Back to resultsA Study of AT2101 (Afegostat Tartrate) in Adult Patients With Type 1 Gaucher Disease Currently Receiving Enzyme Replacement Therapy
Primary Purpose
Gaucher Disease, Type 1, Type 1 Gaucher Disease, Gaucher Disease
Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Afegostat tartrate
Sponsored by
About this trial
This is an interventional treatment trial for Gaucher Disease, Type 1 focused on measuring afegostat tartrate, isofagomine tartrate, AT2101, Amicus Therapeutics
Eligibility Criteria
Inclusion Criteria:
- Had a confirmed diagnosis of type 1 Gaucher disease with a known documented missense gene mutation in at least 1 of the 2 gene-encoding β-glucosidase alleles
- Clinically stable
- Male or female participants, 18 to 74 years old inclusive
- All participants of childbearing potential used adequate birth control
- Provided written informed consent to participate in the study
Exclusion Criteria:
- Clinically significant disease, severe complications from Gaucher disease, or serious illness that precluded participation in the study in the opinion of the Investigator that compromised the safety of the participant or precluded the participant from completing the study
- During the screening period, any clinically significant findings, as deemed by the Investigator
- Partial or total splenectomy (removal of spleen) within the 2 years prior to study entry
- History of pulmonary hypertension or Gaucher related lung disease
- History of allergy or sensitivity to the study drug or any excipients, including any prior serious adverse reaction to iminosugars (for example, N-butyldeoxynojirimycin or miglustat)
- Pregnant or breast-feeding
- Current/recent drug or alcohol abuse
- Treatment with any investigational product in the 90 days before study entry
- Treatment in the previous 90 days with any drug known to have a well-defined potential for toxicity to a major organ
- Presence or symptoms of gastrointestinal, liver or kidney disease, or other conditions known to interfere with the absorption, distribution, metabolism, or excretion of drugs
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm Type
Experimental
Experimental
Experimental
Experimental
Arm Label
Afegostat tartrate 25 milligrams (mg) once per day
Afegostat tartrate 150 mg once per day
Afegostat tartrate 150 mg once every four days
Afegostat tartrate 150 mg once every seven days
Arm Description
Afegostat tartrate was administered orally during the 4-week treatment period.
Afegostat tartrate was administered orally once per day during the 4-week treatment period.
Afegostat tartrate was administered orally once every 4 days during the 4-week treatment period.
Afegostat tartrate was administered orally once every 7 days during the 4-week treatment period.
Outcomes
Primary Outcome Measures
Number Of Participants Who Experienced Severe Treatment-emergent Adverse Events (TEAEs)
TEAEs were defined as any adverse event (AE) with a start date on or after administration of the study drug (on Day 1). A severe AE was 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 7 days after the last dose of study drug (Day 35) is presented. 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 From Baseline To End Of Treatment In Beta-glucocerebrosidase (GCase) Levels In White Blood Cells (WBC)
GCase is a biomarker used to assess the PD effects of afegostat tartrate. Blood samples were collected to assess GCase levels in WBC. The baseline value was defined as the last non-missing value before the start of study drug.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT00433147
Brief Title
A Study of AT2101 (Afegostat Tartrate) in Adult Patients With Type 1 Gaucher Disease Currently Receiving Enzyme Replacement Therapy
Official Title
A Randomized, Open-label Study to Assess the Safety and Tolerability of Multiple Dose Levels and Multiple Dosing Regimens of AT2101 in Adult Patients With Type 1 Gaucher Disease Currently Receiving Enzyme Replacement Therapy
Study Type
Interventional
2. Study Status
Record Verification Date
August 2018
Overall Recruitment Status
Completed
Study Start Date
March 23, 2007 (Actual)
Primary Completion Date
February 19, 2008 (Actual)
Study Completion Date
February 19, 2008 (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
This study was conducted to test the safety and tolerability of afegostat tartrate in participants with type 1 Gaucher disease already receiving enzyme replacement therapy.
