Efficacy and Safety of Dual-targeted Therapy With Upadacitinib and Ustekinumab Versus Intensified Ustekinumab Therapy in Crohn's Disease

February 19, 2026 updated by: Wei Wang, Sixth Affiliated Hospital, Sun Yat-sen University

Evaluation of the Efficacy and Safety of Dual-targeted Therapy With Upadacitinib and Ustekinumab Versus Intensified Ustekinumab Therapy in Crohn's Disease Patients With an Insufficient Response to Standard-dose Ustekinumab: A Randomized Controlled Trial

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

214

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • China
    • Guangdong
      • Guangzhou, Guangdong, China, 510000

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Male or female participants aged 18 to 70 years at baseline (week 0).
  • Active Crohn's Disease: Participants must have active Crohn's disease at baseline, defined as: CDAI > 150 and Endoscopic activity with SES-CD > 6, or SES-CD > 4 (for isolated ileal disease), excluding the contribution of the stricture component (Excluding the stricture component ensures recruitment of patients with a better chance of improvement, given the primary endpoint is endoscopic remission), and at least one of the following: CRP > 10 mg/L (upper limit of normal on local assay), Fecal calprotectin (FC) > 250 μg/g, active disease confirmed by imaging.
  • Prior Ustekinumab Treatment: Participants must have had primary non-response or secondary loss of response to TNFi, and have undergone at least 16-24 weeks of standard-dose ustekinumab treatment, but still have active CD.
  • Consent and Compliance: Participants must be capable and willing to provide written informed consent and comply with the requirements of the study protocol.
  • General Health: The principal investigator (or designee) must determine that the participant is in good general health based on medical history, laboratory test results, physical examination, chest X-ray (CXR), and 12-lead electrocardiogram (ECG) obtained during the screening period.

Exclusion Criteria:

  • Allergies: Participants with known allergies to UPA or UST excipients or components.
  • Colonic Neoplasia: Participants with untreated or unresolved high-grade dysplasia or colon cancer.
  • Active Infections: Participants with active infections at screening or baseline, including but not limited to pneumonia, pyelonephritis, or herpes zoster, or those with evidence of chronic infections that make them unsuitable for the study as per the investigator's assessment.
  • Surgical Intervention: Participants who currently require or are expected to require surgical intervention for CD during the study period.
  • Thrombosis: Participants with thrombosis identified through limb venous Doppler ultrasound or D-dimer screening.
  • Lymphoproliferative Disorders: Participants with a history of lymphoproliferative disorders, including lymphoma, or those with signs and symptoms indicative of possible lymphoproliferative disease such as lymphadenopathy and/or splenomegaly.
  • Immunodeficiency: Participants with any known congenital or acquired immunodeficiency, including common variable immunodeficiency, HIV infection, or organ transplantation.
  • Pregnancy: Female participants with a positive pregnancy test at screening or baseline (week 0).
  • Lactation or Pregnancy Plans: Female participants who are breastfeeding or planning to become pregnant during the study.
  • Substance Abuse: Participants with a history of drug abuse (defined as the use of any illicit drug) or alcohol abuse within 1 year prior to screening.
  • Investigator's Discretion: Participants deemed unsuitable for the study by the investigator for any reason.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Dual-target Therapy Group
Participants in this group will receive the standard maintenance dosage of Ustekinumab administered subcutaneously, combined with the addition of Upadacitinib administered orally.
Drug: Ustekinumab and Upadacitinib
Participants will continue ustekinumab 90 mg administered subcutaneously every 8 weeks. In addition, upadacitinib will be administered orally once daily. During the induction period (Weeks 0-12), upadacitinib will be initiated at 15 mg or 30 mg daily, with escalation up to 45 mg daily permitted based on disease activity, clinical response, and tolerability. From Week 12 to Week 16, dose adjustment (15 0r 30 daily) will be allowed according to clinical judgment. Clinical efficacy will be assessed at Week 16.
Active Comparator: Intensified Ustekinumab Monotherapy Group
Participants in this group will receive an additional induction dose of Ustekinumab administered intravenously, followed by maintenance therapy with Ustekinumab.
Drug: Ustekinumab
Participants will receive an additional induction dose of Ustekinumab administered intravenously at 6 mg/kg at baseline. This will be followed by subcutaneous maintenance therapy of 90 mg every 4 weeks. Clinical efficacy will be evaluated at week 16.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
The primary endpoint of the study is the endoscopic remission rate at week 16.
Time Frame: 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

Outcome Measure
Measure Description
Time Frame
Clinical response rate at week 16
Time Frame: 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
Time Frame: 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
Time Frame: 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
Time Frame: 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
Time Frame: 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
Time Frame: 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)
Time Frame: Week 16 and around Week 52
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.
Time Frame: 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
Time Frame: Around 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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sixth Affiliated Hospital, Sun Yat-sen University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

July 15, 2024

Primary Completion (Estimated)

December 31, 2026

Study Completion (Estimated)

July 31, 2027

Study Registration Dates

First Submitted

July 14, 2024

First Submitted That Met QC Criteria

July 21, 2024

First Posted (Actual)

July 25, 2024

Study Record Updates

Last Update Posted (Actual)

February 23, 2026

Last Update Submitted That Met QC Criteria

February 19, 2026

Last Verified

February 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2024ZSLYEC-070

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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