Study to Evaluate the Safety of AT2220 (Duvoglustat) in Pompe Disease

An Open-Label, Multicenter Study to Evaluate the Safety, Tolerability, Pharmacodynamics, and Pharmacokinetics of Three Dosing Regimens of Oral AT2220 in Patients With Pompe Disease

The main purpose of this study was to determine the safety and tolerability of 3 different doses of duvoglustat (AT2220) in participants affected by Pompe disease. The study also evaluated the effects of duvoglustat on functional parameters in Pompe disease.

This was a Phase 2, open-label study in participants with Pompe disease, a lysosomal storage disorder. Duvoglustat is designed to act as a pharmacological chaperone of alpha-glucosidase, in order to restore enzyme activity. This study consisted of a 28-day screening period, an 11-week treatment period, and a 1-week follow-up period. Three dosing regimens of oral duvoglustat were to be evaluated (Cohort 1: 2.5 g daily for 3 days, followed by no study drug for 4 days; Cohort 2: 5 g daily for 3 days, followed by no study drug for 4 days; Cohort 3: 5 g daily for 7 days, followed by no study drug for 7 days).

Participants meeting all eligibility criteria underwent physical examination, electrocardiogram, spirometry, muscular strength test, functional muscle test, 6-minute walk test (when appropriate), laboratory tests, magnetic resonance imaging, and muscle (needle) biopsy. Quality of life was assessed via the 36-Item Short Form Health Survey questionnaire. Functional ability and level of handicap was assessed by Rotterdam handicap scale.

Inclusion Criteria:

• Male or female, 18 to 74 years of age inclusive
• Diagnosis of Pompe disease based on clinical assessment, enzyme assay, and/or genotyping. Confirmatory genotyping will be performed on all participants who are screened for the study
• Naïve to enzyme replacement therapy (ERT) or has not received ERT in the 3 months prior to screening
• Willing not to initiate ERT or other prohibited treatment during study participation
• Functional grade for arms and/or legs ≥2 OR sitting forced vital capacity ≥30% and <80% of predicted value, reproducible between screening and baseline (±15%)
• Participants of reproductive potential agree to use reliable methods of contraception during the study
• Participant or legal representative is willing and able to provide written informed consent

Exclusion Criteria:

• Any intercurrent condition that may preclude accurate interpretation of study data
• Obstructive pulmonary disease
• Invasive ventilatory support
• Use of noninvasive ventilatory support >8 hours/day while awake
• History of QTc prolongation >450 milliseconds (msec) for males and >470 msec for females
• History of allergy or sensitivity to the study drug, including any prior serious adverse reaction to iminosugars (such as miglustat or miglitol)
• Pregnancy or breast-feeding
• Current or recent drug or alcohol abuse
• Treatment with another investigational drug within 30 days of study start
• Use of prohibited medications ≤3 months prior to screening
• Otherwise unsuitable for the study in the opinion of the Investigator