Ulcerative Colitis
Conditions
Brief summary
This study is designed to evaluate the efficacy, safety, and pharmacokinetics of UTTR1147A compared with vedolizumab and with placebo in the treatment of participants with moderate to severe UC. This study will consist of two parts, Part A and Part B. Part A will test the induction of clinical remission and Part B will test the durability of clinical remission.
Interventions
DRUGUTTR1147A
UTTR1147A will be administered intravenously (IV) at dose levels 1, 2, or 3 in Part A, and at the maintenance dose level in Part B, per the respective arm descriptions.
DRUGUTTR1147A Placebo
The matching placebo to UTTR1147A (UTTR1147A Placebo) will be administered IV.
DRUGVedolizumab
Vedolizumab will be administered IV, as specified in the prescribing information.
The matching placebo to vedolizumab (Vedolizumab Placebo) will be administered IV.
Sponsors
Genentech, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Diagnosis of UC * Confirmation of moderately to severely active UC, defined by the Mayo Clinic Score * Inadequate response, loss of response, or intolerance to prior immunosuppressant treatment (i.e., azathioprine, 6-mercaptopurine, methotrexate, or tumor necrosis factor \[TNF\] inhibitors \[maximum of 2 prior TNF inhibitors\]) and/or corticosteroid treatment * Use of highly effective contraception as defined by the protocol
Exclusion criteria
* History of psoriasis or psoriatic arthritis; any other inflammatory skin disorders requiring oral corticosteroids, immunosuppressants, or biological therapy within the previous year; or primary sclerosing cholangitis * History of cancer as defined by the protocol * Significant uncontrolled comorbidity, such as cardiac, pulmonary, renal, hepatic, endocrine, or gastrointestinal disorders (excluding UC) * Prior extensive colonic resection, subtotal or total colectomy, or proctocolectomy, or planned surgery for UC * Diagnosis of indeterminate colitis or granulomatous (Crohn's) colitis or toxic megacolon within 12 months prior to screening * Suspicion of ischemic colitis, radiation colitis, or microscopic colitis * Current fistula or history of fistula, pericolonic abscess and stricture (stenosis) of the colon * History or current evidence of unresectable colonic mucosal dysplasia or history of high-grade colonic mucosal dysplasia * Prior treatment with UTTR1147A * Prior treatment with vedolizumab, etrolizumab, natalizumab, efalizumab, or any other anti-integrin agents * Prior treatment with rituximab * Use of prohibited therapies, as defined by the protocol, prior to randomization * Congenital or acquired immune deficiency * Evidence or treatment of infections or history of infections, as defined by the protocol
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Clinical Remission at Week 8 | 8 weeks | Clinical remission is defined as modified Mayo Clinic Score (mMCS) \<= 2 with Mayo rectal bleeding subscore = 0, Mayo stool frequency subscore \<=1 and Centrally read endoscopic score \<= 1. Patients were classified as Non-Remitters if Week 8 assessments were missing or patient received permitted/ prohibited Rescue Therapy prior to assessment. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Serum Concentration (Cmax) of UTTR1147A | Days 1 - 29, Visit: Day 57 | — |
| Minimum Serum Concentration (Cmin) of UTTR1147A | Days 1 - 29, Visit: Day 57 | — |
| Percentage of Participants With Clinical Response at Week 8 | At Week 8 | Clinical response is defined as achieving clinical remission or as meeting both of the following criteria: A \>= 3-point decrease from baseline in modified Mayo Clinic Score (mMCS); A \>= 1-point decrease from baseline in rectal bleeding subscore or a rectal bleeding subscore of 0 or 1. Patients were classified as Non-Responders if assessments were missing or patient received permitted/prohibited Rescue Therapy prior to assessment. NOTE: An Outcome Measure Description has not been entered. |
| Percentage of Participants With Clinical Response at Week 30 | At Week 30 | Clinical response is defined as achieving clinical remission or as meeting both of the following criteria: A \>= 3-point decrease from baseline in modified Mayo Clinic Score (mMCS); A \>= 1-point decrease from baseline in rectal bleeding subscore or a rectal bleeding subscore of 0 or 1. Patients were classified as Non-Responders if assessments were missing or patient received permitted/prohibited Rescue Therapy prior to assessment. |
| Percentage of Participants With Endoscopic Healing at Week 8 | At Week 8 | Endoscopic healing is defined as a Mayo endoscopic subscore \<= 1. Patients were classified as Non-Responders if assessments were missing or patient received permitted/prohibited Rescue Therapy prior to assessment. |
