Comaprison of Efficacy and Safety Between Etrasimod vs Mesalazine in Chinese Adults With Active UC

NCT07782242 | Not Yet Recruiting Phase 4

• 1 other identifier: 2026-2585-01
• Study Type: interventional
• Target: 320
• Locations: 0 countries
• Sites: N/A

Brief Summary

Ulcerative colitis (UC) is a chronic, relapsing inflammatory disease of the colon that causes diarrhea, bleeding, and abdominal pain. Mesalazine (5-aminosalicylic acid) is the current standard first-line treatment for mild-to-moderate UC, but many patients do not respond well enough, and some experience side effects. Etrasimod is an oral, selective sphingosine-1-phosphate (S1P) receptor modulator that helps reduce gut inflammation by keeping immune cells from moving into the intestinal wall. This study will test whether etrasimod works better than mesalazine in Chinese adults with active UC. The study plans to enroll about 320 patients from multiple hospitals across China. Eligible participants are adults aged 18 years or older with active UC, defined by a modified Mayo score of 3 to 6 (including specific endoscopic and bleeding criteria). Both newly diagnosed patients (within the past 4 weeks, with no prior UC treatment) and those who had an inadequate response, intolerance, or non-standard use of conventional therapies-but who have never taken biologics or other small-molecule drugs-may join. Patients will be randomly assigned in a 1:1 ratio to receive either etrasimod 2 mg once daily or mesalazine (starting at 4 g/day for 12 weeks, then at least 2 g/day based on response) for 24 weeks. Randomisation will balance important factors like steroid use and baseline endoscopic severity. The primary research objective is whether more patients on etrasimod achieve clinical remission at week 24. Clinical remission means no rectal bleeding, normal or near-normal stool frequency, and an endoscopic score of 1 or less (without easy bleeding). The study will also measure other benefits, such as symptom improvement, endoscopic healing, normalisation of blood and stool inflammation markers, bowel ultrasound response, tissue healing, and quality of life using standard questionnaires. Safety will be carefully tracked by recording all adverse events during treatment and follow-up. This is an open-label study (patients and clinical staff know which drug is given) to reflect real-world practice, but the clinical staff who read the colonoscopy results and tissue samples will not know the treatment assignment. An independent statistician will analyse the results. One interim analysis is planned to check for early evidence of benefit or futility. The study involves 24 weeks of treatment, with visits at baseline, week 6, week 12, and week 24, plus a 4-week safety follow-up. Sample size calculation indicates that 320 participants (160 per group) will provide 90% power to detect a clinically important difference, accounting for a 30% dropout rate. The primary analysis will compare remission rates between groups, adjusting for the stratification factors. All findings will be published to share knowledge with the medical community and help guide future treatment decisions for UC patients in China.

Conditions

Head-to-head; Etrasimod; Mesalazine; Ulcerative Colitis (UC)

Keywords

Etrasimod; Active UC; Mesalazine

Outcome Measures

Primary Outcomes (1)

• Percentage of participants achieving clinical remission

  Proportion of participants achieving clinical remission at Week 24. Clinical remission is defined as meeting all three of the following criteria: (1) rectal bleeding score (RBS) = 0; (2) stool frequency score (SFS) = 0, or SFS = 1 with a decrease of ≥1 point from baseline; and (3) Mayo endoscopic score (ES) ≤ 1 (excluding mucosal friability). RBS and SFS are derived from the modified Mayo score and assessed via participant-reported daily diaries. Endoscopic score is obtained by colonoscopy (sigmoidoscopy), with central independent reading performed by readers blinded to treatment allocation. The assessment window is Week 24 ± 4 weeks. For missing data, non-responder imputation (NRI) is applied, meaning that participants with missing data or who discontinue early are counted as not having achieved remission.

  week 24

Secondary Outcomes (10)

• Percentage of Participants Achieving Clinical Response

  week 12 and week 24

• Percentage of Participants Achieving Symptomatic Remission

  week 12 and week 24

• Percentage of Participants Achieving Endoscopic Remission

  week 12 and week 24

• Percentage of Participants Achieving Endoscopic Normalization

  week 12 and week 24

• Percentage of Participants Achieving Normalization of Inflammatory Markers

  week 12 and week 24

Study Arms (2)

Etrasimod

EXPERIMENTAL

Participants receive etrasimod 2 mg film-coated tablets orally once daily for 24 weeks. Etrasimod is a selective S1P receptor modulator that traps lymphocytes in lymph nodes, reducing gut inflammation. Dose is fixed; no adjustments, but may be interrupted/discontinued for safety (e.g., liver enzyme elevation, bradycardia, infection). After 24 weeks, a 4-week safety follow-up occurs without study drug. Baseline steroids are allowed but must be tapered.

