InflammatoryBowelDisease,IBD
Conditions
Interventions
Control group:Placebo
Sponsors
Sir Run Run Shaw Hospital, Affiliated to Zhejiang University School of Medicine
Eligibility
Sex/Gender
All
Age
18 Years to 65 Years
Inclusion criteria
Inclusion criteria: 1. Age 18-65 years (inclusive), gender unrestricted, BMI 18-30 kg/m^2 (inclusive); 2. Trial participants voluntarily sign the informed consent form, can understand the research requirements, and can complete all visits, examinations and evaluations as per the protocol; 3. Previously diagnosed with ulcerative colitis (UC), disease duration >= 3 months; during the screening period, differential diagnosis tests for infectious enteritis and other diseases that can cause similar symptoms (including but not limited to fecal routine/fecal occult blood, Clostridium difficile toxin A/B test) must be completed, and the investigator determines that it meets the criteria for an active episode of UC; 4. Baseline disease activity meets the criteria for moderate to severe active UC: modified Mayo score (mMayo) is 5-9 points (inclusive), and endoscopic score (MES) >= 2, rectal bleeding (RB) sub-score >= 1 and stool frequency (SFS) sub-score >= 1; the lesion range is not limited to the rectum, and baseline endoscopy confirms that the inflammation involves a range more than 15 cm from the anal verge; Baseline endoscopy assessment can use sigmoidoscopy or total colonoscopy; if the trial participant has a high-quality, complete total colonoscopy record within 1 year before screening, sigmoidoscopy can be used for the current activity assessment; otherwise, total colonoscopy must be completed during the baseline period. 5. If the trial participant has previously used the following drugs, the corresponding washout period must be completed before baseline (calculated from the last day of drug use to the baseline date; if the investigator determines a longer washout period is needed, follow their instructions): (1) Immunosuppressants (azathioprine, 6-MP, methotrexate, etc.): >= 8 weeks before baseline; (2) Biologics: anti-TNFa, anti-integrin monoclonal antibodies or other monoclonal antibodies: >= 8 weeks before baseline; anti-IL-12/23 or IL-23 monoclonal antibodies: >= 12 weeks before baseline; (3) Targeted small molecules: Anti-TNFa, anti-IL-12/23 or IL-23 monoclonal antibodies, anti-integrin monoclonal antibodies, or other monoclonal antibodies: =8 weeks prior to baseline; (4) Intravenous corticosteroids: =4 weeks prior to baseline; (5) Rectal corticosteroids: =2 weeks before baseline; (6) Rectal 5-ASA preparations: >= 2 weeks before baseline. 6.If participants have previously used any of the following medications, they must maintain a stable dose prior to baseline and, in principle, keep the same dose unchanged during induction therapy (unless otherwise determined by the investigator for safety reasons; self-adjustment, increase, decrease, or discontinuation is not permitted during induction therapy): 1)Oral 5-ASA: Must be maintained at a stable dose for at least 2 weeks prior to baseline. 2)Oral corticosteroids: Must be maintained at a stable dose for at least 2 weeks prior to baseline, with dosages not exceeding the following upper limits: prednisone or equivalent <20 mg/day, budesonide or equivalent =9 mg/day, beclomethasone or equivalent =5 mg/day. 3)If participants have recently discontinued oral corticosteroids, they must discontinue the medication for at least 2 weeks prior to baseline. 7. Fertility-related requirements: Female trial participants are not pregnant or lactating; women of childbearing age have a negative pregnancy test during the screening period; Women of childbearing age and male trial parti
Exclusion criteria
Exclusion criteria: 1. Currently diagnosed with Crohn's disease (CD), indeterminate colitis, or other non-UC inflammatory bowel diseases such as ischemic colitis. 2. Presence of acute severe ulcerative colitis during the screening period or at baseline, or severe colitis requiring hospitalization as judged by the investigator, or existence of acute complications requiring emergency treatment (including but not limited to uncontrollable severe bleeding, toxic megacolon, intestinal perforation, peritonitis, etc.). Acute severe UC can be defined by the modified Truelove and Witts criteria: >= 6 bloody loose stools within 24 hours, accompanied by at least one of the following systemic toxic manifestations: body temperature > 37.8°C, or heart rate > 90 beats/min, or hemoglobin 30 mm/h, or CRP > 30 mg/L. 3. Presence of severe active autoimmune diseases outside the intestine (such as systemic lupus erythematosus, multiple sclerosis, active uveitis, etc.) that the investigator believes may affect safety or efficacy assessment. 