Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
This study evaluated the long-term safety and efficacy of afegostat tartrate in participants with Gaucher disease who were enrolled in a previous Phase 2 study of afegostat tartrate.
This was an open-label, long-term extension study of afegostat tartrate in participants with type 1 Gaucher disease who successfully completed Study GAU-CL-202 (NCT00446550). Participants could enter the study immediately upon completion of participation in the lead-in study GAU-CL-202, or at any later time point. Participants received 225 milligram (mg) afegostat tartrate, administered orally for 30 months, and remained in 1 of the 2 randomized treatment regimens of Study GAU-CL-202: afegostat tartrate once daily (QD) for 3 consecutive days, then no afegostat tartrate for 4 consecutive days (consecutive 3-days-on/4-days-off) or QD for 7 consecutive days, then no afegostat tartrate for 7 days (consecutive 7-days-on/7-days-off). Amendment 2 removed the 7-days-on/7-days-off regimen and added an alternative 3-days-on/4-days-off regimen: afegostat tartrate QD on Monday, Wednesday, and Friday, then no afegostat tartrate on Tuesday, Thursday, Saturday, and Sunday (MWF 3-days-on/4-days-off). Once Amendment 2 was implemented at a site, participants assigned to the 7-days-on/7-days-off regimen switched to a 3-days-on/4-days-off regimen; those on the original 3-days-on/4-days-off regimen could switch to the MWF 3-days-on/4-days-off regimen. Amendment 4 removed the original 3-days-on/4-days-off regimen and any participants still on that regimen switched to the MWF 3-days-on/4-days-off regimen. Study visits occurred every 3 months for 30 months. Participants were contacted approximately 1, 3, and 6 months after the end of treatment (EOT) or early termination for follow-up assessments.
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Afegostat Tartrate Treatment Regimen 1 | Experimental | Afegostat tartrate was administered orally at a dose of 225 mg QD for 3 or 7 consecutive days followed by no study medication for 4 or 7 consecutive days (consecutive 3-days-on/4-days-off or 7-days-on/7-days-off, respectively). Amendment 2 added a MWF 3-days-on/4-days-off regimen. After Amendment 2 was implemented, all participants were assigned to one of the two 3-days-on/4-days-off regimens. Amendment 4 removed the consecutive 3-days-on/4-days-off regimen, and all participants were assigned to the MWF 3-days-on/4-days-off regimen. Participants were to receive afegostat tartrate for 30 months and be followed for 6 months after EOT. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| afegostat tartrate | Drug |
|
|
| Measure | Description | Time Frame |
|---|---|---|
| Number Of Participants Who Experienced Severe Treatment-emergent Adverse Events (TEAEs) | A TEAE was defined as any adverse event (AE) with start date on or after administration of study drug or pre-existing conditions that worsened on or after the start of the first study drug administration (on Day 1). A severe AE defined as an AE that was incapacitating and required medical intervention. The number of participants who experienced 1 or more severe TEAEs after dosing on Day 1 through the end of follow-up is presented. A summary of serious and all other non-serious AEs regardless of causality is located in the Reported Adverse Events module. | Day 1 (after dosing) through end of follow-up (6 months after EOT) |
| Measure | Description | Time Frame |
|---|---|---|
| Change From Baseline To EOT In Volume Of Spleen As Assessed By Magnetic Resonance Imaging (MRI) | Standard MRI procedures were used to measure the volume of the spleen. The baseline value was defined as the value recorded on Days 1 to 3 of the study (certain values could have been carried over from the last assessment in the lead-in study, GAU-CL-202). A negative change from Baseline indicates that spleen volume decreased. |
Not provided
Inclusion Criteria:
Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| Medical Director | Amicus Therapeutics, Inc. | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Coral Springs | Florida | 33065 | United States | |||
Participants were screened for evaluation of eligibility to participate in the study. Eight participants received at least 1 dose of study drug.
Not provided
Not provided
| ID | Title | Description |
|---|---|---|
| FG000 | Afegostat Tartrate | Afegostat tartrate was administered orally at a dose of 225 milligram (mg) once daily (QD) on Monday, Wednesday, and Friday, with no study medication on Tuesday, Thursday, Saturday, and Sunday (MWF 3-days-on/4-days-off). Participants were to receive afegostat tartrate for 30 months and be followed for 6 months after the end of treatment (EOT). |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
All participants who received at least 1 dose of study drug.
