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A Study of the Efficacy and Safety of Upadacitinib (ABT-494) in Participants With Moderately to Severely Active Ulcerative Colitis (U-Accomplish)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03653026
Recruitment Status : Completed
First Posted : August 31, 2018
Results First Posted : November 26, 2021
Last Update Posted : November 26, 2021
Sponsor:
Information provided by (Responsible Party):
AbbVie

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Ulcerative Colitis (UC)
Interventions Drug: Placebo
Drug: Upadacitinib
Enrollment 522
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).
Arm/Group Title Part 1: Upadacitinib 45 mg Part 1: Placebo Part 2: Upadacitinib 45 mg / Upadacitinib 45 mg Part 2: Placebo / Upadacitinib 45 mg
Hide Arm/Group Description Participants received 45 mg upadacitinib once daily (QD) for 8 weeks. Participants received placebo matching to upadacitinib once daily for 8 weeks. Participants initially assigned to upadacitinib who did not achieve clinical response per Adapted Mayo score at Week 8 in Part 1 received upadacitinib 45 mg once daily for 8 additional weeks in the open-label extension period. Participants initially assigned to placebo who did not achieve clinical response per Adapted Mayo score at Week 8 in Part 1 received upadacitinib 45 mg once daily for 8 weeks in the open-label extension period.
Period Title: Part 1: Placebo-controlled Period
Started 345 177 0 0
Received Treatment 344 177 0 0
Completed 334 164 0 0
Not Completed 11 13 0 0
Reason Not Completed
Adverse Event             5             6             0             0
Withdrawal by Subject             6             4             0             0
Other             0             3             0             0
Period Title: Part 2: Open-label Extension
Started [1] 0 0 68 116
Completed 0 0 65 111
Not Completed 0 0 3 5
Reason Not Completed
Adverse Event             0             0             1             1
Withdrawal by Subject             0             0             1             2
Other             0             0             1             2
[1]
Part 2 was an extended treatment period for participants who did not achieve clinical response per Adapted Mayo score at Week 8 in Part 1.
Arm/Group Title Upadacitinib 45 mg Placebo Total
Hide Arm/Group Description Participants received 45 mg upadacitinib once daily (QD) for 8 weeks. Participants received placebo matching to upadacitinib once daily for 8 weeks. Total of all reporting groups
Overall Number of Baseline Participants 345 177 522
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 345 participants 177 participants 522 participants
42.2  (14.73) 42.2  (14.44) 42.2  (14.62)
Age, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 345 participants 177 participants 522 participants
< 18 years
6
   1.7%
3
   1.7%
9
   1.7%
≥ 18 years to < 40 years
160
  46.4%
81
  45.8%
241
  46.2%
≥ 40 years to < 65 years
146
  42.3%
79
  44.6%
225
  43.1%
≥ 65 years
33
   9.6%
14
   7.9%
47
   9.0%
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 345 participants 177 participants 522 participants
Female
129
  37.4%
67
  37.9%
196
  37.5%
Male
216
  62.6%
110
  62.1%
326
  62.5%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 345 participants 177 participants 522 participants
Hispanic or Latino
26
   7.5%
16
   9.0%
42
   8.0%
Not Hispanic or Latino
319
  92.5%
161
  91.0%
480
  92.0%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 345 participants 177 participants 522 participants
White
238
  69.0%
127
  71.8%
365
  69.9%
Black or African American
11
   3.2%
6
   3.4%
17
   3.3%
Asian
94
  27.2%
41
  23.2%
135
  25.9%
American Indian or Alaska Native
0
   0.0%
1
   0.6%
1
   0.2%
Native Hawaiian or Other Pacific Islander
0
   0.0%
1
   0.6%
1
   0.2%
Multiple
2
   0.6%
1
   0.6%
3
   0.6%
Biologic-inadequate Responder (Bio-IR) Status   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 345 participants 177 participants 522 participants
Bio-IR
175
  50.7%
91
  51.4%
266
  51.0%
Non-Bio-IR
170
  49.3%
86
  48.6%
256
  49.0%
[1]
Measure Description:

Biologic-inadequate responders (Bio-IR) are defined as participants who had inadequate response, loss of response, or intolerance to biologic therapy.

