- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00446550
A Study of Oral AT2101 (Afegostat Tartrate) in Treatment-naive Patients With Gaucher Disease
July 23, 2018 updated by: Amicus Therapeutics
A Randomized, Open-label Study To Assess the Safety and Tolerability of AT2101 in Treatment-naive Adult Patients With Type 1 Gaucher Disease
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).
Study Overview
Status
Completed
Intervention / Treatment
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).
Study Type
Interventional
Enrollment (Actual)
19
Phase
- Phase 2
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
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Haifa, Israel
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Tel Aviv, Israel
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Johannesburg, South Africa
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London, United Kingdom
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California
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Beverly Hills, California, United States, 90211
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Florida
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Coral Springs, Florida, United States, 33065
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Georgia
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Decatur, Georgia, United States, 30033
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Iowa
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Iowa City, Iowa, United States, 52242
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Kansas
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Kansas City, Kansas, United States, 66160
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Massachusetts
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Boston, Massachusetts, United States, 02114
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Ohio
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Cincinnati, Ohio, United States, 45229
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years to 74 years (Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
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
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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Experimental: Afegostat Tartrate Treatment Regimen 1
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.
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Other Names:
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Experimental: Afegostat Tartrate Treatment Regimen 2
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.
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Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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Number Of Participants Who Experienced Severe Treatment-emergent Adverse Events (TEAEs)
Time Frame: Day 1 (after dosing) through Day 183
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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.
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Day 1 (after dosing) through Day 183
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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Change From Baseline To End Of Treatment In β-glucocerebrosidase (GCase) Levels In White Blood Cells (WBC)
Time Frame: Baseline, Day 169
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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.
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Baseline, Day 169
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
June 11, 2008
Primary Completion (Actual)
August 20, 2009
Study Completion (Actual)
August 20, 2009
Study Registration Dates
First Submitted
March 9, 2007
First Submitted That Met QC Criteria
March 9, 2007
First Posted (Estimate)
March 13, 2007
Study Record Updates
Last Update Posted (Actual)
August 15, 2018
Last Update Submitted That Met QC Criteria
July 23, 2018
Last Verified
July 1, 2018
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Metabolic Diseases
- Brain Diseases
- Central Nervous System Diseases
- Nervous System Diseases
- Genetic Diseases, Inborn
- Metabolism, Inborn Errors
- Lysosomal Storage Diseases
- Lipid Metabolism Disorders
- Brain Diseases, Metabolic
- Brain Diseases, Metabolic, Inborn
- Sphingolipidoses
- Lysosomal Storage Diseases, Nervous System
- Lipidoses
- Lipid Metabolism, Inborn Errors
- Gaucher Disease
Other Study ID Numbers
- GAU-CL-202
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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