Ulcerative Colitis
Conditions
Keywords
Ulcerative Colitis, Etrasimod, APD334
Brief summary
The purpose of this study is to assess the efficacy of etrasimod on clinical remission in participants with moderately to severely active ulcerative colitis (UC).
Interventions
DRUGEtrasimod
Etrasimod 2 mg tablet by mouth, once daily up to 12-Week Induction Treatment Period
DRUGPlacebo
Etrasimod matching placebo tablet by mouth, once daily up to 12-Week Induction Treatment Period
Sponsors
Arena Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
16 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Diagnosed with ulcerative colitis (UC) ≥ 3 months prior to screening * Active UC confirmed by endoscopy
Exclusion criteria
* Severe extensive colitis * Diagnosis of Crohn's disease (CD) or indeterminate colitis or the presence or history of a fistula consistent with CD * Diagnosis of microscopic colitis, ischemic colitis, or infectious colitis
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Achieving Clinical Remission | Week 12 | Clinical remission was based on the modified Mayo score (MMS). The MMS is a composite score of 3 assessments consisting of participant-reported symptoms using daily electronic (e)-diary and centrally read endoscopy: stool frequency (SF), rectal bleeding (RB) and endoscopic score (ES). Clinical remission was defined as SF sub-score = 0 (or = 1 with a greater than or equal to \[\>=\] 1-point decrease from Baseline), RB sub-score = 0, and ES less than or equal to (\<=) 1 (excluding friability). Each component sub-score ranged from 0 to 3 and total score range of the MMS was from 0 to 9, with higher scores indicating more severe disease. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Achieving Symptomatic Remission | Week 12 | Symptomatic remission was defined as an SF sub-score = 0 (or = 1 with a \>= 1 point decrease from Baseline) and RB sub-score = 0. The SF sub-score ranged from 0 to 3 (where 0 = normal number of stools and 3 = at least 5 stools more than normal) and RB sub-score ranged from 0 to 3 (where 0 = no blood and 3 = blood alone passes). Higher scores indicated more severe disease. |
| Percentage of Participants With Mucosal Healing | Week 12 | Mucosal healing was defined as an ES \<= 1 (excluding friability) with histologic remission measured by a Geboes Index score less than \[\<\] 2.0). The ES ranged from 0 to 3 (where 0 = normal/inactive disease and 3 = severe disease). 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. |
| Percentage of Participants Achieving Clinical Response | Week 12 | Clinical response was based on the MMS which is a composite score of 3 assessments: SF, RB and ES. Clinical response was defined as a \>= 2-point and \>= 30 percent (%) decrease from Baseline MMS, and a \>= 1-point decrease from Baseline in RB sub-score or an absolute RB sub-score \<= 1. Each component sub-score ranged from 0 to 3 and total score range of the MMS was from 0 to 9, with higher scores indicating more severe disease. |
| Percentage of Participants Achieving Endoscopic Normalization | Week 12 | Endoscopic normalization was defined as an ES = 0. The ES ranged from 0 to 3 (where 0= normal/inactive disease and 3= severe disease); higher score indicated more severe disease. |
| Percentage of Participants Achieving Endoscopic Improvement | Week 12 | Endoscopic improvement was defined as an ES \<= 1 (excluding friability). The ES ranged from 0 to 3 (where 0 = normal/inactive disease and 3 = severe disease); higher score indicated more severe disease. |
| Percentage of Participants Achieving Complete Symptomatic Remission | Weeks 2, 4, 8 and 12 | Complete symptomatic remission was defined as an SF sub-score = 0 and RB sub-score = 0. The SF sub-score ranged from 0 to 3 (where 0 = normal number of stools and 3 = at least 5 stools more than normal) and RB sub-score ranged from 0 to 3 (where 0 = no blood and 3 = blood alone passes). Higher scores indicated more severe disease. |
| Percentage of Participants Achieving Non-invasive Clinical Response | Weeks 2, 4, 8 and 12 | Non-invasive clinical response was defined as a \>= 30% decrease from Baseline in composite RB and SF sub-scores, and a \>= 1 point decrease from Baseline in RB sub-score or RB sub-score \<= 1. The SF subscore ranged from 0 to 3 (where 0 = normal number of stools and 3 = at least 5 stools more than normal) and RB sub-score ranged from 0 to 3 (where 0 = no blood and 3 = blood alone passes). The composite RB and SF score range was from 0 to 6, with higher scores indicating more severe disease. |
