Ulcerative Colitis (UC)
Conditions
Keywords
Upadacitinib, ABT-494, Ulcerative Colitis
Brief summary
The objective of this study is to evaluate the efficacy and safety of upadacitinib compared to placebo in inducing clinical remission (per Adapted Mayo score) in participants with moderately to severely active ulcerative colitis (UC).
Detailed description
Study M14-675 consists of 2 parts, Part 1 and Part 2. Part 1 is a randomized, double-blind, placebo-controlled 8-week induction period. Part 2 is an open-label, 8-week extended treatment period for participants who did not achieve clinical response at Week 8 in Part 1. Eligible participants are randomized in a 2:1 ratio to one of the two treatment groups (upadacitinib 45 mg or matching placebo) for 8 weeks. The randomization is stratified by biologic inadequate responder (bio-IR) status (bio-IR vs non-bio-IR), corticosteroid use (yes or no), and Adapted Mayo score (≤ 7 or \> 7) at Baseline. Within bio-IR, the randomization is further stratified by number of prior biologic treatments (≤ 1 or \> 1). Within non-bio-IR, the randomization is further stratified by previous biologic use (yes or no). Participants who achieve clinical response defined by Adapted Mayo Score at Week 8 or Week 16 and do not meet any study discontinuation criteria are eligible to enroll into Study M14-234 Substudy 3 (NCT02819635; 52-week maintenance study) or Study M14-533 Cohort 1 (NCT03006068; long-term follow-up study).
Interventions
DRUGPlacebo
Tablet for oral administration
DRUGUpadacitinib
Tablet for oral administration
Sponsors
AbbVie
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
16 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
\- Male or female participants ≥ 16 and ≤ 75 years of age at Baseline Note: Adolescent participants at the age of 16 or 17 years old will be eligible to participate if approved by the country or regulatory/health authorities. Note: Adolescent participants at the age of 16 or 17 years old must weigh ≥ 40 kilograms and meet the definition of Tanner Stage 5 at the Screening Visit. * Diagnosis of Ulcerative Colitis (UC) for 90 days or greater prior to Baseline, confirmed by colonoscopy during the Screening Period, with exclusion of current infection, colonic dysplasia and/or malignancy. Appropriate documentation of biopsy results consistent with the diagnosis of UC, in the assessment of the Investigator, must be available. * Active UC with an Adapted Mayo score of 5 to 9 points and endoscopic subscore of 2 to 3. * Demonstrated an inadequate response, loss of response, or intolerance to at lease one of the following treatments including, oral aminosalicylates, corticosteroids, immunosuppressants, and/or biologic therapies. Note: Participants who have had inadequate response, loss of response to conventional therapy but have not failed biologic therapy (Non-bio-IR) and have received a prior biologic for up to 1 year may be enrolled, however they must have discontinued the biologic for reasons other than inadequate response or intolerance (e.g., change of insurance, well controlled disease), and must meet criteria for inadequate response, loss of response, or intolerance as defined above. * Female Participants of childbearing potential must have a negative serum pregnancy test at the Screening Visit and a negative urine pregnancy test at the Baseline Visit. * If female, participant must meet the contraception recommendation criteria.
