Etrasimod Dose-Ranging Versus Placebo as Induction Therapy Study in Adult Japanese Subjects With Moderately to Severely Active Ulcerative Colitis

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

The purpose of this Japan-only study is to assess the safety and efficacy of etrasimod at 2 doses in Japanese subjects with moderately to severely active ulcerative colitis (UC) when administered for 12 weeks.

Study Overview

• Status: Completed
• Conditions: Ulcerative Colitis
• Intervention / Treatment: Drug: Etrasimod; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 54
• Phase: Phase 2

Contacts and Locations

Study Locations

• Japan
  • Fukushima, Japan, 960-1295
    • Fukushima Medical University Hospital
  • Kagoshima, Japan, 890-8520
    • Kagoshima University Hospital
  • Osaka, Japan, 540-0006
    • NHO Osaka National Hospital
  • Osaka, Japan, 540-0006
    • Osaka National Hospital Institutional Review Board
  • Tokyo, Japan, 173-8606
    • Teikyo University Hospital
  • Aichi
    • Nagakute, Aichi, Japan, 480-1195
      • Aichi Medical University Hospital
    • Nagoya-shi, Aichi, Japan, 467-8602
      • Nagoya City University Hospital
    • Nagoya-shi, Aichi, Japan, 457-8511
      • Kojunkai Daido Clinic
    • Toyoake-City, Aichi, Japan, 470-1192
      • Fujita Health University Hospital
  • Aichi- KEN
    • Toyohashi-shi, Aichi- KEN, Japan, 441-8570
      • Toyohashi Municipal Hospital
  • Aixhi-ken
    • Nagoya-shi, Aixhi-ken, Japan, 457-8511
      • Kojunkai Daido Hospital
  • Aomori KEN
    • Hirosaki-shi, Aomori KEN, Japan, 036-8563
      • Hirosaki University Hospital(OCT/PFT/DLCO)
    • Hirosaki-shi, Aomori KEN, Japan, 036-8563
      • Hirosaki University Hospital
  • Aomori-ken
    • Hirosaki-shi, Aomori-ken, Japan, 036-8545
      • NHO Hirosaki General Medical Center
  • Chiba
    • Kashiwa-shi, Chiba, Japan, 277-0871
      • Tsujinaka Hospital Kashiwanoha
    • Nagareyama-shi, Chiba, Japan, 270-0116
      • Ishii Eye Clinic
    • Sakura, Chiba, Japan, 285-8741
      • Toho University Sakura Medical Center
  • Ehime
    • Matsuyama-shi, Ehime, Japan, 791-8026
      • Saiseikai Matsuyama Hospital
    • Toon-shi, Ehime, Japan, 791-0295
      • Ehime University Hospital
  • Fukuoka
    • Fukuoka-shi, Fukuoka, Japan, 814-0180
      • Fukuoka University Hospital
    • Kitakyushu, Fukuoka, Japan, 806-8501
      • Japan Community Health Care Organization Kyushu Hospital
    • Kitakyushu-shi, Fukuoka, Japan, 802-8555
      • Kokura Memorial Hospital
    • Kitakyushu-shi, Fukuoka, Japan, 802-8561
      • Kitakyushu Municipal Medical Center
    • Kitakyushu-shi, Fukuoka, Japan, 807-1266
      • Koyanose Eye Clinic
    • Kurume, Fukuoka, Japan, 830-8543
      • Our Lady of the Snow St. Mary's Hospital
    • Kurume-shi, Fukuoka, Japan, 830-0011
      • Kurume University Hospital
    • Kutakyushu-shi, Fukuoka, Japan, 802-8555
      • Kokura Memorial Hospital
    • Onga-gun, Fukuoka, Japan, 807-0051
      • Fukuoka Shinmizumaki Hospital
  • Gifu-ken
    • Gifu-shi, Gifu-ken, Japan, 501-1194
      • Gifu University Hospital
  • Gunma
    • Ota-shi, Gunma, Japan, 373-8585
      • SUBARU Health Insurance Society Ota Memorial Hospital
  • Hiroshima
    • Fukuyama-shi, Hiroshima, Japan, 720-0822
      • Nakayama EYE Clinic
    • Fukuyama-shi, Hiroshima, Japan, 720-8520
      • NHO Fukuyama Medical Center
    • Hiroshima-shi, Hiroshima, Japan, 734-8551
      • Hiroshima University Hospital
  • Hokkaido
    • Asahikawa-shi, Hokkaido, Japan, 070-8610
      • Asahikawa City Hospital
    • Sapporo-shi, Hokkaido, Japan, 004-0041
      • Tokushukai Sapporo Tokushukai Hospital
    • Sapporo-shi, Hokkaido, Japan, 060-0033
      • Sapporo-Kosei General Hospital
  • Ibaraki
    • Higashiibaraki-gun, Ibaraki, Japan, 311-3193
      • NHO Mito Medical Center
    • Koga-shi, Ibaraki, Japan, 306-0232
      • Yuai Memorial Hospital
    • Sashima-gun, Ibaraki, Japan, 306-0433
      • Ibaraki Seinan Medical Center Hospital
