):

• Male and female subjects between 18 and 75 years of age, inclusive
• Had been receiving ERT with alglucosidase alfa for ≥7 years, inclusive
• Was receiving alglucosidase alfa at a frequency of once every other week
• Must have been able to walk 75-600 meters on the 6MWT
• Had upright FVC 30-85% of predicted normal value

Exclusion criteria

• Received treatment with prohibited medications within 30 days of Baseline Visit
• Subject, if female, was pregnant or breastfeeding at screening
• Subject, whether male or female, planned to conceive a child during the study
• Had 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
• Had a history of allergy or sensitivity to alglucosidase alfa, miglustat or other iminosugars (Cohorts 1, 2, and 4)
• Required invasive ventilatory support, or used noninvasive ventilatory support ≥ 6 hours a day while awake (Cohorts 1, 3, and 4)
• Had active systemic autoimmune disease such as lupus, scleroderma, or rheumatoid arthritis; subjects with autoimmune disease must have been discussed with the Amicus Medical Monitor
• Had active bronchial asthma; subjects with bronchial asthma must have been discussed with the Amicus Medical Monitor