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

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

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

Interventions

DRUG

Etrasimod

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.

DRUG

mesalazine

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.

Sponsors & Collaborators

• Everest Medicines

  collaborator INDUSTRY

• Sir Run Run Shaw Hospital

  lead OTHER

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

18 Years

Max Age

100 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2026-07-31

Primary Completion

2027-06-30

Completion

2027-12-31