Non-biologic-inadequate responders (non-bio-IR) are defined as participants who had inadequate response, loss of response, or intolerance to conventional therapy but had not failed biologic therapy.

Baseline Corticosteroid Use  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 345 participants 177 participants 522 participants
Yes
123
  35.7%
75
  42.4%
198
  37.9%
No
222
  64.3%
102
  57.6%
324
  62.1%
Adapted Mayo Score Strata   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 345 participants 177 participants 522 participants
≤ 7
205
  59.4%
104
  58.8%
309
  59.2%
> 7
138
  40.0%
73
  41.2%
211
  40.4%
Missing
2
   0.6%
0
   0.0%
2
   0.4%
[1]
Measure Description:

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.

Bio-IR: Number of Prior Biologic Treatments   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 175 participants 91 participants 266 participants
≤ 1 prior biologic
58
  33.1%
33
  36.3%
91
  34.2%
> 1 prior biologic
117
  66.9%
58
  63.7%
175
  65.8%
[1]
Measure Analysis Population Description: Biologic-inadequate responders
Non-Bio-IR: Prior Exposure to Biologic Therapy   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 170 participants 86 participants 256 participants
Yes
1
   0.6%
5
   5.8%
6
   2.3%
No
169
  99.4%
81
  94.2%
250
  97.7%
[1]
Measure Analysis Population Description: Non-biologic-inadequate responders
Disease Duration  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 345 participants 177 participants 522 participants
7.273  (6.4459) 7.584  (7.6701) 7.379  (6.8804)
Adapted Mayo Score   [1] [2] 
Mean (Standard Deviation)
Unit of measure:  Units on a scale
Number Analyzed 343 participants 177 participants 520 participants
7.00  (1.216) 7.05  (1.236) 7.02  (1.222)
[1]
Measure Description:

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 score ranges from 0 to 9 where higher scores represent more severe disease.
[2]
Measure Analysis Population Description: Participants with available data
Average Stool Frequency Subscore   [1] [2] 
Mean (Standard Deviation)
Unit of measure:  Units on a scale
Number Analyzed 343 participants 177 participants 520 participants
2.55  (0.626) 2.64  (0.551) 2.58  (0.603)
[1]
Measure Description:

Participants recorded stool frequency using an electronic subject diary on a daily basis. The stool frequency subscore (SFS) ranges from 0 to 3 according to the following scale:

Score 0: Normal number of stools

Score 1: 1 to 2 stools more than normal

Score 2: 3 to 4 stools more than normal

Score 3: 5 or more stools more than normal

[2]
Measure Analysis Population Description: Participants with available data
Average Rectal Bleeding Subscore   [1] [2] 
Mean (Standard Deviation)
Unit of measure:  Units on a scale
Number Analyzed 343 participants 177 participants 520 participants
1.77  (0.966) 1.71  (1.049) 1.75  (0.995)
[1]
Measure Description:

Participants recorded rectal bleeding in an electronic subject diary on a daily basis. The rectal bleeding subscore ranges from 0 to 3 according to the following scale:

Score 0: No blood seen

Score 1: Streaks of blood with stool less than half the time

Score 2: Obvious blood with stool most of the time

Score 3: Blood alone passed

[2]
Measure Analysis Population Description: Participants with available data
Average Endoscopy Subscore   [1] [2] 
Mean (Standard Deviation)
Unit of measure:  Units on a scale
Number Analyzed 344 participants 177 participants 521 participants
2.7  (0.47) 2.7  (0.46) 2.7  (0.46)
[1]
Measure Description:

Findings on endoscopy were scored according to the following:

Score 0: Normal or inactive disease

Score 1: Mild disease (erythema, decreased vascular pattern)

Score 2: Moderate disease (marked erythema, lack of vascular pattern, any friability, erosions)

Score 3: Severe disease (spontaneous bleeding, ulceration)

