NCT04706793

Oral Etrasimod Versus Placebo for the Treatment of Moderately to Severely Active Ulcerative Colitis in Adult Japanese Participants (ELEVATE UC 40 JAPAN)

Completed Phase 3 Results posted Last updated 16 October 2023

What this trial tests

Phase 3 trial testing Etrasimod in Ulcerative Colitis in 42 participants. Completed in 3 August 2022.

Timeline

25 December 2020

Primary endpoint
3 August 2022

3 August 2022

Quick facts

Lead sponsor	Pfizer
Phase	Phase 3
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	double
Primary purpose	treatment
Enrollment	42
Start date	25 December 2020
Primary completion	3 August 2022
Estimated completion	3 August 2022
Sites	38 locations across Japan

Drugs / interventions tested

• Etrasimod (ETRASIMOD) — full drug profile →
• Placebo

Conditions studied

• Ulcerative Colitis — all drugs for Ulcerative Colitis →

Sponsor

Pfizer — full company profile →

Who can join

Adults 16 to 80, any sex, with Ulcerative Colitis. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Percentage of Participants Achieving Clinical Remission at Week 40 of Study APD334-308 Primary · Week 40 of APD334-308

Clinical remission was based on the modified Mayo score (MMS). The MMS is a composite score of 3 assessments consisting of participant-reported symptoms using daily electronic (e)-diary and centrally read endoscopy: stool frequency (SF), rectal bleeding (RB) and endoscopic score (ES). Clinical remission was defined as SF sub-score = 0 (or = 1 with a greater than or equal to \[\>=\] 1-point decrease from Baseline), RB sub-score = 0, and ES less than or equal to (\<=) 1 (excluding friability). Each component sub-score ranged from 0 to 3 and total score range of the MMS was from 0 to 9, with high

Group	Value	95% CI
Placebo Comparator: Placebo	7.1
Experimental: Etrasimod 2 mg	25.0

Percentage of Participants Achieving Endoscopic Improvement at Week 40 of Study APD334-308 Secondary · Week 40 of APD334-308

Endoscopic improvement was defined as an ES \<=1 (excluding friability) at Week 40 of APD334-308 compared with Week 12 of APD334-302. The ES ranged from 0 to 3 (where 0 = normal/inactive disease and 3 = severe disease); higher score indicated more severe disease.

Group	Value	95% CI
Placebo Comparator: Placebo	7.1
Experimental: Etrasimod 2 mg	35.7

Percentage of Participants Achieving Symptomatic Remission at Week 40 of Study APD334-308 Secondary · Week 40 of APD334-308

Symptomatic remission was defined as an SF sub-score = 0 (or = 1 with a \>= 1 point decrease from Baseline) and RB sub-score = 0. The SF sub-score ranged from 0 to 3 (where 0 = normal number of stools and 3 = at least 5 stools more than normal) and RB sub-score ranged from 0 to 3 (where 0 = no blood and 3 = blood alone passes). Higher scores indicated more severe disease.

Group	Value	95% CI
Placebo Comparator: Placebo	7.1
Experimental: Etrasimod 2 mg	39.3

Percentage of Participants With Mucosal Healing at Week 40 of Study APD334-308 Secondary · Week 40 of APD334-308

Mucosal healing was defined as an ES \<= 1 (excluding friability) with histologic remission measured by a Geboes Index score less than \[\<\] 2.0). The ES ranged from 0 to 3 (where 0 = normal/inactive disease and 3 = severe disease). The Geboes score grading system, was a validated score for evaluating histologic disease activity in UC as follows: grade 0 = structural and architectural changes; grade 1 = chronic inflammatory infiltrate; grade 2 = lamina propria neutrophils and eosinophils; grade 3 = neutrophils in the epithelium; grade 4 = crypt destruction; grade 5 = erosions or ulceration. A

Group	Value	95% CI
Placebo Comparator: Placebo	7.1
Experimental: Etrasimod 2 mg	28.6

Percentage of Participants, Who Had Not Been Receiving Corticosteroids for ≥ 12 Weeks, Achieving Clinical Remission at Week 40 of Study APD334-308 Among Participants Receiving Corticosteroids at C5041015 (APD334-302) Study Entry Secondary · Week 40 of APD334-308

Clinical remission was based on the modified Mayo score (MMS). The MMS is a composite score of 3 assessments consisting of participant-reported symptoms using daily electronic (e)-diary and centrally read endoscopy: stool frequency (SF), rectal bleeding (RB) and endoscopic score (ES). Clinical remission was defined as SF sub-score = 0 (or = 1 with a greater than or equal to \[\>=\] 1-point decrease from Baseline), RB sub-score = 0, and ES less than or equal to (\<=) 1 (excluding friability). Each component sub-score ranged from 0 to 3 and total score range of the MMS was from 0 to 9, with high

Group	Value	95% CI
Placebo Comparator: Placebo	7.1
Experimental: Etrasimod 2 mg	25.0

Percentage of Participants Achieving Sustained Clinical Remission Secondary · Week 40 of APD334-308

Clinical remission was based on the modified Mayo score (MMS). The MMS is a composite score of 3 assessments consisting of participant-reported symptoms using daily electronic (e)-diary and centrally read endoscopy: stool frequency (SF), rectal bleeding (RB) and endoscopic score (ES). Clinical remission was defined as SF sub-score = 0 (or = 1 with a greater than or equal to \[\>=\] 1-point decrease from Baseline), RB sub-score = 0, and ES less than or equal to (\<=) 1 (excluding friability). Each component sub-score ranged from 0 to 3 and total score range of the MMS was from 0 to 9, with high

Group	Value	95% CI
Placebo Comparator: Placebo	0
Experimental: Etrasimod 2 mg	7.1

Adverse events — posted to ClinicalTrials.gov

Time frame: All-cause mortality, non-serious treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs) were collected during the 40-week continuous treatment period, followed by a 4-week follow-up period up to Week 44 of C5041013 (APD334-308).. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Placebo Comparator: Placebo

Serious: 1/14 (7%)

Deaths: 0/14

Experimental: Etrasimod 2 mg

Serious: 1/28 (4%)

Deaths: 0/28

Serious adverse events (2 terms)

Reaction	System	Placebo Comparator: Placebo	Experimental: Etrasimod 2 mg
COVID-19	Infections and infestations	—	—
Colitis ulcerative	Gastrointestinal disorders	—	—

Other adverse events (17 terms — click to expand)

Reaction	System	Placebo Comparator: Placebo	Experimental: Etrasimod 2 mg
Headache	Nervous system disorders	—	—
Pyrexia	General disorders	—	—
Malaise	General disorders	—	—
Colitis ulcerative	Gastrointestinal disorders	—	—
Vaccination site pain	General disorders	—	—
Stomatitis	Gastrointestinal disorders	—	—
Infected dermal cyst	Infections and infestations	—	—
Sinusitis	Infections and infestations	—	—
Tonsillitis	Infections and infestations	—	—
Cervicobrachial syndrome	Nervous system disorders	—	—
Cataract	Eye disorders	—	—
Back pain	Musculoskeletal and connective tissue disorders	—	—
Contusion	Injury, poisoning and procedural complications	—	—
Anaemia	Blood and lymphatic system disorders	—	—
Glucose urine present	Investigations	—	—
Depression	Psychiatric disorders	—	—
Oropharyngeal discomfort	Respiratory, thoracic and mediastinal disorders	—	—

Most-reported serious reactions: COVID-19, Colitis ulcerative.

Data from ClinicalTrials.gov NCT04706793 adverse events section.

Sponsor's own description

The purpose of this study is to determine whether oral etrasimod is a safe and effective treatment in adult Japanese participants with moderately to severely active ulcerative colitis (UC). This study is an extension of study APD334-302 (NCT03996369). Participants will continue with the same blinded treatment assigned in Study APD334-302 for a total treatment duration of 52 weeks (12 weeks in Study APD334-302 plus 40 weeks in Study APD334-308).

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Colorectal Cancer in Ulcerative Colitis: Mechanisms, Surveillance and Chemoprevention.
   Li W, Zhao T, Wu D, Li J, et al · · 2022 · cited 59× · PMID 36135048 · DOI 10.3390/curroncol29090479
2. Review article: the sphingosine 1 phosphate/sphingosine 1 phosphate receptor axis - a unique therapeutic target in inflammatory bowel disease.
   Wang J, Goren I, Yang B, Lin S, et al · · 2022 · cited 31× · PMID 34932238 · DOI 10.1111/apt.16741
3. Targeting the Sphingosine-1-Phosphate Pathway: New Opportunities in Inflammatory Bowel Disease Management.
   Kitsou K, Kokkotis G, Rivera-Nieves J, Bamias G. · · 2024 · cited 22× · PMID 39322927 · DOI 10.1007/s40265-024-02094-5
4. Immunity in digestive diseases: new drugs for inflammatory bowel disease treatment-insights from Phase II and III trials.
   Massironi S, Furfaro F, Bencardino S, Allocca M, et al · · 2024 · cited 19× · PMID 38980426 · DOI 10.1007/s00535-024-02130-x
5. How sphingolipids affect T cells in the resolution of inflammation.
   Hartel JC, Merz N, Grösch S. · · 2022 · cited 17× · PMID 36176439 · DOI 10.3389/fphar.2022.1002915
6. Barrier maintenance by S1P during inflammation and sepsis.
   Ziegler AC, Gräler MH. · · 2021 · cited 10× · PMID 34152926 · DOI 10.1080/21688370.2021.1940069
7. Efficacy and Safety of Etrasimod in Patients with Ulcerative Colitis in Japan: Data from the Phase 3 ELEVATE UC 12 and ELEVATE UC 40 JAPAN Trials.
   Takeuchi K, Hisamatsu T, Nakase H, Matsuoka K, et al · · 2025 · cited 4× · PMID 39317165 · DOI 10.1159/000541383
8. Efficacy and safety of etrasimod in Japanese patients with ulcerative colitis: results from a phase 2 dose-ranging study.
   Takeuchi K, Nakase H, Hisamatsu T, Matsuoka K, et al · · 2026 · cited 1× · PMID 40275818 · DOI 10.5217/ir.2024.00213