Efficacy and Safety of Dual-targeted Therapy With Upadacitinib and Ustekinumab Versus Intensified Ustekinumab Therapy in Crohn's Disease
NCT Number: NCT06520397
Status: NOT_YET_RECRUITING
Study Type: INTERVENTIONAL
Phases: PHASE4
Conditions: Crohn Disease
Interventions: DRUG: Ustekinumab and Upadacitinib|DRUG: Ustekinumab
Sponsor: Sixth Affiliated Hospital, Sun Yat-sen University
Sex: ALL
Age: ADULT, OLDER_ADULT
Enrollment: 214
Study Design: Allocation: RANDOMIZED|Intervention Model: PARALLEL|Masking: NONE|Primary Purpose: PREVENTION
Start Date: 2024-07-15
Completion Date: 2027-07-31
Locations: Wei Wang, Guangzhou, Guangdong, 510000, China

Summary:
The goal of this clinical trial is to evaluate the efficacy and safety of dual-target therapy (Ustekinumab combined with Upadacitinib) versus intensified Ustekinumab monotherapy in patients with Crohn's disease who have an inadequate response to standard doses of Ustekinumab. The main questions it aims to answer are:

Is dual-target therapy more effective than intensified Ustekinumab monotherapy in achieving endoscopic remission in Crohn's disease patients?

Is dual-target therapy as safe as intensified Ustekinumab monotherapy in terms of adverse events?

Participants will:

Receive either dual-target therapy (Ustekinumab combined with Upadacitinib) or intensified Ustekinumab monotherapy.

Attend regular clinic visits for monitoring and assessments. Complete questionnaires about their symptoms and quality of life. Undergo routine blood tests and endoscopic evaluations to assess disease activity.

Researchers will compare the dual-target therapy group to the intensified Ustekinumab monotherapy group to see if dual-target therapy is more effective in achieving endoscopic remission and is as safe in terms of adverse events.

Primary Outcome Measures: The primary endpoint of the study is the endoscopic remission rate at week 16., Endoscopic remission is defined as an SES-CD score of less than 3, with no individual variable subscore exceeding 1., Week 16
Secondary Outcome Measures: Clinical response rate at week 16, Comparison of the clinical response rate (CDAI score reduction by ≥100 points from baseline, or CDAI score \<150) between the UPA+UST group and the UST-M group at week 16., Week 16.|Endoscopic response rate at week 16, Comparison of the endoscopic response rate (defined as a reduction in SES-CD score by \>50% from baseline, or for ileal-limited disease with a baseline SES-CD score ≥4, a reduction of at least 50%) between the UPA+UST group and the UST-M group., Week 16|Deep remission rate at week 16, Comparison of the deep remission rate (defined as clinical remission and no ulcers on endoscopy, SES-CD score \<3, with no individual variable subscore exceeding 1) between the UPA+UST group and the UST-M group., Week 16|Biochemical remission rate at week 16, omparison of the biochemical remission rate (defined as CRP levels within the normal reference range) between the UPA+UST group and the UST-M group, Week 16|Normalization rate of fecal calprotectin levels at week 16, Comparison of the normalization rate of fecal calprotectin levels (defined as fecal calprotectin \<200 μg/g) between the UPA+UST group and the UST-M group., Week 16|Normalization rate of intestinal wall thickness on ultrasound at week 16, Comparison of the normalization rate of intestinal wall thickness on ultrasound (defined as intestinal wall thickness \<3 mm) between the UPA+UST group and the UST-M group., Week 16|Health-related quality of life assessment using the Inflammatory Bowel Disease Questionnaire (IBDQ), Evaluation of health-related quality of life using the Inflammatory Bowel Disease Questionnaire (IBDQ). Assessment of the average change in total IBDQ score from baseline at week 16 and around week 52. The IBDQ score ranges from 32 to 224, with higher scores indicating better quality of life., Week 16 and around Week 52|Number of participants with treatment-related adverse events as assessed by CTCAE v4.0 at week 16., The short-term safety of the treatment regimen will be evaluated by assessing the number of participants with treatment-related adverse events. Adverse events will be categorized and graded according to the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. The evaluation will occur at week 16., Week 16|Number of participants with treatment-related adverse events as assessed by CTCAE v4.0 at week 52, The long-term safety of the treatment regimen will be evaluated by assessing the number of participants with treatment-related adverse events at week 52. Adverse events will be categorized and graded according to the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0., Around Week 52