Date: 2011-11-07
Type of information: Results
phase: 3
Announcement: results
Company: Novartis (Switzerland)
Product: ACZ885 (canakimumab)
Action
mechanism: ACZ885 is an investigational fully human monoclonal antibody which neutralizes the key inflammatory mediator, interleukin-1 beta (IL-1 beta), which plays an important role in a number of diseases including SJIA.
Disease: systemic juvenile idiopathic arthritis (SJIA)
Therapeutic area: Autoimmune diseases - Rare diseases
Country:
Trial
details: The Phase III, two-part study had an open-label, single-arm active treatment in Part I followed by a randomized, double-blind, placebo-controlled, event-driven withdrawal design in Part II. A total of 177 patients between the ages of 1 and 19 years with active SJIA were enrolled in the study. In Part I, patients received a subcutaneous (s.c.) dose of ACZ885 (4 mg/kg, up to 300 mg) every 4 weeks. After 8 weeks, patients who met the adapted ACR Pediatric 30 criteria began tapering (reducing) their steroid use until either: a) the dose had been decreased to <= 0.5 mg/kg while maintaining the adapted ACR Pediatric 30 Criteria (successful tapering of steroids); or b) a maximum of 20 weeks passed without reaching this goal (unsuccessful tapering of steroids). In Part II of the study, patients were randomized to either continue receiving ACZ885, or to receive placebo every 4 weeks, until a pre-specified number (37) of flare-events ("flares") had occurred. The primary endpoints were to: a) assess if ACZ885 allows tapering of steroids in at least 25% of SJIA patients (Part I); and b) demonstrate that time to flare is extended with ACZ885 vs. placebo (Part II). MAS is a known, potentially fatal condition associated with SJIA that is characterized by liver abnormalities, bleeding disorders, central nervous system dysfunction and multiple organ failure. Approximately 10% of SJIA patients are diagnosed with MAS, some of whom suffer repeated episodes.
In Part I of the study (representing 58 patient years), 138 of 177 patients (78%) reported an adverse event (AE), with the most common being nasopharyngitis, headache and cough. Serious adverse events (SAEs) were reported in 15 patients, with the most common being infections, MAS (four cases) or flare-associated events. Five SAEs led to discontinuation and one patient died of MAS. During Part II, AEs (the most common being arthralgia, cough, nasopharyngitis and pyrexia) were reported by 40 of 50 (80%) ACZ885-treated patients (vs. 35 of 50 [70%] placebo-after-ACZ885-treated patients) [3]; and six patients in each arm experienced one or more SAE, which mainly included infections, MAS and flare-associated events.Six patients, all in the placebo arm, discontinued the study due to AEs or SAEs during Part II. One patient died from MAS after study discontinuation in the placebo group.
Latest
news: Novartis has announced new pivotal Phase III data showing 45% of children with active systemic juvenile idiopathic arthritis (SJIA) were able to substantially reduce their use of oral corticosteroids (often described as steroids) within 28 weeks of commencing treatment with ACZ885 (canakinumab) (p<0.0001). In addition, patients with SJIA on ACZ885 were nearly three times (0.37 hazard ratio) less likely to suffer a new flare. Therefore, only 27% of ACZ885-treated patients experienced a new flare, vs. 75% of patients on placebo during the study (p=0.0043). Data from this trial support the safety and efficacy profile of ACZ885 in the study population. These results, along with data from a second pivotal study, are planned to form the basis for worldwide regulatory submissions in 2012. Side effects observed in this study were similar to those already seen for ACZ885's approved indication, including infections and neutropenia. In addition, cases of macrophage activation syndrome (MAS) were reported in this study.
