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

NCT ID: NCT00446550

Last Updated: 2018-08-15

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 19 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-06-11
• Study Completion Date: 2009-08-20

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).

Conditions

Gaucher Disease; Type 1 Gaucher Disease; Gaucher Disease, Type 1

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

afegostat tartrate

Intervention Type: DRUG

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.

Group Type: EXPERIMENTAL

afegostat tartrate

Intervention Type: DRUG

Interventions

afegostat tartrate

Intervention Type: DRUG

Other Intervention Names

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 74 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Amicus Therapeutics

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Medical Monitor, Clinical Research

Role: STUDY_DIRECTOR

Amicus Therapeutics

Locations

Beverly Hills, California, United States

Coral Springs, Florida, United States

Decatur, Georgia, United States

Iowa City, Iowa, United States

Kansas City, Kansas, United States

Boston, Massachusetts, United States

Cincinnati, Ohio, United States

Haifa, , Israel

Tel Aviv, , Israel

Johannesburg, , South Africa

London, , United Kingdom

Countries

United States; Israel; South Africa; United Kingdom

Other Identifiers

GAU-CL-202

Identifier Type: -

Identifier Source: org_study_id