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

Amicus Therapeutics

Status and phase: Completed; Phase 2

Conditions: Gaucher Disease; Gaucher Disease, Type 1; Type 1 Gaucher Disease

Treatments: Drug: afegostat tartrate

Study type: Interventional

Funder types: Industry

Identifiers

NCT00446550

GAU-CL-202

Details and patient eligibility

About

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).

Full 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).

Enrollment: 19 patients

Sex: All

Ages: 18 to 74 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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19 participants in 2 patient groups

Afegostat Tartrate Treatment Regimen 1

Experimental group

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.

Treatment:

Drug: afegostat tartrate

Afegostat Tartrate Treatment Regimen 2

Experimental group

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.

Treatment:

Drug: afegostat tartrate