Ulcerative Colitis
Conditions
Keywords
Ulcerative Colitis, Etrasimod, APD334, UC
Brief summary
The purpose of this study is to determine whether oral etrasimod is a safe and effective treatment in adult Japanese participants with moderately to severely active ulcerative colitis (UC). This study is an extension of study APD334-302 (NCT03996369). Participants will continue with the same blinded treatment assigned in Study APD334-302 for a total treatment duration of 52 weeks (12 weeks in Study APD334-302 plus 40 weeks in Study APD334-308).
Interventions
DRUGEtrasimod
Etrasimod 2 mg tablet by mouth, once daily up to 52 weeks
DRUGPlacebo
Etrasimod matching placebo tablet by mouth, once daily up to 52 weeks
Sponsors
Arena is a wholly owned subsidiary of Pfizer
Pfizer
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
16 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
Participants with moderately to severely active ulcerative colitis (UC) are eligible to enroll into this study if they fulfill all of the following: * Must have completed the Week 12 visit of Study APD334-302 * Ability to provide written informed consent or assent (parent or legal guardian must provide consent for a participant \< 20 years of age or as required per local regulations who has assented to participate in the study) and to be compliant with the schedule of protocol assessments. Enrollment of participants \< 20 years should be conducted only if acceptable according to local laws and regulations. * Both men and women subjects agree to use a highly effective method of birth control if the possibility of conception exists
Exclusion criteria
Participants who meet any of the following
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Achieving Clinical Remission at Week 40 of Study APD334-308 | Week 40 of APD334-308 | 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 Endoscopic Improvement at Week 40 of Study APD334-308 | Week 40 of APD334-308 | Endoscopic improvement was defined as an ES \<=1 (excluding friability) at Week 40 of APD334-308 compared with Week 12 of APD334-302. 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 Symptomatic Remission at Week 40 of Study APD334-308 | Week 40 of APD334-308 | 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 at Week 40 of Study APD334-308 | Week 40 of APD334-308 | 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, Who Had Not Been Receiving Corticosteroids for ≥ 12 Weeks, Achieving Clinical Remission at Week 40 of Study APD334-308 Among Participants Receiving Corticosteroids at C5041015 (APD334-302) Study Entry | Week 40 of APD334-308 | 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. |
| Percentage of Participants Achieving Sustained Clinical Remission | Week 40 of APD334-308 | 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. A subject with sustained clinical remission is defined as someone who achieved clinical remission at both Week 12 of APD334-302 and Week 40 of APD334-308. |
Countries
Japan
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo Comparator: Placebo Participants received etrasimod matching placebo 1 tablet by mouth, once daily up to 40 weeks in APD334-308 | 14 |
| Experimental: Etrasimod 2 mg Participants received etrasimod 2 mg tablet by mouth, once daily up to 40 weeks in APD334-308 | 28 |
| Total | 42 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Follow-up | Adverse Event | 1 | 0 |
| Follow-up | Disease worsening | 8 | 10 |
| Follow-up | Lack of Efficacy | 1 | 0 |
| Treatment | Disease worsening | 10 | 10 |
Baseline characteristics
| Characteristic | Experimental: Etrasimod 2 mg | Total | Placebo Comparator: Placebo |
|---|---|---|---|
| Age, Continuous | 43.9 Years STANDARD_DEVIATION 14.29 | 44.0 Years STANDARD_DEVIATION 14.06 | 44.2 Years STANDARD_DEVIATION 14.12 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 28 Participants | 42 Participants | 14 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 28 Participants | 42 Participants | 14 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 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 | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Female | 10 Participants | 17 Participants | 7 Participants |
| Sex: Female, Male Male | 18 Participants | 25 Participants | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 14 | 0 / 28 |
| other Total, other adverse events | 8 / 14 | 16 / 28 |
| serious Total, serious adverse events | 1 / 14 | 1 / 28 |
Outcome results
Primary
Percentage of Participants Achieving Clinical Remission at Week 40 of Study APD334-308
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 40 of APD334-308