Drug: Etrasimod

Mesalazine (5-ASA)

ACTIVE COMPARATOR

Participants receive mesalazine 0.5 g enteric-coated tablets orally. Induction: 4 g/day (8 tablets) for first 12 weeks; maintenance: ≥2 g/day (4 tablets) from weeks 13-24, adjusted by investigator based on response. Mesalazine acts topically on colonic mucosa. Dose reduction allowed in maintenance; may be interrupted/discontinued for intolerance (e.g., renal issues). 4-week safety follow-up after 24 weeks. Same steroid tapering applies.

Drug: mesalazine

Interventions

Etrasimod DRUG

Etrasimod is an oral, once-daily, small-molecule selective S1P receptor modulator (targeting S1P₁,₄,₅) that traps lymphocytes in lymph nodes to reduce gut inflammation without broad immunosuppression. FDA-approved (VELSIPITY, Oct 2023), EMA-approved (2024), and NMPA-approved in China (Feb 2026, Velsipity) for moderately-to-severely active UC. Global Phase 3 trials (ELEVATE UC 12/52, n=741) showed etrasimod significantly outperformed placebo in clinical remission (25% vs 15% at Wk12, 32% vs 7% at Wk52), endoscopic normalisation, and steroid-free remission. The Asian ENLIGHT UC trial confirmed benefits in 320 Chinese patients. Safety data over 4 years show mostly mild-to-moderate AEs with low serious events. This head-to-head superiority trial against mesalazine addresses a key evidence gap in Chinese UC management, assessing whether earlier etrasimod improves outcomes over current standard care.

Also known as: Velsipity, ADP334

Etrasimod

mesalazine DRUG

Mesalazine (5-ASA) is the current first-line standard treatment for mild-to-moderate ulcerative colitis in China and worldwide. It works directly on the inflamed gut lining by reducing local inflammatory chemicals (prostaglandins and leukotrienes), with very little drug absorbed into the bloodstream - making it generally safe. It comes in oral tablets and rectal forms, depending on disease location. Most people tolerate mesalazine well. Common, mild side effects include stomach upset, nausea, headache, or dizziness. Rare but serious risks include kidney inflammation (so regular blood tests are needed), pancreatitis, liver problems, and allergic reactions. Long-term use may also lower the risk of colon cancer in UC patients. This trial compares mesalazine head-to-head against etrasimod to see if the newer drug offers better outcomes for Chinese adults with active UC.

Also known as: 5-ASA

Mesalazine (5-ASA)

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female, aged 18 years or above.
• Patients diagnosed with active ulcerative colitis at multiple centers including Sir Run Run Shaw Hospital, Zhejiang University School of Medicine (lead center), defined as having a modified Mayo Score (without physician's global assessment) ranging from 3 to 6 points. If ES = 1 point, RBS ≥ 1 point is required. Patients with proctitis are allowed to be enrolled, provided that the proctitis lesion extends more than 5 cm from the anal verge.
• Treatment-naive patients at initial visit accounting for no more than 30% of the total sample size; Or patients who have previously received conventional pharmacological therapy (including mesalazine, corticosteroids and immunosuppressants) but have inadequate response, intolerance (excluding mesalazine), or non-standard treatment (including but not limited to insufficient dosage or duration of oral 5-ASA, corticosteroids or immunosuppressants, which shall be determined by the investigator based on individual patient conditions). The proportion of patients receiving combined glucocorticoid therapy at baseline shall not exceed 30% of the total sample size.
• Voluntarily participate in this study and sign the informed consent form.