[2]
Measure Analysis Population Description: Participants with available data
1.Primary Outcome
Title Percentage of Participants Who Achieved Clinical Remission Per Adapted Mayo Score at Week 8
Hide Description

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
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Upadacitinib 45 mg Placebo
Hide Arm/Group Description:
Participants received 45 mg upadacitinib once daily for 8 weeks.
Participants received placebo matching to upadacitinib once daily for 8 weeks.
Overall Number of Participants Analyzed 341 174
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
33.5
(28.5 to 38.5)
4.1
(1.1 to 7.1)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Upadacitinib 45 mg, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments The primary and ranked secondary efficacy endpoints were tested with multiplicity adjustment using a fixed-sequence multiple testing procedure to ensure a strong control of family-wise type I error rate at significance level alpha = 0.05 (2-sided).
Method Cochran-Mantel-Haenszel
Comments Adjusted for Baseline corticosteroid use (yes or no), Baseline Adapted Mayo score (≤ 7 or > 7), and bio-IR status (bio-IR or non-bio-IR).
Method of Estimation Estimation Parameter Adjusted Response Rate Difference
Estimated Value 29.0
Confidence Interval (2-Sided) 95%
23.2 to 34.7
Estimation Comments Difference = Upadacitinib 45 mg - Placebo
2.Secondary Outcome
Title Percentage of Participants With Endoscopic Improvement at Week 8
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
ITT1 population; non-responder imputation incorporating multiple imputation to handle missing data due to COVID-19 was used.
Arm/Group Title Upadacitinib 45 mg Placebo
Hide Arm/Group Description:
Participants received 45 mg upadacitinib once daily for 8 weeks.
Participants received placebo matching to upadacitinib once daily for 8 weeks.
Overall Number of Participants Analyzed 341 174
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
44.0
(38.8 to 49.3)
8.3
(4.1 to 12.5)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Upadacitinib 45 mg, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments The primary and ranked secondary efficacy endpoints were tested with multiplicity adjustment using a fixed-sequence multiple testing procedure to ensure a strong control of family-wise type I error rate at significance level alpha = 0.05 (2-sided).
Method Cochran-Mantel-Haenszel
Comments Adjusted for Baseline corticosteroid use (yes or no), Baseline Adapted Mayo score (≤ 7 or > 7), and bio-IR status (bio-IR or non-bio-IR).
Method of Estimation Estimation Parameter Adjusted Response Rate Difference
Estimated Value 35.1
Confidence Interval (2-Sided) 95%
28.6 to 41.6
Estimation Comments Difference = Upadacitinib 45 mg - Placebo
3.Secondary Outcome
Title Percentage of Participants With Endoscopic Remission at Week 8
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
ITT1 population; non-responder imputation incorporating multiple imputation to handle missing data due to COVID-19 was used.
Arm/Group Title Upadacitinib 45 mg Placebo
Hide Arm/Group Description:
Participants received 45 mg upadacitinib once daily for 8 weeks.
Participants received placebo matching to upadacitinib once daily for 8 weeks.
Overall Number of Participants Analyzed 341 174
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
18.2
(14.1 to 22.3)
1.7
(0.0 to 3.7)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Upadacitinib 45 mg, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments The primary and ranked secondary efficacy endpoints were tested with multiplicity adjustment using a fixed-sequence multiple testing procedure to ensure a strong control of family-wise type I error rate at significance level alpha = 0.05 (2-sided).
Method Cochran-Mantel-Haenszel
Comments Adjusted for Baseline corticosteroid use (yes or no), Baseline Adapted Mayo score (≤ 7 or > 7), and bio-IR status (bio-IR or non-bio-IR).
Method of Estimation Estimation Parameter Adjusted Response Rate Difference
Estimated Value 15.9
Confidence Interval (2-Sided) 95%
11.4 to 20.3
Estimation Comments Difference = Upadacitinib 45 mg - Placebo
4.Secondary Outcome
Title Percentage of Participants Who Achieved Clinical Response Per Adapted Mayo Score at Week 8
Hide Description