Exclusion criteria
* Participant with current diagnosis of Crohn's disease (CD) or diagnosis of indeterminate colitis (IC). * Current diagnosis of fulminant colitis and/or toxic megacolon. * Participant with disease limited to the rectum (ulcerative proctitis) during the Screening endoscopy. * Received cyclosporine, tacrolimus, mycophenolate mofetil, or thalidomide within 30 days prior to Baseline. * Participant who received azathioprine or 6-mercaptopurine (6-MP) within 10 days of Baseline. * Received intravenous corticosteroids within 14 days prior to Screening or during the Screening Period. * Participant with previous exposure to Janus Activated Kinase (JAK) inhibitor (e.g., tofacitinib, baricitinib, filgotinib, upadacitinib). * Screening laboratory and other analyses show any prespecified abnormal hematologic results.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Who Achieved Clinical Remission Per Adapted Mayo Score at Week 8 | Week 8 | The Adapted Mayo Score is a composite score of UC disease activity based on the following 3 subscores: 1. Stool frequency subscore (SFS), scored from 0 (normal number of stools) to 3 (5 or more stools more than normal). 2. Rectal bleeding subscore (RBS), scored from 0 (no blood seen) to 3 (blood alone passed). 3. Endoscopic subscore, scored from 0 (normal or inactive disease) to 3 (severe disease, spontaneous bleeding, ulceration). The overall Adapted Mayo score ranges from 0 to 9 where higher scores represent more severe disease. Clinical remission is defined as an Adapted Mayo score ≤ 2, with SFS ≤ 1 and not higher than Baseline, RBS of 0, and endoscopic subscore ≤ 1. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Endoscopic Remission at Week 8 | Week 8 | Endoscopic remission is defined as an endoscopic subscore of 0. Endoscopies were assessed by a blinded central reader and scored according to the following scale: 0 = Normal or inactive disease; 1 = Mild disease (erythema, decreased vascular pattern); 2 = Moderate disease (marked erythema, lack of vascular pattern, any friability, erosions); 3 = Severe disease (spontaneous bleeding, ulceration). |
| Percentage of Participants Who Achieved Clinical Response Per Adapted Mayo Score at Week 8 | Week 8 | The Adapted Mayo Score is a composite score of UC disease activity based on the following 3 subscores: 1. Stool frequency subscore (SFS), scored from 0 (normal number of stools) to 3 (5 or more stools more than normal). 2. Rectal bleeding subscore (RBS), scored from 0 (no blood seen) to 3 (blood alone passed). 3. Endoscopic subscore, scored from 0 (normal or inactive disease) to 3 (severe disease with spontaneous bleeding, ulceration). The overall Adapted Mayo score ranges from 0 to 9 with higher scores representing more severe disease. Clinical response per the Adapted Mayo Score is defined as a decrease in Adapted Mayo score ≥ 2 points and ≥ 30% from Baseline, plus a decrease in RBS ≥ 1 or an absolute RBS ≤ 1. |
| Percentage of Participants Who Achieved Clinical Response Per Partial Adapted Mayo Score at Week 2 | Week 2 | The Partial Adapted Mayo Score is a composite score of UC disease activity based on the following 2 subscores: 1. Stool frequency subscore (SFS), scored from 0 (normal number of stools) to 3 (5 or more stools more than normal). 2. Rectal bleeding subscore (RBS), scored from 0 (no blood seen) to 3 (blood alone passed). The overall Partial Adapted Mayo score ranges from 0 to 6 with higher scores representing more severe disease. Clinical response per Partial Adapted Mayo Score is defined as a decrease in Partial Adapted Mayo score ≥ 1 point and ≥ 30% from Baseline, plus a decrease in RBS ≥ 1 or an absolute RBS ≤ 1. |
| Percentage Of Participants Who Achieved Histologic-Endoscopic Mucosal Improvement at Week 8 | Week 8 | Histologic endoscopic mucosal improvement is defined as an endoscopic subscore of 0 or 1 and a Geboes score ≤ 3.1. The endoscopic subscore ranges from 0 (normal or inactive disease) to 3 (severe disease with spontaneous bleeding, ulceration). The Geboes histologic index includes seven histological features (architectural change, chronic inflammatory infiltrate, lamina propria neutrophils and eosinophils, neutrophils in epithelium, crypt destruction and erosion or ulcers). The Geboes score has 6 grades, each with 3-5 subgrades: Grade 0, structural change only; Grade 1, chronic inflammation; Grade 2, lamina propria neutrophils and eosinophils; Grade 3, neutrophils in epithelium; Grade 4, crypt destruction; and Grade 5, erosions or ulceration. |
