Ulcerative Colitis
Conditions
Brief summary
The purpose of this study is to determine whether etrasimod (APD334) is a safe and effective treatment for ulcerative colitis after 52 weeks of treatment.
Interventions
DRUGEtrasimod
DRUGPlacebo
Sponsors
Arena Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Participants who completed the APD334-003 (NCT02447302) study
Exclusion criteria
* Participants who did not complete the APD334-003 study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (SAEs) | Up to Week 48 (up to 30 days following discontinuation of the study drug) | A TEAE was defined as any adverse event (AE) that occurred after the first dose of study drug in the APD334-005 (NCT02536404) study, including any AE that started in Study APD334-003 (NCT02447302) and was ongoing, worsened, or ended in Study APD334-005. A SAE was any untoward medical occurrence that at any dose resulted in the following outcomes: death, was life-threatening, required/prolonged hospitalization, disability/incapacity, congenital anomaly/birth defect, and important medical events. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of Participants Who Achieved Clinical Response | Week 46 (extension study APD334-005) | A participant was considered to have achieved clinical response if he/she met the criteria of clinical remission or met criteria of clinical response. Clinical remission was defined as individual subscores of the 3-component Mayo Clinic score as follows: (1) an endoscopy score (using flexible proctosigmoidoscopy) of 0 or 1, (2) a rectal bleeding score of 0, and (3) a stool frequency score of 0 or 1 with a decrease of ≥ 1 point at Week 46 compared to APD334-003 baseline. Clinical response was defined as a decrease in 3-component Mayo Clinic score of ≥ 2 points and at least 30% with either a decrease of rectal bleeding of ≥ 1 or rectal bleeding score of 0 or 1 at Week 46 compared with baseline of study APD334-003. A score of 0 = normal and 1 = mild disease. |
| Proportion of Participants Who Achieved Clinical Response at Week 12 in APD334-003 and Maintained Clinical Response at Week 46 in APD334-005 | Week 12 (core study APD334-003) and Week 46 (extension study APD334-005) | A participant was considered to have achieved clinical response if he/she met the criteria of clinical remission or met criteria of clinical response. Clinical remission was defined as individual subscores of the 3-component Mayo Clinic score as follows: (1) an endoscopy score (using flexible proctosigmoidoscopy) of 0 or 1, (2) a rectal bleeding score of 0, and (3) a stool frequency score of 0 or 1 with a decrease of ≥ 1 point at Week 46 compared to APD334-003 baseline. Clinical response was defined as a decrease in 3-component Mayo Clinic score of ≥ 2 points and at least 30% with either a decrease of rectal bleeding of ≥ 1 or rectal bleeding score of 0 or 1 at Week 46 compared with baseline of study APD334-003. A score of 0 = normal and 1 = mild disease. |
| Proportion of Participants Who Achieved Clinical Remission | Week 46 (extension study APD334-005) | A participant was considered to have achieved clinical remission if he/she had: (1) an endoscopy score (using flexible proctosigmoidoscopy) of 0 or 1, (2) a rectal bleeding score of 0, and (3) a stool frequency score of 0 or 1 with a decrease of ≥ 1 point at Week 46 compared with baseline of study APD334-003. A score of 0 = normal and 1 = mild disease. |
| Proportion of Participants Who Achieved Clinical Remission at Week 12 in APD334-003 and Also Maintained Clinical Remission at Week 46 in APD334-005 | Week 12 (core study APD334-003) and Week 46 (extension study APD334-005) | A participant was considered to have achieved clinical remission if he/she had: (1) an endoscopy score (using flexible proctosigmoidoscopy) of 0 or 1, (2) a rectal bleeding score of 0, and (3) a stool frequency score of 0 or 1 with a decrease of ≥ 1 point at Week 46 compared with baseline of study APD334-003. A score of 0 = normal and 1 = mild disease. |
Countries
Australia, Austria, Belgium, Bulgaria, Canada, Czechia, France, Germany, Hungary, Israel, Latvia, Lithuania, New Zealand, Poland, Romania, Russia, South Korea, Spain, Ukraine, United Kingdom, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Etrasimod 2 mg Participants received etrasimod 2 milligrams (mg) tablet by mouth, once daily for 34 weeks in fasted state. | 112 |
| Placebo Participants received matching placebo tablet by mouth, once daily for 34 weeks in fasted state. | 6 |
| Total | 118 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 5 | 0 |
| Overall Study | Physician Decision | 10 | 0 |
| Overall Study | Sponsor decision | 1 | 0 |
| Overall Study | Withdrawal by Subject | 4 | 1 |
Baseline characteristics
| Characteristic | Etrasimod 2 mg | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 43.7 Years STANDARD_DEVIATION 13.25 | 50.2 Years STANDARD_DEVIATION 13.93 | 44.0 Years STANDARD_DEVIATION 13.3 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 4 Participants | 0 Participants | 4 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 108 Participants | 6 Participants | 114 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 | 4 Participants | 0 Participants | 4 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) White | 104 Participants | 6 Participants | 110 Participants |
| Sex: Female, Male Female | 44 Participants | 3 Participants | 47 Participants |
| Sex: Female, Male Male | 68 Participants | 3 Participants | 71 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 112 | 0 / 6 |
| other Total, other adverse events | 66 / 112 | 5 / 6 |
| serious Total, serious adverse events | 7 / 112 | 0 / 6 |
Outcome results
Primary
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (SAEs)
A TEAE was defined as any adverse event (AE) that occurred after the first dose of study drug in the APD334-005 (NCT02536404) study, including any AE that started in Study APD334-003 (NCT02447302) and was ongoing, worsened, or ended in Study APD334-005. A SAE was any untoward medical occurrence that at any dose resulted in the following outcomes: death, was life-threatening, required/prolonged hospitalization, disability/incapacity, congenital anomaly/birth defect, and important medical events.
