OP0075 A 6-Month, Phase 2, Open–Label, Single-Arm Study to Evaluate the Safety and Efficacy of Treatment with Canakinumab of Pediatric Patients with Colchicine Resistant Familial Mediterranean Fever

Background Familial Mediterranean fever (FMF) is the most common hereditary autoinflammatory syndrome, affecting > 100,000 people. FMF is caused by mutations in the MEFV gene, which encodes for the pyrin protein that is part of the inflammation complex that activates IL-1β. Evidence from case reports/series and one controlled study support IL-1 blockage as a potential treatment for FMF. Canakinumab (CAN) is a selective fully human monoclonal anti-IL-1β antibody approved in the EU and US for the treatment of cryopyrin associated periodic syndrome (CAPS). Objectives This study served as a proof of concept to evaluate the role of CAN in the treatment of pediatric colchicine resistant (CR)-FMF. Methods This was a 2-center open-label, single-arm study. The population consisted of CR FMF patients (pts) 4-20 years of age, with a history of at least 3 documented FMF attacks in the 3 months prior to enrollment. Pts entered a 30-day run-in period (RI) during which FMF attacks were documented in a diary. Pts who experienced an investigator-confirmed FMF attack during RI were eligible to enter the treatment phase and receive a SC injection of CAN 2 mg/kg (max 150 mg) every 4 weeks for three times with the 1st dose given during an attack. The dose was doubled to 4 mg/kg (max 300 mg) if an attack occurred between Day 1 Baseline and Day 29 visits. Following the end of the treatment period, pts were followed until day 144 or until an attack occurred, whichever occurred first. Primary outcome was the proportion of pts with ≥50% reduction in FMF attack rate during the treatment vs. pretreatment period. Results Fifteen Israeli pts (9 males, 6 females) entered the RI period and 7 (median age 9.5 yrs; 6.8-14.9 yrs) all with CR FMF advanced to the treatment period. In total, 6/7 (86%) pts had a ≥50% reduction in their FMF attack rate during the treatment period. The median attack rate prior to CAN was 2.7 per 28 days, this decreased to 0.3 per 28 days during treatment, representing a median 89% reduction. Five mild and 3 moderate attacks were experienced by 4 pts (1 with 4 attacks, 1 with 2 attacks and 2 with 1 attack) during the treatment period; 2 pts had their CAN dose uptitrated. Investigators rated FMF control as very poor (n=3), poor (n=3) or fair (n=1) at baseline; this improved to good (n=3) /very good (n=4) for all pts during the treatment period. Elevated median baseline CRP and SAA normalized by Day 8, ESR by Day 28 and all remained normal for remainder of trial. Onl