Clinical trial NCT00433147: A Study of AT2101 (Afegostat Tartrate) in Adult Patients With Type 1 Gaucher Disease Currently Receiving Enzyme Replacement Therapy
Official title: A Randomized, Open-label Study to Assess the Safety and Tolerability of Multiple Dose Levels and Multiple Dosing Regimens of AT2101 in Adult Patients With Type 1 Gaucher Disease Currently Receiving Enzyme Replacement Therapy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Gaucher Disease, Type 1
Type 1 Gaucher Disease
Gaucher Disease
Keywords: afegostat tartrate
isofagomine tartrate
AT2101
Amicus Therapeutics
Lead sponsor: Amicus Therapeutics
Sponsor class: INDUSTRY
First posted: 2007-02-09
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Maximum age (years): 74
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

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 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.

Eligibility criteria: 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

Primary outcomes:
measure: Number Of Participants Who Experienced Severe Treatment-emergent Adverse Events (TEAEs)
timeFrame: Day 1 (after dosing) through Day 35
Secondary outcomes:
measure: Change From Baseline To End Of Treatment In Beta-glucocerebrosidase (GCase) Levels In White Blood Cells (WBC)
timeFrame: Baseline, Day 28
Other outcomes:
Locations:
city: San Francisco
country: United States
state: California
city: Coral Springs
country: United States
state: Florida
city: Decatur
country: United States
state: Georgia
city: Iowa City
country: United States
state: Iowa
city: New York
country: United States
state: New York
city: Cincinnati
country: United States
state: Ohio
city: Portland
country: United States
state: Oregon
city: Philadelphia
country: United States
state: Pennsylvania
city: Pittsburgh
country: United States
state: Pennsylvania
city: Houston
country: United States
state: Texas
Study officials:
affiliation: Amicus Therapeutics
name: Medical Monitor, Clinical Research
role: STUDY_DIRECTOR
References: