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NCT02447302

Safety and Efficacy of Etrasimod (APD334) in Patients With Ulcerative Colitis

Completed Phase 2 Results posted Last updated 5 April 2021
What this trial tests

Phase 2 trial testing Etrasimod in Ulcerative Colitis in 156 participants. Completed in 14 February 2018.

Timeline
15 October 2015
Primary endpoint
14 February 2018
14 February 2018

Quick facts

Lead sponsorArena Pharmaceuticals
PhasePhase 2
StatusCompleted
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingtriple
Primary purposetreatment
Enrollment156
Start date15 October 2015
Primary completion14 February 2018
Estimated completion14 February 2018
Sites134 locations across Poland, South Korea, New Zealand, Russia, Belgium, Lithuania, Bulgaria, United States

Drugs / interventions tested

Conditions studied

Sponsor

Arena Pharmaceuticals — full company profile →

Who can join

Adults 18 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.

Change From Baseline in Adapted Mayo Score (MCS) at Week 12 Primary · Baseline and Week 12

The adapted MCS was used to measure disease activity of ulcerative colitis. It consisted of 3 subscores (stool frequency, rectal bleeding, and findings of endoscopy), each of which was rated on a scale from 0 to 3, indicating normal to severe. The adapted MCS was calculated as the sum of the 3 subscores, and the overall score values ranged from 0 to 9, with a higher score indicating more severe disease. Multiple imputation method was used to handle missing data.

GroupValue95% CI
Etrasimod 1 mg-1.94-2.45 – -1.42
Etrasimod 2 mg-2.49-3.01 – -1.98
Placebo-1.50-2.00 – -1.01
Percentage of Participants Who Achieved Endoscopic Improvement at Week 12 Secondary · Week 12

For determination of the endoscopic subscore of the MCS, a flexible proctosigmoidoscopy, performed with a videoendoscope following a cleansing prep (oral or rectal cathartic) was performed at screening (within 10 days prior to administration of the first dose of study drug) and the Week 12 visit. This efficacy procedure assessed endoscopic mucosal appearance. The results were rated on a scale from 0 to 3, indicating normal to severe. Endoscopic improvement was defined as Mayo endoscopic subscore (using findings of flexible proctosigmoidoscopy) of ≤1 point. Multiple imputation method was used t

GroupValue95% CI
Etrasimod 1 mg22.5
Etrasimod 2 mg41.8
Placebo17.8
Change From Baseline in 2-component MCS at Week 12 Secondary · Baseline and Week 12

The 2-component MCS was used to measure disease activity of ulcerative colitis. It consisted of 2 subscores (rectal bleeding and findings on endoscopy), each of which was rated on a scale from 0 to 3, indicating normal to severe. The 2-component MCS was calculated as the sum of the 2 subscores, and the overall score value ranged from 0 to 6, with a higher score indicating more severe disease. Multiple imputation method was used to handle missing data.

GroupValue95% CI
Etrasimod 1 mg-1.30-1.66 – -0.95
Etrasimod 2 mg-1.75-2.11 – -1.40
Placebo-0.92-1.26 – -0.57
Change From Baseline in Total Mayo Score (TMS) at Week 12 Secondary · Baseline and Week 12

The TMS was used to measure disease activity of ulcerative colitis. It consisted of 4 subscores \[stool frequency, rectal bleeding, findings of endoscopy (flexible proctosigmoidoscopy), and Physician's Global Assessment (PGA) score\], each of which was rated on a scale from 0 to 3, indicating normal to severe. The TMS was calculated as the sum of the 4 subscores, and the overall score values ranged from 0 to 12, with a higher score indicating more severe disease. Multiple imputation method was used to handle missing data.

GroupValue95% CI
Etrasimod 1 mg-2.69-3.36 – -2.02
Etrasimod 2 mg-3.35-4.03 – -2.68
Placebo-2.08-2.73 – -1.44
Trichotomous Composite Score of Clinical Remission and Clinical Response at Week 12 Secondary · Week 12

The trichotomous composite score of clinical remission and clinical response at Week 12 is an ordinal categorical endpoint with 3 categories (score ranging 0 to 2: score 2 for achieving both clinical remission and clinical response; 1 for only achieving clinical response, and 0 for achieving neither). Multiple imputation method was used to handle missing data.

GroupValue95% CI
Etrasimod 1 mg0.60± 0.11
Etrasimod 2 mg0.84± 0.13
Placebo0.41± 0.09
Percentage of Participants Who Achieved Clinical Remission at Week 12 Secondary · Week 12

A participant was considered to have achieved clinical remission if he/she had: 1) an endoscopy score using flexible proctosigmoidoscopy of 0 or 1 (excluding friability), 2) a rectal bleeding score of 0 or 1, and 3) a stool frequency score of 0 or 1 with a decrease of ≥1 point from baseline. Multiple imputation method was used to handle missing data.