| Percentage of Participants Who Reported No Bowel Urgency at Week 8 | Week 8 | Bowel urgency was assessed by participants in a subject diary completed once a day. |
| Percentage of Participants With Endoscopic Improvement at Week 8 | Week 8 | Endoscopic improvement is defined as an endoscopic subscore of 0 or 1. Endoscopies were assessed by a blinded central reader and scored according to the following scale: 0 = Normal or inactive disease; 1 = Mild disease (erythema, decreased vascular pattern); 2 = Moderate disease (marked erythema, lack of vascular pattern, any friability, erosions); 3 = Severe disease (spontaneous bleeding, ulceration). |
| Percentage of Participants Who Achieved Histologic Improvement at Week 8 | Week 8 | Histologic improvement is defined as a decrease from Baseline in Geboes score. The Geboes histologic index includes seven histological features (architectural change, chronic inflammatory infiltrate, lamina propria neutrophils and eosinophils, neutrophils in epithelium, crypt destruction and erosion or ulcers). The Geboes score has 6 grades, each with 3-5 subgrades: Grade 0, structural change only; Grade 1, chronic inflammation; Grade 2, lamina propria neutrophils and eosinophils; Grade 3, neutrophils in epithelium; Grade 4, crypt destruction; and Grade 5, erosions or ulceration. |
| Change From Baseline in Inflammatory Bowel Disease Questionnaire (IBDQ) Total Score at Week 8 | Baseline (Week 0) to Week 8 | The Inflammatory Bowel Disease Questionnaire (IBDQ) is used to assess health-related quality of life (HRQoL) in patients with ulcerative colitis. It consists of 32 questions evaluating bowel and systemic symptoms, as well as emotional and social functions. Each question is answered on a scale from 1 (worst) to 7 (best). The total score ranges from 32 to 224 with higher scores indicating better health-related quality of life. A positive change from Baseline indicates improvement. |
| Percentage of Participants Who Achieved Mucosal Healing at Week 8 | Week 8 | Mucosal healing is defined as an endoscopic score of 0 and Geboes score \< 2.0. The endoscopic subscore ranges from 0 (normal or inactive disease) to 3 (severe disease with spontaneous bleeding, ulceration). The Geboes histologic index includes seven histological features (architectural change, chronic inflammatory infiltrate, lamina propria neutrophils and eosinophils, neutrophils in epithelium, crypt destruction and erosion or ulcers). The Geboes score has 6 grades, each with 3-5 subgrades: Grade 0, structural change only; Grade 1, chronic inflammation; Grade 2, lamina propria neutrophils and eosinophils; Grade 3, neutrophils in epithelium; Grade 4, crypt destruction; and Grade 5, erosions or ulceration. |
| Change From Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Score at Week 8 | Baseline (Week 0) to Week 8 | The FACIT fatigue questionnaire was developed to assess fatigue associated with anemia. It consists of 13 fatigue-related questions. Each question is answered on a 5-point Likert scale: 0 (not at all); 1 (a little bit); 2 (somewhat); 3 (quite a bit); and 4 (very much). The total score ranges from 0 to 52, where higher scores represent less fatigue, and a positive change from Baseline indicates improvement. |
| Percentage of Participants Who Reported No Abdominal Pain at Week 8 | Week 8 | Abdominal pain was assessed by participants in a subject diary completed once a day. |
Countries
Argentina, Australia, Austria, Belgium, Bosnia and Herzegovina, Brazil, Canada, Chile, China, Colombia, Croatia, Czechia, Estonia, Finland, France, Germany, Greece, Hungary, Ireland, Israel, Italy, Japan, Latvia, Lithuania, Malaysia, Mexico, Netherlands, Norway, Poland, Portugal, Puerto Rico, Russia, Serbia, Singapore, Slovakia, South Africa, South Korea, Spain, Switzerland, Taiwan, Turkey (Türkiye), Ukraine, United Kingdom, United States
Participant flow
Recruitment details
This study included a Screening Period of up to 5 weeks, Part 1, and Part 2. Part 1 was a randomized, double-blind, placebo-controlled 8-week induction period. Part 2 was an open-label, 8-week extended treatment period for participants who were clinical non-responders in Part 1. Participants with moderately to severely active ulcerative colitis (UC) were randomized at 204 sites in 41 countries.
