Crohn's Disease AggravatedPhase 3NCT07149467
Ustekinumab and Upadacitinib for Induction and Maintenance Therapy in Patients With Refractory Crohn's Disease: A Multicenter, Randomized, Parallel-Controlled Study
A Phase 3 study testing Ustekinumab (approximately 6 mg/kg) and Upadacitinib in people with Crohn's Disease Aggravated and Crohn's Disease in Remission, run by Sixth Affiliated Hospital, Sun Yat-sen University.
Trial summary
Crohn's disease is a chronic inflammatory bowel disorder characterized primarily by abdominal pain and diarrhea [1,2]. Conventional treatments include corticosteroids and immunosuppressants (such as azathioprine, mercaptopurine, and methotrexate) [2,3]. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Crohn's Disease Aggravated, Crohn's Disease in Remission
- What is being tested?
- Ustekinumab (approximately 6 mg/kg) and Upadacitinib
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 454 participants
- Where
- No sites listed yet
- Study dates
- 10 Sep 2025to 31 Dec 2027
- Phase
- Phase 3
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age ≥ 18 years, regardless of gender;
- Diagnosis of Crohn's disease for at least 3 months or more based on medical history, laboratory tests, endoscopy, and imaging, in accordance with the Chinese Consensus on Inflammatory Bowel Disease;
- Presence of one or more ulcers (in the ileum or colon) during colonoscopy, with an SES-CD score of at least 3;
- Current or previous failure or intolerance to at least one anti-TNF-α therapy (infliximab or adalimumab);
- Subjects taking oral corticosteroids (e.g., prednisone) are allowed a prednisone equivalent dose of up to 40 mg/day, provided the dose has been stable for 3 weeks prior to baseline (Week 0) or documented discontinuation of these medications at least 3 weeks before baseline;
- Subjects using anti-TNF-α agents (infliximab or adalimumab) must discontinue these drugs at least 8 weeks (for infliximab) or 4 weeks (for adalimumab) prior to baseline;
Show all 18Show fewer
- Meeting the following tuberculosis (TB) screening criteria:
- No history of latent or active TB prior to screening, except for the following:
- Currently receiving treatment for latent TB without evidence of active TB (or starting treatment for latent TB before administration at Week 0);
- History of latent TB with evidence of adequate treatment completed within 5 years prior to the first dose of the study drug.
- The investigator should fully verify the prior TB treatment history and provide corresponding documentation.
- No signs or symptoms suggestive of active TB based on medical history and/or physical examination;
- No known recent close contact with an active TB patient, or if such contact has occurred, the subject should be referred to a TB specialist for additional evaluation and, if necessary, receive appropriate treatment for latent TB before or concurrently with the first dose of the study drug;
- Within 2 months prior to the first dose of the study drug:
- A negative T-SPOT® test, or a newly positive T-SPOT® test with active TB excluded, and appropriate treatment for latent TB initiated before or concurrently with the first dose of the study drug. Subjects with an indeterminate initial T-SPOT® test result should undergo repeat testing. If the additional T-SPOT® test result remains persistently indeterminate, the subject should also start treatment for latent TB to be eligible for the study;
- Within 3 months prior to the first dose of the study drug, a chest imaging examination performed by a qualified radiologist shows no evidence of current active TB or old inactive TB;
- For female subjects, a negative pregnancy test confirmed before screening and strict contraception during the study period or postmenopausal status. Male subjects should practice strict contraception;
- Signed informed consent form indicating that the subject understands the purpose of the study and the required procedures and is willing to participate in the study.
Who cannot join
- Crohn's disease potentially requiring surgery, or conditions that may affect the assessment of ustekinumab or upadacitinib treatment efficacy using CDAI, such as short bowel syndrome, severe or symptomatic strictures, or active stoma.
- Current or suspected abscess. Recent cutaneous and perianal abscesses are not excluded if drained and adequately treated at least 3 weeks prior to baseline. Intra-abdominal abscesses are not excluded if drained and adequately treated at least 8 weeks before baseline and no further surgery is anticipated. Subjects with active fistulas may be included if no further surgery is expected and there is no current abscess.
- Any form of intestinal resection or intra-abdominal surgery within 6 months prior to baseline, or hospitalization for intestinal obstruction within 3 months prior to baseline.
- Use of any of the following medications or treatments within the specified timeframes before baseline:
- Any other experimental drug for Crohn's disease, unless at least 3 months or 5 half-lives have passed since the last dose;
- Intravenous corticosteroid therapy within 3 weeks prior to baseline;
Show all 27Show fewer
- Immunosuppressants such as azathioprine, 6-mercaptopurine, methotrexate, etc., within 4 weeks prior to baseline;
- Plasmapheresis within 3 weeks prior to baseline.
