Baricitinib in the Treatment of Intestinal Behçet's Syndrome

Official title

A Multi-center, Prospective, Open-label, Randomized Study to Explore Efficacy and Safety of Baricitinib in Refractory Intestinal Behçet's Syndrome Patients

Overview

This study aims to conduct a randomized controlled trial to compare the efficacy and safety of Baricitinib and Adalimumab (ADA) in the treatment of refractory intestinal Behçet's Syndrome (BS). The objective is to demonstrate if Baricitinib is non-inferior to ADA in controlling BS inflammation, reducing BS recurrence， alleviating gastrointestinal symptoms and promoting intestinal mucosal healing.

Detailed description

The non-inferiority will be established by comparing the lower bound of the two-sided 95% confidence interval with the non-inferiority margin. If the lower bound was larger than the margin, Baricitinib would be regarded as non-inferiror to ADA. Superority will be further assessed in case that the non-inferiority is established. Both ITT and PP analysis will be conducted for the primary outcome given the non-inferiority design. Trial result will be primarily interpreted based on ITT analysis.

Interventions

• Drug Baricitinib
  Participants randomized to this arm will maintain their original steroids and/or immunomodulators, combined with Baricitinib 4 mg/day for 6 months.
• Drug Adalimumab
  Participants randomized to this arm will maintain their original steroids and/or immunomodulators, combined with ADA (initially ADA 160 mg subcutaneous injection, followed by 80 mg ADA after 2 weeks, then 40 mg ADA every 2 weeks thereafter) for 6 months.

Primary outcome measures

• Proportion of patients with marked improvement (MI) at week 24 of follow-up [Time frame: Baseline to week 24]

Secondary outcome measures (9)

• Proportion of patients with CR (complete response) at week 24 of follow-up [Time frame: Baseline to week 24]
• Proportion of patients with improvement of ≥1 point in gastrointestinal symptom scores compared to baseline at week 24 of follow-up [Time frame: Baseline to week 24]
• Changes in C-reactive protein (CRP) compared to baseline [Time frame: Baseline to week 24]
• Changes in erythrocyte sedimentation rate (ESR) compared to baseline [Time frame: Baseline to week 24]
• Changes in DAIBD scores compared to baseline [Time frame: Baseline to week 24]
• Changes in BDCAF scores compared to baseline [Time frame: Baseline to week 24]
• Changes in SF-36 of life questionnaires compared to baseline [Time frame: Baseline to week 24]
• Changes in IBDQ quality of life questionnaires compared to baseline [Time frame: Baseline to week 24]
• Incidence of Treatment-Emergent Adverse Events [Time frame: Baseline to week 24]

Eligibility criteria

Inclusion criteria

• Refer to the consensus on the diagnosis and treatment of intestinal Behçet's syndrome in China: Patients who meet the 2013 International Criteria for Behçet's Disease (ICBD) and have typical Behçet's syndrome-related intestinal ulcers confirmed by colonoscopy, or patients diagnosed according to the criteria for Behçet's syndrome established by the Korean Behçet's Disease Collaborative Group in 2009;
• Patients have a DAIBD score ≥ 40 points or intestinal symptom score ≥ 3 points at baseline;
• Endoscopic examination conducted within 60 days before inclusion suggests active intestinal ulcers;
• Patients who have been treated with medium to high-dose steroids (prednisolone equivalent of 0.5-1 mg/kg/day) for more than 1 month continuously, or any immunomodulator/Immunosuppressants for more than 3 months regularly or biologics for more than 2 months, as judged by the doctor to be treatment failure or intolerance;
• Currently steroid dose ≤ 30 mg prednisolone equivalent, stabilized for ≥ 2 weeks, and/or stabilized immunomodulator dose for ≥ 4 weeks;
• Understanding the research process, voluntary participation, and signing of informed consent.

Exclusion criteria

• Diagnosis of other diseases such as Crohn's disease, ulcerative colitis, lymphoma, etc.;
• Other active organ damage related to BS requires intensified immunosuppressive therapy, including aneurysms, uveitis, and substantial involvement of the central nervous system; skin lesions and joint involvement can be included;
• Severe organ dysfunction including ALT, AST, TBIL levels exceeding twice the upper limit of normal, creatinine levels exceeding 1.5 times the upper limit of normal, white blood cell count < 3×10\^9/L, ANC < 2×10\^9/L, hemoglobin < 80g/L, platelets < 100×10\^9/L;
• Active infections such as active tuberculosis, active hepatitis B or C, syphilis, chronic Epstein-Barr virus infection, HIV infection, sustained or severe bacterial or viral infections, and history of severe herpes zoster;
• Patients with latent tuberculosis must undergo ≥3 weeks of prophylactic anti-tuberculosis treatment before inclusion;
• Primary immunodeficiency disease;
• History of cancer, or endoscopic intestinal histopathology indicating intraepithelial neoplasia or malignancy, or presence of other malignancies;
• Patients who did not respond to infliximab treatment for primary refractory BS (patients with secondary failure, intolerance, or allergy to infliximab should be included);
• Patients treated with biologics/small molecule targeting therapies within 5 half-lives (including use of tofacitinib within 10 days, etanercept within 4 weeks, infliximab within 8 weeks, golimumab, certolizumab, abatacept, and tocilizumab within 10 weeks, ustekinumab within 6 months);
• Patients with prior use of baricitinib or ADA;
• Complications of intestinal BS such as symptomatic stenosis, short bowel syndrome, intestinal fistula, or suspected intra-abdominal abscess; potential need for surgery or situations not conducive to DAIBD and efficacy assessment; any form of intestinal resection or other abdominal surgery within 6 months before baseline; presence of a functioning (i.e., patent) stoma or ostomy;
• Patients requiring parenteral nutrition due to disease severity;
• Pregnant, lactating, or planning pregnancy soon;
• Patients unwilling or unable to comply with regular visits;
• History of severe thrombotic events or chronic cardiovascular events.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

China · 2 centers

• Peking Union Medical College Hospital — Beijing
• Peking Union Medical College Hospital — Beijing

Identifiers

NCT: NCT06849908 · Baricitinib-IBS-PUMCH

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