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

Sponsor
Arena Pharmaceuticals (Industry)
Overall Status
Completed
CT.gov ID
NCT02447302
Collaborator
(none)
156
Enrollment
134
Locations
3
Arms
28
Actual Duration (Months)
1.2
Patients Per Site
0
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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

Condition or Disease Intervention/Treatment Phase
Phase 2

Study Design

Study Type:
Interventional
Actual Enrollment :
156 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Triple (Participant, Care Provider, Investigator)
Primary Purpose:
Treatment
Official Title:
A Phase 2, Randomized, Double-Blind, Placebo-Controlled, Parallel Group, Multi-Center Study to Investigate the Safety and Efficacy of APD334 in Patients With Moderately to Severely Active Ulcerative Colitis
Actual Study Start Date :
Oct 15, 2015
Actual Primary Completion Date :
Feb 14, 2018
Actual Study Completion Date :
Feb 14, 2018

Arms and Interventions

Arm Intervention/Treatment
Experimental: Etrasimod Low Dose

Oral, low dose, daily for 12 Weeks

Drug: Etrasimod
Other Names:
  • APD334

    		•
    Experimental: Etrasimod High Dose

    Oral, high dose, daily for 12 weeks

    Drug: Etrasimod
    Other Names:
  • APD334

    		•
    Placebo Comparator: Placebo

    Oral, placebo, daily for 12 weeks.

    Drug: Placebo

    Outcome Measures

    Primary Outcome Measures

    1. Change From Baseline in Adapted Mayo Score (MCS) at Week 12 [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.

    Secondary Outcome Measures

    1. Percentage of Participants Who Achieved Endoscopic Improvement at Week 12 [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 to handle missing data.

    2. Change From Baseline in 2-component MCS at Week 12 [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.

    3. Change From Baseline in Total Mayo Score (TMS) at Week 12 [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.

    Other Outcome Measures

    1. Trichotomous Composite Score of Clinical Remission and Clinical Response at Week 12 [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.

    2. Percentage of Participants Who Achieved Clinical Remission at Week 12 [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.

    3. Percentage of Participants Who Achieved Clinical Response at Week 12 [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.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 80 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:

    • Moderately to severely active ulcerative colitis defined as a 3-component Mayo Clinic score

    • Evidence of colonic ulcerative colitis activity on endoscopy

    Exclusion Criteria:

    • Within 30 days prior to randomization, receipt of any of the following for the treatment of underlying disease: Non-biologic therapies (eg, cyclosporine, tacrolimus, tofacitinib, thalidomide), a non-biologic investigational therapy or an approved non-biologic therapy in an investigational protocol

    • Within 60 days prior to randomization, receipt of any of the following: Infliximab, adalimumab, golimumab, certolizumab, vedolizumab, any other investigational or approved biologic agent

