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A Study of Oral AT2101 (Afegostat Tartrate) in Treatment-naive Patients With Gaucher Disease

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00446550
Recruitment Status : Completed
First Posted : March 13, 2007
Results First Posted : August 15, 2018
Last Update Posted : August 15, 2018
Information provided by (Responsible Party):
Amicus Therapeutics

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).

Condition or disease Intervention/treatment Phase
Gaucher Disease Type 1 Gaucher Disease Gaucher Disease, Type 1 Drug: afegostat tartrate Phase 2

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).

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 19 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : June 11, 2008
Actual Primary Completion Date : August 20, 2009
Actual Study Completion Date : August 20, 2009

Arm Intervention/treatment
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.
Drug: afegostat tartrate
Other Names:
  • isofagomine tartrate
  • AT2101

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.
Drug: afegostat tartrate
Other Names:
  • isofagomine tartrate
  • AT2101

Primary Outcome Measures :
  1. Number Of Participants Who Experienced Severe Treatment-emergent Adverse Events (TEAEs) [ Time Frame: Day 1 (after dosing) through Day 183 ]
    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 :
  1. Change From Baseline To End Of Treatment In β-glucocerebrosidase (GCase) Levels In White Blood Cells (WBC) [ Time Frame: Baseline, Day 169 ]
    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.

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 74 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00446550

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United States, California
Beverly Hills, California, United States, 90211
United States, Florida
Coral Springs, Florida, United States, 33065
United States, Georgia
Decatur, Georgia, United States, 30033
United States, Iowa
Iowa City, Iowa, United States, 52242
United States, Kansas
Kansas City, Kansas, United States, 66160
United States, Massachusetts
Boston, Massachusetts, United States, 02114
United States, Ohio
Cincinnati, Ohio, United States, 45229
Haifa, Israel
Tel Aviv, Israel
South Africa
Johannesburg, South Africa
United Kingdom
London, United Kingdom
Sponsors and Collaborators
Amicus Therapeutics
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Study Director: Medical Monitor, Clinical Research Amicus Therapeutics
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Responsible Party: Amicus Therapeutics Identifier: NCT00446550    
Other Study ID Numbers: GAU-CL-202
First Posted: March 13, 2007    Key Record Dates
Results First Posted: August 15, 2018
Last Update Posted: August 15, 2018
Last Verified: July 2018
Keywords provided by Amicus Therapeutics:
Amicus Therapeutics
afegostat tartrate
isofagomine tartrate
Additional relevant MeSH terms:
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Gaucher Disease
Lysosomal Storage Diseases, Nervous System
Brain Diseases, Metabolic, Inborn
Brain Diseases, Metabolic
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Metabolism, Inborn Errors
Genetic Diseases, Inborn
Lipid Metabolism, Inborn Errors
Lysosomal Storage Diseases
Metabolic Diseases
Lipid Metabolism Disorders