This is a Phase Ⅱb, multicenter, randomized, parallel-group, double-blind, placebo-controlled, dose-finding study of AC-101 tablets in patients with moderately to severely active ulcerative colitis (UC). The study will evaluate the efficacy, safety, and pharmacokinetics of AC-101 compared with placebo in patients who have had an inadequate response, loss of response, or intolerance to prior advanced therapies or to prior conventional therapies. The study consists of a screening period (up to 4 weeks), a 12-week induction period, a 40-week extension period, and a 4-week safety follow-up period.
Placebo tablets will be administered orally twice daily.
Eligibility
Sex: ALLMin age: 18 YearsMax age: 75 Years
Medical Language ↔ Plain English
Inclusion Criteria:
1. Male or female participants aged ≥ 18 and ≤ 75 years；
2. Must sign the Informed Consent Form and be willing to participate in the study.
3. Diagnosis of UC confirmed at least 3 months prior to screening, supported by both endoscopic and histological evidence.
4. Evidence of UC extending ≥ 15 cm from the anal verge as assessed by colonoscopy. Moderately to severely active UC, defined as a modified Mayo Score of 5 to 9, with an Endoscopic Subscore ≥ 2.
5. Documented failure to prior advanced therapies or prior conventional therapies
6. Female participants must meet either criterion a) or b), and male participants must meet criterion c) to be eligible for enrollment:
1. Female participants of non-childbearing potential;
2. Female participants of childbearing potential who are not pregnant must agree to use highly effective contraception during the treatment period and for at least 1 month after the last dose of study treatment;
3. Male participants with a pregnant or non-pregnant female partner of childbearing potential must agree to use contraception during the treatment period and for at least 1 month after the last dose of study treatment.
Exclusion Criteria:
1. Severe extensive colitis.
2. Hospitalization for exacerbation of UC within 12 weeks prior to screening.
3. History of gastrointestinal dysplasia, or presence of dysplasia detected in any biopsy performed during the screening colonoscopy.
4. Adenomatous colonic polyps that have not been removed prior to study enrollment.
5. Diagnosis of indeterminate colitis, microscopic colitis, ischemic colitis, or Crohn's disease, or clinical findings suggestive of Crohn's disease.
6. Positive stool pathogen test or positive test for Clostridioides difficile toxin at screening.
7. Presence of an ostomy or fistula.
8. Risk of tuberculosis .
9. History of current or prior serious opportunistic infection.
10. Presence of active or chronic recurrent infection.
11. Patients with any of the following hepatitis B screening results:
Acute or chronic hepatitis B infection; or Positive hepatitis B virus (HBV) test at screening (HBsAg positive); or HBsAg negative, hepatitis B core antibody (HBcAb) positive, with detectable HBV-DNA.
12. Current hepatitis C infection, or positive hepatitis C virus (HCV) test at screening.
13. Human immunodeficiency virus (HIV) infection/acquired immunodeficiency syndrome , or positive HIV antibody test at screening.
14. Syphilis, or positive syphilis-specific antibody test at screening.
15. Treatment with advanced therapies for UC within 8 weeks or 5 half-lives prior to randomization.
16. Treatment with intravenous corticosteroids within 2 weeks prior to randomization.
17. Treatment with leukocyte apheresis within 12 weeks prior to randomization.
18. Treatment with intravenous immunoglobulins or plasmapheresis within 12 weeks prior to randomization.
19. Treatment with lymphocyte-depleting therapy.
20. History of fecal microbiota transplantation.
21. Vaccination with live attenuated vaccines within 4 weeks prior to randomization, or a plan to receive such vaccines during the study period.
22. Requirement for parenteral nutrition.
23. History of myocardial infarction, acute stroke, transient ischemic attack, thromboembolic events, clinically significant arrhythmia, unstable angina, coronary artery bypass grafting, or severe pulmonary heart disease/pulmonary hypertension within 3 months prior to randomization, which, in the investigator's judgment, may affect the evaluation of study results.
24. Presence of any other unstable or uncontrolled cardiovascular, pulmonary, hepatic, renal, gastrointestinal, genitourinary, hematological, coagulation, immunological, endocrine/metabolic, neurological/psychiatric, or other medical condition that, in the investigator's judgment, may interfere with the study results.
25. Known history of immunodeficiency; other acquired or congenital immunodeficiency disorders; or history of organ transplantation.
26. History of malignancy within 5 years prior to screening, with the exception of adequately treated carcinoma in situ of the cervix, or basal cell or squamous cell carcinoma of the skin.
27. Female patients who are pregnant, lactating, or have a positive serum pregnancy test at screening.
28. Any other condition that, in the investigator's opinion, may affect the patient's safety or compliance, or preclude the patient from completing the study.
Outcomes
Primary Outcomes
Clinical Remission
Clinical remission at Week 12, defined as stool frequency subscore of 0 or 1, rectal bleeding subscore of 0, AND centrally read endoscopy subscore of 0 or 1
Time frame: Week 12
Secondary Outcomes
Clinical response
Clinical response at Week 12, defined as a decrease from baseline in the modified Mayo Score of greater than or equal to 2 points AND at least a 30 percent reduction from baseline, AND a decrease in RB of greater than or equal to 1 or an absolute rectal bleeding subscore of 0 or 1
Time frame: Week 12
Symptomatic remission
Symptomatic remission at Week 12, defined as RB=0 and SF=0, OR RB=0, SF≤1 and at least 1 point reduction from baseline