    • Any prior exposure to natalizumab, efalizumab, or rituximab

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Arena 1119 Birmingham Alabama United States 35294
    2 Arena 1133 Dothan Alabama United States 36305
    3 Arena 1143 Thousand Oaks California United States 91360
    4 Arena 1107 Hollywood Florida United States 33021
    5 Arena 1138 Miami Florida United States 33134
    6 Arena 1123 Naples Florida United States 34102
    7 Arena 1141 Orlando Florida United States 32825
    8 Arena 1106 Port Orange Florida United States 32127
    9 Arena 1137 Sweetwater Florida United States 33172
    10 Arena 1131 Chicago Illinois United States 60611
    11 Arena 1139 Hoffman Estates Illinois United States 60169
    12 Arena 1127 Urbana Illinois United States 61801
    13 Arena 1142 Traverse City Michigan United States 49686
    14 Arena 1111 Troy Michigan United States 48098
    15 Arena 1109 Great Neck New York United States 11021
    16 Arena 1114 Rochester New York United States 14642
    17 Arena 1118 Raleigh North Carolina United States 27612
    18 Arena 1112 Cincinnati Ohio United States 45267
    19 Arena 1117 Pittsburgh Pennsylvania United States 15219
    20 Arena 1105 Germantown Tennessee United States 38138
    21 Arena 1102 Hermitage Tennessee United States 37076
    22 Arena 1136 DeSoto Texas United States 75115
    23 Arena 1121 Houston Texas United States 77030
    24 Arena 1116 Temple Texas United States 76508
    25 Arena 1103 Ogden Utah United States 84405
    26 Arena 1130 Richmond Virginia United States 23298
    27 Arena 1128 Roanoke Virginia United States 24014
    28 Arena 1115 Seattle Washington United States 98101
    29 Arena 1101 Seattle Washington United States 98195
    30 Arena 1108 Wauwatosa Wisconsin United States 53226
    31 Arena 1604 Kingswood Australia 2747
    32 Arena 1605 Randwick Australia 2031
    33 Arena 1607 Subiaco Australia 6008
    34 Arena 1490 Wien Austria 1090
    35 Arena 1472 Edegem Belgium 2650
    36 Arena 1464 Kortrijk Belgium 8500
    37 Arena 1473 Löwen Belgium 3000
    38 Arena 1421 Ruse Bulgaria 7002
    39 Arena 1409 Sofia Bulgaria 1407
    40 Arena 1410 Sofia Bulgaria 1407
    41 Arena 1417 Sofia Bulgaria 1407
    42 Arena 1407 Sofia Bulgaria 1797
    43 Arena 1425 Varna Bulgaria 9010
    44 Arena 1202 Winnipeg Manitoba Canada R3A 1R9
    45 Arena 1210 Bridgewater Nova Scotia Canada B4V 3N2
    46 Arena 1206 London Ontario Canada N6A 4G5
    47 Arena 1208 Sudbury Ontario Canada P3E 1H5
    48 Arena 1209 Sudbury Ontario Canada P3E 6C3
    49 Arena 1204 Toronto Ontario Canada M5G 1X5
    50 Arena 1455 Praha 4 Czechia 140 59
    51 Arena 1443 Amiens Cedex 1 France 80054
    52 Arena 1418 Clichy France 92110
    53 Arena 1437 Lille Cedex 1443 France 59037
    54 Arena 1476 Paris France 75010
    55 Arena 1480 Pierre-Benite France 693110
    56 Arena 1423 Saint-Etienne Cedex 1 France 42055
    57 Arena 1457 Vandoeuvre-les-Nancy France 54511
    58 Arena 1479 Hamburg Germany 20249
    59 Arena 1422 Hamburg Germany
    60 Arena 1470 Hanover Germany 30625
    61 Arena 1446 Kiel Germany 24105
    62 Arena 1489 Leipzig Germany 04103
    63 Arena 1497 Oldenburg Germany 26123
    64 Arena 1444 Ulm Germany 89073
    65 Arena 1478 Bekescsaba Hungary 5600
    66 Arena 1471 Budapest Hungary 1062
    67 Arena 1492 Budapest Hungary 1062
    68 Arena 1431 Budapest Hungary 1076
    69 Arena 1505 Debrecen Hungary 4025
    70 Arena 1474 Debrecen Hungary 4032
    71 Arena 1477 Szombathely Hungary 9700
    72 Arena 1705 Beer Sheva Israel 84101
    73 Arena 1702 Haifa Israel 31096
    74 Arena 1706 Holon Israel 58100
    75 Arena 1704 Jerusalem Israel 91031
    76 Arena 1703 Petah-Tikva Israel 49100
    77 Arena 1613 Busan Korea, Republic of 49241
    78 Arena 1614 Daegu Korea, Republic of 42415
    79 Arena 1610 Incheon Korea, Republic of 21565
    80 Arena 1612 Seoul Korea, Republic of 05505
    81 Arena 1611 Seoul Korea, Republic of 06519
    82 Arena 1608 Suwon-si Korea, Republic of 16247
    83 Arena 1615 Wonju Korea, Republic of 26426
    84 Arena 1462 Riga Latvia 1002
    85 Arena 1475 Riga Latvia 1006
    86 Arena 1484 Vilnius Lithuania 8661
    87 Arena 1601 Christchurch New Zealand 8011
    88 Arena 1439 Bydgoszcz Poland 85-681
    89 Arena 1486 Elblag Poland 03-580
    90 Arena 1495 Kielce Poland 25-364
    91 Arena 1451 Krakow Poland 31-009
    92 Arena 1438 Lodz Poland 90-302
    93 Arena 1458 Posen Poland 61-485
    94 Arena 1428 Rzeszow Poland 35-068
    95 Arena 1456 Sopot Poland 81-756
    96 Arena 1494 Wroclaw Poland 54-144
    97 Arena 1441 Bucharest Romania 050098
    98 Arena 1491 Bucharest Romania 10719
    99 Arena 1406 Bucharest Romania
    100 Arena 1436 Iasi Romania 700506
    101 Arena 1420 Oradea Romania 410159
    102 Arena 1405 Timisoara Romania 300002
    103 Arena 1493 Timisoara Romania 300736
    104 Arena 1440 Kazan' Russian Federation 420029
    105 Arena 1500 Krasnoyarsk Russian Federation 660022
    106 Arena 1504 Novosibirsk Russian Federation 630091
    107 Arena 1419 Rostov on Don Russian Federation 197022
    108 Arena 1452 Ryazan' Russian Federation 197022
    109 Arena 1498 Saint Petersburg Russian Federation 191015
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    114 Arena 1403 Barcelona Spain 08022
    115 Arena 1460 Barcelona Spain 08036
    116 Arena 1481 Madrid Spain 28046
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    118 Arena 1432 Santiago de Compostela Spain 15706
    119 Arena 1469 Sevilla Spain 41007
    120 Arena 1424 Chernivtsi Ukraine 3110
    121 Arena 1445 Ivano-Frankivsk Ukraine 07601
    122 Arena 1454 Kharkov Ukraine 6100
    123 Arena 1459 Kharkov Ukraine 61039
    124 Arena 1466 Kiev Ukraine 01030
    125 Arena 1408 Kyiv Ukraine 01030
    126 Arena 1502 Kyiv Ukraine 01133
    127 Arena 1506 Kyiv Ukraine 02091
    128 Arena 1414 Odessa Ukraine 65025
    129 Arena 1433 Uzhgorod Ukraine 88000
    130 Arena 1501 Vinnytsia Ukraine 21029
    131 Arena 1416 Vinnytsya Ukraine 21018
    132 Arena 1302 London United Kingdom E1 1BB
    133 Arena 1304 Torquay United Kingdom TQ2 7AA
    134 Arena 1303 Wolverhampton United Kingdom WV10 0QP

