Inclusion Criteria:
* Patient able to read and understand, and willing to sign the informed consent form;
* Weight≥40kg;
* Clinical diagnosis of Ulcerative colitis (UC) that has been present for at least 3 years before the screening visit;
* Mayo score of 5-9 at the baseline visits, including Mayo Endoscopic Score ≥2 and Rectal Bleeding Subscore ≥1, and disease extent from the anal verge ≥ 15 cm at screening.
* Participants with a history of extensive colitis of ≥8 years' duration, or left-sided colitis of ≥10 years' duration, must have had a complete coloscopy within the past 1 year to exclude the presence fo dysplastic lesions.
* Participants who have had an inadequate response to prior treatment with biologic agents or JAK inhibitors.
* Willing and able to comply with clinic visits and study-related procedures.
* Willing to use adequate birth control, if of reproductive potential and sexually active
Exclusion Criteria:
* Evidence or history (within 6 months) of fulminant colitis, toxic megacolon, or intestinal perforation.
* Prior colectomy (partial or total), or anticipated need for surgical intervention for UC during the study.
* Prior or current diagnosis of Crohn's disease, fistulas/abscesses, indeterminate colitis, unclassified IBD, microscopic colitis, ischemic colitis, infectious colitis, radiation colitis, active diverticulitis, or other colitis/enteritis that may confound efficacy assessment.
* Current unresolved colonic dysplasia, adenoma, adenomatous polyps, or neoplastic lesions. Patients with history of adenomatous polyps are eligible if polyps were completely removed (documented) and screening colonoscopy/histology shows no residual polyps or dysplasia.
* Concomitant primary sclerosing cholangitis or autoimmune hepatitis.
* Malignancy within 5 years prior to screening, except fully resected non-metastatic basal cell carcinoma, squamous cell carcinoma, cervical carcinoma in situ, breast ductal carcinoma in situ, or papillary thyroid carcinoma with no recurrence.
* Major surgery within 6 weeks prior to screening, or planned surgery during the study, unless judged not to increase patient risk or affect study compliance.
* Any condition precluding endoscopic evaluation.
* Unstable or poorly controlled cardiovascular (including atrial fibrillation requiring Class IA/III antiarrhythmics or QT-prolonging agents; unstable ischemic heart disease; Class I/II heart failure; cardiac arrest; cerebrovascular disease; uncontrolled hypertension; symptomatic bradycardia; recurrent cardiogenic syncope; untreated severe sleep apnea; history of second-degree AV block without a functional pacemaker), respiratory, gastrointestinal (excluding UC), hepatic, renal, endocrine, hematologic, neurologic, or psychiatric disease that may compromise patient safety or confound efficacy assessment. - Patients requiring systemic corticosteroids for non-UC conditions (e.g., asthma, adrenal insufficiency, post-transplant) or with peripheral venous access issues are excluded.
* Diabetes mellitus, uveitis, history of ocular surgery/laser, history of maculopathy, or active/uncontrolled macular edema at screening.
* Clinically significant 12-lead ECG abnormalities that may affect safety or interpretation, including QTcF \>450 msec (males) or \>470 msec (females), QRS \>120 msec, or resting heart rate \<50 bpm (average of 3 measurements used for qualification).
* Any of the following laboratory abnormalities:
1. Hemoglobin \<8.0 g/dL
2. WBC \<2,500/mm³
3. Neutrophils \<1,000/mm³
4. Platelets \<100,000/mm³
5. Absolute lymphocyte count \<500/mm³
6. Serum creatinine \>2× ULN
7. ALT or AST \>2× ULN
8. Total bilirubin \>1.5× ULN
9. Any other laboratory abnormality considered by the investigator to pose unacceptable risk.
* History of alcohol, drug, or chemical abuse within 1 year prior to screening.
* Receipt of live or live-attenuated vaccine within 3 months prior to Day 1, or planned during the study or within 5 weeks post-treatment. VZV antibody testing required for patients without documented history or complete vaccination; antibody-positive patients are eligible; antibody-negative patients may rescreen after complete VZV vaccination (≥4 weeks before etrasimod initiation).
* Severe bacterial infection within 3 months (unless resolved with antibiotics), or chronic bacterial infection (e.g., pyelonephritis, osteomyelitis, bronchiectasis).
* C. difficile infection within 30 days prior to Day 1 (may be retested once after 2 weeks of antibiotic therapy; persistent infection excludes enrollment).
* Active invasive fungal infection (e.g., histoplasmosis) or parasitic infection.
* Diagnosis of CMV colitis within 60 days (including screening period). CMV testing on colonic biopsy is required during screening only if clinically suspected.
* Herpes zoster reactivation or CMV infection resolved within 2 months prior to screening.
* Positive for HBsAg, or HBcAb positive with detectable HBV DNA; positive HCV antibody with detectable HCV RNA; positive Treponema pallidum antibody; or positive HIV antibody at screening.
* Positive QuantiFERON-TB Gold or T-SPOT.TB test at screening.
* Use of JAK inhibitors (e.g., tofacitinib, upadacitinib, filgotinib) within 4 weeks (or 5 half-lives, whichever is longer), or anti-TNF agents (e.g., adalimumab, infliximab), vedolizumab, or anti-IL-12/23 agents (e.g., ustekinumab) within 8 weeks (or 5 half-lives, whichever is longer) prior to Day 1.
* Prior S1P receptor modulator therapy without a 3-month washout.
* Use of investigational chemical drugs within 30 days, or investigational biologics within 8 weeks (or 5 half-lives, whichever is longer) prior to Day 1.
* IV corticosteroids within 2 weeks prior to Day 1 or planned during the study.
* Corticosteroid enemas within 4 weeks, or corticosteroid suppositories and/or topical rectal 5-ASA within 2 weeks prior to Day 1, or planned during the study.
* Topical (rectal) herbal enemas or suppositories within 1 week prior to Day 1 or planned during the study.
* Immunosuppressants (e.g., tacrolimus, methotrexate, cyclosporine, mycophenolate mofetil, leflunomide, thalidomide) within 4 weeks (or 5 half-lives, whichever is longer) prior to Day 1 or planned during the study.
* Immunoadsorption or fecal microbiota transplantation within 2 weeks prior to Day 1 or planned during the study.
* NSAIDs (e.g., aspirin \>100 mg/day) within 2 weeks prior to Day 1.
* Immunoglobulin or blood products within 1 month prior to Day 1, or any condition likely to require such therapy during the study.
