Back to resultsA Study of Oral AT2101 (Afegostat Tartrate) in Treatment-naive Patients With Gaucher Disease
Primary Purpose
Gaucher Disease, Type 1 Gaucher Disease, Gaucher Disease, Type 1
Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
afegostat tartrate
Sponsored by
About this trial
This is an interventional treatment trial for Gaucher Disease focused on measuring Amicus Therapeutics, afegostat tartrate, isofagomine tartrate, AT2101
Eligibility Criteria
Inclusion Criteria:
- Confirmed diagnosis of type 1 Gaucher disease with a known genotype and a documented missense gene mutation in at least 1 of the 2 gene-encoding β-glucosidase (GBA) alleles
- Clinically stable
- Treatment naïve to ERT and SRT or had not received ERT or SRT in the 12 months before screening
- Willing to not initiate ERT or SRT treatment during study participation
- Male or female participants, 18 to 74 years old, inclusive
- At the screening period (Day -21 to Day -1), participants must have met at least 2 of the following criteria: platelet count of ≤150,000 per microliter, hemoglobin ≤12 grams/deciliter (g/dL) for females and ≤13 g/dL for males, liver volume ≥1.25 multiples of normal (MN), and spleen volume ≥2 MN
- All participants of reproductive potential were required to practice an acceptable method of contraception
- Provided written informed consent to participate in the study
Exclusion Criteria:
- A clinically significant disease other than Gaucher disease, severe complications from Gaucher disease, or serious intercurrent illness that precluded participation in the study in the opinion of the investigator
- During the screening period, had any clinically significant findings as deemed by the investigator
- Partial or total splenectomy
- Documentation of moderate or severe pulmonary hypertension, defined as pulmonary arterial pressure >35 millimeters of mercury (mmHg) or significant Gaucher-related lung disease
- History of allergy or sensitivity to the study drug or any excipients, including any prior serious allergic reaction to iminosugars
- Pacemaker or other contraindication for magnetic resonance imaging (MRI) scanning
- Pregnant or breast-feeding
- Current/recent drug or alcohol abuse
- Treatment with any investigational product in the last 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 of 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 Type
Experimental
Experimental
Arm Label
Afegostat Tartrate Treatment Regimen 1
Afegostat Tartrate Treatment Regimen 2
Arm Description
For the first 2 weeks, afegostat tartrate was administered orally at a dose of 225 milligrams (mg) once daily (QD) for 7 consecutive days, followed by no study medication for 7 consecutive days. After 2 weeks, participants then took 225 mg afegostat tartrate QD for 3 consecutive days, followed by no study medication for 4 consecutive days. This 3-days-on/4-days-off treatment regimen was followed for 22 weeks.
Afegostat tartrate was administered orally at a dose of 225 mg QD for 7 consecutive days, followed by no study medication for 7 consecutive days. This 7-days-on/7-days-off treatment regimen was followed for 24 weeks.
Outcomes
Primary Outcome Measures
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 (Day 183) 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 β-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
NCT00446550
Brief Title
A Study of Oral AT2101 (Afegostat Tartrate) in Treatment-naive Patients With Gaucher Disease
Official Title
A Randomized, Open-label Study To Assess the Safety and Tolerability of AT2101 in Treatment-naive Adult Patients With Type 1 Gaucher Disease
Study Type
Interventional
2. Study Status
Record Verification Date
July 2018
Overall Recruitment Status
Completed
Study Start Date
June 11, 2008 (Actual)
Primary Completion Date
August 20, 2009 (Actual)
Study Completion Date
August 20, 2009 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Amicus Therapeutics
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
This study evaluated the safety and tolerability of afegostat tartrate in participants with type 1 Gaucher disease who were not receiving enzyme replacement therapy (ERT) or substrate reduction therapy (SRT).
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 21-day screening period, a 24-week treatment period, and follow-up visit (Day 183, end-of-study). Participants were randomized in a 1:1 ratio to 1 of 2 treatment regimens for afegostat tartrate (3 days on treatment/4 days off or 7 days on treatment/7 days off).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Gaucher Disease, Type 1 Gaucher Disease, Gaucher Disease, Type 1
Keywords
Amicus Therapeutics, afegostat tartrate, isofagomine tartrate, AT2101
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
19 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Afegostat Tartrate Treatment Regimen 1
Arm Type
Experimental
Arm Description
For the first 2 weeks, afegostat tartrate was administered orally at a dose of 225 milligrams (mg) once daily (QD) for 7 consecutive days, followed by no study medication for 7 consecutive days. After 2 weeks, participants then took 225 mg afegostat tartrate QD for 3 consecutive days, followed by no study medication for 4 consecutive days. This 3-days-on/4-days-off treatment regimen was followed for 22 weeks.
Arm Title
Afegostat Tartrate Treatment Regimen 2
Arm Type
Experimental
Arm Description
Afegostat tartrate was administered orally at a dose of 225 mg QD for 7 consecutive days, followed by no study medication for 7 consecutive days. This 7-days-on/7-days-off treatment regimen was followed for 24 weeks.
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
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 (Day 183) 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 183
Secondary Outcome Measure Information:
Title
Change From Baseline To End Of Treatment In β-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 169
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:
Confirmed diagnosis of type 1 Gaucher disease with a known genotype and a documented missense gene mutation in at least 1 of the 2 gene-encoding β-glucosidase (GBA) alleles
Clinically stable
Treatment naïve to ERT and SRT or had not received ERT or SRT in the 12 months before screening
Willing to not initiate ERT or SRT treatment during study participation
Male or female participants, 18 to 74 years old, inclusive
At the screening period (Day -21 to Day -1), participants must have met at least 2 of the following criteria: platelet count of ≤150,000 per microliter, hemoglobin ≤12 grams/deciliter (g/dL) for females and ≤13 g/dL for males, liver volume ≥1.25 multiples of normal (MN), and spleen volume ≥2 MN
All participants of reproductive potential were required to practice an acceptable method of contraception
Provided written informed consent to participate in the study
Exclusion Criteria:
A clinically significant disease other than Gaucher disease, severe complications from Gaucher disease, or serious intercurrent illness that precluded participation in the study in the opinion of the investigator
During the screening period, had any clinically significant findings as deemed by the investigator
Partial or total splenectomy
Documentation of moderate or severe pulmonary hypertension, defined as pulmonary arterial pressure >35 millimeters of mercury (mmHg) or significant Gaucher-related lung disease
History of allergy or sensitivity to the study drug or any excipients, including any prior serious allergic reaction to iminosugars
Pacemaker or other contraindication for magnetic resonance imaging (MRI) scanning
Pregnant or breast-feeding
Current/recent drug or alcohol abuse
Treatment with any investigational product in the last 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 of 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
Beverly Hills
State/Province
California
ZIP/Postal Code
90211
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
Kansas City
State/Province
Kansas
ZIP/Postal Code
66160
Country
United States
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45229
Country
United States
City
Haifa
Country
Israel
City
Tel Aviv
Country
Israel
City
Johannesburg
Country
South Africa
City
London
Country
United Kingdom
12. IPD Sharing Statement
Learn more about this trial
A Study of Oral AT2101 (Afegostat Tartrate) in Treatment-naive Patients With Gaucher Disease
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