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

Sponsor
Sixth Affiliated Hospital, Sun Yat-sen University
Study ID
NCT07510191
Phase
PHASE4
Status
Recruiting
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Conditions

  • Crohn Disease (CD)

Eligibility Criteria

Sex
ALL
Age
18 Years - 65 Years
Healthy Volunteers
Not accepted

Interventions

  • Upadacitinib — DRUG
    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
  • Infliximab Dose Intensification — DRUG
    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.
  • Adalimumab Dose Intensification — DRUG
    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.
  • Standard-Dose infliximab — DRUG
    In the experimental arm, participants will continue standard-dose infliximab at 5 mg/kg every 8 weeks.
  • Standard-Dose Adalimumab — DRUG
    In the experimental arm, participants will continue standard-dose adalimumab at 40 mg every 2 weeks.

Study Details

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.

Key Dates

Start date
Mar 1, 2026
Status verified
Mar 2026
Primary completion
Dec 31, 2028
Completion
Dec 31, 2029

Study Design

Enrollment
312 participants (estimated)
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT

Arms

  • Experimental: Standard-Dose TNFi Plus Low-Dose Upadacitinib
    Participants will continue their current standard-dose TNF inhibitor therapy and receive oral upadacitinib. Standard-dose TNF inhibitor therapy includes infliximab 5 mg/kg intravenously every 8 weeks or adalimumab 40 mg subcutaneously every 2 weeks, with no dose intensification or switching during the study. Upadacitinib will be initiated at 15 mg orally once daily for 14 weeks. If inflammatory biomarkers such as 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 protocol.
  • Active Comparator: TNFi Dose Intensification
    Participants will continue their current TNF inhibitor with protocol-defined dose intensification. For infliximab, the dosing interval will be shortened from every 8 weeks to every 4 weeks at 5 mg/kg intravenously. For adalimumab, the dose will be increased from 40 mg every 2 weeks to 80 mg every 2 weeks by subcutaneous injection. No switching to another TNF inhibitor, no additional biologic therapy, and no new JAK inhibitor will be permitted during the intervention period. The treatment period is 14 weeks.

Primary Outcome Measure

Clinical remission rate [ Time Frame: Week 14 ]

Central Contacts

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