NCT07510191

TNFi Plus Low-Dose Upadacitinib vs TNFi Intensification in Crohn's Disease With Suboptimal Response

Efficacy and Safety of Standard-Dose TNF Inhibitor Plus Low-Dose Upadacitinib Versus TNF Inhibitor Intensification for Crohn's Disease With Suboptimal Response to Standard-Dose TNF Inhibitors: A Multicenter, Randomized, Controlled Trial

• Status: Recruiting
• Phase: Phase 4
• Study type: Interventional
• Enrollment: 312 (estimated)
• Sponsor: Sixth Affiliated Hospital, Sun Yat-sen University · Academic / Other
• Sex: All
• Age: 18 Years – 65 Years
• Healthy volunteers: Not accepted

Summary

This multicenter, randomized, controlled trial aims to evaluate the efficacy and safety of standard-dose tumor necrosis factor inhibitor (TNFi) plus low-dose upadacitinib compared with TNFi dose intensification in patients with moderate-to-severe Crohn's disease who have a suboptimal response to standard-dose TNFi therapy. Eligible participants are adults with active Crohn's disease receiving standard-dose infliximab or adalimumab who remain inadequately controlled despite ongoing treatment. Participants will be randomly assigned in a 1:1 ratio to either continue standard-dose TNFi with oral upadacitinib 15 mg once daily, or receive TNFi dose intensification according to the protocol. Clinical assessments will be performed at baseline and during follow-up, with the primary endpoint assessed at Week 14. The primary outcome is the proportion of participants achieving clinical remission, defined as a Crohn's Disease Activity Index (CDAI) score \<150 at Week 14. Secondary outcomes include clinical response, endoscopic response and remission, changes in inflammatory biomarkers such as C-reactive protein and fecal calprotectin, quality of life, and safety outcomes including adverse events and serious adverse events. Participants will continue follow-up after Week 14 to evaluate treatment durability and longer-term safety. This study is designed to determine whether a dual-target strategy with standard-dose TNFi plus low-dose upadacitinib provides superior short-term efficacy and acceptable safety compared with conventional TNFi intensification in Crohn's disease patients with insufficient benefit from standard-dose TNFi therapy.

Conditions

• Crohn Disease (CD)

Interventions

Type	Name	Description
DRUG	Upadacitinib	Upadacitinib will be administered orally in combination with ongoing standard-dose TNF inhibitor therapy in the experimental arm. The initial dose is 15 mg once daily for 14 weeks. If inflammatory biomarkers, including C-reactive protein or fecal calprotectin, do not decrease by at least 30% from baseline at Week 4 and treatment is well tolerated, the dose may be increased to 30 mg once daily according to the study protocol
DRUG	Infliximab Dose Intensification	In the active comparator arm, infliximab dose intensification will be performed by shortening the dosing interval from every 8 weeks to every 4 weeks at 5 mg/kg, according to the study protocol.
DRUG	Adalimumab Dose Intensification	In the active comparator arm, adalimumab dose intensification will be performed by increasing the dose from 40 mg every 2 weeks to 80 mg every 2 weeks, according to the study protocol.
DRUG	Standard-Dose infliximab	In the experimental arm, participants will continue standard-dose infliximab at 5 mg/kg every 8 weeks.
DRUG	Standard-Dose Adalimumab	In the experimental arm, participants will continue standard-dose adalimumab at 40 mg every 2 weeks.

Timeline

• Start date: 2026-03-01
• Primary completion: 2028-12-31
• Completion: 2029-12-31
• First posted: 2026-04-03
• Last updated: 2026-04-03

Locations

1 site across 1 country: China