- Positive stool culture or test for other intestinal pathogens, including Clostridium difficile toxin, within 4 months before screening, unless repeated testing is negative and there are no signs of ongoing infection.
- Receipt of BCG vaccine within 12 months before screening or any other live bacterial or viral vaccine within 2 weeks after baseline.
- History of chronic or recurrent infectious diseases, including but not limited to chronic kidney infection, chronic chest infection, recurrent urinary tract infection, or infected skin wounds or ulcers.
- Current signs or symptoms of infection, or recent history (within 8 weeks before baseline) of herpes zoster or serious infection (including any condition requiring hospitalization).
- Evidence of current active infection on screening or any other available chest imaging, including tuberculosis, or nodules suspected to be pulmonary malignancy, unless confirmed by surgery or additional imaging with supporting documentation.
- History of latent or active granulomatous infections, including histoplasmosis or coccidioidomycosis, before screening. For information on latent tuberculosis, refer to the inclusion criteria.
- History of non-tuberculous mycobacterial infection or severe opportunistic infection.
- Patients with viral hepatitis or HIV.
- Comorbid diagnosis or any history of congestive heart failure or demyelinating disease.
- Recent history of severe, progressive, or uncontrolled renal, hepatic, hematological, endocrine, pulmonary, cardiac, neurological, systemic lupus erythematosus, or psychiatric disorders.
- History of organ transplantation (except corneal transplantation performed more than 3 months before screening).
- Lymphoproliferative disorders (including lymphoma) or signs and symptoms suggestive of possible lymphoproliferative disease.
- Known malignancy or history of malignancy.
- Previous allergy immunotherapy for anaphylaxis prevention.
- Inability or unwillingness to undergo multiple venipunctures due to poor tolerance or lack of easily accessible veins.
- Known allergy, hypersensitivity, or intolerance to ustekinumab or upadacitinib or their excipients.
- Clinically significant drug abuse issues (e.g., drugs or alcohol) at screening or within 12 months before baseline.
- Current or planned participation in any other clinical study within the first 52 weeks of this study.
- Any condition that, in the investigator's opinion, would make participation not in the subject's best interest or may prevent, limit, or confound the protocol-specified assessments.
Trial locations and contacts
No sites are listed yet. Contact the study team or a site near you to ask about taking part.
About this study
Official title: Ustekinumab and Upadacitinib for Induction and Maintenance Therapy in Patients With Refractory Crohn's Disease-A Multicenter, Randomized, Parallel-Controlled Study
Crohn's disease is a chronic inflammatory bowel disorder characterized primarily by abdominal pain and diarrhea [1,2]. Conventional treatments include corticosteroids and immunosuppressants (such as azathioprine, mercaptopurine, and methotrexate) [2,3]. The introduction of anti-tumor necrosis factor-α (TNF-α) inhibitors, such as infliximab and adalimumab, has significantly improved outcomes for patients with Crohn's disease, reducing complications and hospitalization rates [4]. However, both infliximab and adalimumab may lead to primary or secondary failure due to various reasons, including immunogenicity [5]. Novel biologics and small molecule drugs, such as ustekinumab and upadacitinib, offer new hope for the treatment of refractory Crohn's disease patients.
Ustekinumab is a monoclonal antibody targeting the p40 subunit of human interleukin (IL)-12/23. In the UNITI-2 study, the clinical remission rate at week 8 was 40% in the ustekinumab group, significantly higher than the 20% observed in the placebo group [6]. In the STARDUST study, the clinical remission rate at week 16 reached 68% in biologic-naïve patients and remained as high as 65% even in patients who had failed prior biologic therapy [7]. Upadacitinib is an orally administered JAK1 inhibitor that has now been approved for Crohn's disease in our region. In the recent U-EXCEED study, which enrolled refractory Crohn's disease patients who had failed at least one prior biologic therapy, the clinical remission rate at week 12 was 38.9%, significantly higher than that of the placebo group [8]. However, there is a lack of active head-to-head studies comparing the efficacy and safety of these two novel agents.
Our objective is to evaluate the efficacy and safety of ustekinumab and upadacitinib in the treatment of refractory Crohn's disease, thereby providing a theoretical basis for clinicians and patients in making informed therapeutic decisions.