Population: Full Analysis Set Population (All randomized participants who received at least 1 dose of study intervention). Only those participants with data available at the specified time points were analyzed. Overall number of participants analyzed signifies participants evaluable for this outcome measure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo Comparator: Placebo | Percentage of Participants Achieving Clinical Remission at Week 40 of Study APD334-308 | 7.1 Percentage of participants |
| Experimental: Etrasimod 2 mg | Percentage of Participants Achieving Clinical Remission at Week 40 of Study APD334-308 | 25.0 Percentage of participants |
95% CI: [-3.1, 38.82]
Secondary
Percentage of Participants Achieving Endoscopic Improvement at Week 40 of Study APD334-308
Endoscopic improvement was defined as an ES \<=1 (excluding friability) at Week 40 of APD334-308 compared with Week 12 of APD334-302. 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 40 of APD334-308
Population: Full Analysis Set Population. Only those participants with data available at the specified time points were analyzed. Overall number of participants analyzed signifies participants evaluable for this outcome measure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo Comparator: Placebo | Percentage of Participants Achieving Endoscopic Improvement at Week 40 of Study APD334-308 | 7.1 Percentage of participants |
| Experimental: Etrasimod 2 mg | Percentage of Participants Achieving Endoscopic Improvement at Week 40 of Study APD334-308 | 35.7 Percentage of participants |
95% CI: [6.28, 50.86]
Secondary
Percentage of Participants Achieving Sustained 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. A subject with sustained clinical remission is defined as someone who achieved clinical remission at both Week 12 of APD334-302 and Week 40 of APD334-308.
Time frame: Week 40 of APD334-308
Population: Full Analysis Set Population. Overall number of participants analyzed signifies participants evaluable for this outcome measure. Only those participants with data available at the specified time points were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo Comparator: Placebo | Percentage of Participants Achieving Sustained Clinical Remission | 0 Percentage of participants |
| Experimental: Etrasimod 2 mg | Percentage of Participants Achieving Sustained Clinical Remission | 7.1 Percentage of participants |
95% CI: [-2.4, 16.68]
Secondary
Percentage of Participants Achieving Symptomatic Remission at Week 40 of Study APD334-308
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 40 of APD334-308
Population: Full Analysis Set Population. Overall number of participants analyzed signifies participants evaluable for this outcome measure. Only those participants with data available at the specified time points were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo Comparator: Placebo | Percentage of Participants Achieving Symptomatic Remission at Week 40 of Study APD334-308 | 7.1 Percentage of participants |
| Experimental: Etrasimod 2 mg | Percentage of Participants Achieving Symptomatic Remission at Week 40 of Study APD334-308 | 39.3 Percentage of participants |
95% CI: [9.58, 54.71]
Secondary
Percentage of Participants, Who Had Not Been Receiving Corticosteroids for ≥ 12 Weeks, Achieving Clinical Remission at Week 40 of Study APD334-308 Among Participants Receiving Corticosteroids at C5041015 (APD334-302) Study Entry
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 40 of APD334-308
Population: Full Analysis Set Population. Overall number of participants analyzed signifies participants evaluable for this outcome measure. Only those participants with data available at the specified time points were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo Comparator: Placebo | Percentage of Participants, Who Had Not Been Receiving Corticosteroids for ≥ 12 Weeks, Achieving Clinical Remission at Week 40 of Study APD334-308 Among Participants Receiving Corticosteroids at C5041015 (APD334-302) Study Entry | 7.1 Percentage of participants |
| Experimental: Etrasimod 2 mg | Percentage of Participants, Who Had Not Been Receiving Corticosteroids for ≥ 12 Weeks, Achieving Clinical Remission at Week 40 of Study APD334-308 Among Participants Receiving Corticosteroids at C5041015 (APD334-302) Study Entry | 25.0 Percentage of participants |
95% CI: [-3.1, 38.82]
Secondary
Percentage of Participants With Mucosal Healing at Week 40 of Study APD334-308
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 40 of APD334-308
Population: Full Analysis Set Population. Overall number of participants analyzed signifies participants evaluable for this outcome measure. Only those participants with data available at the specified time points were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo Comparator: Placebo | Percentage of Participants With Mucosal Healing at Week 40 of Study APD334-308 | 7.1 Percentage of participants |
| Experimental: Etrasimod 2 mg | Percentage of Participants With Mucosal Healing at Week 40 of Study APD334-308 | 28.6 Percentage of participants |
95% CI: [-0.07, 42.92]