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Crohn DiseasePhase 4NCT06520397

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

A Phase 4 study testing Ustekinumab and Upadacitinib and Ustekinumab in people with Crohn Disease, run by Sixth Affiliated Hospital, Sun Yat-sen University at 1 site in China.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 to 70 years
Conditions the study is for
Crohn Disease
What is being tested?
Ustekinumab and Upadacitinib and Ustekinumab
Could I receive a placebo?
No, everyone receives an active treatment
How many people
214 participants
Where
1 siteChina
Study dates
15 Jul 2024to 31 Jul 2027
Phase
Phase 4
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 70 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.

Who cannot join

  • 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.
Show all 11Show fewer
  • 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.

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

Wei Wang contact

86-020-38254101

wangw239@mail.sysu.edu.cn

China1 site, 1 recruiting

  • Wei Wang

    Guangzhou, Guangdong, 510000

    Wei Wang, +86-020-38254101, wangw239@mail.sysu.edu.cn

    Recruiting

Other trials in China

About this study

Official 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

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?

Read more

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.

Conditions
Crohn Disease
Being tested
Ustekinumab and Upadacitinib, Ustekinumab
Keywords
Ustekinumab, Upadacitinib, Dual-target therapy, Intensified therapy, Endoscopic remission
Medical subject headings
Crohn Disease

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Ustekinumab and UpadacitinibDrug

    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.

  • UstekinumabDrug

    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.

Study groups in NCT06520397
Study groupRoleWhat they receive
Dual-target Therapy GroupExperimentalParticipants in this group will receive the standard maintenance dosage of Ustekinumab administered subcutaneously, combined with the addition of Upadacitinib administered orally.
Receives: Drug: Ustekinumab and Upadacitinib
Intensified Ustekinumab Monotherapy GroupActive comparatorParticipants in this group will receive an additional induction dose of Ustekinumab administered intravenously, followed by maintenance therapy with Ustekinumab.
Receives: Drug: Ustekinumab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: Week 16

Secondary outcomes (9)

  1. 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.

    Measured: Week 16.

  2. 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.

    Measured: Week 16

  3. 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.

    Measured: Week 16

  4. 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

    Measured: Week 16

  5. 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.

    Measured: Week 16

  6. 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.

    Measured: Week 16

  7. 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.

    Measured: Week 16 and around Week 52

  8. 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.

    Measured: Week 16

  9. 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.

    Measured: Around Week 52

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted25 Jul 2024
  2. Study start15 Jul 2024
  3. Primary completion31 Dec 2026 (estimated)
  4. Study completion31 Jul 2027 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 4
Primary purpose
Prevention
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
214 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06520397
Sponsor's protocol ID
2024ZSLYEC-070
Status last verified
Feb 2026
First submitted
14 Jul 2024
Last updated
23 Feb 2026
Results posted
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Undecided

Publications

  • Raine T, Danese S. Breaking Through the Therapeutic Ceiling: What Will It Take? Gastroenterology. 2022 Apr;162(5):1507-1511. doi: 10.1053/j.gastro.2021.09.078. Epub 2022 Jan 4.

    PubMed 34995533

  • Schultheiss JPD, Mahmoud R, Louwers JM, van der Kaaij MT, van Hellemondt BP, van Boeckel PG, Mahmmod N, Jharap B, Fidder HH, Oldenburg B. Loss of response to anti-TNFalpha agents depends on treatment duration in patients with inflammatory bowel disease. Aliment Pharmacol Ther. 2021 Nov;54(10):1298-1308. doi: 10.1111/apt.16605. Epub 2021 Sep 24.

    PubMed 34559428

  • Noor NM, Lee JC, Bond S, Dowling F, Brezina B, Patel KV, Ahmad T, Banim PJ, Berrill JW, Cooney R, De La Revilla Negro J, de Silva S, Din S, Durai D, Gordon JN, Irving PM, Johnson M, Kent AJ, Kok KB, Moran GW, Mowat C, Patel P, Probert CS, Raine T, Saich R, Seward A, Sharpstone D, Smith MA, Subramanian S, Upponi SS, Wiles A, Williams HRT, van den Brink GR, Vermeire S, Jairath V, D'Haens GR, McKinney EF, Lyons PA, Lindsay JO, Kennedy NA, Smith KGC, Parkes M; PROFILE Study Group. A biomarker-stratified comparison of top-down versus accelerated step-up treatment strategies for patients with newly diagnosed Crohn's disease (PROFILE): a multicentre, open-label randomised controlled trial. Lancet Gastroenterol Hepatol. 2024 May;9(5):415-427. doi: 10.1016/S2468-1253(24)00034-7. Epub 2024 Feb 22.

    PubMed 38402895

  • Singh S, George J, Boland BS, Vande Casteele N, Sandborn WJ. Primary Non-Response to Tumor Necrosis Factor Antagonists is Associated with Inferior Response to Second-line Biologics in Patients with Inflammatory Bowel Diseases: A Systematic Review and Meta-analysis. J Crohns Colitis. 2018 May 25;12(6):635-643. doi: 10.1093/ecco-jcc/jjy004.

    PubMed 29370397

  • Parigi TL, D'Amico F, Abreu MT, Rubin DT, Dignass A, Dotan I, Jairath V, Magro F, Peyrin-Biroulet L, Ghosh S, Danese S. Difficult-to-treat inflammatory bowel disease: results from a global IOIBD survey. Lancet Gastroenterol Hepatol. 2022 May;7(5):390-391. doi: 10.1016/S2468-1253(22)00085-1. No abstract available.