Pre-assignment details
In Part 1 participants were randomized in a 2:1 ratio to upadacitinib or placebo. Randomization was stratified by biologic-inadequate responder (Bio-IR) status (bio-IR vs non-bio-IR), corticosteroid use (yes or no), and Adapted Mayo score (≤ 7 or \> 7) at Baseline. Within bio-IR, randomization was further stratified by number of prior biologic treatments (≤ 1 or \> 1). Within non-bio-IR, randomization was further stratified by previous biologic use (yes or no).
Participants by arm
| Arm | Count |
|---|---|
| Upadacitinib 45 mg Participants received 45 mg upadacitinib once daily (QD) for 8 weeks. | 345 |
| Placebo Participants received placebo matching to upadacitinib once daily for 8 weeks. | 177 |
| Total | 522 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Part 1: Placebo-controlled Period | Adverse Event | 5 | 6 | 0 | 0 |
| Part 1: Placebo-controlled Period | Other | 0 | 3 | 0 | 0 |
| Part 1: Placebo-controlled Period | Withdrawal by Subject | 6 | 4 | 0 | 0 |
| Part 2: Open-label Extension | Adverse Event | 0 | 0 | 1 | 1 |
| Part 2: Open-label Extension | Other | 0 | 0 | 1 | 2 |
| Part 2: Open-label Extension | Withdrawal by Subject | 0 | 0 | 1 | 2 |
Baseline characteristics
| Characteristic | Upadacitinib 45 mg | Placebo | Total |
|---|---|---|---|
| Adapted Mayo Score | 7.00 units on a scale STANDARD_DEVIATION 1.216 | 7.05 units on a scale STANDARD_DEVIATION 1.236 | 7.02 units on a scale STANDARD_DEVIATION 1.222 |
| Adapted Mayo Score Strata ≤ 7 | 205 Participants | 104 Participants | 309 Participants |
| Adapted Mayo Score Strata > 7 | 138 Participants | 73 Participants | 211 Participants |
| Adapted Mayo Score Strata Missing | 2 Participants | 0 Participants | 2 Participants |
| Age, Continuous | 42.2 years STANDARD_DEVIATION 14.73 | 42.2 years STANDARD_DEVIATION 14.44 | 42.2 years STANDARD_DEVIATION 14.62 |
| Age, Customized < 18 years | 6 Participants | 3 Participants | 9 Participants |
| Age, Customized ≥ 18 years to < 40 years | 160 Participants | 81 Participants | 241 Participants |
| Age, Customized ≥ 40 years to < 65 years | 146 Participants | 79 Participants | 225 Participants |
| Age, Customized ≥ 65 years | 33 Participants | 14 Participants | 47 Participants |
| Average Endoscopy Subscore | 2.7 units on a scale STANDARD_DEVIATION 0.47 | 2.7 units on a scale STANDARD_DEVIATION 0.46 | 2.7 units on a scale STANDARD_DEVIATION 0.46 |
| Average Rectal Bleeding Subscore | 1.77 units on a scale STANDARD_DEVIATION 0.966 | 1.71 units on a scale STANDARD_DEVIATION 1.049 | 1.75 units on a scale STANDARD_DEVIATION 0.995 |
| Average Stool Frequency Subscore | 2.55 units on a scale STANDARD_DEVIATION 0.626 | 2.64 units on a scale STANDARD_DEVIATION 0.551 | 2.58 units on a scale STANDARD_DEVIATION 0.603 |
| Baseline Corticosteroid Use No | 222 Participants | 102 Participants | 324 Participants |
| Baseline Corticosteroid Use Yes | 123 Participants | 75 Participants | 198 Participants |
| Bio-IR: Number of Prior Biologic Treatments ≤ 1 prior biologic | 58 Participants | 33 Participants | 91 Participants |
| Bio-IR: Number of Prior Biologic Treatments > 1 prior biologic | 117 Participants | 58 Participants | 175 Participants |
| Biologic-inadequate Responder (Bio-IR) Status Bio-IR | 175 Participants | 91 Participants | 266 Participants |
| Biologic-inadequate Responder (Bio-IR) Status Non-Bio-IR | 170 Participants | 86 Participants | 256 Participants |