| Percentage of Participants With Endoscopic Healing at Week 30 | At Week 30 | Endoscopic healing is defined as a Mayo endoscopic subscore \<= 1. Patients were classified as Non-Responders if assessments were missing or patient received permitted/prohibited Rescue Therapy prior to assessment. |
| Percentage of Participants With Endoscopic Remission at Week 8 | At Week 8 | Endoscopic remission is defined as a Mayo endoscopic subscore of 0. Patients were classified as Non-Responders if assessments were missing or patient received permitted/prohibited Rescue Therapy prior to assessment. |
| Percentage of Participants With Endoscopic Remission at Week 30 | At Week 30 | Endoscopic remission is defined as a Mayo endoscopic subscore of 0. Patients were classified as Non-Responders if assessments were missing or patient received permitted/prohibited Rescue Therapy prior to assessment. |
| Percentage of Participants With Sustained Remission | At Weeks 8 and 30 | Sustained remission is defined as clinical remission at both Week 8 and Week 30, where clinical remission is defined as modified Mayo Clinic Score (mMCS) \<= 2 with Mayo rectal bleeding subscore = 0, Mayo stool frequency subscore \<=1 and Centrally read endoscopic score \<= 1. Patients were classified as Non-Remitters at Week 8 or at Week 30 if assessments were missing or patient received permitted/prohibited Rescue Therapy prior to assessment |
| Change From Baseline in UC Bowel Movement Signs and Symptoms at Week 30, as Assessed by Ulcerative Colitis Patient-Reported Outcome Signs and Symptoms (UC-PRO/SS) Score | At Week 30 | The UC-PRO is being reported in three domains; two domains are key endpoints and reported as UC-PRO Signs and Symptoms (UC-PRO/SS). The bowel domain score ranges from 0-27, with a higher score indicating a worse disease state. |
| Change From Baseline in UC Abdominal Signs and Symptoms at Week 8, as Assessed by Ulcerative Colitis Patient-Reported Outcome Signs and Symptoms (UC-PRO/SS) Score | At Week 8 | The UC-PRO is being reported in three domains; two domains are key endpoints and reported as UC-PRO Signs and Symptoms (UC-PRO/SS). The functional (abdominal symptoms) domain score ranges from 0-12, with a higher score indicating a worse disease state. |
| Change From Baseline in UC Abdominal Signs and Symptoms at Week 30, as Assessed by Ulcerative Colitis Patient-Reported Outcome Signs and Symptoms (UC-PRO/SS) Score | At Week 30 | The UC-PRO is being reported in three domains; two domains are key endpoints and reported as UC-PRO Signs and Symptoms (UC-PRO/SS). The functional (abdominal symptoms) domain score ranges from 0-12, with a higher score indicating a worse disease state. |
| Change From Baseline in Patient-Reported Inflammatory Bowel Disease Questionnaire (IBDQ) Score at Week 8 | At Week 8 | The IBDQ score is a Total Score summed up from across all 32 questions on the questionnaire. The Total Score range is from 32 to 224 with higher scores representing a better quality of life. |
| Change From Baseline in Patient-Reported Inflammatory Bowel Disease Questionnaire (IBDQ) Score at Week 30 | At Week 30 | The IBDQ score is a Total Score summed up from across all 32 questions on the questionnaire. The Total Score range is from 32 to 224 with higher scores representing a better quality of life. |
| Percentage of Participants With Adverse Events | Up to 30 weeks | — |
| Percentage of Participants With Presence of Anti-Drug Antibodies (ADA) at Baseline and After Drug Administration | Baseline up to 30 | — |
| Change From Baseline in UC Bowel Movement Signs and Symptoms at Week 8, as Assessed by Ulcerative Colitis Patient-Reported Outcome Signs and Symptoms (UC-PRO/SS) Score | At Week 8 | The UC-PRO is being reported in three domains; two domains are key endpoints and reported as UC-PRO Signs and Symptoms (UC-PRO/SS). The bowel domain score ranges from 0-27, with a higher score indicating a worse disease state. |
Countries
Bulgaria, Georgia, Germany, Greece, Hungary, Ireland, Israel, Italy, Moldova, Poland, Russia, Serbia, Spain, Ukraine, United Kingdom, United States
Participant flow
Recruitment details
Patients were assigned in a 1:1:1:1:1:1:2:1 ratio to one of eight treatment arms. Following completion of the screening period and after all patient eligibility requirements were confirmed, patients were assigned a patient number and randomly assigned to a treatment arm through an interactive voice or Web-based response system (IxRS).