You may not qualify if:

• Subjects with contraindications to etrolimod or mesalazine.
• Previously treated with etrasimod or other biologics and small-molecule drugs.
• Patients are currently receiving full-dose conventional therapy yet still have active disease, including any one of the following:
• Treatment with mesalazine (≥3 g/day) for ≥8 weeks; Or continuous treatment with prednisone ≥40 mg/day or equivalent dose for ≥3 days (intravenous administration); Or continuous oral treatment with prednisone \>20 mg/day or equivalent dose for ≥2 weeks; or oral azathioprine (≥0.75 mg/kg/day), 6-mercaptopurine (≥0.5 mg/kg/day), methotrexate (≥15 mg/week) for ≥3 months.
• Recent history of acute severe ulcerative colitis (ASUC), toxic megacolon, etc.
• Patients with stomas or patients with UC scheduled for inpatient surgical intervention.
• Pregnant and lactating women.
• Vulnerable groups excluding the elderly and illiterate, including people with mental illnesses, individuals with cognitive impairment, critically ill patients, etc.
• Other circumstances where researchers consider participation in this study inappropriate.

Sponsors & Collaborators

• Sir Run Run Shaw Hospital: lead
• Everest Medicines: collaborator

Related Publications (2)

• Sandborn WJ, Vermeire S, Peyrin-Biroulet L, Dubinsky MC, Panes J, Yarur A, Ritter T, Baert F, Schreiber S, Sloan S, Cataldi F, Shan K, Rabbat CJ, Chiorean M, Wolf DC, Sands BE, D'Haens G, Danese S, Goetsch M, Feagan BG. Etrasimod as induction and maintenance therapy for ulcerative colitis (ELEVATE): two randomised, double-blind, placebo-controlled, phase 3 studies. Lancet. 2023 Apr 8;401(10383):1159-1171. doi: 10.1016/S0140-6736(23)00061-2. Epub 2023 Mar 2.

  PMID: 36871574 RESULT

• Wu K, Zheng C, Cao Q, Ding Y, Gao X, Zhong J, Chiu CT, Zhang H, Wang X, Wang B, Liang J, Liu X, Zhou Y, Xu B, Kim TO, Shen X, Chen D, Chen W, Liu Y, Shen J, Liu F, Ding X, Zhan Q, Chou JW, Zeng S, Lin Y, Ying L, Chen X; ENLIGHT UC Study Group. Etrasimod as induction and maintenance treatment for patients with moderately to severely active ulcerative colitis in East Asia (ENLIGHT UC): a randomised, double-blind, placebo-controlled, multicentre, phase 3 study. Lancet Gastroenterol Hepatol. 2025 Dec;10(12):1089-1103. doi: 10.1016/S2468-1253(25)00198-0. Epub 2025 Sep 30.

  PMID: 41043449 RESULT

MeSH Terms

Conditions

Colitis, Ulcerative

Interventions

etrasimod; Mesalamine

Condition Hierarchy (Ancestors)

Colitis; Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Inflammatory Bowel Diseases; Colonic Diseases; Intestinal Diseases

Intervention Hierarchy (Ancestors)

meta-Aminobenzoates; Aminobenzoates; Benzoates; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Aminosalicylic Acids; Salicylates; Hydroxybenzoates; Hydroxy Acids; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Phenols

Central Study Contacts

Qian Cao, Doctor

CONTACT

+8613588706896; caoq@srrsh.com

Jing Liu, Doctor

CONTACT

+8618768116867; liuj319@163.com

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Chief physician

Model Details: Participants are randomized in a 1:1 ratio to receive either Etrasimod (2 mg once daily) or Mesalazine (standard doses: 4 g/day for 12 weeks, then at least 2 g/day) for 24 weeks. Randomization is stratified by two factors: baseline steroid use (yes/no) and baseline endoscopic score (ES ≤ 2 vs. ES = 3) to ensure balance between the two groups. Each participant remains in their assigned treatment arm for the entire 24-week treatment period and does not cross over to the other treatment.

Study Record Dates

• First Submitted: July 30, 2026
• First Posted: August 24, 2026
• Study Start: July 31, 2026
• Primary Completion (Estimated): June 30, 2027
• Study Completion (Estimated): December 31, 2027
• Last Updated: August 24, 2026

Record last verified: 2026-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Start date: January 2028 (upon publication of primary results). End date: December 2033 (5 years from start). Rationale: The trial completes around mid-2027; data cleaning and publication require \~6-9 months. IPD will be shared after the main paper is accepted. Data remain accessible for 5 years to allow secondary analyses, consistent with standard data-sharing policies and funder requirements. Extension requests beyond 2033 will be considered on a case-by-case basis.
• Access Criteria: Approved academic researchers can access de-identified IPD (efficacy, safety, QoL) plus protocol, SAP, and ICF via secure file transfer after signing a data access agreement. Proposals reviewed by PI/steering committee