    Sponsors and Collaborators

    • Arena Pharmaceuticals

    Investigators

    • Study Director: Arena CT.gov Administrator, Arena Pharmaceuticals

    Study Documents (Full-Text)

    More Information

    Publications

    None provided.
    Responsible Party:
    Arena Pharmaceuticals
    ClinicalTrials.gov Identifier:
    NCT02447302
    Other Study ID Numbers:
    • APD334-003
    • 2015-001942-28
    First Posted:
    May 18, 2015
    Last Update Posted:
    Apr 5, 2021
    Last Verified:
    Mar 1, 2021
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Additional relevant MeSH terms:
    Colitis
    Colitis, Ulcerative
    Ulcer

    Study Results

    Participant Flow

    Recruitment Details The study included a screening period (up to 28 days), a double-blind induction treatment period (12 weeks), and a possible follow-up visit (2 weeks after the last study visit). The target population consisted of male or female participants aged between 18 and 80 years (inclusive), with moderately to severely active Ulcerative Colitis.
    Pre-assignment Detail During the screening period (Days -28 to -1), participants were evaluated for study entry based on the inclusion and exclusion criteria. Screening procedures to evaluate participant eligibility for the study were to be conducted within 28 days prior to study drug administration on Day 1.
    Arm/Group Title Etrasimod 1 mg Etrasimod 2 mg Placebo
    Arm/Group Description Etrasimod 1 mg was administered orally once daily for 12 weeks, administered with approximately 240 mL (8 ounces) of water. The study drug was to be taken on an empty stomach after an overnight fast of approximately 8 hours. Etrasimod 2 mg was administered orally once daily for 12 weeks, administered with approximately 240 mL (8 ounces) of water. The study drug was to be taken on an empty stomach after an overnight fast of approximately 8 hours. Placebo was administered orally once daily for 12 weeks, administered with approximately 240 mL (8 ounces) of water. Placebo was to be taken on an empty stomach after an overnight fast of approximately 8 hours.
    Period Title: Overall Study
    STARTED 52 50 54
    COMPLETED 47 46 48
    NOT COMPLETED 5 4 6