Participants by arm
| Arm | Count |
|---|---|
| Arm 1 Participants received UTTR1147A at a dose of 30 ug/kg | 43 |
| Arm 2 Participants received UTTR1147A at a dose of 60 ug/kg | 44 |
| Arm 3 Participants received UTTR1147A at a dose of 90 ug/kg | 43 |
| Arm 4: Vedolizumab Participants received Vedolizumab and UTTR1147A Placebo | 43 |
| Arm 5: Placebo Participants received UTTR1147A Placebo and Vedolizumab Placebo. | 22 |
| Total | 195 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 |
|---|---|---|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 0 | 1 | 1 | 2 | 1 | 1 | 0 |
| Overall Study | Death | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 |
| Overall Study | Lack of Efficacy | 11 | 11 | 10 | 11 | 14 | 12 | 14 | 13 |
| Overall Study | Miscalculation in mmcs | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 |
| Overall Study | Mistake in calculation | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 |
| Overall Study | Mistake in evaluation of disease status | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 |
| Overall Study | Physician Decision | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 |
| Overall Study | Protocol Violation | 1 | 1 | 0 | 1 | 1 | 0 | 2 | 0 |
| Overall Study | Rolled over in GA40209 due to worsening of disease | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 2 | 3 | 2 | 1 | 1 | 1 | 3 | 2 |
Baseline characteristics
| Characteristic | Arm 1 | Arm 2 | Arm 3 | Arm 4: Vedolizumab | Arm 5: Placebo | Total |
|---|---|---|---|---|---|---|
| Age, Continuous | 40.6 Years STANDARD_DEVIATION 13.2 | 39.4 Years STANDARD_DEVIATION 12.1 | 39.5 Years STANDARD_DEVIATION 12.3 | 43.4 Years STANDARD_DEVIATION 14.8 | 41.9 Years STANDARD_DEVIATION 14 | 40.8 Years STANDARD_DEVIATION 13.2 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 43 Participants | 44 Participants | 43 Participants | 43 Participants | 22 Participants | 195 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 43 Participants | 43 Participants | 43 Participants | 43 Participants | 22 Participants | 194 Participants |
| Sex: Female, Male Female | 15 Participants | 15 Participants | 11 Participants | 13 Participants | 6 Participants | 60 Participants |
| Sex: Female, Male Male | 28 Participants | 29 Participants | 32 Participants | 30 Participants | 16 Participants | 135 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk | EG010 affected / at risk | EG011 affected / at risk | EG012 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 43 | 0 / 44 | 1 / 43 | 0 / 43 | 0 / 22 | 0 / 10 | 0 / 7 | 0 / 10 | 0 / 9 | 0 / 6 | 0 / 8 | 0 / 22 | 0 / 7 |
| other Total, other adverse events | 12 / 43 | 11 / 44 | 15 / 43 | 6 / 43 | 4 / 22 | 2 / 10 | 2 / 7 | 6 / 10 | 3 / 9 | 2 / 6 | 3 / 8 | 2 / 22 | 2 / 7 |
| serious Total, serious adverse events | 1 / 43 | 1 / 44 | 5 / 43 | 0 / 43 | 0 / 22 | 0 / 10 | 0 / 7 | 0 / 10 | 0 / 9 | 0 / 6 | 0 / 8 | 0 / 22 | 0 / 7 |
Outcome results
Primary
Percentage of Participants With Clinical Remission at Week 8
Clinical remission is defined as modified Mayo Clinic Score (mMCS) \<= 2 with Mayo rectal bleeding subscore = 0, Mayo stool frequency subscore \<=1 and Centrally read endoscopic score \<= 1. Patients were classified as Non-Remitters if Week 8 assessments were missing or patient received permitted/ prohibited Rescue Therapy prior to assessment.
Time frame: 8 weeks
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Arm 1 | Percentage of Participants With Clinical Remission at Week 8 | Yes | 5 Participants |
| Arm 1 | Percentage of Participants With Clinical Remission at Week 8 | No | 38 Participants |
| Arm 2 | Percentage of Participants With Clinical Remission at Week 8 | Yes | 4 Participants |
| Arm 2 | Percentage of Participants With Clinical Remission at Week 8 | No | 40 Participants |
| Arm 3 | Percentage of Participants With Clinical Remission at Week 8 | Yes | 5 Participants |
| Arm 3 | Percentage of Participants With Clinical Remission at Week 8 | No | 38 Participants |
| Arm 4: Vedolizumab | Percentage of Participants With Clinical Remission at Week 8 | No | 32 Participants |
| Arm 4: Vedolizumab | Percentage of Participants With Clinical Remission at Week 8 | Yes | 11 Participants |
| Arm 5: Placebo | Percentage of Participants With Clinical Remission at Week 8 | Yes | 2 Participants |
| Arm 5: Placebo | Percentage of Participants With Clinical Remission at Week 8 | No | 20 Participants |
Secondary
Change From Baseline in Patient-Reported Inflammatory Bowel Disease Questionnaire (IBDQ) Score at Week 30
The IBDQ score is a Total Score summed up from across all 32 questions on the questionnaire. The Total Score range is from 32 to 224 with higher scores representing a better quality of life.
Time frame: At Week 30
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Arm 1 | Change From Baseline in Patient-Reported Inflammatory Bowel Disease Questionnaire (IBDQ) Score at Week 30 | 45.13 Points on scale | Standard Deviation 28.62 |
| Arm 2 | Change From Baseline in Patient-Reported Inflammatory Bowel Disease Questionnaire (IBDQ) Score at Week 30 | 35.50 Points on scale | Standard Deviation 27.45 |
| Arm 3 | Change From Baseline in Patient-Reported Inflammatory Bowel Disease Questionnaire (IBDQ) Score at Week 30 | 41.00 Points on scale | Standard Deviation 23.28 |
| Arm 4: Vedolizumab | Change From Baseline in Patient-Reported Inflammatory Bowel Disease Questionnaire (IBDQ) Score at Week 30 | 41.38 Points on scale | Standard Deviation 32 |
| Arm 5: Placebo | Change From Baseline in Patient-Reported Inflammatory Bowel Disease Questionnaire (IBDQ) Score at Week 30 | 72.33 Points on scale | Standard Deviation 19.35 |
| Arm 3b: UTTR1147A Dose Level 3 (Part A) + Placebo (Part B) | Change From Baseline in Patient-Reported Inflammatory Bowel Disease Questionnaire (IBDQ) Score at Week 30 | 55.43 Points on scale | Standard Deviation 56.89 |
| Arm 4: Vedolizumab | Change From Baseline in Patient-Reported Inflammatory Bowel Disease Questionnaire (IBDQ) Score at Week 30 | 61.95 Points on scale | Standard Deviation 34.75 |
| Arm 5: Placebo | Change From Baseline in Patient-Reported Inflammatory Bowel Disease Questionnaire (IBDQ) Score at Week 30 | 53.00 Points on scale | Standard Deviation 45.84 |
Secondary
Change From Baseline in Patient-Reported Inflammatory Bowel Disease Questionnaire (IBDQ) Score at Week 8
The IBDQ score is a Total Score summed up from across all 32 questions on the questionnaire. The Total Score range is from 32 to 224 with higher scores representing a better quality of life.
