2016-001275-80, XOMA-Studie

This is an open-label single-dose study to evaluate 2 dose levels of XOMA 358 in subjects with congenital hyperinsulinism. Two cohorts, with up to 6 subjects in each cohort, are planned for evaluation. Each subject will participate in only 1 cohort.
Cohort A will receive a single 1 mg/kg IV dose of XOMA 358 as an infusion over 30 minutes on 1 occasion. The second dose level (ie, Cohort B) will not take place until the Data Safety Review Committee (DSRC) has reviewed all available data from Cohort A relevant to the safety and tolerability, pharmacodynamics (PD), and pharmacokinetics (PK) of XOMA 358 collected through Day 29. After such review, Cohort B or additional subjects in Cohort A may be enrolled if the DSRC deems it appropriate to repeat a dose level or to study an additional dose level. The dose level of Cohort B will be determined by the DSRC and will not exceed 3 mg/kg.
In each cohort, safety will be monitored throughout the study, and serial blood samples will be collected through Day 105 for the PK of XOMA 358 after single-dose administration. In addition to the scheduled follow-up visits, subjects may be asked, at the Investigator’s discretion, to return to the research unit for safety procedures, additional PK and PD sample collection, or both. Various PD markers, including glucose, ketones (betahydroxybutyrate), insulin, C-peptide, and free fatty acid levels, will be assessed. A monitored fast, protein challenge, and oral glucose tolerance test (OGTT) will be performed on specific days. Induction of biological activity by XOMA 358 will be determined via changes in hypoglycemic events or other parameters.
Interim PK analyses may be performed to reconsider the sampling time points as the study progresses.