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A Phase 2, Randomized, Double-Blind, Placebo-Controlled, 12-Week
Dose-Ranging Study to Assess the Efficacy and Safety of Etrasimod in
Japanese Subjects with Moderately to Severely Active Ulcerative Colitis

Etrasimod Dose-Ranging Versus Placebo as Induction Therapy in
Moderately to Severely Active Ulcerative Colitis

54

Japanese participants, male or female, 20 to 72 years of age, inclusive, with moderately to severely active Ulcerative Colitis (UC) [defined as modified Mayo score (MMS) of 4 to 9, including an endoscopic score >=2 and rectal bleeding subscore >=1], who were diagnosed with UC >=3 months prior to screening, and demonstrated an inadequate response, loss of response to, or intolerance to at least 1 of the therapies for UC: 1.Conventional therapy, and were naive to biologic or Janus kinase (JAK) inhibitor therapy; OR 2.Biologics or JAK inhibitors (participants in this category might also have received prior conventional therapy).

The study consisted of a 28-day screening period, a 12-week induction treatment period, and a 4-week follow-up period. Participants had the option to enter an open-label extension (OLE) study (Study APD334-303) following completion of the 12-Week induction treatment period provided they met all eligibility criteria for the OLE. Participants who discontinued from the study and did not participate in the OLE study had 2-Week and 4-Week follow-up visits after the last on-treatment visit/early termination visit. The participant recruitment for this study was discontinued in the middle of the study.

The most commonly reported System Organ Classes of all-causality adverse events (>10% in participants treated with etrasimod 1 mg and 2 mg combined) were Gastrointestinal disorders, and Infections and infestations (5/36, 13.9% for both), General disorders and administration site conditions, and Investigations (4/36, 11.1% for both). All-causality adverse events reported by more than 1 participant in the etrasimod group (2 mg and 1 mg combined) included: stomatitis (2/17 [11.8%] participants treated with etrasimod 1 mg), and malaise (1/17 [5.9%] participant treated with etrasimod 1 mg and 1/19 [5.3%] participant treated with etrasimod 2 mg). Treatment-related adverse events were reported by 1 participant treated with placebo (nausea), 2 participants with etrasimod 1 mg (eczema, and rash), and 4 participants with etrasimod 2 mg (alanine aminotransferase increased, gamma-glutamyltransferase increased, bradycardia, hepatic function abnormal, and epistaxis). Each of the treatment-related adverse events was reported in 1 participant.

Among participants in the Full Analysis Set with baseline MMS 5 to 9, a greater proportion of participants treated with etrasimod 2 mg (5/19, 26.3%) and 1 mg (1/15, 6.7%) achieved clinical remission (ie, responders) at Week 12, compared with none in the placebo group, corresponding to a % difference from placebo of 26.3% (95% Confidence Interval: 6.52%, 46.12%) for etrasimod 2 mg, and 6.7% (95% Confidence Interval: -5.96%, 19.29%) for etrasimod 1 mg. Analysis of clinical remission was repeated in the predefined subgroups in the Full Analysis Set with actual baseline MMS 5 to 9. A trend in favor of etrasimod over placebo was consistently observed in all subgroups with one or more responders when comparing the etrasimod treated groups with the placebo group. Among participants in the Full Analysis Set with actual baseline MMS 5 to 9: *A greater proportion of participants treated with etrasimod 2 mg (5/19, 26.3%) and etrasimod 1 mg (1/15, 6.7%) achieved endoscopic improvement at Week 12, compared with none treated with placebo, corresponding to a % difference from placebo of 26.3% (95% Confidence Interval: 6.52%, 46.12%) for etrasimod 2 mg, and 6.7% (95% Confidence Interval: -5.96%, 19.29%) for etrasimod 1 mg. *A greater proportion of participants treated with etrasimod 2 mg (6/19, 31.6%) and etrasimod 1 mg (3/15, 20.0%) achieved symptomatic remission at Week 12 compared with none with placebo, corresponding to a % difference from placebo of 31.6% (95% Confidence Interval: 10.68%, 52.48%) for etrasimod 2 mg, and 20.0% (95% Confidence Interval: -0.24%, 40.24%) for etrasimod 1 mg. *One participant each in the etrasimod 1 mg and 2 mg groups achieved mucosal healing at Week 12, compared with none in the placebo group. *A greater proportion of participants treated with etrasimod, ie, 10/19 (52.6%) participants with etrasimod 2 mg and 5/15 (33.3%) participant with etrasimod 1 mg achieved clinical response at Week 12, compared with 1/14 (7.1%) participant with placebo, corresponding to a % difference from placebo of 45.5% (95% Confidence Interval: 19.30%, 71.68%) for etrasimod 2 mg, and 26.2% (95% Confidence Interval: -1.22%, 53.60%) for etrasimod 1 mg. *No participants achieved endoscopic normalization at Week 12. Response rates of primary and key secondary endpoints in participants treated with etrasimod 2 mg once daily were numerically higher than those treated with etrasimod 1 mg once daily.

A 12-week treatment with etrasimod 1 mg or 2 mg resulted in improvements in primary and secondary efficacy endpoints compared with placebo. Overall, etrasimod 1 mg and 2 mg doses were well tolerated throughout the study. Etrasimod 1 mg and 2 mg for up to 12 weeks was overall safe and effective in treating Japanese participants with moderately to severely active ulcerative colitis, however, interpretation of results is limited because the participant recruitment was discontinued in the middle of the study.

Feb. 14, 2025

No

https://jrct.mhlw.go.jp/latest-detail/jRCT2071210052

Tanabe Masakazu

IQVIA Services Japan K.K.

4-10-18 Takanawa, Minato-ku, Tokyo, 108-0074

JP_Arena_ELEVATE_UC@iqvia.com

IQVIA Services Japan K.K. jRCT Call Center

IQVIA Services Japan K.K.

4-10-18 Takanawa, Minato-ku, Tokyo, 108-0074

+81-120-229-053

JP_Arena_ELEVATE_UC@iqvia.com

Complete

Aug. 23, 2021

Interventional

randomized controlled trial

double blind

placebo control

parallel assignment

treatment purpose

- Japanese ancestry
- Diagnosed with ulcerative colitis (UC) => 3 months prior to screening
- Having active UC confirmed by endoscopy
- Moderately to severely active UC

- Severe extensive colitis
- Diagnosis of Crohn's disease (CD) or indeterminate colitis or the presence, history of a fistula consistent with CD
- Diagnosis of microscopic colitis, ischemic colitis, or infectious colitis

Both

Ulcerative colitis

Eligible subjects will be randomized (1:1:1ratio) to receive either etrasimod (dose A), etrasimod (dose B), or matching placebo (once daily) in a double-blind fashion for 12 weeks

The proportion of subjects achieving clinical remission at Week 12

+81-93-641-5111

June. 21, 2021

none