Design and rationale for the VICTRIVA study: A randomized, double-blind, phase 3b study of vedolizumab in combination with upadacitinib in Crohn's disease.

Introduction: Remission rates in patients with Crohn's disease (CD) suggest a therapeutic ceiling with one advanced targeted treatment, representing an unmet need. Dual targeted therapy may provide a more effective treatment approach. Methods: The primary objective of VICTRIVA (NCT06227910), a randomized, double-blind, phase 3b trial in biologic-experienced and biologic-naïve adults with CD, is to assess whether vedolizumab combined with upadacitinib induction improves rates of clinical remission and endoscopic response at week (W)12 vs. vedolizumab alone. Patients will be randomized 1:1 to vedolizumab (300 mg at W0, W2, W6, and W10) and either upadacitinib 45 mg or placebo daily. W12 responders will enter the maintenance arm up to W52 (vedolizumab monotherapy every 8 weeks [Q8W] from W14 to W52; Q4W escalation if needed). Patients who lose response during maintenance treatment despite dose escalation will enter the rescue substudy (vedolizumab Q4W plus upadacitinib 45 mg for 12 weeks, then vedolizumab monotherapy in patients who regain response). Assessments include patient-reported outcomes (PROs), CD activity index (CDAI), and Simple Endoscopic Score for CD (SES-CD). Globally, 396 patients (198 in each group) will be enrolled. Of these, a minimum of 50 and maximum of 50 % will be biologic-naïve. Co-primary endpoints are CDAI clinical remission and SES-CD endoscopic response at W12. Key secondary endpoints include PRO2 clinical remission at W12, and CDAI clinical remission, SES-CD endoscopic response, and PRO2 clinical remission at W52. Safety endpoints include the incidence of treatment-emergent adverse events. Conclusion: VICTRIVA will evaluate the efficacy and safety of combined vedolizumab and upadacitinib induction therapy relative to vedolizumab monotherapy, aiming to break the current therapeutic ceiling. Clinical trials registration: ClinicalTrials.gov, NCT06227910.