Vilobelimab to improve clinical outcomes of moderate-to-severe hidradenitis suppurativa through an adjunctive effect on draining tunnels: Results of the SHINE double-blind, placebo-controlled randomised trial

Abstract Background Previous results of a phase IIa study suggested efficacy of the anti-C5a compound, Vilobelimab in a small number of patients with severe hidradenitis suppurativa (HS) refractory to adalimumab. Efficacy was studied in a larger scale phase IIb study. Methods In the randomized phase IIb SHINE study, 177 patients with moderate to severe (HS) were treated either with placebo or one of four doses of vilobelimab, a monoclonal antibody targeting the complement split product C5a. HS clinical response (HiSCR) at 16 weeks was the primary endpoint. HiSCR responders switched to open-label low dose vilobelimab and HiSCR non-responders to medium dose. This trial is registered with the EU Clinical Trials Register (EudraCT number 2017-004501-40) and ClinicalTrials.gov (NCT03487276). Results The study did not meet the goal for primary endpoint, perhaps due in part to an unexpectedly high HiSCR placebo response of 47.1%. HS flares were decreased and post-hoc analysis showed that high dose vilobelimab significantly decreased the median counts of draining tunnels (dT) and the international HS4 score by 63%. Following switch to medium dose vilobelimab at week 16, non-responders achieved HiSCR in 45.5% at week 40. Conclusion Vilobelimab treatment did not achieve significant HiSCR in moderate to severe HS compared to placebo. Post-hoc analysis revealed significant effects for the highest tested dose on dT reduction and IHS4 score, which captures dT reductions. These findings warrant further investigation.