Time frame: Up to Week 48 (up to 30 days following discontinuation of the study drug)
Population: Safety Population: All randomized participants who received study medication in the extension study APD334-005
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Etrasimod 2 mg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (SAEs) | Treatment-emergent SAEs | 7 Participants |
| Etrasimod 2 mg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (SAEs) | TEAEs | 67 Participants |
| Placebo | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (SAEs) | TEAEs | 5 Participants |
| Placebo | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (SAEs) | Treatment-emergent SAEs | 0 Participants |
Secondary
Proportion of Participants Who Achieved Clinical Remission
A participant was considered to have achieved clinical remission if he/she had: (1) an endoscopy score (using flexible proctosigmoidoscopy) of 0 or 1, (2) a rectal bleeding score of 0, and (3) a stool frequency score of 0 or 1 with a decrease of ≥ 1 point at Week 46 compared with baseline of study APD334-003. A score of 0 = normal and 1 = mild disease.
Time frame: Week 46 (extension study APD334-005)
Population: Completers Population Evaluable Cohort
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Etrasimod 2 mg | Proportion of Participants Who Achieved Clinical Remission | 39.3 Percentage of participants |
| Placebo | Proportion of Participants Who Achieved Clinical Remission | 25.0 Percentage of participants |
Secondary
Proportion of Participants Who Achieved Clinical Remission at Week 12 in APD334-003 and Also Maintained Clinical Remission at Week 46 in APD334-005
A participant was considered to have achieved clinical remission if he/she had: (1) an endoscopy score (using flexible proctosigmoidoscopy) of 0 or 1, (2) a rectal bleeding score of 0, and (3) a stool frequency score of 0 or 1 with a decrease of ≥ 1 point at Week 46 compared with baseline of study APD334-003. A score of 0 = normal and 1 = mild disease.
Time frame: Week 12 (core study APD334-003) and Week 46 (extension study APD334-005)
Population: Completers Population Evaluable Cohort
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Etrasimod 2 mg | Proportion of Participants Who Achieved Clinical Remission at Week 12 in APD334-003 and Also Maintained Clinical Remission at Week 46 in APD334-005 | 14.3 Percentage of participants |
| Placebo | Proportion of Participants Who Achieved Clinical Remission at Week 12 in APD334-003 and Also Maintained Clinical Remission at Week 46 in APD334-005 | 0 Percentage of participants |
Secondary
Proportion of Participants Who Achieved Clinical Response
A participant was considered to have achieved clinical response if he/she met the criteria of clinical remission or met criteria of clinical response. Clinical remission was defined as individual subscores of the 3-component Mayo Clinic score as follows: (1) an endoscopy score (using flexible proctosigmoidoscopy) of 0 or 1, (2) a rectal bleeding score of 0, and (3) a stool frequency score of 0 or 1 with a decrease of ≥ 1 point at Week 46 compared to APD334-003 baseline. Clinical response was defined as a decrease in 3-component Mayo Clinic score of ≥ 2 points and at least 30% with either a decrease of rectal bleeding of ≥ 1 or rectal bleeding score of 0 or 1 at Week 46 compared with baseline of study APD334-003. A score of 0 = normal and 1 = mild disease.
Time frame: Week 46 (extension study APD334-005)
Population: Completers Population Evaluable Cohort: All participants who received at least 1 dose of etrasimod or placebo and completed the extension study APD334-005
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Etrasimod 2 mg | Proportion of Participants Who Achieved Clinical Response | 78.6 Percentage of participants |
| Placebo | Proportion of Participants Who Achieved Clinical Response | 75.0 Percentage of participants |
Secondary
Proportion of Participants Who Achieved Clinical Response at Week 12 in APD334-003 and Maintained Clinical Response at Week 46 in APD334-005
A participant was considered to have achieved clinical response if he/she met the criteria of clinical remission or met criteria of clinical response. Clinical remission was defined as individual subscores of the 3-component Mayo Clinic score as follows: (1) an endoscopy score (using flexible proctosigmoidoscopy) of 0 or 1, (2) a rectal bleeding score of 0, and (3) a stool frequency score of 0 or 1 with a decrease of ≥ 1 point at Week 46 compared to APD334-003 baseline. Clinical response was defined as a decrease in 3-component Mayo Clinic score of ≥ 2 points and at least 30% with either a decrease of rectal bleeding of ≥ 1 or rectal bleeding score of 0 or 1 at Week 46 compared with baseline of study APD334-003. A score of 0 = normal and 1 = mild disease.
Time frame: Week 12 (core study APD334-003) and Week 46 (extension study APD334-005)
Population: Completers Population Evaluable Cohort
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Etrasimod 2 mg | Proportion of Participants Who Achieved Clinical Response at Week 12 in APD334-003 and Maintained Clinical Response at Week 46 in APD334-005 | 39.3 Percentage of participants |
| Placebo | Proportion of Participants Who Achieved Clinical Response at Week 12 in APD334-003 and Maintained Clinical Response at Week 46 in APD334-005 | 50.0 Percentage of participants |