| Disease Duration | 7.273 years STANDARD_DEVIATION 6.4459 | 7.584 years STANDARD_DEVIATION 7.6701 | 7.379 years STANDARD_DEVIATION 6.8804 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 26 Participants | 16 Participants | 42 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 319 Participants | 161 Participants | 480 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Non-Bio-IR: Prior Exposure to Biologic Therapy No | 169 Participants | 81 Participants | 250 Participants |
| Non-Bio-IR: Prior Exposure to Biologic Therapy Yes | 1 Participants | 5 Participants | 6 Participants |
| Race/Ethnicity, Customized American Indian or Alaska Native | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Asian | 94 Participants | 41 Participants | 135 Participants |
| Race/Ethnicity, Customized Black or African American | 11 Participants | 6 Participants | 17 Participants |
| Race/Ethnicity, Customized Multiple | 2 Participants | 1 Participants | 3 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized White | 238 Participants | 127 Participants | 365 Participants |
| Sex: Female, Male Female | 129 Participants | 67 Participants | 196 Participants |
| Sex: Female, Male Male | 216 Participants | 110 Participants | 326 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 344 | 0 / 177 | 0 / 68 | 0 / 116 |
| other Total, other adverse events | 32 / 344 | 11 / 177 | 10 / 68 | 17 / 116 |
| serious Total, serious adverse events | 11 / 344 | 8 / 177 | 1 / 68 | 4 / 116 |
Outcome results
Primary
Percentage of Participants Who Achieved Clinical Remission Per Adapted Mayo Score at Week 8
The Adapted Mayo Score is a composite score of UC disease activity based on the following 3 subscores: 1. Stool frequency subscore (SFS), scored from 0 (normal number of stools) to 3 (5 or more stools more than normal). 2. Rectal bleeding subscore (RBS), scored from 0 (no blood seen) to 3 (blood alone passed). 3. Endoscopic subscore, scored from 0 (normal or inactive disease) to 3 (severe disease, spontaneous bleeding, ulceration). The overall Adapted Mayo score ranges from 0 to 9 where higher scores represent more severe disease. Clinical remission is defined as an Adapted Mayo score ≤ 2, with SFS ≤ 1 and not higher than Baseline, RBS of 0, and endoscopic subscore ≤ 1.
Time frame: Week 8
Population: The Part 1 intent-to-treat population (ITT1) includes randomized participants who received at least 1 dose of study drug in Part 1. The ITT1 population excludes 6 participants from 1 site with non-compliance. Non-responder imputation incorporating multiple imputation to handle missing data due to Coronavirus Disease - 2019 (COVID-19) was used.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Upadacitinib 45 mg | Percentage of Participants Who Achieved Clinical Remission Per Adapted Mayo Score at Week 8 | 33.5 percentage of participants |
| Placebo | Percentage of Participants Who Achieved Clinical Remission Per Adapted Mayo Score at Week 8 | 4.1 percentage of participants |
p-value: <0.00195% CI: [23.2, 34.7]Cochran-Mantel-Haenszel
Secondary
Change From Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Score at Week 8
The FACIT fatigue questionnaire was developed to assess fatigue associated with anemia. It consists of 13 fatigue-related questions. Each question is answered on a 5-point Likert scale: 0 (not at all); 1 (a little bit); 2 (somewhat); 3 (quite a bit); and 4 (very much). The total score ranges from 0 to 52, where higher scores represent less fatigue, and a positive change from Baseline indicates improvement.
