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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
Amicus Therapeutics
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Pompe Disease focused on measuring Amicus Therapeutics, Duvoglustat, AT2220

Eligibility Criteria

18 Years - 74 Years (Adult, Older Adult)All SexesDoes not accept 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

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

First Posted
May 30, 2008
Last Updated
July 23, 2018
Sponsor
Amicus Therapeutics
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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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