| Percentage of Participants Achieving Symptomatic Response | Weeks 2, 4, 8 and 12 | Symptomatic response was defined as a \>= 30% decrease from Baseline in composite RB and SF score. The SF sub-score ranged from 0 to 3 (where 0= normal number of stools and 3= at least 5 stools more than normal) and RB sub-score ranged from 0 to 3 (where 0= no blood and 3= blood alone passes). The composite RB and SF score range was from 0 to 6, with higher scores indicating more severe disease. |
| Percentage of Participants Achieving Symptomatic Remission at Weeks 2, 4 and 8 | Weeks 2, 4 and 8 | Symptomatic remission was defined as an SF sub-score = 0 (or = 1 with a \>= 1 point decrease from Baseline) and RB sub-score = 0. The SF sub-score ranged from 0 to 3 (where 0 = normal number of stools and 3 = at least 5 stools more than normal) and RB sub-score ranged from 0 to 3 (where 0 = no blood and 3 = blood alone passes). Higher scores indicated more severe disease. |
Countries
Argentina, Australia, Austria, Belarus, Belgium, Bulgaria, Canada, Chile, Colombia, Croatia, Czechia, Denmark, Estonia, France, Georgia, Germany, Hungary, India, Israel, Italy, Japan, Lebanon, Lithuania, Mexico, Moldova, Netherlands, Poland, Portugal, Romania, Russia, Serbia, Slovakia, South Africa, South Korea, Spain, Switzerland, Thailand, Turkey (Türkiye), Ukraine, United Kingdom, United States
Participant flow
Recruitment details
The study included a screening period (up to 28 days), a double-blind induction treatment period (12 weeks), and a 2-week and a 4-week follow-up period. The target population consisted of male or female participants aged between 16 and 80 years (inclusive), with moderately to severely active ulcerative colitis (UC).
Pre-assignment details
During the screening period, 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 intervention administration on Day 1.
Participants by arm
| Arm | Count |
|---|---|
| Etrasimod 2 mg Participants were administered one tablet of etrasimod 2 milligrams (mg) orally once daily (QD) for 12 weeks. | 238 |
| Placebo Participants were administered one tablet of placebo orally QD for 12 weeks. | 116 |
| Total | 354 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 9 | 0 |
| Overall Study | Didn't meet Inclusion/Exclusion criteria | 1 | 0 |
| Overall Study | Lack of Efficacy | 4 | 0 |
| Overall Study | Lost to Follow-up | 0 | 1 |
| Overall Study | Participant decision | 0 | 1 |
| Overall Study | Physician Decision | 4 | 2 |
| Overall Study | Protocol deviation | 1 | 1 |
| Overall Study | Withdrawal by Subject | 6 | 8 |
Baseline characteristics
| Characteristic | Placebo | Total | Etrasimod 2 mg |
|---|---|---|---|
| Age, Continuous | 40.4 Years STANDARD_DEVIATION 13.28 | 40.4 Years STANDARD_DEVIATION 13.4 | 40.3 Years STANDARD_DEVIATION 13.49 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 9 Participants | 19 Participants | 10 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 107 Participants | 333 Participants | 226 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 2 Participants | 2 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 7 Participants | 6 Participants |
| Race (NIH/OMB) Asian | 25 Participants | 72 Participants | 47 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 4 Participants | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 6 Participants | 6 Participants |
| Race (NIH/OMB) White | 88 Participants | 264 Participants | 176 Participants |
| Sex: Female, Male Female | 43 Participants | 146 Participants | 103 Participants |
| Sex: Female, Male Male | 73 Participants | 208 Participants | 135 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 238 | 0 / 116 |
| other Total, other adverse events | 112 / 238 | 54 / 116 |
| serious Total, serious adverse events | 6 / 238 | 2 / 116 |
Outcome results
Primary
Percentage of Participants Achieving Clinical Remission
Clinical remission was based on the modified Mayo score (MMS). The MMS is a composite score of 3 assessments consisting of participant-reported symptoms using daily electronic (e)-diary and centrally read endoscopy: stool frequency (SF), rectal bleeding (RB) and endoscopic score (ES). Clinical remission was defined as SF sub-score = 0 (or = 1 with a greater than or equal to \[\>=\] 1-point decrease from Baseline), RB sub-score = 0, and ES less than or equal to (\<=) 1 (excluding friability). Each component sub-score ranged from 0 to 3 and total score range of the MMS was from 0 to 9, with higher scores indicating more severe disease.
