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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.
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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Cohort 1 | Experimental | 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. |
|
| Cohort 2 | Experimental | Regimen 1: High-dose duvoglustat (5.0 g) QD for 3 days, followed by no drug for 4 days, for 11 weeks. |
|
| Cohort 3 | Experimental | Regimen 2: High-dose duvoglustat (5.0 g) QD for 7 days, followed by no drug for 7 days, for 11 weeks. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Duvoglustat | Drug | Powder in a bottle for dissolution in water for oral administration |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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. | Baseline, Week 11 |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Medical Monitor Clinical Research | Amicus Therapeutics | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Decatur | Georgia | 30033 | United States |
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| ID | Title | Description |
|---|---|---|
| FG000 | 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. |
| FG001 | Cohort 2 | Regimen 1: High-dose duvoglustat (5.0 g) QD for 3 days, followed by no drug for 4 days, for 11 weeks. |
| FG002 | Cohort 3 | Regimen 2: High-dose duvoglustat (5.0 g) QD for 7 days, followed by no drug for 7 days, for 11 weeks. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
Safety Population: All participants who received at least 1 dose of duvoglustat.
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| ID | Title | Description |
|---|---|---|
| BG000 | Cohort 1 | Regimen 1: Low-dose duvoglustat (2.5 g) QD for 3 days, followed by no drug for 4 days, for 11 weeks. |
| BG001 | Cohort 2 | Regimen 1: High-dose duvoglustat (5.0 g) QD for 3 days, followed by no drug for 4 days, for 11 weeks. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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. | Safety Population: All participants who received at least 1 dose of duvoglustat. | Posted | Count of Participants | Participants | Baseline, Week 11 |
|
Day 1 (after dosing) through end of follow up.
Due to the discontinuation of the study, AEs were not encoded.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Cohort 1 | Regimen 1: Low-dose duvoglustat (2.5 g) QD for 3 days, followed by no drug for 4 days, for 11 weeks. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Muscular weakness | General disorders | Uncoded | Systematic Assessment | [1] The Adverse Event Term was not coded in the database; therefore, "General disorders" was selected as the System Organ Class (SOC) for this AE. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Muscular weakness | General disorders | Uncoded | Systematic Assessment | The Adverse Event Term was not coded in the database; therefore, "General disorders" was selected as the SOC for this AE. |
The serious adverse event of muscle weakness was the main contributor to the study not reaching the target number of participants needed to achieve target power and statistically reliable results.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Amicus Therapeutics | Patient Advocacy | +1-609-662-2000 | clinicaltrials@amicusrx.com |
| ID | Term |
|---|---|
| D006009 | Glycogen Storage Disease Type II |
| ID | Term |
|---|---|
| D020140 | Lysosomal Storage Diseases, Nervous System |
| D020739 | Brain Diseases, Metabolic, Inborn |
| D001928 | Brain Diseases, Metabolic |
| D001927 | Brain Diseases |
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| ID | Term |
|---|---|
| D017485 | 1-Deoxynojirimycin |
| ID | Term |
|---|---|
| D050112 | Imino Pyranoses |
| D050111 | Imino Sugars |
| D007097 | Imines |
| D009930 | Organic Chemicals |
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| Baseline, Week 11 |
| BG002 | Cohort 3 | Regimen 2: High-dose duvoglustat (5.0 g) QD for 7 days, followed by no drug for 7 days, for 11 weeks. |
| BG003 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Title |
|---|
| Description |
|---|
| OG000 | Cohort 1 | Regimen 1: Low-dose duvoglustat (2.5 g) QD for 3 days, followed by no drug for 4 days, for 11 weeks. |
| OG001 | Cohort 2 | Regimen 1: High-dose duvoglustat (5.0 g) QD for 3 days, followed by no drug for 4 days, for 11 weeks. |
| OG002 | Cohort 3 | Regimen 2: High-dose duvoglustat (5.0 g) QD for 7 days, followed by no drug for 7 days, for 11 weeks. |
|
|
| Secondary | 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 | Safety Population: All participants who received at least 1 dose of duvoglustat. | Posted | Mean | Standard Deviation | m | Baseline, Week 11 |
|
|
|
| 2 |
| 3 |
| 3 |
| 3 |
| EG001 | Cohort 2 | Regimen 1: High-dose duvoglustat (5.0 g) QD for 3 days, followed by no drug for 4 days, for 11 weeks. | 0 | 0 | 0 | 0 |
| EG002 | Cohort 3 | Regimen 2: High-dose duvoglustat (5.0 g) QD for 7 days, followed by no drug for 7 days, for 11 weeks. | 0 | 0 | 0 | 0 |
|
|
| Flatulence | General disorders | Uncoded | Systematic Assessment | The Adverse Event Term was not coded in the database; therefore, "General disorders" was selected as the SOC for this AE. |
|
| Abdominal pain upper | General disorders | Uncoded | Systematic Assessment | The Adverse Event Term was not coded in the database; therefore, "General disorders" was selected as the SOC for this AE. |
|
| Alanine aminotransferase increased | General disorders | Uncoded | Systematic Assessment | The Adverse Event Term was not coded in the database; therefore, "General disorders" was selected as the SOC for this AE. |
|
| Aspartate aminotransferase increased | General disorders | Uncoded | Systematic Assessment | The Adverse Event Term was not coded in the database; therefore, "General disorders" was selected as the SOC for this AE. |
|
| Blood creatine phosphokinase increased | General disorders | Uncoded | Systematic Assessment | The Adverse Event Term was not coded in the database; therefore, "General disorders" was selected as the SOC for this AE. |
|
| Fall | General disorders | Uncoded | Systematic Assessment | The Adverse Event Term was not coded in the database; therefore, "General disorders" was selected as the SOC for this AE. |
|
| Dysphagia | General disorders | Uncoded | Systematic Assessment | The Adverse Event Term was not coded in the database; therefore, "General disorders" was selected as the SOC for this AE. |
|
| Joint injury | General disorders | Uncoded | Systematic Assessment | The Adverse Event Term was not coded in the database; therefore, "General disorders" was selected as the SOC for this AE. |
|
The investigator can only publish the results from this trial provided they supply the sponsor (or authorized entity) a copy of any proposed publication for review. If requested, the investigator will remove information deemed confidential or proprietary by the sponsor and will withhold publication for an additional period of time to allow the sponsor to take appropriate measures to establish and preserve its proprietary rights.
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
| D008661 | Metabolism, Inborn Errors |
| D030342 | Genetic Diseases, Inborn |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D006008 | Glycogen Storage Disease |
| D002239 | Carbohydrate Metabolism, Inborn Errors |
| D016464 | Lysosomal Storage Diseases |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
| D000470 |
| Alkaloids |
| D006571 | Heterocyclic Compounds |
| D010880 | Piperidines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D002241 | Carbohydrates |