    Baseline Characteristics

    Arm/Group Title Etrasimod 1 mg Etrasimod 2 mg Placebo Total
    Arm/Group Description Etrasimod 1 mg was administered orally once daily for 12 weeks, administered with approximately 240 mL (8 ounces) of water. The study drug was to be taken on an empty stomach after an overnight fast of approximately 8 hours. Etrasimod 2 mg was administered orally once daily for 12 weeks, administered with approximately 240 mL (8 ounces) of water. The study drug was to be taken on an empty stomach after an overnight fast of approximately 8 hours. Placebo was administered orally once daily for 12 weeks, administered with approximately 240 mL (8 ounces) of water. Placebo was to be taken on an empty stomach after an overnight fast of approximately 8 hours. Total of all reporting groups
    Overall Participants 52 50 54 156
    Age (years) [Median (Full Range) ]
    Median (Full Range) [years]
    44.0
    38.5
    46.0
    42
    Age, Customized (Subjects) [Number]
    Adults (18-64 years)
    52
    49
    49
    150
    From 65-80 years
    0
    1
    5
    6
    Sex: Female, Male (Count of Participants)
    Female
    22
    42.3%
    23
    46%
    22
    40.7%
    67
    42.9%
    Male
    30
    57.7%
    27
    54%
    32
    59.3%
    89
    57.1%
    Ethnicity (NIH/OMB) (Count of Participants)
    Hispanic or Latino
    3
    5.8%
    1
    2%
    3
    5.6%
    7
    4.5%
    Not Hispanic or Latino
    49
    94.2%
    49
    98%
    51
    94.4%
    149
    95.5%
    Unknown or Not Reported
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Race (NIH/OMB) (Count of Participants)
    American Indian or Alaska Native
    1
    1.9%
    0
    0%
    0
    0%
    1
    0.6%
    Asian
    2
    3.8%
    1
    2%
    2
    3.7%
    5
    3.2%
    Native Hawaiian or Other Pacific Islander
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Black or African American
    0
    0%
    0
    0%
    1
    1.9%
    1
    0.6%
    White
    47
    90.4%
    49
    98%
    51
    94.4%
    147
    94.2%
    More than one race
    1
    1.9%
    0
    0%
    0
    0%
    1
    0.6%
    Unknown or Not Reported
    1
    1.9%
    0
    0%
    0
    0%
    1
    0.6%
    Adapted Mayo Score (MCS) (score on a scale) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [score on a scale]
    6.5
    (1.23)
    6.6
    (1.17)
    6.5
    (1.51)
    6.5
    (1.31)
    The 2-component MCS (score on a scale) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [score on a scale]
    4.2
    (0.75)
    4.2
    (0.75)
    4.2
    (0.91)
    4.2
    (0.80)
    Total Mayo Score (TMS) (score on a scale) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [score on a scale]
    8.8
    (1.43)
    8.9
    (1.47)
    8.7
    (1.72)
    8.8
    (1.54)

    Outcome Measures

    1. Primary Outcome
    Title Change From Baseline in Adapted Mayo Score (MCS) at Week 12
    Description 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.
    Time Frame Baseline and Week 12

    Outcome Measure Data

    Analysis Population Description
    The analysis was performed using the intent-to-treat (ITT) population that consisted of all randomized participants who received at least 1 dose of study drug.
    Arm/Group Title Etrasimod 1 mg Etrasimod 2 mg Placebo
    Arm/Group Description Etrasimod 1 mg was administered orally once daily for 12 weeks, administered with approximately 240 mL (8 ounces) of water. The study drug was to be taken on an empty stomach after an overnight fast of approximately 8 hours. Etrasimod 2 mg was administered orally once daily for 12 weeks, administered with approximately 240 mL (8 ounces) of water. The study drug was to be taken on an empty stomach after an overnight fast of approximately 8 hours. Placebo was administered orally once daily for 12 weeks, administered with approximately 240 mL (8 ounces) of water. Placebo was to be taken on an empty stomach after an overnight fast of approximately 8 hours.
    Measure Participants 52 50 54
    Least Squares Mean (90% Confidence Interval) [score on a scale]
    -1.94
    -2.49
    -1.50
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Etrasimod 2 mg, Placebo
    Comments The primary comparison in the study was between etrasimod 2 mg versus placebo.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value = 0.0091
    Comments The analysis was performed using an analysis of covariance (ANCOVA) model that incorporated treatment, current oral corticosteroid use, prior exposure to tumor necrosis factor alpha (TNFα) antagonists, and baseline value as covariate.
    Method ANCOVA
    Comments The analysis compared the adapted MCS change from baseline between treatment groups using a 1-sided test at the 0.05 level of significance.
    Method of Estimation Estimation Parameter Difference in least square mean
    Estimated Value -0.99
    Confidence Interval (2-Sided) 90%
    -1.68 to -0.30
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.42
    Estimation Comments Estimated least square mean difference in etrasimod 2 mg from placebo
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Etrasimod 1 mg, Placebo
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value = 0.1457
    Comments The analysis was performed using an ANCOVA model that incorporated treatment, current oral corticosteroid use, prior exposure to TNFα antagonists, and baseline value as covariate.
    Method ANCOVA
    Comments The analysis compared the adapted MCS change from baseline between treatment groups using a 1-sided test at the 0.05 level of significance.
    Method of Estimation Estimation Parameter Difference in least square mean
    Estimated Value -0.43
    Confidence Interval (2-Sided) 90%
    -1.11 to 0.24
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.41
    Estimation Comments Estimated least square mean difference in etrasimod 1 mg from placebo
    2. Secondary Outcome
    Title Percentage of Participants Who Achieved Endoscopic Improvement at Week 12
    Description 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 to handle missing data.
    Time Frame Week 12

