A Randomized, Double-Blind, Placebo-Controlled Phase 2 Study of Brodalumab in Patients With Moderate-to-Severe Crohn's Disease.

ABSTRACT

OBJECTIVES: To assess the safety and efficacy of brodalumab, a human anti-interleukin-17 receptor monoclonal antibody, in patients with moderate-to-severe Crohn's disease (CD). METHODS: Phase 2, randomized, double-blind, placebo-controlled, dose-ranging study in patients with moderate-to-severe CD and evidence of active inflammation. Patients were randomized 1111 to receive brodalumab (210, 350, or 700 mg at baseline and week 4) or placebo. The primary end point was proportion of patients achieving Crohn's disease activity index (CDAI) remission (≤150) at week 6. Secondary end points included proportion of patients with CDAI response (reduction from baseline of ≥100) at week 6 and change from baseline in CDAI at week 6. RESULTS: The study was terminated early based on an imbalance in worsening CD in active treatment groups. At the time of termination, 130 patients had been randomized. At week 6, remission rates were 3% (210 mg), 15% (350 mg), 9% (700 mg), and 3% (placebo) and CDAI response occurred in 16% (210 mg), 27% (350 mg), 15% (700 mg), and 13% (placebo) of patients. Mean change in CDAI at week 6 was -8.7 (95.3) (210 mg), -35.4 (105.6) (350 mg), -0.6 (105.9) (700 mg), and -28.2 (86.0) (placebo). Besides worsening of CD, overall incidences of adverse events were similar across treatment groups. CONCLUSIONS: Treatment with brodalumab resulted in a disproportionate number of cases of worsening CD in patients with active CD and no evidence of meaningful efficacy. These analyses did not suggest additional safety risks of brodalumab beyond worsening of CD symptoms in patients with active CD.