Time frame: At Week 8
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Arm 1 | Change From Baseline in Patient-Reported Inflammatory Bowel Disease Questionnaire (IBDQ) Score at Week 8 | 31.85 Points on scale | Standard Deviation 39.64 |
| Arm 2 | Change From Baseline in Patient-Reported Inflammatory Bowel Disease Questionnaire (IBDQ) Score at Week 8 | 31.95 Points on scale | Standard Deviation 30.66 |
| Arm 3 | Change From Baseline in Patient-Reported Inflammatory Bowel Disease Questionnaire (IBDQ) Score at Week 8 | 25.16 Points on scale | Standard Deviation 40 |
| Arm 4: Vedolizumab | Change From Baseline in Patient-Reported Inflammatory Bowel Disease Questionnaire (IBDQ) Score at Week 8 | 44.85 Points on scale | Standard Deviation 30.75 |
| Arm 5: Placebo | Change From Baseline in Patient-Reported Inflammatory Bowel Disease Questionnaire (IBDQ) Score at Week 8 | 27.05 Points on scale | Standard Deviation 41.35 |
Secondary
Change From Baseline in UC Abdominal Signs and Symptoms at Week 30, as Assessed by Ulcerative Colitis Patient-Reported Outcome Signs and Symptoms (UC-PRO/SS) Score
The UC-PRO is being reported in three domains; two domains are key endpoints and reported as UC-PRO Signs and Symptoms (UC-PRO/SS). The functional (abdominal symptoms) domain score ranges from 0-12, with a higher score indicating a worse disease state.
Time frame: At Week 30
Population: Number of analyzed participants reflects number of participants who submitted the EC-PRO questionnaire at Week 30.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Arm 1 | Change From Baseline in UC Abdominal Signs and Symptoms at Week 30, as Assessed by Ulcerative Colitis Patient-Reported Outcome Signs and Symptoms (UC-PRO/SS) Score | -1.76 Points on scale | Standard Deviation 3.21 |
| Arm 2 | Change From Baseline in UC Abdominal Signs and Symptoms at Week 30, as Assessed by Ulcerative Colitis Patient-Reported Outcome Signs and Symptoms (UC-PRO/SS) Score | -0.64 Points on scale | Standard Deviation 0.89 |
| Arm 3 | Change From Baseline in UC Abdominal Signs and Symptoms at Week 30, as Assessed by Ulcerative Colitis Patient-Reported Outcome Signs and Symptoms (UC-PRO/SS) Score | -1.98 Points on scale | Standard Deviation 2.06 |
| Arm 4: Vedolizumab | Change From Baseline in UC Abdominal Signs and Symptoms at Week 30, as Assessed by Ulcerative Colitis Patient-Reported Outcome Signs and Symptoms (UC-PRO/SS) Score | -1.05 Points on scale | Standard Deviation 0.53 |
| Arm 3b: UTTR1147A Dose Level 3 (Part A) + Placebo (Part B) | Change From Baseline in UC Abdominal Signs and Symptoms at Week 30, as Assessed by Ulcerative Colitis Patient-Reported Outcome Signs and Symptoms (UC-PRO/SS) Score | -4.05 Points on scale | Standard Deviation 1.96 |
| Arm 4: Vedolizumab | Change From Baseline in UC Abdominal Signs and Symptoms at Week 30, as Assessed by Ulcerative Colitis Patient-Reported Outcome Signs and Symptoms (UC-PRO/SS) Score | -1.82 Points on scale | Standard Deviation 1.9 |
| Arm 5: Placebo | Change From Baseline in UC Abdominal Signs and Symptoms at Week 30, as Assessed by Ulcerative Colitis Patient-Reported Outcome Signs and Symptoms (UC-PRO/SS) Score | -1.50 Points on scale | Standard Deviation 3.6 |
Secondary
Change From Baseline in UC Abdominal Signs and Symptoms at Week 8, as Assessed by Ulcerative Colitis Patient-Reported Outcome Signs and Symptoms (UC-PRO/SS) Score
The UC-PRO is being reported in three domains; two domains are key endpoints and reported as UC-PRO Signs and Symptoms (UC-PRO/SS). The functional (abdominal symptoms) domain score ranges from 0-12, with a higher score indicating a worse disease state.