    Outcome Measure Data

    Analysis Population Description
    The analysis was performed using the ITT population that consisted of all randomized participants who received at least 1 dose of study drug.
    Arm/Group Title Etrasimod 1 mg Etrasimod 2 mg Placebo
    Arm/Group Description Etrasimod 1 mg was administered orally once daily for 12 weeks, administered with approximately 240 mL (8 ounces) of water. The study drug was to be taken on an empty stomach after an overnight fast of approximately 8 hours. Etrasimod 2 mg was administered orally once daily for 12 weeks, administered with approximately 240 mL (8 ounces) of water. The study drug was to be taken on an empty stomach after an overnight fast of approximately 8 hours. Placebo was administered orally once daily for 12 weeks, administered with approximately 240 mL (8 ounces) of water. Placebo was to be taken on an empty stomach after an overnight fast of approximately 8 hours.
    Measure Participants 52 50 54
    Number [percentage of participants]
    22.5
    43.3%
    41.8
    83.6%
    17.8
    33%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Etrasimod 2 mg, Placebo
    Comments The primary comparison in the study was between etrasimod 2 mg versus placebo.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value = 0.003
    Comments Mantel-Haenszel (MH) estimated common risk difference adjusted for current oral corticosteroid therapy at baseline and previous exposure to TNFα antagonists.
    Method Mantel Haenszel
    Comments The analysis compared the difference in proportions between treatment groups using a 1-sided test at the 0.05 level of significance.
    Method of Estimation Estimation Parameter MH estimate for difference in percentage
    Estimated Value 24.4
    Confidence Interval (2-Sided) 90%
    9.8 to 39.0
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 8.87
    Estimation Comments MH estimated difference in etrasimod 2 mg from Placebo
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Etrasimod 1 mg, Placebo
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value = 0.3059
    Comments MH estimated common risk difference adjusted for current oral corticosteroid therapy at baseline and previous exposure to TNFα antagonists.
    Method Mantel Haenszel
    Comments The analysis compared the difference in proportions between treatment groups using a 1-sided test at the 0.05 level of significance.
    Method of Estimation Estimation Parameter MH estimate for difference in percentage
    Estimated Value 4.1
    Confidence Interval (2-Sided) 90%
    -9.1 to 17.2
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 7.98
    Estimation Comments MH estimated difference in etrasimod 1 mg from Placebo
    3. Secondary Outcome
    Title Change From Baseline in 2-component MCS at Week 12
    Description 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.
    Time Frame Baseline and Week 12

    Outcome Measure Data

    Analysis Population Description
    The analysis was performed using the ITT population that consisted of all randomized participants who received at least 1 dose of study drug.
    Arm/Group Title Etrasimod 1 mg Etrasimod 2 mg Placebo
    Arm/Group Description Etrasimod 1 mg was administered orally once daily for 12 weeks, administered with approximately 240 mL (8 ounces) of water. The study drug was to be taken on an empty stomach after an overnight fast of approximately 8 hours. Etrasimod 2 mg was administered orally once daily for 12 weeks, administered with approximately 240 mL (8 ounces) of water. The study drug was to be taken on an empty stomach after an overnight fast of approximately 8 hours. Placebo was administered orally once daily for 12 weeks, administered with approximately 240 mL (8 ounces) of water. Placebo was to be taken on an empty stomach after an overnight fast of approximately 8 hours.
    Measure Participants 52 50 54
    Least Squares Mean (90% Confidence Interval) [score on a scale]
    -1.30
    -1.75
    -0.92
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Etrasimod 2 mg, Placebo
    Comments The primary comparison in the study was between etrasimod 2 mg versus placebo.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value = 0.0020
    Comments The analysis was performed using an ANCOVA model that incorporated treatment, current oral corticosteroid use, prior exposure to TNFα antagonists, and baseline value as covariate.
    Method ANCOVA
    Comments The analysis compared the 2-component MCS change from baseline between treatment groups using a 1-sided test at the 0.05 level of significance.
    Method of Estimation Estimation Parameter Difference in least square mean
    Estimated Value -0.84
    Confidence Interval (2-Sided) 90%
    -1.32 to -0.36
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.29
    Estimation Comments Estimated least square mean difference in etrasimod 2 mg from placebo
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Etrasimod 1 mg, Placebo
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value = 0.0858
    Comments The analysis was performed using an ANCOVA model that incorporated treatment, current oral corticosteroid use, prior exposure to TNFα antagonists, and baseline value as covariate.
    Method ANCOVA
    Comments The analysis compared the 2-component MCS change from baseline between treatment groups using a 1-sided test at the 0.05 level of significance.
    Method of Estimation Estimation Parameter Difference in least square mean
    Estimated Value -0.39
    Confidence Interval (2-Sided) 90%
    -0.85 to 0.08
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.28
    Estimation Comments Estimated least square mean difference in etrasimod 1 mg from placebo
    4. Secondary Outcome
    Title Change From Baseline in Total Mayo Score (TMS) at Week 12
    Description 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.
    Time Frame Baseline and Week 12