Time frame: Week 12
Population: Full Analysis Set Population (All randomized participants who received at least 1 dose of study intervention), with actual Baseline MMS 5 to 9. Only those participants with data available at the specified time points were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Etrasimod 2 mg | Percentage of Participants Achieving Clinical Remission | 24.8 Percentage of participants |
| Placebo | Percentage of Participants Achieving Clinical Remission | 15.2 Percentage of participants |
Comparison: Week 12p-value: =0.02695% CI: [1.14, 18.23]Cochran-Mantel-Haenszel
Secondary
Percentage of Participants Achieving Clinical Response
Clinical response was based on the MMS which is a composite score of 3 assessments: SF, RB and ES. Clinical response was defined as a \>= 2-point and \>= 30 percent (%) decrease from Baseline MMS, and a \>= 1-point decrease from Baseline in RB sub-score or an absolute RB sub-score \<= 1. Each component sub-score ranged from 0 to 3 and total score range of the MMS was from 0 to 9, with higher scores indicating more severe disease.
Time frame: Week 12
Population: Full Analysis Set Population with actual Baseline MMS 5 to 9. Only those participants with data available at the specified time points were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Etrasimod 2 mg | Percentage of Participants Achieving Clinical Response | 62.2 Percentage of participants |
| Placebo | Percentage of Participants Achieving Clinical Response | 41.1 Percentage of participants |
Comparison: Week 12p-value: <0.00195% CI: [10.18, 32.29]Cochran-Mantel-Haenszel
Secondary
Percentage of Participants Achieving Complete Symptomatic Remission
Complete symptomatic remission was defined as an SF sub-score = 0 and RB sub-score = 0. The SF sub-score ranged from 0 to 3 (where 0 = normal number of stools and 3 = at least 5 stools more than normal) and RB sub-score ranged from 0 to 3 (where 0 = no blood and 3 = blood alone passes). Higher scores indicated more severe disease.
Time frame: Weeks 2, 4, 8 and 12
Population: Full Analysis Set Population with actual Baseline MMS 5 to 9. Only those participants with data available at the specified time points were analyzed.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Etrasimod 2 mg | Percentage of Participants Achieving Complete Symptomatic Remission | Week 2 | 4.5 Percentage of participants |
| Etrasimod 2 mg | Percentage of Participants Achieving Complete Symptomatic Remission | Week 4 | 11.7 Percentage of participants |
| Etrasimod 2 mg | Percentage of Participants Achieving Complete Symptomatic Remission | Week 8 | 14.0 Percentage of participants |
| Etrasimod 2 mg | Percentage of Participants Achieving Complete Symptomatic Remission | Week 12 | 18.0 Percentage of participants |
| Placebo | Percentage of Participants Achieving Complete Symptomatic Remission | Week 12 | 8.9 Percentage of participants |
| Placebo | Percentage of Participants Achieving Complete Symptomatic Remission | Week 2 | 1.8 Percentage of participants |
| Placebo | Percentage of Participants Achieving Complete Symptomatic Remission | Week 8 | 7.1 Percentage of participants |
| Placebo | Percentage of Participants Achieving Complete Symptomatic Remission | Week 4 | 3.6 Percentage of participants |
Comparison: Week 2p-value: =0.12895% CI: [-0.81, 6.48]Cochran-Mantel-Haenszel
Comparison: Week 4p-value: =0.00295% CI: [3.01, 13.64]Cochran-Mantel-Haenszel
Comparison: Week 8p-value: =0.03295% CI: [0.62, 13.49]Cochran-Mantel-Haenszel
Comparison: Week 12p-value: =0.01495% CI: [1.82, 16.54]Cochran-Mantel-Haenszel
Secondary
Percentage of Participants Achieving Endoscopic Improvement
Endoscopic improvement was defined as an ES \<= 1 (excluding friability). The ES ranged from 0 to 3 (where 0 = normal/inactive disease and 3 = severe disease); higher score indicated more severe disease.
Time frame: Week 12
Population: Full Analysis Set Population with actual Baseline MMS 5 to 9. Only those participants with data available at the specified time points were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Etrasimod 2 mg | Percentage of Participants Achieving Endoscopic Improvement | 30.6 Percentage of participants |
| Placebo | Percentage of Participants Achieving Endoscopic Improvement | 18.8 Percentage of participants |
Comparison: Week 12p-value: =0.00995% CI: [3, 21.23]Cochran-Mantel-Haenszel
Secondary
Percentage of Participants Achieving Endoscopic Normalization
Endoscopic normalization was defined as an ES = 0. The ES ranged from 0 to 3 (where 0= normal/inactive disease and 3= severe disease); higher score indicated more severe disease.