Time frame: Baseline (Week 0) to Week 8
Population: ITT1 population with available data; a mixed effect model repeat measurement (MMRM) analysis with data from observed cases up to Week 8 was used except for measurements at or after the occurrence of UC-related corticosteroids intercurrent event were excluded.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Upadacitinib 45 mg | Change From Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Score at Week 8 | 9.4 units on a scale |
| Placebo | Change From Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Score at Week 8 | 3.5 units on a scale |
p-value: <0.00195% CI: [4.19, 7.73]Mixed-effect model repeated measurement
Secondary
Change From Baseline in Inflammatory Bowel Disease Questionnaire (IBDQ) Total Score at Week 8
The Inflammatory Bowel Disease Questionnaire (IBDQ) is used to assess health-related quality of life (HRQoL) in patients with ulcerative colitis. It consists of 32 questions evaluating bowel and systemic symptoms, as well as emotional and social functions. Each question is answered on a scale from 1 (worst) to 7 (best). The total score ranges from 32 to 224 with higher scores indicating better health-related quality of life. A positive change from Baseline indicates improvement.
Time frame: Baseline (Week 0) to Week 8
Population: ITT1 population with available data; a mixed effect model repeat measurement (MMRM) analysis with data from observed cases up to Week 8 was used except for measurements at or after the occurrence of UC-related corticosteroids intercurrent event were excluded.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Upadacitinib 45 mg | Change From Baseline in Inflammatory Bowel Disease Questionnaire (IBDQ) Total Score at Week 8 | 52.2 units on a scale |
| Placebo | Change From Baseline in Inflammatory Bowel Disease Questionnaire (IBDQ) Total Score at Week 8 | 21.1 units on a scale |
p-value: <0.00195% CI: [24.98, 37.36]Mixed-effect model repeated measurement
Secondary
Percentage of Participants Who Achieved Clinical Response Per Adapted Mayo Score at Week 8
The Adapted Mayo Score is a composite score of UC disease activity based on the following 3 subscores: 1. Stool frequency subscore (SFS), scored from 0 (normal number of stools) to 3 (5 or more stools more than normal). 2. Rectal bleeding subscore (RBS), scored from 0 (no blood seen) to 3 (blood alone passed). 3. Endoscopic subscore, scored from 0 (normal or inactive disease) to 3 (severe disease with spontaneous bleeding, ulceration). The overall Adapted Mayo score ranges from 0 to 9 with higher scores representing more severe disease. Clinical response per the Adapted Mayo Score is defined as a decrease in Adapted Mayo score ≥ 2 points and ≥ 30% from Baseline, plus a decrease in RBS ≥ 1 or an absolute RBS ≤ 1.
Time frame: Week 8
Population: ITT1 population; non-responder imputation incorporating multiple imputation to handle missing data due to COVID-19 was used.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Upadacitinib 45 mg | Percentage of Participants Who Achieved Clinical Response Per Adapted Mayo Score at Week 8 | 74.5 percentage of participants |
| Placebo | Percentage of Participants Who Achieved Clinical Response Per Adapted Mayo Score at Week 8 | 25.4 percentage of participants |
p-value: <0.00195% CI: [41.7, 57.1]Cochran-Mantel-Haenszel
Secondary
Percentage of Participants Who Achieved Clinical Response Per Partial Adapted Mayo Score at Week 2
The Partial Adapted Mayo Score is a composite score of UC disease activity based on the following 2 subscores: 1. Stool frequency subscore (SFS), scored from 0 (normal number of stools) to 3 (5 or more stools more than normal). 2. Rectal bleeding subscore (RBS), scored from 0 (no blood seen) to 3 (blood alone passed). The overall Partial Adapted Mayo score ranges from 0 to 6 with higher scores representing more severe disease. Clinical response per Partial Adapted Mayo Score is defined as a decrease in Partial Adapted Mayo score ≥ 1 point and ≥ 30% from Baseline, plus a decrease in RBS ≥ 1 or an absolute RBS ≤ 1.