    Outcome Measure Data

    Analysis Population Description
    The analysis was performed using the ITT population that consisted of all randomized participants who received at least 1 dose of study drug.
    Arm/Group Title Etrasimod 1 mg Etrasimod 2 mg Placebo
    Arm/Group Description Etrasimod 1 mg was administered orally once daily for 12 weeks, administered with approximately 240 mL (8 ounces) of water. The study drug was to be taken on an empty stomach after an overnight fast of approximately 8 hours. Etrasimod 2 mg was administered orally once daily for 12 weeks, administered with approximately 240 mL (8 ounces) of water. The study drug was to be taken on an empty stomach after an overnight fast of approximately 8 hours. Placebo was administered orally once daily for 12 weeks, administered with approximately 240 mL (8 ounces) of water. Placebo was to be taken on an empty stomach after an overnight fast of approximately 8 hours.
    Measure Participants 52 50 54
    Least Squares Mean (90% Confidence Interval) [score on a scale]
    -2.69
    -3.35
    -2.08
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Etrasimod 2 mg, Placebo
    Comments The primary comparison in the study was between etrasimod 2 mg versus placebo.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value = 0.0100
    Comments The analysis was performed using an ANCOVA model that incorporated treatment, current oral corticosteroid use, prior exposure to TNFα antagonists, and baseline value as covariate.
    Method ANCOVA
    Comments The analysis compared the TMS change from baseline between treatment groups using a 1-sided test at the 0.05 level of significance.
    Method of Estimation Estimation Parameter Difference in least square mean
    Estimated Value -1.27
    Confidence Interval (2-Sided) 90%
    -2.17 to -0.37
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.55
    Estimation Comments Estimated least square mean difference in etrasimod 2 mg from placebo
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Etrasimod 1 mg, Placebo
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value = 0.1277
    Comments The analysis was performed using an ANCOVA model that incorporated treatment, current oral corticosteroid use, prior exposure to TNFα antagonists, and baseline value as covariate.
    Method ANCOVA
    Comments The analysis compared the TMS change from baseline between treatment groups using a 1-sided test at the 0.05 level of significance.
    Method of Estimation Estimation Parameter Difference in least square mean
    Estimated Value -0.60
    Confidence Interval (2-Sided) 90%
    -1.48 to 0.27
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.53
    Estimation Comments Estimated least square mean difference in etrasimod 1 mg from placebo
    5. Other Pre-specified Outcome
    Title Trichotomous Composite Score of Clinical Remission and Clinical Response at Week 12
    Description 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.
    Time Frame Week 12

    Outcome Measure Data

    Analysis Population Description
    The analysis was performed using the ITT population that consisted of all randomized participants who received at least 1 dose of study drug.
    Arm/Group Title Etrasimod 1 mg Etrasimod 2 mg Placebo
    Arm/Group Description Etrasimod 1 mg was administered orally once daily for 12 weeks, administered with approximately 240 mL (8 ounces) of water. The study drug was to be taken on an empty stomach after an overnight fast of approximately 8 hours. Etrasimod 2 mg was administered orally once daily for 12 weeks, administered with approximately 240 mL (8 ounces) of water. The study drug was to be taken on an empty stomach after an overnight fast of approximately 8 hours. Placebo was administered orally once daily for 12 weeks, administered with approximately 240 mL (8 ounces) of water. Placebo was to be taken on an empty stomach after an overnight fast of approximately 8 hours.
    Measure Participants 52 50 54
    Mean (Standard Error) [score on a scale]
    0.60
    (0.11)
    0.84
    (0.13)
    0.41
    (0.09)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Etrasimod 2 mg, Placebo
    Comments The primary comparison in the study was between etrasimod 2 mg versus placebo.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value = 0.0071
    Comments The analysis was performed using an ordered logistic regression model with terms for treatment, current oral corticosteroid use, and prior exposure to TNFα antagonists.
    Method ANCOVA
    Comments The analysis compared the odds of achieving higher trichotomous composite score between the groups using 1-sided test at 0.05 level of significance.
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 2.78
    Confidence Interval (2-Sided) 90%
    1.40 to 5.51
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Etrasimod 1 mg, Placebo
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value = 0.1192
    Comments The analysis was performed using an ordered logistic regression model with terms for treatment, current oral corticosteroid use, and prior exposure to TNFα antagonists.
    Method ANCOVA
    Comments The analysis compared the odds of achieving higher trichotomous composite score between the groups using 1-sided test at 0.05 level of significance.
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 1.61
    Confidence Interval (2-Sided) 90%
    0.83 to 3.14
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    6. Other Pre-specified Outcome
    Title Percentage of Participants Who Achieved Clinical Remission at Week 12
    Description 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.
    Time Frame Week 12