Time frame: At Week 8
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Arm 1 | Change From Baseline in UC Abdominal Signs and Symptoms at Week 8, as Assessed by Ulcerative Colitis Patient-Reported Outcome Signs and Symptoms (UC-PRO/SS) Score | -0.96 Points on scale | Standard Deviation 1.81 |
| Arm 2 | Change From Baseline in UC Abdominal Signs and Symptoms at Week 8, as Assessed by Ulcerative Colitis Patient-Reported Outcome Signs and Symptoms (UC-PRO/SS) Score | -1.83 Points on scale | Standard Deviation 1.76 |
| Arm 3 | Change From Baseline in UC Abdominal Signs and Symptoms at Week 8, as Assessed by Ulcerative Colitis Patient-Reported Outcome Signs and Symptoms (UC-PRO/SS) Score | -1.82 Points on scale | Standard Deviation 2.44 |
| Arm 4: Vedolizumab | Change From Baseline in UC Abdominal Signs and Symptoms at Week 8, as Assessed by Ulcerative Colitis Patient-Reported Outcome Signs and Symptoms (UC-PRO/SS) Score | -1.69 Points on scale | Standard Deviation 2.25 |
| Arm 5: Placebo | Change From Baseline in UC Abdominal Signs and Symptoms at Week 8, as Assessed by Ulcerative Colitis Patient-Reported Outcome Signs and Symptoms (UC-PRO/SS) Score | -1.15 Points on scale | Standard Deviation 2.06 |
Secondary
Change From Baseline in UC Bowel Movement Signs and Symptoms at Week 30, as Assessed by Ulcerative Colitis Patient-Reported Outcome Signs and Symptoms (UC-PRO/SS) Score
The UC-PRO is being reported in three domains; two domains are key endpoints and reported as UC-PRO Signs and Symptoms (UC-PRO/SS). The bowel domain score ranges from 0-27, with a higher score indicating a worse disease state.
Time frame: At Week 30
Population: Number of analyzed participants reflects number of participants who submitted the EC-PRO questionnaire at Week 30.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Arm 1 | Change From Baseline in UC Bowel Movement Signs and Symptoms at Week 30, as Assessed by Ulcerative Colitis Patient-Reported Outcome Signs and Symptoms (UC-PRO/SS) Score | -5.66 Points on scale | Standard Deviation 7.92 |
| Arm 2 | Change From Baseline in UC Bowel Movement Signs and Symptoms at Week 30, as Assessed by Ulcerative Colitis Patient-Reported Outcome Signs and Symptoms (UC-PRO/SS) Score | -3.62 Points on scale | Standard Deviation 4.11 |
| Arm 3 | Change From Baseline in UC Bowel Movement Signs and Symptoms at Week 30, as Assessed by Ulcerative Colitis Patient-Reported Outcome Signs and Symptoms (UC-PRO/SS) Score | -9.63 Points on scale | Standard Deviation 5.15 |
| Arm 4: Vedolizumab | Change From Baseline in UC Bowel Movement Signs and Symptoms at Week 30, as Assessed by Ulcerative Colitis Patient-Reported Outcome Signs and Symptoms (UC-PRO/SS) Score | -6.63 Points on scale | Standard Deviation 3.6 |
| Arm 5: Placebo | Change From Baseline in UC Bowel Movement Signs and Symptoms at Week 30, as Assessed by Ulcerative Colitis Patient-Reported Outcome Signs and Symptoms (UC-PRO/SS) Score | -12.0 Points on scale | — |
| Arm 3b: UTTR1147A Dose Level 3 (Part A) + Placebo (Part B) | Change From Baseline in UC Bowel Movement Signs and Symptoms at Week 30, as Assessed by Ulcerative Colitis Patient-Reported Outcome Signs and Symptoms (UC-PRO/SS) Score | -5.44 Points on scale | Standard Deviation 9.47 |
| Arm 4: Vedolizumab | Change From Baseline in UC Bowel Movement Signs and Symptoms at Week 30, as Assessed by Ulcerative Colitis Patient-Reported Outcome Signs and Symptoms (UC-PRO/SS) Score | -8.32 Points on scale | Standard Deviation 3.69 |
| Arm 5: Placebo | Change From Baseline in UC Bowel Movement Signs and Symptoms at Week 30, as Assessed by Ulcerative Colitis Patient-Reported Outcome Signs and Symptoms (UC-PRO/SS) Score | -6.86 Points on scale | Standard Deviation 5.32 |
Secondary
Change From Baseline in UC Bowel Movement Signs and Symptoms at Week 8, as Assessed by Ulcerative Colitis Patient-Reported Outcome Signs and Symptoms (UC-PRO/SS) Score
The UC-PRO is being reported in three domains; two domains are key endpoints and reported as UC-PRO Signs and Symptoms (UC-PRO/SS). The bowel domain score ranges from 0-27, with a higher score indicating a worse disease state.
