Long-Term Safety in the Open-Label Period of a Phase 2a Study of Brazikumab, an Antibody Against Interleukin-23

Abstract

Introduction: Brazikumab (MEDI2070), a human monoclonal antibody that is an anti-p19 subunit inhibitor of interleukin-23, was shown to be effective over 8 weeks of treatment for patients with moderate-to-severe active Crohn's disease.[1] Here, we report the long-term safety and tolerability of brazikumab. Methods: The Phase 2a study (NCT01714726) consisted of a 12-week double-blind induction period with randomization to intravenous brazikumab (700 mg) or placebo, followed by the open-label (OL) period where all patients were administered subcutaneous brazikumab (210 mg) every 4 weeks. Patients were aged 18-65 years, had a ≥6-month history of moderate-to-severe active Crohn's disease, had failed on or were intolerant to ≥1 anti-tumor necrosis factor alpha (TNFa) agent, successfully completed the double-blind period, and signed consent for inclusion in the OL period. Adverse events (AEs) and vital signs were recorded every 4 weeks until patients discontinued or completed the study at 100 weeks. Results: 104 patients entered (n=52 from placebo to brazikumab and n=52 from brazikumab to brazikumab) and 57 (54.8%) patients completed the OL period. Overall, 87 (83.7%) patients experienced ≥1 treatment-emergent AE (TEAE); 12 (11.5%) experienced ≥1 TEAE leading to permanent discontinuation of study drug and 20 (19.2%) experienced ≥1 serious AE (SAE). The most common TEAEs were headache (22.1%), nasopharyngitis (22.1%), abdominal pain (18.3%), and Crohn's disease (16.3%) [Table]. Half of the SAEs observed were gastrointestinal disorders associated with Crohn's disease. Five SAEs of infection were reported, none of which were opportunistic, such as herpes zoster or tuberculosis; all resolved and the investigational product was permanently discontinued for only one patient. No cases of cancer were reported. The AE profile was similar between patients who completed a previous 12-week course of either placebo or brazikumab treatment. Conclusion: In this 100-week OL period, brazikumab was well tolerated in patients with moderate-tosevere active Crohn's disease, warranting future studies in larger patient populations.590 Figure 1. Treatment-emergent adverse events in the 100-week open-label period