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
Hide Outcome Measure Data
Hide Analysis Population Description
ITT1 population; non-responder imputation incorporating multiple imputation to handle missing data due to COVID-19 was used.
Arm/Group Title Upadacitinib 45 mg Placebo
Hide Arm/Group Description:
Participants received 45 mg upadacitinib once daily for 8 weeks.
Participants received placebo matching to upadacitinib once daily for 8 weeks.
Overall Number of Participants Analyzed 341 174
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
74.5
(69.9 to 79.1)
25.4
(18.9 to 31.8)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Upadacitinib 45 mg, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments The primary and ranked secondary efficacy endpoints were tested with multiplicity adjustment using a fixed-sequence multiple testing procedure to ensure a strong control of family-wise type I error rate at significance level alpha = 0.05 (2-sided).
Method Cochran-Mantel-Haenszel
Comments Adjusted for Baseline corticosteroid use (yes or no), Baseline Adapted Mayo score (≤ 7 or > 7), and bio-IR status (bio-IR or non-bio-IR).
Method of Estimation Estimation Parameter Adjusted Response Rate Difference
Estimated Value 49.4
Confidence Interval (2-Sided) 95%
41.7 to 57.1
Estimation Comments Difference = Upadacitinib 45 mg - Placebo
5.Secondary Outcome
Title Percentage of Participants Who Achieved Clinical Response Per Partial Adapted Mayo Score at Week 2
Hide Description

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
Hide Outcome Measure Data
Hide Analysis Population Description
ITT1 population; non-responder imputation incorporating multiple imputation to handle missing data due to COVID-19 was used.
Arm/Group Title Upadacitinib 45 mg Placebo
Hide Arm/Group Description:
Participants received 45 mg upadacitinib once daily for 8 weeks.
Participants received placebo matching to upadacitinib once daily for 8 weeks.
Overall Number of Participants Analyzed 341 174
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
63.3
(58.2 to 68.5)
25.9
(19.4 to 32.4)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Upadacitinib 45 mg, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments The primary and ranked secondary efficacy endpoints were tested with multiplicity adjustment using a fixed-sequence multiple testing procedure to ensure a strong control of family-wise type I error rate at significance level alpha = 0.05 (2-sided).
Method Cochran-Mantel-Haenszel
Comments Adjusted for Baseline corticosteroid use (yes or no), Baseline Adapted Mayo score (≤ 7 or > 7), and bio-IR status (bio-IR or non-bio-IR).
Method of Estimation Estimation Parameter Adjusted Response Rate Difference
Estimated Value 37.0
Confidence Interval (2-Sided) 95%
28.8 to 45.1
Estimation Comments Difference = Upadacitinib 45 mg - Placebo
6.Secondary Outcome
Title Percentage Of Participants Who Achieved Histologic-Endoscopic Mucosal Improvement at Week 8
Hide Description

