Ustekinumab and Upadacitinib for Induction and Maintenance Therapy in Patients With Refractory Crohn's Disease: A Multicenter, Randomized, Parallel-Controlled Study

NCT07149467 | Not Yet Recruiting Phase 3

• 1 other identifier: 2024ZSLYEC-312
• Study Type: interventional
• Target: 454
• Locations: 0 countries
• Sites: N/A

Brief 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) \[2,3\]. 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.

Conditions

Crohn's Disease Aggravated; Crohn's Disease in Remission

Keywords

Crohn's Disease

Outcome Measures

Primary Outcomes (1)

• 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.

  16th week

Study Arms (2)

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.

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.

Drug: Ustekinumab (approximately 6 mg/kg)

Interventions

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.

Upadacitinib Group

Upadacitinib DRUG

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.

Ustekinumab Group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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;
• 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;

You may not qualify if:

• 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;
• 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 non-tuberculous mycobacterial infection or severe opportunistic infection.
• Patients with viral hepatitis or HIV.

Sponsors & Collaborators

• Sixth Affiliated Hospital, Sun Yat-sen University: lead

MeSH Terms

Interventions

Ustekinumab; upadacitinib

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Central Study Contacts

Xiang Peng Xiang Peng, Dr

CONTACT

+86 18302076916; pengxiang5@mail.sysu.edu.cn

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Dr

Study Record Dates

• First Submitted: August 24, 2025
• First Posted: September 2, 2025
• Study Start: September 10, 2025
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2027
• Last Updated: September 2, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share