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | Afegostat Tartrate | Afegostat tartrate was administered orally at a dose of 225 mg QD MWF 3-days-on/4-days-off. Participants were to receive afegostat tartrate for 30 months and be followed for 6 months after EOT. |
| 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 | Number Of Participants Who Experienced Severe Treatment-emergent Adverse Events (TEAEs) | A TEAE was defined as any adverse event (AE) with start date on or after administration of study drug or pre-existing conditions that worsened on or after the start of the first study drug administration (on Day 1). A severe AE defined as an AE that was incapacitating and required medical intervention. The number of participants who experienced 1 or more severe TEAEs after dosing on Day 1 through the end of follow-up is presented. 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 study drug. | Posted | Count of Participants | Participants | Day 1 (after dosing) through end of follow-up (6 months after EOT) |
|
Day 1 (after dosing) through end of follow-up (6 months after EOT)
Not provided
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Afegostat Tartrate | Afegostat tartrate was administered orally at a dose of 225 mg QD MWF 3-days-on/4-days-off. Participants were to receive afegostat tartrate for 30 months and be followed for 6 months after EOT. |
Not provided
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Splenomegaly | Blood and lymphatic system disorders | MedDRA (15.0) | Systematic Assessment |
Due to the early withdrawal of 7 of the 8 study participants, there were no comparative data. Accordingly, no definitive conclusions regarding afegostat tartrate safety, efficacy, or pharmacodynamic effects can be made based on this information.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Amicus Therapeutics | Patient Advocacy | +1-609-662-2000 | Clinicaltrials@amicusrx.com |
| ID | Term |
|---|---|
| D005776 | Gaucher Disease |
| ID | Term |
|---|---|
| D013106 | Sphingolipidoses |
| D020140 | Lysosomal Storage Diseases, Nervous System |
| D020739 | Brain Diseases, Metabolic, Inborn |
| D001928 | Brain Diseases, Metabolic |
Not provided
Not provided
| ID | Term |
|---|---|
| C000599126 | AT2101 |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Baseline, Month 30 |
| Change From Baseline To EOT In Volume Of Liver As Assessed By MRI | Standard MRI procedures were used to measure the volume of the liver. The baseline value was defined as the value recorded on Days 1 to 3 of the study (certain values could have been carried over from the last assessment in the lead-in study, GAU-CL-202). A negative change from Baseline indicates that liver volume decreased. | Baseline, Month 30 |
| Decatur |
| Georgia |
| 30033 |
| United States |
| Boston | Massachusetts | 02114 | United States |
| London | United Kingdom |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
|
|
| Secondary | Change From Baseline To EOT In Volume Of Spleen As Assessed By Magnetic Resonance Imaging (MRI) | Standard MRI procedures were used to measure the volume of the spleen. The baseline value was defined as the value recorded on Days 1 to 3 of the study (certain values could have been carried over from the last assessment in the lead-in study, GAU-CL-202). A negative change from Baseline indicates that spleen volume decreased. | PD Population: all participants in the Safety Population who had a baseline and at least 1 post-baseline PD measurement. Seven of 8 participants did not complete the study and did not contribute data to this endpoint. | Posted | Number | cubic centimeters (cm^3) | Baseline, Month 30 |
|
|
|
| Secondary | Change From Baseline To EOT In Volume Of Liver As Assessed By MRI | Standard MRI procedures were used to measure the volume of the liver. The baseline value was defined as the value recorded on Days 1 to 3 of the study (certain values could have been carried over from the last assessment in the lead-in study, GAU-CL-202). A negative change from Baseline indicates that liver volume decreased. | PD Population: all participants in the Safety Population who had a baseline and at least 1 post-baseline PD measurement. Seven of 8 participants did not complete the study and did not contribute data to this endpoint. | Posted | Number | cm^3 | Baseline, Month 30 |
|
|
|
| 0 |
| 8 |
| 6 |
| 8 |
| Splenic infarction | Blood and lymphatic system disorders | MedDRA (15.0) | Systematic Assessment |
|
| Blepharitis | Eye disorders | MedDRA (15.0) | Systematic Assessment |
|
| Conjunctivitis | Eye disorders | MedDRA (15.0) | Systematic Assessment |
|
| Lacrimation increased | Eye disorders | MedDRA (15.0) | Systematic Assessment |
|
| Macular scar | Eye disorders | MedDRA (15.0) | Systematic Assessment |
|
| Vision blurred | Eye disorders | MedDRA (15.0) | Systematic Assessment |
|
| Abdominal pain | Gastrointestinal disorders | MedDRA (15.0) | Systematic Assessment |
|
| Chest pain | General disorders | MedDRA (15.0) | Systematic Assessment |
|
| Gait disturbance | General disorders | MedDRA (15.0) | Systematic Assessment |
|
| Hepatomegaly | Hepatobiliary disorders | MedDRA (15.0) | Systematic Assessment |
|
| Ligament sprain | Injury, poisoning and procedural complications | MedDRA (15.0) | Systematic Assessment |
|
| Muscle strain | Injury, poisoning and procedural complications | MedDRA (15.0) | Systematic Assessment |
|
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA (15.0) | Systematic Assessment |
|
| Intervertebral disc protrusion | Musculoskeletal and connective tissue disorders | MedDRA (15.0) | Systematic Assessment |
|
| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA (15.0) | Systematic Assessment |
|
| Pruritus | Skin and subcutaneous tissue disorders | MedDRA (15.0) | Systematic Assessment |
|
| Skin exfoliation | Skin and subcutaneous tissue disorders | MedDRA (15.0) | Systematic Assessment |
|
| Skin hyperpigmentation | Skin and subcutaneous tissue disorders | MedDRA (15.0) | Systematic Assessment |
|
The investigator can publish only the results from this trial, provided they supply the sponsor (or authorized entity) a copy of any proposed publication for review prior to submission for publication. If requested and prior to publication, 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.
| D001927 | Brain Diseases |
| 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 |
| D008064 | Lipidoses |
| D008052 | Lipid Metabolism, Inborn Errors |
| D016464 | Lysosomal Storage Diseases |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
| D052439 | Lipid Metabolism Disorders |