    PubMed 35397241

  • Feagan BG, Sandborn WJ, Gasink C, Jacobstein D, Lang Y, Friedman JR, Blank MA, Johanns J, Gao LL, Miao Y, Adedokun OJ, Sands BE, Hanauer SB, Vermeire S, Targan S, Ghosh S, de Villiers WJ, Colombel JF, Tulassay Z, Seidler U, Salzberg BA, Desreumaux P, Lee SD, Loftus EV Jr, Dieleman LA, Katz S, Rutgeerts P; UNITI-IM-UNITI Study Group. Ustekinumab as Induction and Maintenance Therapy for Crohn's Disease. N Engl J Med. 2016 Nov 17;375(20):1946-1960. doi: 10.1056/NEJMoa1602773.

    PubMed 27959607

  • Adedokun OJ, Xu Z, Gasink C, Jacobstein D, Szapary P, Johanns J, Gao LL, Davis HM, Hanauer SB, Feagan BG, Ghosh S, Sandborn WJ. Pharmacokinetics and Exposure Response Relationships of Ustekinumab in Patients With Crohn's Disease. Gastroenterology. 2018 May;154(6):1660-1671. doi: 10.1053/j.gastro.2018.01.043. Epub 2018 Feb 1.

    PubMed 29409871

  • Ollech JE, Normatov I, Peleg N, Wang J, Patel SA, Rai V, Yi Y, Singer J, Dalal SR, Sakuraba A, Cohen RD, Rubin DT, Pekow J. Effectiveness of Ustekinumab Dose Escalation in Patients With Crohn's Disease. Clin Gastroenterol Hepatol. 2021 Jan;19(1):104-110. doi: 10.1016/j.cgh.2020.02.035. Epub 2020 Feb 26.

    PubMed 32109634

  • Haider SA, Yadav A, Perry C, Su L, Akanbi O, Kudaravalli P, Tripathi N, Hashim MA, Abdelsalam M, Hussein M, Elkheshen A, Patel V, Ali SE, Lamb L, Ingram K, Mayne C, Stuffelbeam AB, Flomenhoft D, Stromberg A, Barrett TA. Ustekinumab dose escalation improves clinical responses in refractory Crohn's disease. Ther Adv Gastroenterol. 2020 Oct 13;13:1756284820959245. doi: 10.1177/1756284820959245. eCollection 2020.

    PubMed 33133239

  • Bermejo F, Jimenez L, Algaba A, Vela M, Bastida G, Merino O, Lopez-Garcia A, Melcarne L, Rodriguez-Lago I, de la Maza S, Bouhmidi A, Barreiro-de Acosta M, Lopez-Serrano P, Carrillo-Palau M, Mesonero F, Orts B, Bonillo D, Granja A, Guerra I. Re-induction With Intravenous Ustekinumab in Patients With Crohn's Disease and a Loss of Response to This Therapy. Inflamm Bowel Dis. 2022 Jan 5;28(1):41-47. doi: 10.1093/ibd/izab015.

    PubMed 33528018

  • Privitera G, Pugliese D, Lopetuso LR, Scaldaferri F, Neri M, Guidi L, Gasbarrini A, Armuzzi A. Novel trends with biologics in inflammatory bowel disease: sequential and combined approaches. Ther Adv Gastroenterol. 2021 Apr 27;14:17562848211006669. doi: 10.1177/17562848211006669. eCollection 2021.

    PubMed 33995579

  • Yang E, Panaccione N, Whitmire N, Dulai PS, Vande Casteele N, Singh S, Boland BS, Collins A, Sandborn WJ, Panaccione R, Battat R. Efficacy and safety of simultaneous treatment with two biologic medications in refractory Crohn's disease. Aliment Pharmacol Ther. 2020 Jun;51(11):1031-1038. doi: 10.1111/apt.15719. Epub 2020 Apr 24.

    PubMed 32329532

  • Gold SL, Steinlauf AF. Efficacy and Safety of Dual Biologic Therapy in Patients With Inflammatory Bowel Disease: A Review of the Literature. Gastroenterol Hepatol (N Y). 2021 Sep;17(9):406-414.

    PubMed 34602905

  • Penagini F, Lonoce L, Abbattista L, Silvera V, Rendo G, Cococcioni L, Dilillo D, Calcaterra V, Zuccotti GV. Dual biological therapy and small molecules in pediatric inflammatory bowel disease. Pharmacol Res. 2023 Oct;196:106935. doi: 10.1016/j.phrs.2023.106935. Epub 2023 Sep 23.

    PubMed 37748559

  • Feng Z, Kang G, Wang J, Gao X, Wang X, Ye Y, Liu L, Zhao J, Liu X, Huang H, Cao X. Breaking through the therapeutic ceiling of inflammatory bowel disease: Dual-targeted therapies. Biomed Pharmacother. 2023 Feb;158:114174. doi: 10.1016/j.biopha.2022.114174. Epub 2022 Dec 31.

    PubMed 36587559

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Ustekinumab and Upadacitinib and Ustekinumab in people with Crohn Disease, run by Sixth Affiliated Hospital, Sun Yat-sen University at 1 site in China.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 23 Feb 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Wei Wang (86-020-38254101, wangw239@mail.sysu.edu.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

The primary endpoint of the study is the endoscopic remission rate at week 16. (time frame: Week 16). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT06520397, which also lists 22 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Feb 2026.

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