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
Hide Outcome Measure Data
Hide Analysis Population Description
ITT1 population; non-responder imputation incorporating multiple imputation to handle missing data due to COVID-19 was used.
Arm/Group Title Upadacitinib 45 mg Placebo
Hide Arm/Group Description:
Participants received 45 mg upadacitinib once daily for 8 weeks.
Participants received placebo matching to upadacitinib once daily for 8 weeks.
Overall Number of Participants Analyzed 341 174
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
36.7
(31.6 to 41.8)
5.8
(2.3 to 9.4)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Upadacitinib 45 mg, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments The primary and ranked secondary efficacy endpoints were tested with multiplicity adjustment using a fixed-sequence multiple testing procedure to ensure a strong control of family-wise type I error rate at significance level alpha = 0.05 (2-sided).
Method Cochran-Mantel-Haenszel
Comments Adjusted for Baseline corticosteroid use (yes or no), Baseline Adapted Mayo score (≤ 7 or > 7), and bio-IR status (bio-IR or non-bio-IR).
Method of Estimation Estimation Parameter Adjusted Response Rate Difference
Estimated Value 30.2
Confidence Interval (2-Sided) 95%
24.1 to 36.2
Estimation Comments Difference = Upadacitinib 45 mg - placebo
7.Secondary Outcome
Title Percentage of Participants Who Reported No Bowel Urgency at Week 8
Hide Description Bowel urgency was assessed by participants in a subject diary completed once a day.
Time Frame Week 8
Hide Outcome Measure Data
Hide Analysis Population Description
ITT1 population; non-responder imputation incorporating multiple imputation to handle missing data due to COVID-19 was used.
Arm/Group Title Upadacitinib 45 mg Placebo
Hide Arm/Group Description:
Participants received 45 mg upadacitinib once daily for 8 weeks.
Participants received placebo matching to upadacitinib once daily for 8 weeks.
Overall Number of Participants Analyzed 341 174
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
53.7
(48.4 to 59.0)
25.9
(19.4 to 32.4)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Upadacitinib 45 mg, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments The primary and ranked secondary efficacy endpoints were tested with multiplicity adjustment using a fixed-sequence multiple testing procedure to ensure a strong control of family-wise type I error rate at significance level alpha = 0.05 (2-sided).
Method Cochran-Mantel-Haenszel
Comments Adjusted for Baseline corticosteroid use (yes or no), Baseline Adapted Mayo score (<= 7 or > 7), and bio-IR status (bio-IR or non-bio-IR).
Method of Estimation Estimation Parameter Adjusted Response Rate Difference
Estimated Value 27.1
Confidence Interval (2-Sided) 95%
19.0 to 35.3
Estimation Comments Difference = Upadacitinib 45 mg - Placebo
8.Secondary Outcome
Title Percentage of Participants Who Reported No Abdominal Pain at Week 8
Hide Description Abdominal pain was assessed by participants in a subject diary completed once a day.
Time Frame Week 8
Hide Outcome Measure Data
Hide Analysis Population Description
ITT1 population; non-responder imputation incorporating multiple imputation to handle missing data due to COVID-19 was used.
Arm/Group Title Upadacitinib 45 mg Placebo
Hide Arm/Group Description:
Participants received 45 mg upadacitinib once daily for 8 weeks.
Participants received placebo matching to upadacitinib once daily for 8 weeks.
Overall Number of Participants Analyzed 341 174
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
53.7
(48.4 to 59.0)
24.1