Detailed Description
This was a Phase 2, open-label study in participants with Gaucher disease, a lysosomal storage disorder. Afegostat tartrate (also known as AT2101 or isofagomine tartrate) is designed to act as a pharmacological chaperone by selectively binding to misfolded β-glucocerebrosidase (GCase) and helping it fold correctly, intended to restore GCase activity. The study consisted of a 14-day screening period, a 28-day treatment period, and a 7-day wash-out period. Participants received 1 of 4 dosing regimens for afegostat tartrate.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Gaucher Disease, Type 1, Type 1 Gaucher Disease, Gaucher Disease
Keywords
afegostat tartrate, isofagomine tartrate, AT2101, Amicus Therapeutics
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
30 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Afegostat tartrate 25 milligrams (mg) once per day
Arm Type
Experimental
Arm Description
Afegostat tartrate was administered orally during the 4-week treatment period.
Arm Title
Afegostat tartrate 150 mg once per day
Arm Type
Experimental
Arm Description
Afegostat tartrate was administered orally once per day during the 4-week treatment period.
Arm Title
Afegostat tartrate 150 mg once every four days
Arm Type
Experimental
Arm Description
Afegostat tartrate was administered orally once every 4 days during the 4-week treatment period.
Arm Title
Afegostat tartrate 150 mg once every seven days
Arm Type
Experimental
Arm Description
Afegostat tartrate was administered orally once every 7 days during the 4-week treatment period.
Intervention Type
Drug
Intervention Name(s)
Afegostat tartrate
Other Intervention Name(s)
isofagomine tartrate, AT2101
Primary Outcome Measure Information:
Title
Number Of Participants Who Experienced Severe Treatment-emergent Adverse Events (TEAEs)
Description
TEAEs were defined as any adverse event (AE) with a start date on or after administration of the study drug (on Day 1). A severe AE was 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 7 days after the last dose of study drug (Day 35) is presented. A summary of serious and all other non-serious AEs regardless of causality is located in the Reported Adverse Events module.
Time Frame
Day 1 (after dosing) through Day 35
Secondary Outcome Measure Information:
Title
Change From Baseline To End Of Treatment In Beta-glucocerebrosidase (GCase) Levels In White Blood Cells (WBC)
Description
GCase is a biomarker used to assess the PD effects of afegostat tartrate. Blood samples were collected to assess GCase levels in WBC. The baseline value was defined as the last non-missing value before the start of study drug.
Time Frame
Baseline, Day 28
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:
Had a confirmed diagnosis of type 1 Gaucher disease with a known documented missense gene mutation in at least 1 of the 2 gene-encoding β-glucosidase alleles
Clinically stable
Male or female participants, 18 to 74 years old inclusive
All participants of childbearing potential used adequate birth control
Provided written informed consent to participate in the study
Exclusion Criteria:
Clinically significant disease, severe complications from Gaucher disease, or serious illness that precluded participation in the study in the opinion of the Investigator that compromised the safety of the participant or precluded the participant from completing the study
During the screening period, any clinically significant findings, as deemed by the Investigator
Partial or total splenectomy (removal of spleen) within the 2 years prior to study entry
History of pulmonary hypertension or Gaucher related lung disease
History of allergy or sensitivity to the study drug or any excipients, including any prior serious adverse reaction to iminosugars (for example, N-butyldeoxynojirimycin or miglustat)
Pregnant or breast-feeding
Current/recent drug or alcohol abuse
Treatment with any investigational product in the 90 days before study entry
Treatment in the previous 90 days with any drug known to have a well-defined potential for toxicity to a major organ
Presence or symptoms of gastrointestinal, liver or kidney disease, or other conditions known to interfere with the absorption, distribution, metabolism, or excretion of drugs
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
San Francisco
State/Province
California
ZIP/Postal Code
94143
Country
United States
City
Coral Springs
State/Province
Florida
ZIP/Postal Code
33065
Country
United States
City
Decatur
State/Province
Georgia
ZIP/Postal Code
30033
Country
United States
City
Iowa City
State/Province
Iowa
ZIP/Postal Code
52242
Country
United States
City
New York
State/Province
New York
ZIP/Postal Code
10016
Country
United States
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45229
Country
United States
City
Portland
State/Province
Oregon
ZIP/Postal Code
97239
Country
United States
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15213
Country
United States
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
12. IPD Sharing Statement
Learn more about this trial
A Study of AT2101 (Afegostat Tartrate) in Adult Patients With Type 1 Gaucher Disease Currently Receiving Enzyme Replacement Therapy
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