GroupValue95% CI
Etrasimod 1 mg16.0
Etrasimod 2 mg33.0
Placebo8.1
Percentage of Participants Who Achieved Clinical Response at Week 12 Secondary · Week 12

A participant was considered to have achieved clinical response if he/she met the criteria of clinical remission defined above, or met criteria of clinical response. Clinical response was defined as a decrease in the adapted MCS of ≥ 2 points and a decrease of ≥ 30% with either a decrease of rectal bleeding of ≥ 1 or rectal bleeding score of 0 or 1.

GroupValue95% CI
Etrasimod 1 mg43.7
Etrasimod 2 mg50.6
Placebo32.5

Adverse events — posted to ClinicalTrials.gov

Time frame: Up to approximately 16 weeks i.e. from the time of administration of the first dose of study drug up to 30 days after the administration of the last dose of study drug.. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Etrasimod 1 mg
Serious: 3/52 (6%)
Deaths: 0/52
Etrasimod 2 mg
Serious: 0/50 (0%)
Deaths: 0/50
Placebo
Serious: 6/54 (11%)
Deaths: 0/54

Serious adverse events (6 terms)

ReactionSystemEtrasimod 1 mgEtrasimod 2 mgPlacebo
Colitis ulcerativeGastrointestinal disorders
Abdominal painGastrointestinal disorders
Duodenal ulcer perforationGastrointestinal disorders
JaundiceHepatobiliary disorders
Anal abscessInfections and infestations
HydronephrosisRenal and urinary disorders
Other adverse events (5 terms — click to expand)

ReactionSystemEtrasimod 1 mgEtrasimod 2 mgPlacebo
NasopharyngitisInfections and infestations
Upper respiratory tract infectionInfections and infestations
Colitis ulcerativeGastrointestinal disorders
HeadacheNervous system disorders
AnaemiaBlood and lymphatic system disorders

Most-reported serious reactions: Colitis ulcerative, Abdominal pain, Duodenal ulcer perforation, Jaundice, Anal abscess, Hydronephrosis.

Data from ClinicalTrials.gov NCT02447302 adverse events section.

Sponsor's own description

The purpose of this study is to determine whether etrasimod is a safe and effective treatment for ulcerative colitis.

Publications & conference data

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

  1. Efficacy and Safety of Etrasimod in a Phase 2 Randomized Trial of Patients With Ulcerative Colitis.
    Sandborn WJ, Peyrin-Biroulet L, Zhang J, Chiorean M, et al · · 2020 · cited 171× · PMID 31711921 · DOI 10.1053/j.gastro.2019.10.035
  2. Targeting Sphingosine-1-Phosphate Signaling in Immune-Mediated Diseases: Beyond Multiple Sclerosis.
    Pérez-Jeldres T, Alvarez-Lobos M, Rivera-Nieves J. · · 2021 · cited 150× · PMID 33983615 · DOI 10.1007/s40265-021-01528-8
  3. Long-term Safety and Efficacy of Etrasimod for Ulcerative Colitis: Results from the Open-label Extension of the OASIS Study.
    Vermeire S, Chiorean M, Panés J, Peyrin-Biroulet L, et al · · 2021 · cited 75× · PMID 33475734 · DOI 10.1093/ecco-jcc/jjab016
  4. The S1P-S1PR Axis in Neurological Disorders-Insights into Current and Future Therapeutic Perspectives.
    Lucaciu A, Brunkhorst R, Pfeilschifter JM, Pfeilschifter W, et al · · 2020 · cited 53× · PMID 32580348 · DOI 10.3390/cells9061515
  5. Immunotherapy in inflammatory bowel disease: Novel and emerging treatments.
    Catalan-Serra I, Brenna Ø. · · 2018 · cited 33× · PMID 29624476 · DOI 10.1080/21645515.2018.1461297
  6. Sphingosine 1-Phosphate Modulation in Inflammatory Bowel Diseases: Keeping Lymphocytes Out of the Intestine.
    Dal Buono A, Gabbiadini R, Alfarone L, Solitano V, et al · · 2022 · cited 32× · PMID 35885040 · DOI 10.3390/biomedicines10071735
  7. Frontiers in Drug Research and Development for Inflammatory Bowel Disease.
    Currò D, Pugliese D, Armuzzi A. · · 2017 · cited 30× · PMID 28690543 · DOI 10.3389/fphar.2017.00400
  8. 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

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