Eldelumab [Anti-IP-10] Induction Therapy for Ulcerative Colitis: A Randomised, Placebo-Controlled, Phase 2b Study.

BACKGROUND AND AIMS Interferon-γ-inducible protein-10 [IP-10] mediates immune cell trafficking from the circulation to the inflamed colon and decreases gut epithelial cell survival. IP-10 expression is increased in patients with ulcerative colitis [UC]. We report efficacy and safety results from a dose-ranging induction study of eldelumab, a fully human monoclonal antibody to IP-10, in moderately to severely active UC. METHODS A total of 252 adults with UC [Mayo score ≥ 6 and endoscopic subscore ≥ 2] were randomised 1:1:1 to placebo or eldelumab 15 or 25 mg/kg administered intravenously on Days 1 and 8 and every other week thereafter. The primary endpoint was clinical remission [Mayo score ≤ 2; no individual subscale score > 1] at Week 11. Key secondary endpoints included Mayo score clinical response and mucosal healing at Week 11. RESULTS Neither eldelumab 15 or 25 mg/kg resulted in significant increases vs placebo in the proportion of patients achieving Week 11 clinical remission. Remission and response rates were 17.6% and 47.1% with eldelumab 25mg/kg, 13.1% and 44.0% with eldelumab 15mg/kg, and 9.6% and 31.3% with placebo. Clinical remission and response rates were higher in anti-tumour necrosis factor [TNF]-naïve patients treated with eldelumab compared with placebo. Eldelumab treatment was well tolerated and no immunogenicity was observed. CONCLUSIONS The primary endpoint was not achieved with induction treatment with eldelumab 15 or 25 mg/kg in patients with UC. Trends towards clinical remission and response were observed in the overall population and were more pronounced in anti-TNF naïve patients. Eldelumab safety signals were consistent with those reported previously [ClinicalTrials.gov number, NCT01294410].