(17.8 to 30.5)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Upadacitinib 45 mg, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments The primary and ranked secondary efficacy endpoints were tested with multiplicity adjustment using a fixed-sequence multiple testing procedure to ensure a strong control of family-wise type I error rate at significance level alpha = 0.05 (2-sided).
Method Cochran-Mantel-Haenszel
Comments Adjusted for Baseline corticosteroid use (yes or no), Baseline Adapted Mayo score (≤ 7 or > 7), and bio-IR status (bio-IR or non-bio-IR).
Method of Estimation Estimation Parameter Adjusted Response Rate Difference
Estimated Value 29.1
Confidence Interval (2-Sided) 95%
20.9 to 37.4
Estimation Comments Difference = Upadacitinib 45 mg - Placebo
9.Secondary Outcome
Title Percentage of Participants Who Achieved Histologic Improvement at Week 8
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
ITT1 population; non-responder imputation incorporating multiple imputation to handle missing data due to COVID-19 was used.
Arm/Group Title Upadacitinib 45 mg Placebo
Hide Arm/Group Description:
Participants received 45 mg upadacitinib once daily for 8 weeks.
Participants received placebo matching to upadacitinib once daily for 8 weeks.
Overall Number of Participants Analyzed 341 174
Measure Type: Number
Number (90% Confidence Interval)
Unit of Measure: percentage of participants
62.2
(57.0 to 67.3)
24.5
(18.0 to 30.9)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Upadacitinib 45 mg, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments The primary and ranked secondary efficacy endpoints were tested with multiplicity adjustment using a fixed-sequence multiple testing procedure to ensure a strong control of family-wise type I error rate at significance level alpha = 0.05 (2-sided).
Method Cochran-Mantel-Haenszel
Comments Adjusted for Baseline corticosteroid use (yes or no), Baseline Adapted Mayo score (≤ 7 or > 7), and bio-IR status (bio-IR or non-bio-IR).
Method of Estimation Estimation Parameter Adjusted Response Rate Difference
Estimated Value 37.9
Confidence Interval (2-Sided) 95%
29.8 to 46.1
Estimation Comments Difference = Upadacitinib 45 mg - Placebo
10.Secondary Outcome
Title Change From Baseline in Inflammatory Bowel Disease Questionnaire (IBDQ) Total Score at Week 8
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Upadacitinib 45 mg Placebo
Hide Arm/Group Description:
Participants received 45 mg upadacitinib once daily for 8 weeks.
Participants received placebo matching to upadacitinib once daily for 8 weeks.
Overall Number of Participants Analyzed 315 156
Least Squares Mean (95% Confidence Interval)
Unit of Measure: units on a scale
52.2
(48.57 to 55.92)
21.1
(15.98 to 26.17)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Upadacitinib 45 mg, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments The primary and ranked secondary efficacy endpoints were tested with multiplicity adjustment using a fixed-sequence multiple testing procedure to ensure a strong control of family-wise type I error rate at significance level alpha = 0.05 (2-sided).
Method Mixed-effect model repeated measurement
Comments MMRM with Baseline, treatment, visit, treatment-by-visit interaction, and strata (Baseline Adapted Mayo score, corticosteroid use, and bio-IR status).
Method of Estimation Estimation Parameter Least Squares (LS) Mean Difference
Estimated Value 31.2
Confidence Interval (2-Sided) 95%
24.98 to 37.36
Parameter Dispersion
Type: Standard Error of the Mean
Value: 3.15
Estimation Comments Difference = Upadacitinib 45 mg - Placebo
11.Secondary Outcome
Title Percentage of Participants Who Achieved Mucosal Healing at Week 8
Hide Description