    • Toride-shi, Ibaraki, Japan, 302-0014
      • Matsumoto Eye Clinic
    • Tsuchiura-shi, Ibaraki, Japan, 300-0028
      • Tsuchiura Kyodo General Hospital
  • Ishikawa
    • Kanazawa-shi, Ishikawa, Japan, 920-8650
      • NHO Kanazawa Medical Center
  • Iwate
    • Morioka-shi, Iwate, Japan, 020-8505
      • Iwate Medical University Uchimaru Medical Center
  • Iwate-ken
    • Morioka-shi, Iwate-ken, Japan, 020-0871
      • Kudo Internist Heart Clinic
  • Kagawa
    • Takamatsu-shi, Kagawa, Japan, 760-0017
      • Takamatsu Red Cross Hospital
  • Kagoshima
    • Kagoshima-shi, Kagoshima, Japan, 892-0846
      • Sameshima Hospital
    • Kagoshima-shi, Kagoshima, Japan, 890-0062
      • JA- Kagoshima Koseiren Hospital (PET/DLCO)
    • Kagoshima-shi, Kagoshima, Japan, 892-0813
      • Clinical Pathology Laboratory (Diagnostick center)
    • Kagoshima-shi, Kagoshima, Japan, 892-0825
      • Sameshima Eye Clinic (OCT)
  • Kanagawa
    • Sagamihara, Kanagawa, Japan, 252-5188
      • Sagamihara Kyodo Hospital
    • Yokohama-shi, Kanagawa, Japan, 245-8575
      • NHO Yokohama Medical Center
    • Yokohama-shi, Kanagawa, Japan, 234-0054
      • Social Welfare Organization Imperial Gift Foundation,Inc.Saiseikai Yokohamashi Nanbu Hospital
  • Kumamoto
    • Kumamoto-shi, Kumamoto, Japan, 861-8520
      • Japanese Red Cross Kumamoto Hospital
  • Kyoto
    • Kyoto-shi, Kyoto, Japan, 602-8566
      • University Hospital Kyoto Prefectural University of Medicine
    • Kyoto-shi, Kyoto, Japan, 612-8555
      • National Hospital Organization Kyoto Medical Center
  • MIE
    • Tsu-shi, MIE, Japan, 514-8507
      • Mie University Hospital
  • Mie-ken
    • Yokkaichi- Shi, Mie-ken, Japan, 510-0891
      • Hinaga Nishi Ophthalmology Clinic
    • Yokkaichi-shi, Mie-ken, Japan, 510-8561
      • Mie Prefectural General Medical Center
  • Miyagi
    • Sendai, Miyagi, Japan, 980-8574
      • Tohoku University Hospital
    • Sendai-shi, Miyagi, Japan, 981-8563
      • JOHAS Tohoku Rosai Hospital
  • Niigata
    • Nagaoka-shi, Niigata, Japan, 940-2085
      • Nagaoka Red Cross Hospital
  • Osaka
    • Hirakata-shi, Osaka, Japan, 573-1191
      • Kansai Medical University Hospital
    • Kishiwada-shi, Osaka, Japan, 596-0042
      • Medical Corporation Tokushukai Kishiwada Tokushukai Hospital
    • Osaka-shi, Osaka, Japan, 545-8586
      • Osaka City University Hospital
    • Osaka-shi, Osaka, Japan, 553-0003
      • Japan Community Health care Organization Osaka Hospital
    • Takatsuki-City, Osaka, Japan, 569-8686
      • Osaka Medical and Pharmaceutical University Hospital
  • Saga
    • Saga-shi, Saga, Japan, 849-8501
      • Saga University Hospital
  • Saitama
    • Iruma-gun, Saitama, Japan, 350-0495
      • Saitama Medical University Hospital
  • Saitama-ken
    • Saitama-shi, Saitama-ken, Japan, 330-0074
      • Japan Community Health Care Organization Saitama Medical Center
  • Shiga
    • Otsu, Shiga, Japan, 520-2192
      • Shiga University of Medical Science Hospital
  • Shizuoka
    • Hamamatsu, Shizuoka, Japan, 432-8061
      • Matsuda Hospital
    • Hamamatsu-shi, Shizuoka, Japan, 431-3192
      • Hamamatsu University Hospital
  • Shizuoka-ken
    • Hamamatsu-shi, Shizuoka-ken, Japan, 432-8580
      • Hamamatsu Medical Centre
  • Tokyo
    • Bunkyo-ku, Tokyo, Japan, 113-8519
      • Tokyo Medical and Dental University Hospital
    • Hachioji, Tokyo, Japan, 192-0032
      • Tokai University Hachioji Hospital
    • Kodaira-shi, Tokyo, Japan, 187-8510
      • Showa General Hospital
    • Minato-ku, Tokyo, Japan, 108-8642
      • Kitasato University Kitasato Institute Hospital
    • Shinjuku-ku, Tokyo, Japan, 169-0073
      • JCHO Tokyo Yamate Medical Center
  • Wakayama
    • Wakayama-shi, Wakayama, Japan, 641-8510
      • Wakayama Medical University Hospital
  • Yamanashi
    • Kofu-shi, Yamanashi, Japan, 400-8506
      • Yamanashi Prefectural Central Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

