Efficacy and safety study of mesalazine in patients with immune checkpoint inhibitor-induced colitis

JRCT ID: jRCT2061240103

Registered date:14/01/2025

Basic Information

• Recruitment status: Pending
• Health condition(s) or Problem(s) studied: Immune-related adverse events, particularly colitis (irAE-colitis)
• Date of first enrollment: 02/06/2025
• Target sample size: 68
• Study type: Interventional
• Intervention(s): Mesalazine 3.6 g/day or placebo (Asacol 400 mg tablet or placebo: 3 tablets 3 times a day after each meal)

Outcome(s)

• Primary Outcome: Percentage of patients achieving clinical improvement and steroid avoidance at 4 weeks post-treatment

Secondary Outcome

1) Percentage of patients achieving clinical remission and steroid avoidance at 4 weeks post-treatment
2) Endoscopic complete remission rate and endoscopic improvement rate at 4 weeks post-treatment
3) Endoscopic score at each time point*
4) Clinical improvement rate at each time point**
5) Clinical remission rate at each time point**
6) Percentage of steroid-free improvement at each time point**, prednisolone equivalent 0.25 mg/kg or less
7) Steroid-free remission rate at each time point*, remission rate at 0.25 mg/kg or less prednisolone equivalent
8) Complete remission rate and improvement rate at 24 weeks post-treatment
9) Avoidance rate of biologic agents at each time point**.
10) Defecation frequency at each time point**.
11) Steroid withdrawal rate in corticosteroid-using population
12) Time to clinical improvement and steroid avoidance
13) Dose of study drug at each time point during the continuation phase
14) Percentage of adverse events
* Time points refer to the 4-week post-dose point and the time of colonoscopy.
** Each time point refers to the Visit time point as indicated in the clinical trial schedule.

Key inclusion & exclusion criteria

• Age minimum: >= 18age old
• Age maximum: Not applicable
• Gender: Both

Include criteria

1. Patients aged 18 years or older (regardless of gender) at the time of consent
2. patients with CTCAE Grade 2 or 3 diarrhea or Grade 2 colitis diagnosed as irAE after receiving or discontinuing PD-1 inhibitors, PD-L1 inhibitors, or CTLA-4 inhibitors
3. patients whose antineoplastic agents are judged by the attending physician to be necessary for withdrawal of antineoplastic agents due to irAE colitis
4. patients who are expected to survive for more than 30 days at the time of enrollment
5. Patients whose latest blood test results within 14 days prior to enrollment (not including the day of enrollment) confirm that the following criteria are met
AST and ALT less than or equal to 5 times the upper limit of the reference value of the implementing institution
Total bilirubin is 3 times or less than the upper limit of the reference value of the institution
Total bilirubin is 3 times or less than the upper limit of the reference value at the institution.
Patients whose written consent to participate in this study is obtained.

Exclude criteria

1. Patients with a history of hypersensitivity to any component of mesalazine
2. Patients with a history of hypersensitivity to salicylates
3. Patients undergoing dialysis therapy
4. Patients with clinically or endoscopically documented severe colitis who meet any of the following criteria
Diarrhea of CTCAE Grade 4 or higher
Colitis of CTCAE Grade 3 or higher
Shallow ulcer or deep ulcer on colonoscopy (according to UCEIS erosions and ulcers subscore)
Other findings requiring immediate treatment with corticosteroids or infliximab, etc. Perform abdominal CT or other tests as necessary. 5.
Patients receiving the following drugs within the prescribed time period
5-ASA, salazosulfapyridine (SASP), corticosteroids*, cyclosporine, tacrolimus, methotrexate: 4 weeks prior to registration
Infliximab, adalimumab, golimumab, vedolizumab, risankizumab: 12 weeks prior to enrollment
*The use of topical agents is acceptable. In addition, temporary use as antiemetic agents, etc. in combination with antineoplastic drugs (oral or injectable) is acceptable.
6. Patients for whom the following drugs have been initiated or whose dosage and administration have been changed within the respective specified time periods
Azathioprine, 6-mercaptopurine, mofetil mycophenolate: 8 weeks prior to registration
Tofacitinib, filgotinib, and upadacitinib: 4 weeks prior to enrollment
Patients diagnosed with or previously diagnosed with ulcerative colitis, Crohn's disease, enteric Behcet's disease, or familial Mediterranean fever-related enterocolitis
8. patients diagnosed or clinically suspected to have bacterial enteritis, viral enteritis, ischemic colitis, parasitic enteritis, or GVHD enteritis at screening
9. patients who have a colostomy
10. patients scheduled for gastrointestinal surgery
Pregnant or lactating patients
Other patients who are judged by the investigator or subinvestigator to be inappropriate to participate in the clinical trial.

Related Information

• Primary Sponsor: Yamashita Ken
• Source(s) of Monetary Support: Japan Agency for Medical Research and Development