Phase 3b, Randomized, Open‑Label, Active‑Controlled Trial Comparing Guselkumab Versus Risankizumab for Efficacy and Safety in Moderately to Severely Active Crohn’s Disease

The primary objective is to compare the efficacy of subcutaneously administered guselkumab with intravenously or subcutaneously administered risankizumab at Week 52 in participants with moderately to severely active Crohn’s disease. Establishing relative clinical response will guide therapeutic decision‑making for this refractory inflammatory condition, while concurrent assessment of safety will characterize the tolerability profile of the two agents.

The trial enrolled 228 participants diagnosed with moderately to severely active Crohn’s Disease. Both male and female patients were eligible, and the age range corresponded to the adult categories indicated by the protocol’s age‑group codes. Inclusion required disease of at least 12 weeks’ duration with colitis, ileitis, or ileocolitis confirmed by radiography, histology, or endoscopy, a baseline Crohn’s Disease Activity Index score between 220 and 450, and endoscopic evidence of active ileal or colonic disease meeting specified SES‑CD thresholds. Participants must have shown an inadequate response, loss of response, or intolerance to one or two prior advanced therapies targeting TNF‑α, integrin, IL‑12/23, or JAK pathways; exposure to three or more such classes was an exclusion criterion. Selection was based on these clinical parameters, and no specific dietary, physical activity, or other lifestyle requirements were stipulated.

The study is a Phase 3b, multicenter, randomized, open-label, active‑controlled trial comparing guselkumab with risankizumab in participants with moderately to severely active Crohn’s disease. Eligible individuals undergo a screening visit to confirm diagnosis, disease activity (CDAI ≥ 220 ≤ 450), and endoscopic criteria (SES‑CD score ≥4 or ≥6). Baseline assessments and the first dose are administered at the enrollment visit, after which participants receive guselkumab 200 mg subcutaneously every 4 weeks or risankizumab 360 mg subcutaneously every 8 weeks for a total duration of 52 weeks. Follow‑up visits are scheduled at weeks 4, 8, 12, 24, 36, and 48 to evaluate efficacy, safety, and laboratory parameters, with an end‑of‑study visit at week 52 to determine the primary endpoint of deep remission. Participant involvement therefore extends for approximately one year from the first dose to the final assessment. Early termination may occur if a participant experiences a serious adverse event, fails to meet predefined safety criteria, withdraws consent, or requires prohibited concomitant therapy.

The investigational product is guselkumab, supplied as a solution for injection in a pre‑filled syringe. It is administered by subcutaneous injection. The study protocol specifies a dose of 0 U per administration, with dosing frequency defined by the trial schedule.

The active‑comparator arm utilizes two formulations of Skyrizi, containing the monoclonal antibody risankizumab. One formulation is a 600 mg concentrate for solution for infusion, administered by intravenous infusion. The second formulation is a 360 mg solution for injection in a cartridge, administered by subcutaneous injection. Both comparator products are also dosed at 0 U per administration according to the study’s dosing schedule.

All study medications are dispensed in accordance with the assigned dosing schedule, and administration times are recorded in the case report form. Compliance is monitored through site‑performed verification of dose preparation, administration logs, and participant adherence checks at each study visit.

Efficacy will be evaluated by the proportion of participants achieving deep remission at Week 52, which constitutes the primary endpoint for comparison of guselkumab versus risankizumab.