Randomised clinical trial: a placebo-controlled study of intravenous golimumab induction therapy for XXXX .

@entity5 @entity1 @entity310 @entity31
BACKGROUND: @entity5 factor alpha ( @entity310 )-antagonism effectively treats @entity31 ( @entity31 ). The golimumab clinical programme evaluated subcutaneous (SC) and intravenous (IV) induction, and SC maintenance regimens, in @entity310 -antagonist-na  ve @entity1 with moderate-to-severe active @entity31 despite conventional treatment. AIM: To evaluate dose-response relationship, select IV golimumab induction doses for continued development, and evaluate the safety and efficacy of selected doses. METHODS: Adults with Mayo scores of 6-12 and endoscopic subscores >= 2 were enrolled into this multicentre, randomised, double-blind, placebo-controlled, integrated Phase 2/3 dose-finding/dose-confirming study. In Phase 2, 176 @entity1 were randomised (1:1:1:1) to a single IV infusion of placebo, 1-, 2- or 4-mg/kg golimumab. While Phase 2 data were analysed to select doses for continued development, 71 additional @entity1 were randomised. Phase 3 enrolment stopped after 44 additional @entity1 were randomised (1:1:1) to placebo, 2- or 4-mg/kg golimumab. Due to insufficient power for the Phase 3 primary endpoint analysis (clinical response at week 6), efficacy analyses are considered exploratory and include all randomised @entity1 . RESULTS: No dose-response was observed in Phase 2; however, higher serum golimumab exposure was associated with greater proportions of @entity1 achieving more favourable clinical outcomes, clinical response and greater improvement in Mayo scores compared with placebo-treated @entity1 and those with lower serum concentrations. Among all randomised @entity1 , numerically greater proportions were in clinical response at week 6 in the 2- and 4-mg/kg golimumab groups compared with placebo [44.0% (33/75) and 41.6% (32/77) vs. 30.1% (22/73)]. CONCLUSIONS: Efficacy with single-dose golimumab IV induction was lower than expected and less than observed in the SC induction study. No new safety findings were observed. ClinicalTrials.gov Number, NCT00488774.