Time frame: Week 2
Population: ITT1 population; non-responder imputation incorporating multiple imputation to handle missing data due to COVID-19 was used.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Upadacitinib 45 mg | Percentage of Participants Who Achieved Clinical Response Per Partial Adapted Mayo Score at Week 2 | 63.3 percentage of participants |
| Placebo | Percentage of Participants Who Achieved Clinical Response Per Partial Adapted Mayo Score at Week 2 | 25.9 percentage of participants |
p-value: <0.00195% CI: [28.8, 45.1]Cochran-Mantel-Haenszel
Secondary
Percentage Of Participants Who Achieved Histologic-Endoscopic Mucosal Improvement at Week 8
Histologic endoscopic mucosal improvement is defined as an endoscopic subscore of 0 or 1 and a Geboes score ≤ 3.1. The endoscopic subscore ranges from 0 (normal or inactive disease) to 3 (severe disease with spontaneous bleeding, ulceration). The Geboes histologic index includes seven histological features (architectural change, chronic inflammatory infiltrate, lamina propria neutrophils and eosinophils, neutrophils in epithelium, crypt destruction and erosion or ulcers). The Geboes score has 6 grades, each with 3-5 subgrades: Grade 0, structural change only; Grade 1, chronic inflammation; Grade 2, lamina propria neutrophils and eosinophils; Grade 3, neutrophils in epithelium; Grade 4, crypt destruction; and Grade 5, erosions or ulceration.
Time frame: Week 8
Population: ITT1 population; non-responder imputation incorporating multiple imputation to handle missing data due to COVID-19 was used.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Upadacitinib 45 mg | Percentage Of Participants Who Achieved Histologic-Endoscopic Mucosal Improvement at Week 8 | 36.7 percentage of participants |
| Placebo | Percentage Of Participants Who Achieved Histologic-Endoscopic Mucosal Improvement at Week 8 | 5.9 percentage of participants |
p-value: <0.00195% CI: [24.1, 36.2]Cochran-Mantel-Haenszel
Secondary
Percentage of Participants Who Achieved Histologic Improvement at Week 8
Histologic improvement is defined as a decrease from Baseline in Geboes score. The Geboes histologic index includes seven histological features (architectural change, chronic inflammatory infiltrate, lamina propria neutrophils and eosinophils, neutrophils in epithelium, crypt destruction and erosion or ulcers). The Geboes score has 6 grades, each with 3-5 subgrades: Grade 0, structural change only; Grade 1, chronic inflammation; Grade 2, lamina propria neutrophils and eosinophils; Grade 3, neutrophils in epithelium; Grade 4, crypt destruction; and Grade 5, erosions or ulceration.
Time frame: Week 8
Population: ITT1 population; non-responder imputation incorporating multiple imputation to handle missing data due to COVID-19 was used.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Upadacitinib 45 mg | Percentage of Participants Who Achieved Histologic Improvement at Week 8 | 62.2 percentage of participants |
| Placebo | Percentage of Participants Who Achieved Histologic Improvement at Week 8 | 24.5 percentage of participants |
p-value: <0.00195% CI: [29.8, 46.1]Cochran-Mantel-Haenszel
Secondary
Percentage of Participants Who Achieved Mucosal Healing at Week 8
Mucosal healing is defined as an endoscopic score of 0 and Geboes score \< 2.0. The endoscopic subscore ranges from 0 (normal or inactive disease) to 3 (severe disease with spontaneous bleeding, ulceration). The Geboes histologic index includes seven histological features (architectural change, chronic inflammatory infiltrate, lamina propria neutrophils and eosinophils, neutrophils in epithelium, crypt destruction and erosion or ulcers). The Geboes score has 6 grades, each with 3-5 subgrades: Grade 0, structural change only; Grade 1, chronic inflammation; Grade 2, lamina propria neutrophils and eosinophils; Grade 3, neutrophils in epithelium; Grade 4, crypt destruction; and Grade 5, erosions or ulceration.
