a study of oral at2101 (afegostat tartrate) in treatment-naive patients with gaucher disease

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

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).

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

Keywords: amicus therapeutics afegostat tartrate isofagomine tartrate at2101