- Being tested
- Ustekinumab (approximately 6 mg/kg), Upadacitinib
- Keywords
- Crohn's Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Ustekinumab (approximately 6 mg/kg)Drug
At Week 0:
≤55 kg: 260 mg administered by intravenous (IV) infusion.
>55 kg and ≤85 kg: 390 mg administered by intravenous (IV) infusion.
>85 kg: 520 mg administered by intravenous (IV) infusion.
From Week 8 onward (i.e., at Week 8 and then every 8 weeks up to Week 52 or the end of the follow-up period):
90 mg administered by subcutaneous (SC) injection.
UpadacitinibDrug
From Week 0 to Week 12: 45 mg once daily, administered orally.
From Week 13 through Week 52 or the end of the follow-up period: 30 mg once daily, administered orally.
| Study group | Role | What they receive |
|---|---|---|
| Ustekinumab Group | Experimental | At Week 0:
≤55 kg: 260 mg administered by intravenous (IV) infusion.
>55 kg and ≤85 kg: 390 mg administered by intravenous (IV) infusion.
>85 kg: 520 mg administered by intravenous (IV) infusion.
From Week 8 onward (i.e., at Week 8 and then every 8 weeks up to Week 52 or the end of the follow-up period):
90 mg administered by subcutaneous (SC) injection. Receives: Drug: Upadacitinib |
| Upadacitinib Group | Active comparator | From Week 0 to Week 12: 45 mg once daily, administered orally.
From Week 13 through Week 52 or the end of the follow-up period: 30 mg once daily, administered orally. Receives: Drug: Ustekinumab (approximately 6 mg/kg) |
What is being measured
The primary outcome is the main question the study is designed to answer.
clinical remission rate
To compare the efficacy of ustekinumab versus upadacitinib in subjects with refractory Crohn's disease who had prior failure or intolerance to at least one anti-TNF-α therapy (infliximab or adalimumab), as assessed by the clinical remission rate at Week 16.
Measured: 16th week
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Sep 2025
- Study start10 Sep 2025 (estimated)
- Primary completion31 Dec 2026 (estimated)
- Study completion31 Dec 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Crohn's Disease AggravatedStudies of the same condition, open and under way.
- More trials run by Sixth Affiliated Hospital, Sun Yat-sen UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 454 participants (estimated)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Xiang Peng, Sixth Affiliated Hospital, Sun Yat-sen University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07149467
- Sponsor's protocol ID
- 2024ZSLYEC-312
- Status last verified
- Aug 2025
- First submitted
- 24 Aug 2025
- Last updated
- 2 Sep 2025
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 2 Sep 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Ustekinumab and Upadacitinib for Induction and Maintenance Therapy in Patients With Refractory Crohn's Disease-A Multicenter, Randomized, Parallel-Controlled Study
- ClinicalTrials.gov ID
- NCT07149467
- Acronym / sponsor ID
- 2024ZSLYEC-312
- Keywords
- Crohn's Disease
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 454 participants (estimated)
- Lead sponsor
- Sixth Affiliated Hospital, Sun Yat-sen UniversityUniversity, hospital or other
- Study start
- 10 Sep 2025 (estimated)
- Primary completion
- 31 Dec 2026 (estimated)
- Study completion
- 31 Dec 2027 (estimated)
- First posted
- 2 Sep 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Crohn's disease is a chronic inflammatory bowel disorder characterized primarily by abdominal pain and diarrhea [1,2]. Conventional treatments include corticosteroids and immunosuppressants (such as azathioprine, mercaptopurine, and methotrexate) [2,3]. The introduction of anti-tumor necrosis factor-α (TNF-α) inhibitors, such as infliximab and adalimumab, has significantly improved outcomes for patients with Crohn's disease, reducing complications and hospitalization rates [4]. However, both infliximab and adalimumab may lead to primary or secondary failure due to various reasons, including immunogenicity [5]. Novel biologics and small molecule drugs, such as ustekinumab and upadacitinib, offer new hope for the treatment of refractory Crohn's disease patients.
Ustekinumab is a monoclonal antibody targeting the p40 subunit of human interleukin (IL)-12/23. In the UNITI-2 study, the clinical remission rate at week 8 was 40% in the ustekinumab group, significantly higher than the 20% observed in the placebo group [6]. In the STARDUST study, the clinical remission rate at week 16 reached 68% in biologic-naïve patients and remained as high as 65% even in patients who had failed prior biologic therapy [7]. Upadacitinib is an orally administered JAK1 inhibitor that has now been approved for Crohn's disease in our region. In the recent U-EXCEED study, which enrolled refractory Crohn's disease patients who had failed at least one prior biologic therapy, the clinical remission rate at week 12 was 38.9%, significantly higher than that of the placebo group [8]. However, there is a lack of active head-to-head studies comparing the efficacy and safety of these two novel agents.