Time frame: Week 8
Population: ITT1 population; non-responder imputation incorporating multiple imputation to handle missing data due to COVID-19 was used.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Upadacitinib 45 mg | Percentage of Participants Who Achieved Mucosal Healing at Week 8 | 13.5 percentage of participants |
| Placebo | Percentage of Participants Who Achieved Mucosal Healing at Week 8 | 1.7 percentage of participants |
p-value: <0.00195% CI: [7.2, 15.3]Cochran-Mantel-Haenszel
Secondary
Percentage of Participants Who Reported No Abdominal Pain at Week 8
Abdominal pain was assessed by participants in a subject diary completed once a day.
Time frame: Week 8
Population: ITT1 population; non-responder imputation incorporating multiple imputation to handle missing data due to COVID-19 was used.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Upadacitinib 45 mg | Percentage of Participants Who Reported No Abdominal Pain at Week 8 | 53.7 percentage of participants |
| Placebo | Percentage of Participants Who Reported No Abdominal Pain at Week 8 | 24.1 percentage of participants |
p-value: <0.00195% CI: [20.9, 37.4]Cochran-Mantel-Haenszel
Secondary
Percentage of Participants Who Reported No Bowel Urgency at Week 8
Bowel urgency was assessed by participants in a subject diary completed once a day.
Time frame: Week 8
Population: ITT1 population; non-responder imputation incorporating multiple imputation to handle missing data due to COVID-19 was used.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Upadacitinib 45 mg | Percentage of Participants Who Reported No Bowel Urgency at Week 8 | 53.7 percentage of participants |
| Placebo | Percentage of Participants Who Reported No Bowel Urgency at Week 8 | 25.9 percentage of participants |
p-value: <0.00195% CI: [19, 35.3]Cochran-Mantel-Haenszel
Secondary
Percentage of Participants With Endoscopic Improvement at Week 8
Endoscopic improvement is defined as an endoscopic subscore of 0 or 1. Endoscopies were assessed by a blinded central reader and scored according to the following scale: 0 = Normal or inactive disease; 1 = Mild disease (erythema, decreased vascular pattern); 2 = Moderate disease (marked erythema, lack of vascular pattern, any friability, erosions); 3 = Severe disease (spontaneous bleeding, ulceration).
Time frame: Week 8
Population: ITT1 population; non-responder imputation incorporating multiple imputation to handle missing data due to COVID-19 was used.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Upadacitinib 45 mg | Percentage of Participants With Endoscopic Improvement at Week 8 | 44.0 percentage of participants |
| Placebo | Percentage of Participants With Endoscopic Improvement at Week 8 | 8.3 percentage of participants |
p-value: <0.00195% CI: [28.6, 41.6]Cochran-Mantel-Haenszel
Secondary
Percentage of Participants With Endoscopic Remission at Week 8
Endoscopic remission is defined as an endoscopic subscore of 0. Endoscopies were assessed by a blinded central reader and scored according to the following scale: 0 = Normal or inactive disease; 1 = Mild disease (erythema, decreased vascular pattern); 2 = Moderate disease (marked erythema, lack of vascular pattern, any friability, erosions); 3 = Severe disease (spontaneous bleeding, ulceration).
Time frame: Week 8
Population: ITT1 population; non-responder imputation incorporating multiple imputation to handle missing data due to COVID-19 was used.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Upadacitinib 45 mg | Percentage of Participants With Endoscopic Remission at Week 8 | 18.2 percentage of participants |
| Placebo | Percentage of Participants With Endoscopic Remission at Week 8 | 1.7 percentage of participants |
p-value: <0.00195% CI: [11.4, 20.3]Cochran-Mantel-Haenszel