- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00688597
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
Study Overview
Detailed 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.
Study Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
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Georgia
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Decatur, Georgia, United States, 30033
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: TREATMENT
- Allocation: NON_RANDOMIZED
- Interventional Model: PARALLEL
- Masking: NONE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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EXPERIMENTAL: Cohort 1
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.
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Powder in a bottle for dissolution in water for oral administration
Other Names:
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EXPERIMENTAL: Cohort 2
Regimen 1: High-dose duvoglustat (5.0 g) QD for 3 days, followed by no drug for 4 days, for 11 weeks.
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Powder in a bottle for dissolution in water for oral administration
Other Names:
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EXPERIMENTAL: Cohort 3
Regimen 2: High-dose duvoglustat (5.0 g) QD for 7 days, followed by no drug for 7 days, for 11 weeks.
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Powder in a bottle for dissolution in water for oral administration
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Proportion Of Participants Experiencing Severe Treatment-emergent Adverse Events (TEAEs)
Time Frame: Baseline, Week 11
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The number of participants experiencing severe TEAEs is presented for participants who received duvoglustat treatment in this open-label study.
The duration of duvoglustat exposure for Cohort 1 ranged from 2 to 24 days, and their exposure ranged from a total of 7,500 to 32,500 milligrams of duvoglustat.
An adverse event (AE) refers to any unfavorable and unintended sign, symptom, syndrome, or illness that develops or worsens during the period of observation in the clinical study.
The following guideline was used to grade the intensity of an AE: mild, the AE is easily tolerated and does not interfere with daily activity; moderate, the AE interferes with the daily activity but the participant is still able to function; severe, the AE is incapacitating and requires medical intervention.
A summary of serious and all other non-serious AEs regardless of causality is located in the Reported Adverse Events module.
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Baseline, Week 11
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Change In 6-minute Walk Test (6MWT) From Baseline To End Of Study
Time Frame: Baseline, Week 11
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The 6MWT (American Thoracic Society standards) was evaluated in ambulatory participants at screening, baseline, and to the end of the study.
It was a standardized test that measured the distance in meters (m) covered over a 6-minute walk.
Reference equations used (for 6MWT distance in healthy adults) included: (height in centimeters [cm], weight in kilograms [kg]) 6MWT distance for men = [7.57
× height (cm)] - [5.02 × age] - [1.76 × weight (kg)] - 309 m; 6MWT distance for women = [2.11
× height (cm)] - [5.78 × age] - [2.29 × weight (kg)] + 667 m
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Baseline, Week 11
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Collaborators and Investigators
Sponsor
Study record dates
Study Major Dates
Study Start (ACTUAL)
Primary Completion (ACTUAL)
Study Completion (ACTUAL)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (ESTIMATE)
Study Record Updates
Last Update Posted (ACTUAL)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Metabolic Diseases
- Brain Diseases
- Central Nervous System Diseases
- Nervous System Diseases
- Genetic Diseases, Inborn
- Carbohydrate Metabolism, Inborn Errors
- Metabolism, Inborn Errors
- Lysosomal Storage Diseases
- Brain Diseases, Metabolic
- Brain Diseases, Metabolic, Inborn
- Lysosomal Storage Diseases, Nervous System
- Glycogen Storage Disease
- Glycogen Storage Disease Type II
- Molecular Mechanisms of Pharmacological Action
- Anti-Infective Agents
- Antiviral Agents
- Enzyme Inhibitors
- 1-Deoxynojirimycin
Other Study ID Numbers
- POM-CL-201
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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