Time frame: Week 12
Population: Full Analysis Set Population with actual Baseline MMS 5 to 9. Only those participants with data available at the specified time points were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Etrasimod 2 mg | Percentage of Participants Achieving Endoscopic Normalization | 17.1 Percentage of participants |
| Placebo | Percentage of Participants Achieving Endoscopic Normalization | 8.0 Percentage of participants |
Comparison: Week 12p-value: =0.00995% CI: [2.27, 16.2]Cochran-Mantel-Haenszel
Secondary
Percentage of Participants Achieving Non-invasive Clinical Response
Non-invasive clinical response was defined as a \>= 30% decrease from Baseline in composite RB and SF sub-scores, and a \>= 1 point decrease from Baseline in RB sub-score or RB sub-score \<= 1. The SF subscore ranged from 0 to 3 (where 0 = normal number of stools and 3 = at least 5 stools more than normal) and RB sub-score ranged from 0 to 3 (where 0 = no blood and 3 = blood alone passes). The composite RB and SF score range was from 0 to 6, with higher scores indicating more severe disease.
Time frame: Weeks 2, 4, 8 and 12
Population: Full Analysis Set Population with actual Baseline MMS 5 to 9. Only those participants with data available at the specified time points were analyzed.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Etrasimod 2 mg | Percentage of Participants Achieving Non-invasive Clinical Response | Week 2 | 39.2 Percentage of participants |
| Etrasimod 2 mg | Percentage of Participants Achieving Non-invasive Clinical Response | Week 4 | 55.9 Percentage of participants |
| Etrasimod 2 mg | Percentage of Participants Achieving Non-invasive Clinical Response | Week 8 | 68.0 Percentage of participants |
| Etrasimod 2 mg | Percentage of Participants Achieving Non-invasive Clinical Response | Week 12 | 67.6 Percentage of participants |
| Placebo | Percentage of Participants Achieving Non-invasive Clinical Response | Week 12 | 50.0 Percentage of participants |
| Placebo | Percentage of Participants Achieving Non-invasive Clinical Response | Week 2 | 24.1 Percentage of participants |
| Placebo | Percentage of Participants Achieving Non-invasive Clinical Response | Week 8 | 45.5 Percentage of participants |
| Placebo | Percentage of Participants Achieving Non-invasive Clinical Response | Week 4 | 41.1 Percentage of participants |
Comparison: Week 2p-value: =0.00295% CI: [5.65, 25.46]Cochran-Mantel-Haenszel
Comparison: Week 4p-value: =0.00795% CI: [4.05, 25.91]Cochran-Mantel-Haenszel
Comparison: Week 8p-value: <0.00195% CI: [11.95, 33.25]Cochran-Mantel-Haenszel
Comparison: Week 12p-value: =0.00295% CI: [6.7, 28.47]Cochran-Mantel-Haenszel
Secondary
Percentage of Participants Achieving Symptomatic Remission
Symptomatic remission was defined as an SF sub-score = 0 (or = 1 with a \>= 1 point decrease from Baseline) and RB sub-score = 0. The SF sub-score ranged from 0 to 3 (where 0 = normal number of stools and 3 = at least 5 stools more than normal) and RB sub-score ranged from 0 to 3 (where 0 = no blood and 3 = blood alone passes). Higher scores indicated more severe disease.
Time frame: Week 12
Population: Full Analysis Set Population with actual Baseline MMS 5 to 9. Only those participants with data available at the specified time points were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Etrasimod 2 mg | Percentage of Participants Achieving Symptomatic Remission | 46.8 Percentage of participants |
| Placebo | Percentage of Participants Achieving Symptomatic Remission | 29.5 Percentage of participants |
Comparison: Week 12p-value: =0.00195% CI: [6.81, 28.15]Cochran-Mantel-Haenszel
Secondary
Percentage of Participants Achieving Symptomatic Remission at Weeks 2, 4 and 8
Symptomatic remission was defined as an SF sub-score = 0 (or = 1 with a \>= 1 point decrease from Baseline) and RB sub-score = 0. The SF sub-score ranged from 0 to 3 (where 0 = normal number of stools and 3 = at least 5 stools more than normal) and RB sub-score ranged from 0 to 3 (where 0 = no blood and 3 = blood alone passes). Higher scores indicated more severe disease.
