A Study of AT2101 (Afegostat Tartrate) in Adult Patients With Type 1 Gaucher Disease Currently Receiving Enzyme Replacement Therapy

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

NCT00433147

GAU-CL-201

Details and patient eligibility

About

This study was conducted to test the safety and tolerability of afegostat tartrate in participants with type 1 Gaucher disease already receiving enzyme replacement therapy.

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 14-day screening period, a 28-day treatment period, and a 7-day wash-out period. Participants received 1 of 4 dosing regimens for afegostat tartrate.

Enrollment: 30 patients

Sex: All

Ages: 18 to 74 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Had a confirmed diagnosis of type 1 Gaucher disease with a known documented missense gene mutation in at least 1 of the 2 gene-encoding β-glucosidase alleles
• Clinically stable
• Male or female participants, 18 to 74 years old inclusive
• All participants of childbearing potential used adequate birth control
• Provided written informed consent to participate in the study

Exclusion criteria

• Clinically significant disease, severe complications from Gaucher disease, or serious illness that precluded participation in the study in the opinion of the Investigator that compromised the safety of the participant or precluded the participant from completing the study
• During the screening period, any clinically significant findings, as deemed by the Investigator
• Partial or total splenectomy (removal of spleen) within the 2 years prior to study entry
• History of pulmonary hypertension or Gaucher related lung disease
• History of allergy or sensitivity to the study drug or any excipients, including any prior serious adverse reaction to iminosugars (for example, N-butyldeoxynojirimycin or miglustat)
• Pregnant or breast-feeding
• Current/recent drug or alcohol abuse
• Treatment with any investigational product in the 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 or 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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30 participants in 4 patient groups

Afegostat tartrate 25 milligrams (mg) once per day

Experimental group

Description:

Afegostat tartrate was administered orally during the 4-week treatment period.

Treatment:

Drug: Afegostat tartrate

Afegostat tartrate 150 mg once per day

Experimental group

Description:

Afegostat tartrate was administered orally once per day during the 4-week treatment period.

Treatment:

Drug: Afegostat tartrate

Afegostat tartrate 150 mg once every four days

Experimental group

Description:

Afegostat tartrate was administered orally once every 4 days during the 4-week treatment period.

Treatment:

Drug: Afegostat tartrate

Afegostat tartrate 150 mg once every seven days

Experimental group

Description:

Afegostat tartrate was administered orally once every 7 days during the 4-week treatment period.

Treatment:

Drug: Afegostat tartrate