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A Phase 3, Double-Blind, Placebo-Controlled, 40-Week Extension Study to Assess the Efficacy and Safety of Etrasimod in Japanese Subjects with Moderately to Severely Active Ulcerative Colitis

ELEVATE UC 40 JAPAN: Etrasimod Versus Placebo for the Treatment of Moderately to Severely Active Ulcerative Colitis in Japanese Subjects

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The demographic and baseline characteristics, including baseline characteristics related to UC, were generally well balanced between treatment groups. The placebo group included 7 (50%) male and 7(50%) female participants, and the etrasimod group included 18 (64.3%) male and 10 (35.7%) female participants. All the participants were Japanese. The mean (standard deviation [SD]) ages were 44.2 (14.12) years (range:17-67 years) and 43.9 (14.29) years (range:19-68 years) in the placebo and etrasimod groups, respectively. Most participants were between 18 to 64 years of age, accounting for 85.7% and 96.4% in the placebo and etrasimod groups, respectively. The median (range) body mass indexes (BMIs) were 23.93 (18.0-30.9) kg/m2 and 22.36 (17.2-37.3) kg/m2 for participants treated with placebo and etrasimod, respectively. Approximately one third (35.7%) of participants in both treatment groups had history of tobacco use. The duration of UC was balanced between the treatment groups (mean [SD] of 4.5 [5.20] years for placebo treated participants and 6.8 [6.77] years for etrasimod treated participants). There was a higher proportion of participants naive to biologics or Janus kinase (JAK) inhibitors in the etrasimod group (85.7%) compared with placebo (50%). There were 5 (35.7%) participants in the placebo group and 2 (7.1%) participants in the etrasimod group with prior failure of anti-tumor necrosis factor (anti-TNF) treatment or vedolizumab. Other than UC, the most reported medical history (by over 10% participants overall) included haemorrhoids (11.9%), headache (16.7%), seasonal allergy (28.6%), hypertension (16.7%), and menopause (14.3%). All participants have received prior treatment(s) for UC. The most common prior therapies for UC were oral 5-aminosalicylic acid (5-ASA) (92.9% and 82.1%, respectively, for participants treated with placebo and etrasimod) and corticosteroids (100% and 75%, respectively, for participants treated with placebo and etrasimod over the last 12 months). The proportion of participants who discontinued prior UC therapy(ies) due to inadequate response was higher in the etrasimod group in all categories of UC treatments compared with placebo except for anti-interleukin 12/23 antibodies (1 participant in the placebo group discontinued due to inadequate response) and antitumor necrosis factor alpha antibodies (2 participants in the placebo group and 1 participant in the etrasimod group discontinued due to inadequate response). Thirteen (92.9%) participants in the placebo group and 27 (96.4%) participants in the etrasimod group received at least 1 concomitant medication for UC. The most frequently used therapeutic class of concomitant medication for UC was antidiarrheals, intestinal anti-inflammatory/anti-infective agents, received by 11 (78.6%) and 26 (92.9%) participants in the placebo and etrasimod groups, respectively.

Among 48 Japanese participants who were randomized in APD334-302, 42 participants were rolled over from Study APD334-302 and continued the same treatment assigned in the parent study, including 14 participants treated with placebo and 28 participants treated with etrasimod 2 mg QD. All 42 participants were included in the FAS and Safety Set.

A total of 24 and 50 TEAEs were reported by 8 (57.1%) and 16 (57.1%) participants treated with placebo and etrasimod, respectively. Of these, 3 (10.7%) participants in the etrasimod group reported 5 TEAEs considered to be treatment-related by the investigator, while the placebo-treated participants experienced no treatment-related TEAEs. Among all-causality TEAEs, all were Grades 1 or 2 in severity, excluding 2 Grade 3 TEAEs of Colitis ulcerative in 1 (7.1%) participant treated with placebo. All the treatment-related TEAEs were Grade 1 in severity. All-causality TEAEs reported by more than 1 participant in the etrasimod group included the following (number [percentage] of participants treated with placebo and etrasimod, respectively): Colitis ulcerative (1 [7.1%] and 2 [7.1%]), Malaise (3 [10.7%] with etrasimod), Pyrexia (2 [14.3%] and 3 [10.7%]), Vaccination site pain (2 [7.1%] with etrasimod), and Headache (2 [14.3%] and 4 [14.3%]). A total of 5 TEAEs reported by 3 (10.7%) participants treated with etrasimod were considered treatment related by the investigator. TEAEs of Hepatic function abnormal and coronavirus disease 2019 (COVID-19) were experienced by 1 participant each and the third participant experienced 2 TEAEs of Alanine aminotransferase increased and Aspartate aminotransferase increased. All the 5 treatment-related TEAEs were of Grade 1 severity. A total of 2 SAEs were reported by 1 (7.1%) participant treated with placebo (Grade 3 Colitis ulcerative) and 1 (3.6%) participant treated with etrasimod (Grade 1 COVID-19). No participants in the etrasimod group experienced any TEAEs that led to study intervention discontinuation. One (7.1%) participant in the placebo group discontinued study intervention due to a Grade 3 non-serious adverse event (NSAE) of Colitis ulcerative, which was considered not related to the study intervention. No death occurred during the study. No clinically meaningful findings in the vital signs measurements, ECGs, physical examination assessments, or other observations related to safety were observed in this study. Lymphocytes and neutrophils reduction during etrasimod treatment was observed during the study. No clinically meaningful differences in basophils, eosinophils, monocytes, erythrocytes, or platelet counts were observed in participants in the etrasimod group compared with placebo.

At Week 52, a greater proportion of participants treated with etrasimod achieved clinical remission compared with placebo (25% with etrasimod vs 7.1% with placebo; % Difference: 17.86 [95% CI: -3.10, 38.82]). A greater proportion of participants treated with etrasimod achieved endoscopic improvement at Week 52 compared with placebo (35.7% with etrasimod vs 7.1% with placebo; % Difference: 28.57 [95% CI:6.28, 50.86]). A greater proportion of participants treated with etrasimod achieved symptomatic remission at Week 52 compared with placebo (39.3% with etrasimod vs 7.1% with placebo; % Difference: 32.14 [95% CI: 9.58, 54.71]). A greater proportion of participants treated with etrasimod achieved corticosteroid-free clinical remission at Week 52 compared with placebo (25% with etrasimod vs 7.1% with placebo; % Difference: 17.86 [95% CI: -3.10, 38.82]). A greater proportion of participants treated with etrasimod achieved mucosal healing at Week 52 compared with placebo (28.6% with etrasimod vs 7.1% with placebo; % Difference: 21.43 [95% CI: -0.07, 42.92]). Two (7.1%) participants in the etrasimod group achieved sustained clinical remission (defined as clinical remission at both Week 12 and Week 52) while no participants in the placebo group had sustained clinical remission (% Difference: 7.14 [95% CI: -2.40, 16.68]).

Treatment with etrasimod 2 mg QD resulted in clinically meaningful improvements in the primary efficacy and key secondary efficacy outcome measures compared with placebo in Japanese adult participants with moderately to severely active UC. The safety profile of etrasimod 2 mg QD treatment for up to 52 weeks was consistent with previous studies, with no new safety findings observed.

May. 30, 2024

No

https://jrct.mhlw.go.jp/latest-detail/jRCT2071200080

IQVIA Services Japan K.K. ICCC:

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 Inquiry Contact

IQVIA Services Japan K.K.

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

+81-3-6859-9500

JP_Arena_ELEVATE_UC@iqvia.com

Complete

Dec. 25, 2020

Interventional

randomized controlled trial

double blind

placebo control

parallel assignment

supportive care

Must have completed the Week 12 visit of Study APD334-302

1. If the Investigator considers the subject to be unsuitable for any reason to participate in the study
2. Subjects requiring partial or total colectomy during the APD334-302 study
3. Subjects requiring treatment with prohibited concomitant medications

Both

Ulcerative colitis

The investigational drug and the placebo are an oral tablet. The investigational drug is APD334 (etrasimod).

Proportion of participants achieving clinical remission

+81-93-641-5111

July. 20, 2020

none