Time frame: Weeks 2, 4 and 8
Population: Full Analysis Set Population with actual Baseline MMS 5 to 9. Only those participants with data available at the specified time points were analyzed.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Etrasimod 2 mg | Percentage of Participants Achieving Symptomatic Remission at Weeks 2, 4 and 8 | Week 2 | 16.2 Percentage of participants |
| Etrasimod 2 mg | Percentage of Participants Achieving Symptomatic Remission at Weeks 2, 4 and 8 | Week 4 | 27.5 Percentage of participants |
| Etrasimod 2 mg | Percentage of Participants Achieving Symptomatic Remission at Weeks 2, 4 and 8 | Week 8 | 38.7 Percentage of participants |
| Placebo | Percentage of Participants Achieving Symptomatic Remission at Weeks 2, 4 and 8 | Week 2 | 10.7 Percentage of participants |
| Placebo | Percentage of Participants Achieving Symptomatic Remission at Weeks 2, 4 and 8 | Week 4 | 16.1 Percentage of participants |
| Placebo | Percentage of Participants Achieving Symptomatic Remission at Weeks 2, 4 and 8 | Week 8 | 24.1 Percentage of participants |
Comparison: Week 2p-value: =0.11595% CI: [-1.42, 13.13]Cochran-Mantel-Haenszel
Comparison: Week 4p-value: =0.00795% CI: [3.19, 20.47]Cochran-Mantel-Haenszel
Comparison: Week 8p-value: =0.00395% CI: [4.98, 24.69]Cochran-Mantel-Haenszel
Secondary
Percentage of Participants Achieving Symptomatic Response
Symptomatic response was defined as a \>= 30% decrease from Baseline in composite RB and SF score. The SF sub-score ranged from 0 to 3 (where 0= normal number of stools and 3= at least 5 stools more than normal) and RB sub-score ranged from 0 to 3 (where 0= no blood and 3= blood alone passes). The composite RB and SF score range was from 0 to 6, with higher scores indicating more severe disease.
Time frame: Weeks 2, 4, 8 and 12
Population: Full Analysis Set Population with actual Baseline MMS 5 to 9. Only those participants with data available at the specified time points were analyzed.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Etrasimod 2 mg | Percentage of Participants Achieving Symptomatic Response | Week 2 | 39.6 Percentage of participants |
| Etrasimod 2 mg | Percentage of Participants Achieving Symptomatic Response | Week 4 | 56.3 Percentage of participants |
| Etrasimod 2 mg | Percentage of Participants Achieving Symptomatic Response | Week 8 | 68.5 Percentage of participants |
| Etrasimod 2 mg | Percentage of Participants Achieving Symptomatic Response | Week 12 | 68.5 Percentage of participants |
| Placebo | Percentage of Participants Achieving Symptomatic Response | Week 12 | 50.0 Percentage of participants |
| Placebo | Percentage of Participants Achieving Symptomatic Response | Week 2 | 24.1 Percentage of participants |
| Placebo | Percentage of Participants Achieving Symptomatic Response | Week 8 | 46.4 Percentage of participants |
| Placebo | Percentage of Participants Achieving Symptomatic Response | Week 4 | 41.1 Percentage of participants |
Comparison: Week 2p-value: =0.00295% CI: [6.07, 25.91]Cochran-Mantel-Haenszel
Comparison: Week 4p-value: =0.00695% CI: [4.54, 26.36]Cochran-Mantel-Haenszel
Comparison: Week 8p-value: <0.00195% CI: [11.43, 32.85]Cochran-Mantel-Haenszel
Comparison: Week 12p-value: <0.00195% CI: [7.65, 29.33]Cochran-Mantel-Haenszel
Secondary
Percentage of Participants With Mucosal Healing
Mucosal healing was defined as an ES \<= 1 (excluding friability) with histologic remission measured by a Geboes Index score less than \[\<\] 2.0). The ES ranged from 0 to 3 (where 0 = normal/inactive disease and 3 = severe disease). 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.
Time frame: Week 12
Population: Full Analysis Set Population with actual Baseline MMS 5 to 9. Only those participants with data available at the specified time points were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Etrasimod 2 mg | Percentage of Participants With Mucosal Healing | 16.2 Percentage of participants |
| Placebo | Percentage of Participants With Mucosal Healing | 8.9 Percentage of participants |
Comparison: Week 12p-value: =0.03695% CI: [0.5, 14.39]Cochran-Mantel-Haenszel