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
Hide Outcome Measure Data
Hide Analysis Population Description
ITT1 population; non-responder imputation incorporating multiple imputation to handle missing data due to COVID-19 was used.
Arm/Group Title Upadacitinib 45 mg Placebo
Hide Arm/Group Description:
Participants received 45 mg upadacitinib once daily for 8 weeks.
Participants received placebo matching to upadacitinib once daily for 8 weeks.
Overall Number of Participants Analyzed 341 174
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
13.5
(9.9 to 17.1)
1.7
(0.0 to 3.7)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Upadacitinib 45 mg, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments The primary and ranked secondary efficacy endpoints were tested with multiplicity adjustment using a fixed-sequence multiple testing procedure to ensure a strong control of family-wise type I error rate at significance level alpha = 0.05 (2-sided).
Method Cochran-Mantel-Haenszel
Comments Adjusted for Baseline corticosteroid use (yes or no), Baseline Adapted Mayo score (≤ 7 or > 7), and bio-IR status (bio-IR or non-bio-IR).
Method of Estimation Estimation Parameter Adjusted Response Rate Difference
Estimated Value 11.3
Confidence Interval (2-Sided) 95%
7.2 to 15.3
Estimation Comments Difference = Upadacitinib 45 mg - Placebo
12.Secondary Outcome
Title Change From Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Score at Week 8
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Upadacitinib 45 mg Placebo
Hide Arm/Group Description:
Participants received 45 mg upadacitinib once daily for 8 weeks.
Participants received placebo matching to upadacitinib once daily for 8 weeks.
Overall Number of Participants Analyzed 312 155
Least Squares Mean (95% Confidence Interval)
Unit of Measure: units on a scale
9.4
(8.38 to 10.48)
3.5
(2.02 to 4.92)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Upadacitinib 45 mg, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments The primary and ranked secondary efficacy endpoints were tested with multiplicity adjustment using a fixed-sequence multiple testing procedure to ensure a strong control of family-wise type I error rate at significance level alpha = 0.05 (2-sided).
Method Mixed-effect model repeated measurement
Comments MMRM with Baseline, treatment, visit, treatment-by-visit interaction, and strata (Baseline Adapted Mayo score, corticosteroid use, and bio-IR status).
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value 6.0
Confidence Interval (2-Sided) 95%
4.19 to 7.73
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.9
Estimation Comments Difference = Upadacitinib 45 mg - Placebo
Time Frame Part 1: From first dose of study drug up to 30 days after the last dose (up to 12 weeks) or until first dose of study drug in Part 2 or first dose of study drug in M14-234 (NCT02819635; maintenance study) or M14-533 (NCT03006068; long term extension). Part 2: From the first dose of study drug in Part 2 up to 30 days after last dose (up to 12 weeks) or until first dose of study drug in M14-234 (maintenance study) or the first dose date of study drug in M14-533 (long-term extension study).
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Part 1: Upadacitinib 45 mg Part 1: Placebo Part 2: Upadacitinib 45 mg / Upadacitinib 45 mg Part 2: Placebo / Upadacitinib 45 mg
Hide Arm/Group Description Participants received 45 mg upadacitinib once daily (QD) for 8 weeks. Participants received placebo matching to upadacitinib once daily for 8 weeks. Participants initially assigned to upadacitinib who did not achieve clinical response per Adapted Mayo score at Week 8 in Part 1 received upadacitinib 45 mg once daily for 8 additional weeks in the open-label extension period. Participants initially assigned to placebo who did not achieve clinical response per Adapted Mayo score at Week 8 in Part 1 received upadacitinib 45 mg once daily for 8 weeks in the open-label extension period.
All-Cause Mortality
Part 1: Upadacitinib 45 mg Part 1: Placebo Part 2: Upadacitinib 45 mg / Upadacitinib 45 mg Part 2: Placebo / Upadacitinib 45 mg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/344 (0.00%)      0/177 (0.00%)      0/68 (0.00%)      0/116 (0.00%)    
Hide Serious Adverse Events
Part 1: Upadacitinib 45 mg Part 1: Placebo Part 2: Upadacitinib 45 mg / Upadacitinib 45 mg Part 2: Placebo / Upadacitinib 45 mg
