a study of eliglustat tartrate (genz-112638) in patients with gaucher disease who have reached therapeutic goals with enzyme replacement therapy (encore)

Conditions: Gaucher Disease, Type 1

Summary: this phase 3 study was designed to confirm the efficacy and safety of eliglustat tartrate (genz-112638) in participants with gaucher disease type 1 who had reached therapeutic goals with enzyme replacement therapy (ert).

gaucher disease is characterized by lysosomal accumulation of glucosylceramide due to impaired glucosylceramide hydrolysis. gaucher disease type 1, which is the most common form, accounts for greater than (\>) 90% of cases and does not involve the central nervous system (cns). typical manifestations of gaucher disease type 1 include splenomegaly, hepatomegaly, thrombocytopenia, anemia, bone disease, and decreased quality of life. the disease manifestations are caused by the accumulation of glucosylceramide (storage material) in macrophages (called gaucher cells) which have infiltrated the spleen and liver as well as other tissues. eliglustat tartrate is a small molecule drug developed as an oral therapy which acts to specifically inhibit production of this storage material in gaucher cells. this study was designed to determine the efficacy, safety, and pk of eliglustat tartrate in adult participants with gaucher disease type 1 who had been stabilized on ert.

Eligibility criteria:
inclusion criteria: * the participant (and/or their parent/legal guardian) was willing and able to provide signed informed consent prior to any study-related procedures to be performed * the participant was at least 18 years old at the time of randomization * the participant had a confirmed diagnosis of gaucher disease type 1 * the participant had received treatment with ert for at least 3 years. within the 9 months prior to randomization, the participant had received a total monthly dose of 30 to 130 units/kilogram for at least 6 months * the participant had reached gaucher disease therapeutic goals prior to randomization * female participants of childbearing potential must have had a documented negative pregnancy test prior to dosing. in addition, all female participants of childbearing potential must use a medically accepted form of contraception throughout the study exclusion criteria: * the participant had a partial or total splenectomy within 3 years prior to randomization * the participant had received substrate reduction therapies for gaucher disease within 6 months prior to randomization * the participant had gaucher disease type 2 or 3 or was suspected of having gaucher disease type 3 * the participant had any clinically significant disease, other than gaucher disease, including cardiovascular, renal, hepatic, gastrointestinal (gi), pulmonary, neurologic, endocrine, metabolic (e.g. hypokalemia, hypomagnesemia), or psychiatric disease, other medical conditions, or serious intercurrent illnesses that may confound the study results or, in the opinion of the investigator, may preclude participation in the study * the participant had tested positive for the human immunodeficiency virus (hiv) antibody, hepatitis c antibody, or hepatitis b surface antigen * the participant had received an investigational product within 30 days prior to randomization * the participant was pregnant or lactating

Keywords: gaucher disease, genz-112638, beta-glucosidase, acid ß-glucosidase, glucocerebrosidase, glucosylceramide, d-glucosyl-n-acylsphingosine glucohydrolase, substrate reduction therapy