    Outcome Measure Data

    Analysis Population Description
    The analysis was performed using the ITT population that consisted of all randomized participants who received at least 1 dose of study drug.
    Arm/Group Title Etrasimod 1 mg Etrasimod 2 mg Placebo
    Arm/Group Description Etrasimod 1 mg was administered orally once daily for 12 weeks, administered with approximately 240 mL (8 ounces) of water. The study drug was to be taken on an empty stomach after an overnight fast of approximately 8 hours. Etrasimod 2 mg was administered orally once daily for 12 weeks, administered with approximately 240 mL (8 ounces) of water. The study drug was to be taken on an empty stomach after an overnight fast of approximately 8 hours. Placebo was administered orally once daily for 12 weeks, administered with approximately 240 mL (8 ounces) of water. Placebo was to be taken on an empty stomach after an overnight fast of approximately 8 hours.
    Measure Participants 52 50 54
    Number [percentage of participants]
    16.0
    30.8%
    33.0
    66%
    8.1
    15%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Etrasimod 2 mg, Placebo
    Comments The primary comparison in the study was between etrasimod 2 mg versus placebo.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value = 0.0003
    Comments The analysis was performed using MH method that was adjusted for current oral corticosteroid therapy at baseline and previous exposure to TNFα antagonists.
    Method Mantel Haenszel
    Comments The analysis compared the difference in proportions between treatment groups using a 1-sided test at the 0.05 level of significance.
    Method of Estimation Estimation Parameter MH estimate for difference in percentage
    Estimated Value 25.8
    Confidence Interval (2-Sided) 90%
    13.5 to 38.1
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 7.47
    Estimation Comments MH estimated difference in etrasimod 2 mg from Placebo
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Etrasimod 1 mg, Placebo
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value = 0.1360
    Comments The analysis was performed using MH method that was adjusted for current oral corticosteroid therapy at baseline and previous exposure to TNFα antagonists.
    Method Mantel Haenszel
    Comments The analysis compared the difference in proportions between treatment groups using a 1-sided test at the 0.05 level of significance.
    Method of Estimation Estimation Parameter MH estimate for difference in percentage
    Estimated Value 7.1
    Confidence Interval (2-Sided) 90%
    -3.5 to 17.7
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 6.46
    Estimation Comments MH estimated difference in etrasimod 1 mg from Placebo
    7. Other Pre-specified Outcome
    Title Percentage of Participants Who Achieved Clinical Response at Week 12
    Description 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.
    Time Frame Week 12