Time frame: At Week 8
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Arm 1 | Change From Baseline in UC Bowel Movement Signs and Symptoms at Week 8, as Assessed by Ulcerative Colitis Patient-Reported Outcome Signs and Symptoms (UC-PRO/SS) Score | -4.14 Points on scale | Standard Deviation 5.06 |
| Arm 2 | Change From Baseline in UC Bowel Movement Signs and Symptoms at Week 8, as Assessed by Ulcerative Colitis Patient-Reported Outcome Signs and Symptoms (UC-PRO/SS) Score | -6.39 Points on scale | Standard Deviation 4.68 |
| Arm 3 | Change From Baseline in UC Bowel Movement Signs and Symptoms at Week 8, as Assessed by Ulcerative Colitis Patient-Reported Outcome Signs and Symptoms (UC-PRO/SS) Score | -3.56 Points on scale | Standard Deviation 6.11 |
| Arm 4: Vedolizumab | Change From Baseline in UC Bowel Movement Signs and Symptoms at Week 8, as Assessed by Ulcerative Colitis Patient-Reported Outcome Signs and Symptoms (UC-PRO/SS) Score | -6.23 Points on scale | Standard Deviation 5.35 |
| Arm 5: Placebo | Change From Baseline in UC Bowel Movement Signs and Symptoms at Week 8, as Assessed by Ulcerative Colitis Patient-Reported Outcome Signs and Symptoms (UC-PRO/SS) Score | -4.95 Points on scale | Standard Deviation 5.7 |
Secondary
Maximum Serum Concentration (Cmax) of UTTR1147A
Time frame: Days 1 - 29, Visit: Day 57
Population: Due to low enrollment in Part B of the study, the PK data from pooled Arms 1-3~(1A + 1B; 2A + 2B; 3A + 3B) are summarized based on data up through Week 8 which is the primary efficacy assessment for Part A (Induction phase). A total of 130 patients who received at least one dose of efmarodocokin alfa and had measurable PK concentrations are included in the analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Arm 1 | Maximum Serum Concentration (Cmax) of UTTR1147A | Visit: Days 1 - 29 | 449 ng/mL | Standard Deviation 658 |
| Arm 1 | Maximum Serum Concentration (Cmax) of UTTR1147A | Visit: Day 57 | 426 ng/mL | Standard Deviation 344 |
| Arm 2 | Maximum Serum Concentration (Cmax) of UTTR1147A | Visit: Day 57 | 693 ng/mL | Standard Deviation 348 |
| Arm 2 | Maximum Serum Concentration (Cmax) of UTTR1147A | Visit: Days 1 - 29 | 590 ng/mL | Standard Deviation 265 |
| Arm 3 | Maximum Serum Concentration (Cmax) of UTTR1147A | Visit: Day 57 | 1340 ng/mL | Standard Deviation 883 |
| Arm 3 | Maximum Serum Concentration (Cmax) of UTTR1147A | Visit: Days 1 - 29 | 837 ng/mL | Standard Deviation 560 |
Secondary
Minimum Serum Concentration (Cmin) of UTTR1147A
Time frame: Days 1 - 29, Visit: Day 57
Population: Due to low enrollment in Part B of the study, the PK data from pooled Arms 1-3~(1A + 1B; 2A + 2B; 3A + 3B) are summarized based on data up through Week 8 which is the primary efficacy assessment for Part A (Induction phase). A total of 130 patients who received at least one dose of efmarodocokin alfa and had measurable PK concentrations are included in the analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Arm 1 | Minimum Serum Concentration (Cmin) of UTTR1147A | Days 1 - 29 | 12.6 ng/mL | Standard Deviation 9.55 |
| Arm 1 | Minimum Serum Concentration (Cmin) of UTTR1147A | Visit: Day 57 | 15.8 ng/mL | Standard Deviation 11.7 |
| Arm 2 | Minimum Serum Concentration (Cmin) of UTTR1147A | Days 1 - 29 | 28.3 ng/mL | Standard Deviation 17.1 |
| Arm 2 | Minimum Serum Concentration (Cmin) of UTTR1147A | Visit: Day 57 | 37.2 ng/mL | Standard Deviation 35.2 |
| Arm 3 | Minimum Serum Concentration (Cmin) of UTTR1147A | Days 1 - 29 | 40.6 ng/mL | Standard Deviation 27.7 |
| Arm 3 | Minimum Serum Concentration (Cmin) of UTTR1147A | Visit: Day 57 | 44.5 ng/mL | Standard Deviation 28.1 |
Secondary
Percentage of Participants With Adverse Events
Time frame: Up to 30 weeks
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Arm 1 | Percentage of Participants With Adverse Events | Non-Serious Adverse Events | 12 Participants |
| Arm 1 | Percentage of Participants With Adverse Events | Serious Adverse Events | 1 Participants |
| Arm 2 | Percentage of Participants With Adverse Events | Non-Serious Adverse Events | 11 Participants |
| Arm 2 | Percentage of Participants With Adverse Events | Serious Adverse Events | 1 Participants |
| Arm 3 | Percentage of Participants With Adverse Events | Non-Serious Adverse Events | 15 Participants |
| Arm 3 | Percentage of Participants With Adverse Events | Serious Adverse Events | 5 Participants |
| Arm 4: Vedolizumab | Percentage of Participants With Adverse Events | Serious Adverse Events | 0 Participants |
| Arm 4: Vedolizumab | Percentage of Participants With Adverse Events | Non-Serious Adverse Events | 6 Participants |
| Arm 5: Placebo | Percentage of Participants With Adverse Events | Non-Serious Adverse Events | 4 Participants |
| Arm 5: Placebo | Percentage of Participants With Adverse Events | Serious Adverse Events | 0 Participants |
Secondary
Percentage of Participants With Clinical Response at Week 30
Clinical response is defined as achieving clinical remission or as meeting both of the following criteria: A \>= 3-point decrease from baseline in modified Mayo Clinic Score (mMCS); A \>= 1-point decrease from baseline in rectal bleeding subscore or a rectal bleeding subscore of 0 or 1. Patients were classified as Non-Responders if assessments were missing or patient received permitted/prohibited Rescue Therapy prior to assessment.