Our objective is to evaluate the efficacy and safety of ustekinumab and upadacitinib in the treatment of refractory Crohn's disease, thereby providing a theoretical basis for clinicians and patients in making informed therapeutic decisions.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Ustekinumab Group | Experimental | Drug: UpadacitinibAt Week 0: ≤55 kg: 260 mg administered by intravenous (IV) infusion. >55 kg and ≤85 kg: 390 mg administered by intravenous (IV) infusion. >85 kg: 520 mg administered by intravenous (IV) infusion. From Week 8 onward (i.e., at Week 8 and then every 8 weeks up to Week 52 or the end of the follow-up period): 90 mg administered by subcutaneous (SC) injection. |
| Upadacitinib Group | Active comparator | Drug: Ustekinumab (approximately 6 mg/kg)From Week 0 to Week 12: 45 mg once daily, administered orally. From Week 13 through Week 52 or the end of the follow-up period: 30 mg once daily, administered orally. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (18 listed)
- Age ≥ 18 years, regardless of gender;
- Diagnosis of Crohn's disease for at least 3 months or more based on medical history, laboratory tests, endoscopy, and imaging, in accordance with the Chinese Consensus on Inflammatory Bowel Disease;
- Presence of one or more ulcers (in the ileum or colon) during colonoscopy, with an SES-CD score of at least 3;
- Current or previous failure or intolerance to at least one anti-TNF-α therapy (infliximab or adalimumab);
- Subjects taking oral corticosteroids (e.g., prednisone) are allowed a prednisone equivalent dose of up to 40 mg/day, provided the dose has been stable for 3 weeks prior to baseline (Week 0) or documented discontinuation of these medications at least 3 weeks before baseline;
Key exclusion criteria (27 listed)
- Crohn's disease potentially requiring surgery, or conditions that may affect the assessment of ustekinumab or upadacitinib treatment efficacy using CDAI, such as short bowel syndrome, severe or symptomatic strictures, or active stoma.
- Current or suspected abscess. Recent cutaneous and perianal abscesses are not excluded if drained and adequately treated at least 3 weeks prior to baseline. Intra-abdominal abscesses are not excluded if drained and adequately treated at least 8 weeks before baseline and no further surgery is anticipated. Subjects with active fistulas may be included if no further surgery is expected and there is no current abscess.
- Any form of intestinal resection or intra-abdominal surgery within 6 months prior to baseline, or hospitalization for intestinal obstruction within 3 months prior to baseline.
- Use of any of the following medications or treatments within the specified timeframes before baseline:
- Any other experimental drug for Crohn's disease, unless at least 3 months or 5 half-lives have passed since the last dose;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Ustekinumab (approximately 6 mg/kg)At Week 0: ≤55 kg: 260 mg administered by intravenous (IV) infusion. >55 kg and ≤85 kg: 390 mg administered by intravenous (IV) infusion. >85 kg: 520 mg administered by intravenous (IV) infusion. From Week 8 onward (i.e., at Week 8 and then every 8 weeks up to Week 52 or the end of the follow-up period): 90 mg administered by subcutaneous (SC) injection. | Drug | Upadacitinib Group |
| UpadacitinibFrom Week 0 to Week 12: 45 mg once daily, administered orally. From Week 13 through Week 52 or the end of the follow-up period: 30 mg once daily, administered orally. | Drug | Ustekinumab Group |
Primary outcome
clinical remission rate
Time frame: 16th week
To compare the efficacy of ustekinumab versus upadacitinib in subjects with refractory Crohn's disease who had prior failure or intolerance to at least one anti-TNF-α therapy (infliximab or adalimumab), as assessed by the clinical remission rate at Week 16.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Sep 2025.
- Individual participant dataSharing planned: No
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Ustekinumab (approximately 6 mg/kg) and Upadacitinib in people with Crohn's Disease Aggravated and Crohn's Disease in Remission, run by Sixth Affiliated Hospital, Sun Yat-sen University.
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 18 inclusion and 27 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: opening soon, as of the sponsor's last update on 2 Sep 2025. Status can change between updates, so confirm with the study contact before making plans.
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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
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 Xiang Peng Xiang Peng, Dr (+86 18302076916, pengxiang5@mail.sysu.edu.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
clinical remission rate (time frame: 16th week). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 2 Sep 2025.