Study to Evaluate the Safety of AT2220 (Duvoglustat) in Pompe Disease
Primary Purpose
Pompe Disease
Status
Terminated
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Duvoglustat
Sponsored by
About this trial
This is an interventional treatment trial for Pompe Disease focused on measuring Amicus Therapeutics, Duvoglustat, AT2220
Eligibility Criteria
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
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Experimental
Experimental
Arm Label
Cohort 1
Cohort 2
Cohort 3
Arm 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.
Regimen 1: High-dose duvoglustat (5.0 g) QD for 3 days, followed by no drug for 4 days, for 11 weeks.
Regimen 2: High-dose duvoglustat (5.0 g) QD for 7 days, followed by no drug for 7 days, for 11 weeks.
Outcomes
Primary Outcome Measures
Proportion Of Participants Experiencing Severe Treatment-emergent Adverse Events (TEAEs)
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.
Secondary Outcome Measures
Change In 6-minute Walk Test (6MWT) From Baseline To End Of Study
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
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT00688597
Brief Title
Study to Evaluate the Safety of AT2220 (Duvoglustat) in Pompe Disease
Official Title
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 Type
Interventional
2. Study Status
Record Verification Date
July 2018
Overall Recruitment Status
Terminated
Why Stopped
Per protocol, 3 sequential dose cohorts were planned. Study discontinued by Sponsor based upon serious adverse events in first 2 of 3 participants in Cohort 1.
Study Start Date
December 8, 2008 (Actual)
Primary Completion Date
December 14, 2009 (Actual)
Study Completion Date
December 14, 2009 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Amicus Therapeutics
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
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.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Pompe Disease
Keywords
Amicus Therapeutics, Duvoglustat, AT2220
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
3 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Cohort 1
Arm Type
Experimental
Arm 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.
Arm Title
Cohort 2
Arm Type
Experimental
Arm Description
Regimen 1: High-dose duvoglustat (5.0 g) QD for 3 days, followed by no drug for 4 days, for 11 weeks.
Arm Title
Cohort 3
Arm Type
Experimental
Arm Description
Regimen 2: High-dose duvoglustat (5.0 g) QD for 7 days, followed by no drug for 7 days, for 11 weeks.
Intervention Type
Drug
Intervention Name(s)
Duvoglustat
Other Intervention Name(s)
Duvoglustat hydrochloride, 1-Deoxynojirimycin hydrochloride, AT2220
Intervention Description
Powder in a bottle for dissolution in water for oral administration
Primary Outcome Measure Information:
Title
Proportion Of Participants Experiencing Severe Treatment-emergent Adverse Events (TEAEs)
Description
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.
Time Frame
Baseline, Week 11
Secondary Outcome Measure Information:
Title
Change In 6-minute Walk Test (6MWT) From Baseline To End Of Study
Description
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
Time Frame
Baseline, Week 11
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
74 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Medical Monitor Clinical Research
Organizational Affiliation
Amicus Therapeutics
Official's Role
Study Director
Facility Information:
City
Decatur
State/Province
Georgia
ZIP/Postal Code
30033
Country
United States
12. IPD Sharing Statement
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Study to Evaluate the Safety of AT2220 (Duvoglustat) in Pompe Disease
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