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

Amicus Therapeutics

Status and phase: Terminated; Phase 2

Conditions: Pompe Disease

Treatments: Drug: Duvoglustat

Study type: Interventional

Funder types: Industry

Identifiers

NCT00688597

POM-CL-201

Details and patient eligibility

About

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.

Full description

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.

Enrollment: 3 patients

Sex: All

Ages: 18 to 74 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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3 participants in 3 patient groups

Cohort 1

Experimental group

Description:

Regimen 1: Low-dose duvoglustat (2.5 grams \[g\]) once a day (QD) for 3 days, followed by no drug for 4 days, for 11 weeks.

Treatment:

Drug: Duvoglustat

Cohort 2

Experimental group

Description:

Regimen 1: High-dose duvoglustat (5.0 g) QD for 3 days, followed by no drug for 4 days, for 11 weeks.

Treatment:

Drug: Duvoglustat

Cohort 3

Experimental group

Description:

Regimen 2: High-dose duvoglustat (5.0 g) QD for 7 days, followed by no drug for 7 days, for 11 weeks.

Treatment:

Drug: Duvoglustat