Time frame: At Week 30
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm 1 | Percentage of Participants With Clinical Response at Week 30 | 9.09 Percentage of Participants |
| Arm 2 | Percentage of Participants With Clinical Response at Week 30 | 4.76 Percentage of Participants |
| Arm 3 | Percentage of Participants With Clinical Response at Week 30 | 4.76 Percentage of Participants |
| Arm 4: Vedolizumab | Percentage of Participants With Clinical Response at Week 30 | 13.04 Percentage of Participants |
| Arm 5: Placebo | Percentage of Participants With Clinical Response at Week 30 | 0.00 Percentage of Participants |
| Arm 3b: UTTR1147A Dose Level 3 (Part A) + Placebo (Part B) | Percentage of Participants With Clinical Response at Week 30 | 4.76 Percentage of Participants |
| Arm 4: Vedolizumab | Percentage of Participants With Clinical Response at Week 30 | 13.95 Percentage of Participants |
| Arm 5: Placebo | Percentage of Participants With Clinical Response at Week 30 | 0.00 Percentage of Participants |
Secondary
Percentage of Participants With Clinical Response at Week 8
Clinical response is defined as achieving clinical remission or as meeting both of the following criteria: A \>= 3-point decrease from baseline in modified Mayo Clinic Score (mMCS); A \>= 1-point decrease from baseline in rectal bleeding subscore or a rectal bleeding subscore of 0 or 1. Patients were classified as Non-Responders if assessments were missing or patient received permitted/prohibited Rescue Therapy prior to assessment. NOTE: An Outcome Measure Description has not been entered.
Time frame: At Week 8
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm 1 | Percentage of Participants With Clinical Response at Week 8 | 30.23 Percentage of Participants |
| Arm 2 | Percentage of Participants With Clinical Response at Week 8 | 36.36 Percentage of Participants |
| Arm 3 | Percentage of Participants With Clinical Response at Week 8 | 20.93 Percentage of Participants |
| Arm 4: Vedolizumab | Percentage of Participants With Clinical Response at Week 8 | 53.49 Percentage of Participants |
| Arm 5: Placebo | Percentage of Participants With Clinical Response at Week 8 | 36.36 Percentage of Participants |
Secondary
Percentage of Participants With Endoscopic Healing at Week 30
Endoscopic healing is defined as a Mayo endoscopic subscore \<= 1. Patients were classified as Non-Responders if assessments were missing or patient received permitted/prohibited Rescue Therapy prior to assessment.
Time frame: At Week 30
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm 1 | Percentage of Participants With Endoscopic Healing at Week 30 | 13.64 Percentage of Participants |
| Arm 2 | Percentage of Participants With Endoscopic Healing at Week 30 | 9.52 Percentage of Participants |
| Arm 3 | Percentage of Participants With Endoscopic Healing at Week 30 | 14.29 Percentage of Participants |
| Arm 4: Vedolizumab | Percentage of Participants With Endoscopic Healing at Week 30 | 13.04 Percentage of Participants |
| Arm 5: Placebo | Percentage of Participants With Endoscopic Healing at Week 30 | 4.55 Percentage of Participants |
| Arm 3b: UTTR1147A Dose Level 3 (Part A) + Placebo (Part B) | Percentage of Participants With Endoscopic Healing at Week 30 | 19.05 Percentage of Participants |
| Arm 4: Vedolizumab | Percentage of Participants With Endoscopic Healing at Week 30 | 30.23 Percentage of Participants |
| Arm 5: Placebo | Percentage of Participants With Endoscopic Healing at Week 30 | 9.09 Percentage of Participants |
Secondary
Percentage of Participants With Endoscopic Healing at Week 8
Endoscopic healing is defined as a Mayo endoscopic subscore \<= 1. Patients were classified as Non-Responders if assessments were missing or patient received permitted/prohibited Rescue Therapy prior to assessment.
Time frame: At Week 8
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm 1 | Percentage of Participants With Endoscopic Healing at Week 8 | 13.95 Percentage of Participants |
| Arm 2 | Percentage of Participants With Endoscopic Healing at Week 8 | 13.64 Percentage of Participants |
| Arm 3 | Percentage of Participants With Endoscopic Healing at Week 8 | 11.63 Percentage of Participants |
| Arm 4: Vedolizumab | Percentage of Participants With Endoscopic Healing at Week 8 | 32.56 Percentage of Participants |
| Arm 5: Placebo | Percentage of Participants With Endoscopic Healing at Week 8 | 13.64 Percentage of Participants |
Secondary
Percentage of Participants With Endoscopic Remission at Week 30
Endoscopic remission is defined as a Mayo endoscopic subscore of 0. Patients were classified as Non-Responders if assessments were missing or patient received permitted/prohibited Rescue Therapy prior to assessment.