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

Exclusion Criteria:

• 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo; Etrasimod matching placebo tablet by mouth, once daily up to 12 weeks
Experimental: Etrasimod Dose 1	Drug: Etrasimod; Etrasimod tablet by mouth, once daily for 12 weeks; Other Names: APD334
Experimental: Etrasimod Dose 2	Drug: Etrasimod; Etrasimod tablet by mouth, once daily for 12 weeks; Other Names: APD334

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Who Achieved Clinical Remission at Week 12	Clinical remission:Participants with stool frequency (SF)subscore=0(or of 1 with greater than or equal to(>=)1 point decrease from baseline,rectal bleeding(RB)subscore=0 and endoscopic score(ES)less than or equal to(<)=1(excluding friability).SF subscore:number of stools in 24-hours relative to normal number of stools for that participant in same period,score ranged from 0(normal number of stools) to 3(5 or more stools than normal),higher scores=more severity.RB subscore:most severe amount of blood passed per rectum in 24-hours,score ranged from 0(no blood seen)to 3(blood alone passes),higher scores=more severity.ES:reported worst appearance of mucosa on flexible sigmoidoscopy or colonoscopy,score ranged from 0(normal or inactive disease) to 3(severe disease [spontaneous bleeding,ulceration]),higher scores=more severity.Modified Mayo score:measure disease activity for UC,score:0(normal) to 9(maximum severity),comprised subscores for SF,RB,ES.higher score=more severe disease activity.	Week 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Who Achieved Endoscopic Improvement at Week 12	Endoscopic improvement was defined as ES <= 1 (excluding friability). ES reported worst appearance of mucosa on flexible sigmoidoscopy or colonoscopy, score ranged from 0 (normal or inactive disease) to 3 (severe disease [spontaneous bleeding, ulceration]), higher scores = more severity. Modified Mayo score (MMS): measure disease activity for UC, score: 0 (normal) to 9 (maximum severity),and comprised the subscores for SF, RB, ES. Higher score = more severe disease activity.	Week 12
Percentage of Participants Who Achieved Symptomatic Remission at Week 12	Symptomatic remission was defined as SF sub score = 0 (or = 1 with a >= 1 point decrease from baseline) and RB sub score = 0. SF subscore: reported number of stools in a 24-hour period relative to normal number of stools for that participant in the same period, score ranged from 0 (normal number of stools) to 3 (5 or more stools than normal), higher scores = more severity. RB subscore: reported the most severe amount of blood passed per rectum in a 24-hour period, score ranged from 0 (no blood seen) to 3 (blood alone passes), higher scores = more severity. MMS: measure disease activity for UC, score: 0 (normal) to 9 (maximum severity), and comprised the subscores for SF, RB, ES. Higher score = more severe disease activity.	Week 12
Percentage of Participants Who Achieved Mucosal Healing at Week 12	Mucosal healing was defined as ES <= 1 (excluding friability) with histologic remission defined as a Geboes index score < 2.0). ES reported worst appearance of mucosa on flexible sigmoidoscopy or colonoscopy, score ranged from 0 (normal or inactive disease) to 3 (severe disease [spontaneous bleeding, ulceration]), higher scores = more severity. 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 higher Geboes score indicated more severe disease. Modified Mayo score (MMS): measure disease activity for UC, score: 0 (normal) to 9 (maximum severity), comprised subscores for SF, RB, ES. Higher score = more severe disease activity.	Week 12
