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NCT Number: NCT06520397

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

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.

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Key information

Conditions

Crohn Disease Digestive System Diseases Gastroenteritis Gastrointestinal Diseases Inflammatory Bowel Diseases Intestinal Diseases

Age range

18 year–70 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 4

Primary location

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

Ustekinumab and Upadacitinib

Drug

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.

Ustekinumab

Drug

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.

Primary outcomes

  1. 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.

Secondary outcomes

  1. 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.

  2. 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.

  3. 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.

  4. 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

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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.

Study contacts

Contact information is provided by the study sponsor or research team.

Wei Wang

CONTACT

[email protected]

86-020-38254101

Sponsors and collaborators

Lead sponsor

Sixth Affiliated Hospital, Sun Yat-sen University

Other

Registry information

Official study title

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

Important dates

Study start
2024
Primary completion
2026
Study completion
2027
First posted
Jul 25, 2024
Registry last updated
Feb 23, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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