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   11/344 (3.20%)      8/177 (4.52%)      1/68 (1.47%)      4/116 (3.45%)    
Blood and lymphatic system disorders         
ANAEMIA  1  1/344 (0.29%)  1 1/177 (0.56%)  1 0/68 (0.00%)  0 0/116 (0.00%)  0
Gastrointestinal disorders         
ABDOMINAL DISCOMFORT  1  0/344 (0.00%)  0 0/177 (0.00%)  0 0/68 (0.00%)  0 1/116 (0.86%)  1
ABDOMINAL PAIN LOWER  1  0/344 (0.00%)  0 0/177 (0.00%)  0 0/68 (0.00%)  0 1/116 (0.86%)  1
COLITIS  1  0/344 (0.00%)  0 1/177 (0.56%)  1 0/68 (0.00%)  0 0/116 (0.00%)  0
COLITIS ULCERATIVE  1  4/344 (1.16%)  4 3/177 (1.69%)  3 1/68 (1.47%)  1 1/116 (0.86%)  1
LARGE INTESTINE PERFORATION  1  0/344 (0.00%)  0 1/177 (0.56%)  1 0/68 (0.00%)  0 0/116 (0.00%)  0
General disorders         
CHEST PAIN  1  1/344 (0.29%)  1 0/177 (0.00%)  0 0/68 (0.00%)  0 0/116 (0.00%)  0
Infections and infestations         
COVID-19 PNEUMONIA  1  1/344 (0.29%)  1 0/177 (0.00%)  0 0/68 (0.00%)  0 1/116 (0.86%)  1
DENGUE FEVER  1  1/344 (0.29%)  1 0/177 (0.00%)  0 0/68 (0.00%)  0 0/116 (0.00%)  0
ENTEROCOCCAL INFECTION  1  0/344 (0.00%)  0 1/177 (0.56%)  1 0/68 (0.00%)  0 0/116 (0.00%)  0
ESCHERICHIA INFECTION  1  0/344 (0.00%)  0 1/177 (0.56%)  1 0/68 (0.00%)  0 0/116 (0.00%)  0
Injury, poisoning and procedural complications         
GASTROINTESTINAL STOMA NECROSIS  1  0/344 (0.00%)  0 1/177 (0.56%)  1 0/68 (0.00%)  0 0/116 (0.00%)  0
HAND FRACTURE  1  1/344 (0.29%)  1 0/177 (0.00%)  0 0/68 (0.00%)  0 0/116 (0.00%)  0
Metabolism and nutrition disorders         
MALNUTRITION  1  1/344 (0.29%)  1 0/177 (0.00%)  0 0/68 (0.00%)  0 0/116 (0.00%)  0
Psychiatric disorders         
ACUTE PSYCHOSIS  1  1/344 (0.29%)  1 0/177 (0.00%)  0 0/68 (0.00%)  0 0/116 (0.00%)  0
Respiratory, thoracic and mediastinal disorders         
CHRONIC OBSTRUCTIVE PULMONARY DISEASE  1  0/344 (0.00%)  0 0/177 (0.00%)  0 0/68 (0.00%)  0 1/116 (0.86%)  1
PULMONARY EMBOLISM  1  0/344 (0.00%)  0 1/177 (0.56%)  1 0/68 (0.00%)  0 0/116 (0.00%)  0
Skin and subcutaneous tissue disorders         
PYODERMA GANGRENOSUM  1  0/344 (0.00%)  0 1/177 (0.56%)  1 0/68 (0.00%)  0 0/116 (0.00%)  0
Vascular disorders         
PELVIC VENOUS THROMBOSIS  1  0/344 (0.00%)  0 1/177 (0.56%)  1 0/68 (0.00%)  0 0/116 (0.00%)  0
1
Term from vocabulary, MedDRA 23.0
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Part 1: Upadacitinib 45 mg Part 1: Placebo Part 2: Upadacitinib 45 mg / Upadacitinib 45 mg Part 2: Placebo / Upadacitinib 45 mg
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   32/344 (9.30%)      11/177 (6.21%)      10/68 (14.71%)      17/116 (14.66%)    
Blood and lymphatic system disorders         
ANAEMIA  1  0/344 (0.00%)  0 0/177 (0.00%)  0 4/68 (5.88%)  4 3/116 (2.59%)  3
General disorders         
PYREXIA  1  0/344 (0.00%)  0 0/177 (0.00%)  0 4/68 (5.88%)  4 4/116 (3.45%)  4
Investigations         
BLOOD CREATINE PHOSPHOKINASE INCREASED  1  0/344 (0.00%)  0 0/177 (0.00%)  0 4/68 (5.88%)  4 5/116 (4.31%)  5
Nervous system disorders         
HEADACHE  1  8/344 (2.33%)  9 9/177 (5.08%)  10 0/68 (0.00%)  0 0/116 (0.00%)  0
Skin and subcutaneous tissue disorders         
ACNE  1  24/344 (6.98%)  25 3/177 (1.69%)  3 0/68 (0.00%)  0 6/116 (5.17%)  6
1
Term from vocabulary, MedDRA 23.0
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
AbbVie requests that any investigator or institution that plans on presenting/publishing results disclosure, provide written notification of their request 60 days prior to their presentation/publication. AbbVie requests that no presentation/publication will be instituted until 12 months after a study is completed, or after the first presentation/publication whichever occurs first. A delay may be proposed of a presentation/publication if AbbVie needs to secure patent or proprietary protection
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Global Medical Services
Organization: AbbVie
Phone: 800-633-9110
EMail: abbvieclinicaltrials@abbvie.com
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Responsible Party: AbbVie
ClinicalTrials.gov Identifier: NCT03653026    
Other Study ID Numbers: M14-675
2016-000642-62 ( EudraCT Number )
First Submitted: August 28, 2018
First Posted: August 31, 2018
Results First Submitted: October 29, 2021
Results First Posted: November 26, 2021
Last Update Posted: November 26, 2021