Percentage of Participants Who Achieved Clinical Response at Week 12	Clinical response was defined as a >= 2-point and >= 30 percentage (%) decrease from baseline in MMS, and a >= 1-point decrease from baseline in RB subscore or an absolute RB subscore <= 1. MMS: measure disease activity for UC, score: 0 (normal) to 9 (maximum severity), and comprised the subscores for SF, RB, ES. Higher score = more severe disease activity. RB subscore: reported the most severe amount of blood passed per rectum in a 24-hour period, score ranged from 0 (no blood seen) to 3 (blood alone passes), higher scores = more severity.	Week 12
Percentage of Participants Who Achieved Endoscopic Normalization at Week 12	Endoscopic normalization was defined as ES= 0. ES reported worst appearance of mucosa on flexible sigmoidoscopy or colonoscopy, score ranged from 0 (normal or inactive disease) to 3 (severe disease [spontaneous bleeding, ulceration]), higher scores = more severity. MMS: measure disease activity for UC, score: 0 (normal) to 9 (maximum severity), and comprised the subscores for SF, RB, ES. Higher score = more severe disease activity.	Week 12

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Adverse Events According to Severity	An adverse event was any untoward medical occurrence in a participant or clinical investigational participant administered a medicinal product and which does not necessarily have a causal relationship with this treatment. An adverse event was therefore any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Severity was classified using common terminology criteria for adverse events (CTCAE), version 5.0, such as Grade 1 for mild, Grade 2 for moderate, Grade 3 for severe, Grade 4 for life-threatening, Grade 5 for death related to adverse event.	Day 1 of first dose of study treatment up to 4 weeks after administration of the final dose of study treatment (maximum up to 16 weeks)

Collaborators and Investigators

• Sponsor: Pfizer
• Collaborators: Arena is a wholly owned subsidiary of Pfizer
• Investigators: Study Director: Pfizer CT.gov Call Center, Pfizer

Publications and helpful links

Helpful Links

• To obtain contact information for a study center near you, click here.

Study record dates

Study Major Dates

• Study Start (Actual): September 10, 2021
• Primary Completion (Actual): October 6, 2023
• Study Completion (Actual): October 6, 2023

Study Registration Dates

• First Submitted: September 20, 2021
• First Submitted That Met QC Criteria: September 20, 2021
• First Posted (Actual): September 29, 2021

Study Record Updates

• Last Update Posted (Actual): October 29, 2024
• Last Update Submitted That Met QC Criteria: October 3, 2024
• Last Verified: October 1, 2024

More Information

Terms related to this study

• Keywords: Ulcerative Colitis; Etrasimod; APD334
• Additional Relevant MeSH Terms: Pathologic Processes; Intestinal Diseases; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Gastroenteritis; Inflammatory Bowel Diseases; Colitis; Colitis, Ulcerative; Ulcer
• Other Study ID Numbers: APD334-203; C5041007 (Other Identifier: Alias Study Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes