Clinical trial NCT00446550: A Study of Oral AT2101 (Afegostat Tartrate) in Treatment-naive Patients With Gaucher Disease
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Gaucher Disease
Type 1 Gaucher Disease
Gaucher Disease, Type 1
Keywords: Amicus Therapeutics
afegostat tartrate
isofagomine tartrate
AT2101
Lead sponsor: Amicus Therapeutics
Sponsor class: INDUSTRY
First posted: 2007-03-13
Enrollment: 19
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 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).

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

Primary outcomes:
measure: Number Of Participants Who Experienced Severe Treatment-emergent Adverse Events (TEAEs)
timeFrame: Day 1 (after dosing) through Day 183
Secondary outcomes:
measure: Change From Baseline To End Of Treatment In β-glucocerebrosidase (GCase) Levels In White Blood Cells (WBC)
timeFrame: Baseline, Day 169
Other outcomes:
Locations:
city: Beverly Hills
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: Kansas City
country: United States
state: Kansas
city: Boston
country: United States
state: Massachusetts
city: Cincinnati
country: United States
state: Ohio
city: Haifa
country: Israel
city: Tel Aviv
country: Israel
city: Johannesburg
country: South Africa
city: London
country: United Kingdom
Study officials:
affiliation: Amicus Therapeutics
name: Medical Monitor, Clinical Research
role: STUDY_DIRECTOR
References: