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 old (including cut-off), gender is not limited, BMI is 18-30kg/m^2 (including cut-off value); 2. The trial participant voluntarily signed the informed consent form, was able to understand the study requirements, and was able to complete all visits, examinations and evaluations according to the protocol; 3. Previously diagnosed with ulcerative colitis (UC), with a duration of >=3 months; During the screening period, differential 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 detection) must be completed, and the investigator judges that it is consistent with the active onset of UC; 4. Baseline disease activity is consistent with active UC: Modified Mayo Score (mMayo) is 4-9 points (including cut-off value), and endoscopic score (MES) >=2, rectal bleeding (RB) subscore >=1 and defecation frequency (SFS) subscore >=1; The scope of the lesion is not limited to the rectum, and the baseline endoscopy confirms that the extent of inflammatory involvement is 15 cm > the anal verge; Meet at least 1 of the following objective inflammatory criteria: FC>=250µg/g or CRP above the upper limit of normal; Baseline endoscopic evaluation can be assessed with orthocolonoscopy. 5. If the trial participant has used the following drugs in the past, the corresponding washout period must be completed before baseline before enrollment (calculated from the date of the last dose to the baseline date; If the investigator determines that a longer washout period is necessary, the prescribed shall apply): Immunomodulators (azathioprine, 6-MP, methotrexate, etc.): complete >=8 weeks of discontinuation before baseline; 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; Targeted small molecules: JAK inhibitors: >=2 weeks before baseline; S1P receptor modulator: >=4 weeks before baseline; Glucocorticoid-related therapy: Intravenous corticosteroids: >=4 weeks before baseline; Rectal glucocorticoids: >=2 weeks before baseline; Rectal administration preparation: Rectal 5-ASA formulation: >=2 weeks before baseline. 6. Fertility related requirements: Female trial participants are not pregnant, non-lactating; Women with childbearing potential have a negative pregnancy test during the screening period; Females of childbearing potential and male trial participants who have sexual intercourse with them must take protocol-required contraceptive measures from signing the ICF to at least 3 months after the last dose; 7. The results of clinical laboratory examination, vital signs, physical examination and 12-lead ECG are within the normal range, or although abnormal but judged by the investigator to have no clinical significance and do not affect the safety of trial participants and research evaluation; 8. The investigator judged that the participants in the trial had good compliance and were able to cooperate with the study drug, endoscopy, sample collection and follow-up; 9. Participants are willing and able to undergo endoscopy and sigmoid tissue sample collection at V1 and V3, and complete the corresponding sample collection and follow-up.
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. 5. Presence of active infection or risk of infection requiring systemic anti-infection treatment, including but not limited to: pneumonia, sepsis; and screening period tests indicating active or uncontrolled HBV/HCV/HIV infections; or the investigator judges that there is a clinically significant CMV, EBV, etc. viral infection. 6. Presence of evidence of intestinal pathogen infection such as bacteria or parasites during the screening period, or the investigator judges that the diarrhea is mainly caused by infection. 7. Received live or attenuated live vaccines within 4 weeks before enrollment. 8. Did not complete the washout period of previous treatment as specified in the protocol 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 that it does not affect the assessment). 9. Underwent major surgery within 4 weeks before screening, or has a history of gastrointestinal surgery that may significantly affect drug absorption (such as extensive small intestine resection, total gastrectomy, etc.). 10. Previously received study drugs containing TAN-118, or previously used systemic AhR pathway modulating drugs as the mechanism of action, and the investigator believes it may affect the safety and efficacy assessment of this study. 11. Previously had primary non-response or secondary loss of response to more than 3 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). 12. Presence of a history of severe cardiovascular, liver, kidney, neurological, mental, endocrine, etc. system diseases, or significant organ function abnormalities indicated by laboratory tests during the screening period, and the investigator judges that the subject is not suitable for enrollment. 13. Baseline endoscopy indicates the need for urgent surgical intervention (such as highly suspected canceration, or the investigator judges that surgery must be performed in the short term). 14. History of prolonged QTc interval, or QTcF > 450 ms (male) or > 470 ms (female) in
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The incidence, severity, outcome and correlation with the study drug of adverse events/serious adverse events that occurred during the treatment period;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 electrocardiograms, etc.;Indicators related to compliance and tolerance;Pharmacokinetic endpoints (plasma PK and tissue PK), exploratory endpoints (induction changes of CYP1A1); | — |
Secondary
| Measure | Time frame |
|---|---|
| The longitudinal changes in key efficacy exploration indicators, CRP and FC levels; | — |
Countries
China
Contacts
Public ContactQian Cao
Sir Run Run Shaw Hospital, Affiliated to Zhejiang University School of Medicine
Outcome results
None listed