Time frame: At Week 30
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm 1 | Percentage of Participants With Endoscopic Remission at Week 30 | 9.09 Percentage of Participants |
| Arm 2 | Percentage of Participants With Endoscopic Remission at Week 30 | 4.76 Percentage of Participants |
| Arm 3 | Percentage of Participants With Endoscopic Remission at Week 30 | 4.76 Percentage of Participants |
| Arm 4: Vedolizumab | Percentage of Participants With Endoscopic Remission at Week 30 | 13.04 Percentage of Participants |
| Arm 5: Placebo | Percentage of Participants With Endoscopic Remission at Week 30 | 0.00 Percentage of Participants |
| Arm 3b: UTTR1147A Dose Level 3 (Part A) + Placebo (Part B) | Percentage of Participants With Endoscopic Remission at Week 30 | 4.76 Percentage of Participants |
| Arm 4: Vedolizumab | Percentage of Participants With Endoscopic Remission at Week 30 | 13.95 Percentage of Participants |
| Arm 5: Placebo | Percentage of Participants With Endoscopic Remission at Week 30 | 0.00 Percentage of Participants |
Secondary
Percentage of Participants With Endoscopic Remission at Week 8
Endoscopic remission is defined as a Mayo endoscopic subscore of 0. Patients were classified as Non-Responders if assessments were missing or patient received permitted/prohibited Rescue Therapy prior to assessment.
Time frame: At Week 8
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm 1 | Percentage of Participants With Endoscopic Remission at Week 8 | 4.65 Percentage of Participants |
| Arm 2 | Percentage of Participants With Endoscopic Remission at Week 8 | 0.00 Percentage of Participants |
| Arm 3 | Percentage of Participants With Endoscopic Remission at Week 8 | 4.65 Percentage of Participants |
| Arm 4: Vedolizumab | Percentage of Participants With Endoscopic Remission at Week 8 | 11.63 Percentage of Participants |
| Arm 5: Placebo | Percentage of Participants With Endoscopic Remission at Week 8 | 0.00 Percentage of Participants |
Secondary
Percentage of Participants With Presence of Anti-Drug Antibodies (ADA) at Baseline and After Drug Administration
Time frame: Baseline up to 30
Population: Participants in placebo groups were not analyzed for post-baseline Anti-Drug Antibodies (ADA)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Arm 1 | Percentage of Participants With Presence of Anti-Drug Antibodies (ADA) at Baseline and After Drug Administration | 0 Participants |
| Arm 2 | Percentage of Participants With Presence of Anti-Drug Antibodies (ADA) at Baseline and After Drug Administration | 2 Participants |
| Arm 3 | Percentage of Participants With Presence of Anti-Drug Antibodies (ADA) at Baseline and After Drug Administration | 1 Participants |
| Arm 4: Vedolizumab | Percentage of Participants With Presence of Anti-Drug Antibodies (ADA) at Baseline and After Drug Administration | 1 Participants |
| Arm 5: Placebo | Percentage of Participants With Presence of Anti-Drug Antibodies (ADA) at Baseline and After Drug Administration | 2 Participants |
| Arm 3b: UTTR1147A Dose Level 3 (Part A) + Placebo (Part B) | Percentage of Participants With Presence of Anti-Drug Antibodies (ADA) at Baseline and After Drug Administration | 1 Participants |
Secondary
Percentage of Participants With Sustained Remission
Sustained remission is defined as clinical remission at both Week 8 and Week 30, where clinical remission is defined as modified Mayo Clinic Score (mMCS) \<= 2 with Mayo rectal bleeding subscore = 0, Mayo stool frequency subscore \<=1 and Centrally read endoscopic score \<= 1. Patients were classified as Non-Remitters at Week 8 or at Week 30 if assessments were missing or patient received permitted/prohibited Rescue Therapy prior to assessment
Time frame: At Weeks 8 and 30
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm 1 | Percentage of Participants With Sustained Remission | 4.55 Percentage of Participants |
| Arm 2 | Percentage of Participants With Sustained Remission | 0.00 Percentage of Participants |
| Arm 3 | Percentage of Participants With Sustained Remission | 0.00 Percentage of Participants |
| Arm 4: Vedolizumab | Percentage of Participants With Sustained Remission | 8.70 Percentage of Participants |
| Arm 5: Placebo | Percentage of Participants With Sustained Remission | 4.55 Percentage of Participants |
| Arm 3b: UTTR1147A Dose Level 3 (Part A) + Placebo (Part B) | Percentage of Participants With Sustained Remission | 4.76 Percentage of Participants |
| Arm 4: Vedolizumab | Percentage of Participants With Sustained Remission | 20.93 Percentage of Participants |
| Arm 5: Placebo | Percentage of Participants With Sustained Remission | 9.09 Percentage of Participants |