    Outcome Measure Data

    Analysis Population Description
    The analysis was performed using the ITT population that consisted of all randomized participants who received at least 1 dose of study drug.
    Arm/Group Title Etrasimod 1 mg Etrasimod 2 mg Placebo
    Arm/Group Description Etrasimod 1 mg was administered orally once daily for 12 weeks, administered with approximately 240 mL (8 ounces) of water. The study drug was to be taken on an empty stomach after an overnight fast of approximately 8 hours. Etrasimod 2 mg was administered orally once daily for 12 weeks, administered with approximately 240 mL (8 ounces) of water. The study drug was to be taken on an empty stomach after an overnight fast of approximately 8 hours. Placebo was administered orally once daily for 12 weeks, administered with approximately 240 mL (8 ounces) of water. Placebo was to be taken on an empty stomach after an overnight fast of approximately 8 hours.
    Measure Participants 52 50 54
    Number [percentage of participants]
    43.7
    84%
    50.6
    101.2%
    32.5
    60.2%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Etrasimod 2 mg, Placebo
    Comments The primary comparison in the study was between etrasimod 2 mg versus placebo.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value = 0.0282
    Comments The analysis was performed using MH method that was adjusted for current oral corticosteroid therapy at baseline and previous exposure to TNFα antagonists.
    Method Mantel Haenszel
    Comments The analysis compared the difference in proportions between treatment groups using a 1-sided test at the 0.05 level of significance.
    Method of Estimation Estimation Parameter MH estimate for difference in percentage
    Estimated Value 18.9
    Confidence Interval (2-Sided) 90%
    2.6 to 35.3
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 9.92
    Estimation Comments MH estimated difference in etrasimod 2 mg from Placebo
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Etrasimod 1 mg, Placebo
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value = 0.1309
    Comments The analysis was performed using MH method that was adjusted for current oral corticosteroid therapy at baseline and previous exposure to TNFα antagonists.
    Method Mantel Haenszel
    Comments The analysis compared the difference in proportions between treatment groups using a 1-sided test at the 0.05 level of significance.
    Method of Estimation Estimation Parameter MH estimate for difference in percentage
    Estimated Value 11.4
    Confidence Interval (2-Sided) 90%
    -5.3 to 28.1
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 10.14
    Estimation Comments MH estimated difference in etrasimod 1 mg from Placebo

    Adverse Events

    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.
    Adverse Event Reporting Description Treatment-Emergent Adverse Event (TEAE) were collected during the study.
    Arm/Group Title Etrasimod 1 mg Etrasimod 2 mg Placebo
    Arm/Group Description Etrasimod 1 mg was administered orally once daily for 12 weeks, administered with approximately 240 mL (8 ounces) of water. The study drug was to be taken on an empty stomach after an overnight fast of approximately 8 hours. Etrasimod 2 mg was administered orally once daily for 12 weeks, administered with approximately 240 mL (8 ounces) of water. The study drug was to be taken on an empty stomach after an overnight fast of approximately 8 hours. Placebo was administered orally once daily for 12 weeks, administered with approximately 240 mL (8 ounces) of water. Placebo was to be taken on an empty stomach after an overnight fast of approximately 8 hours.
    All Cause Mortality
    Etrasimod 1 mg Etrasimod 2 mg Placebo
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/52 (0%) 0/50 (0%) 0/54 (0%)
    Serious Adverse Events
    Etrasimod 1 mg Etrasimod 2 mg Placebo
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 3/52 (5.8%) 0/50 (0%) 6/54 (11.1%)
    Gastrointestinal disorders
    Abdominal pain 0/52 (0%) 0/50 (0%) 1/54 (1.9%)
    Colitis ulcerative 2/52 (3.8%) 0/50 (0%) 3/54 (5.6%)
    Duodenal ulcer perforation 0/52 (0%) 0/50 (0%) 1/54 (1.9%)
    Hepatobiliary disorders
    Jaundice 0/52 (0%) 0/50 (0%) 1/54 (1.9%)
    Infections and infestations
    Anal abscess 1/52 (1.9%) 0/50 (0%) 0/54 (0%)
    Renal and urinary disorders
    Hydronephrosis 0/52 (0%) 0/50 (0%) 1/54 (1.9%)
    Other (Not Including Serious) Adverse Events
    Etrasimod 1 mg Etrasimod 2 mg Placebo
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 11/52 (21.2%) 11/50 (22%) 9/54 (16.7%)
    Blood and lymphatic system disorders
    Anaemia 2/52 (3.8%) 3/50 (6%) 2/54 (3.7%)
    Gastrointestinal disorders
    Colitis ulcerative 3/52 (5.8%) 2/50 (4%) 1/54 (1.9%)
    Infections and infestations
    Nasopharyngitis 2/52 (3.8%) 1/50 (2%) 4/54 (7.4%)
    Upper respiratory tract infection 4/52 (7.7%) 2/50 (4%) 2/54 (3.7%)
    Nervous system disorders
    Headache 0/52 (0%) 3/50 (6%) 1/54 (1.9%)

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    Results Point of Contact

    Name/Title Arena CT.gov Administrator
    Organization Arena Pharmaceuticals, Inc.
    Phone +1 855-218-9153
    Email ct.gov@arenapharm.com
    Responsible Party:
    Arena Pharmaceuticals
    ClinicalTrials.gov Identifier:
    NCT02447302
    Other Study ID Numbers:
    • APD334-003
    • 2015-001942-28
    First Posted:
    May 18, 2015
    Last Update Posted:
    Apr 5, 2021
    Last Verified:
    Mar 1, 2021