4. History of or current malignant tumors, or having received tumor chemotherapy.If the malignant tumor has been in complete remission for =5 years with no active disease, and the investigator determines that it will not affect the safety and efficacy assessment of this study, enrollment may be considered. 5. Presence of active infection or risk of infection requiring systemic anti-infection treatment, including but not limited to: pneumonia, sepsis; and active or uncontrolled HBV/HCV/HIV infections indicated by baseline tests; or the investigator judges that there are clinically significant CMV, EBV, etc. viral infections. 6. Stool tests during the screening period indicate Clostridioides difficile infection or evidence of other intestinal pathogens such as bacteria or parasites, or the investigator determines that diarrhea is primarily caused by an infection. 7. Received live or attenuated live vaccines within 3 months before enrollment. 8. Did not complete the washout period as specified in the protocol for previous treatments before screening, or need to use prohibited biological agents (such as anti-TNFa, anti-IL-12/23, etc.), JAK inhibitors, or other targeted small molecule drugs during the screening period or the expected study period (unless the washout period has been completed and confirmed by the investigator not to affect the assessment). 9. Patients who did not maintain a stable dose of prior medications (such as oral 5-ASA or oral corticosteroids) as required by the protocol, or exceeded the specified upper limit; or those who discontinued oral corticosteroids less than 2 weeks before baseline, and those unable to comply with the requirement for maintaining a stable medication dose during the study period. 10. Previously had primary non-response or secondary loss of response to more than two advanced treatments for UC (biological agents or small molecule drugs), including but not limited to JAK inhibitors, S1P receptor modulators, etc. (judged based on previous medical records, treatment courses, and efficacy evidence). 11.Exclude patients who have undergone major surgery within the past 4 weeks, or have a history of gastrointestinal surgery that may significantly affect drug absorption (e.g., extensive small bowel resection, total gastrectomy). 12. Presence of a history of severe cardiovascular, liver, kidney, neurological, mental, endocrine, etc. system diseases, or significant organ function abnormalities
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Proportion of trial participants achieving clinical response (based on mMayo score) at Week12; | — |
Secondary
| Measure | Time frame |
|---|---|
| The incidence rate of adverse events leading to the suspension or permanent discontinuation of the study drug;The occurrence of abnormalities and baseline changes in clinical laboratory tests, vital signs, physical examinations, 12-lead electrocardiogram (ECG), etc.;Indicators related to compliance and tolerance (such as gastrointestinal intolerance, medication interruption, etc.);Key secondary efficacy endpoints: proportion of trial participants achieving clinical remission (based on mMayo score) at Week 12; proportion of trial participants achieving mucosal healing at Week 12; change in mMayo score from baseline at Week 12.;The longitudinal changes in CRP levels from baseline to Week 4Week 8Week 12;The longitudinal changes in FC levels from baseline to Week 4Week 8Week 12;The longitudinal changes in the total score of the Inflammatory Bowel Disease Questionnaire (IBDQ) from baseline to Week 4Week 8Week 12;Plasma PK: PK parameters are calculated based on plasma drug concentration-time data.;Urinary PK (Exploratory): Urine samples were collected at the scheduled visit points to measure the concentration of TAN-118 (and its major metabolites) in the urine. The concentration data in the urine were obtained to explore the exposure characteristics in the urine.;Fecal PK (Exploratory): Fecal samples were collected within the pre-specified time window to determine the concentration of TAN-118 (and its major metabolites) in feces, for the purpose of exploring the local exposure characteristics in the intestinal tract.;Tissue PK (Exploratory): At the pre-scheduled endoscopic sampling time point, intestinal mucosal tissue samples (sigmoid colon) will be collected to determine the concentration of TAN-118 (and its major metabolites) in the tissue. This is to explore the local exposure characteristics of the intestinal mucosa and its relationship with plasma exposure and pharmacodynamic/efficacy indicators.;The change in CYP1A1 mRNA expression;The correlation between biomarker | — |
Countries
China
Contacts
Public ContactQian Cao
Sir Run Run Shaw Hospital, Affiliated to Zhejiang University School of Medicine
Outcome results
None listed