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Efficacy and Safety of Adalimumab in Pediatric Subjects With Moderate to Severe Ulcerative Colitis

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ClinicalTrials.gov Identifier: NCT02065557
Recruitment Status : Completed
First Posted : February 19, 2014
Results First Posted : October 5, 2020
Last Update Posted : October 5, 2020
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
Interventions Biological: Adalimumab
Biological: Placebo
Enrollment 101
Recruitment Details Prior to Protocol Amendment 4, participants were randomized 3:2 at baseline to adalimumab induction high dose or adalimumab induction standard dose. At Week 8, those demonstrating a clinical response per Partial Mayo Score (PMS) were randomized 2:2:1 to adalimumab maintenance standard dose, adalimumab maintenance high dose, or maintenance placebo.
Pre-assignment Details After Protocol Amendment 4, participants received adalimumab induction high dose open-label. At Week 8, those demonstrating a clinical response per PMS were randomized in a 1:1 ratio to adalimumab maintenance standard dose or adalimumab maintenance high dose. "Integrated Study" data includes data from both the Main Study and the Japan Sub-Study.
Arm/Group Title Integrated Study: Induction Standard Dose (I-SD) Integrated Study: Induction High Dose (I-HD) Integrated Study: Induction High Dose Open Label (I-HD-OL) Integrated Study: Maintenance Placebo (M-PL) Integrated Study: Maintenance Standard Dose (M-SD) Integrated Study: Maintenance High Dose (M-HD)
Hide Arm/Group Description Participants randomized to receive adalimumab 2.4 mg/kg (maximum dose of 160 mg) at Baseline and matching placebo at Week 1, 1.2 mg/kg (maximum dose of 80 mg) at Week 2, followed by 0.6 mg/kg (maximum dose of 40 mg) at Week 4 and Week 6. Participants randomized to receive adalimumab 2.4 mg/kg (maximum dose of 160 mg) at Baseline and at Week 1, 1.2 mg/kg (maximum dose of 80 mg) at Week 2, followed by 0.6 mg/kg (maximum dose of 40 mg) at Week 4 and Week 6. (After Amendment 4) participants assigned to open-label adalimumab 2.4 mg/kg (maximum dose of 160 mg) at Baseline and at Week 1, 1.2 mg/kg (maximum dose of 80 mg) at Week 2, followed by 0.6 mg/kg (maximum dose of 40 mg) at Week 4 and Week 6. (Prior to Amendment 4) participants demonstrating a clinical response per PMS (defined as a decrease in PMS ≥ 2 points and ≥ 30% from Baseline) at Week 8 randomized to maintenance placebo. Participants were to continue their blinded treatment during the maintenance period until Week 52 unless they had ≥ 2 flares and got open label rescue therapy after the second flare. Participants demonstrating a clinical response per PMS (defined as a decrease in PMS ≥ 2 points and ≥ 30% from Baseline) at Week 8 randomized to adalimumab maintenance standard dose (0.6 mg/kg [maximum dose of 40 mg] every other week [eow]). Participants were to continue their blinded treatment during the maintenance period until Week 52 unless they had ≥ 2 flares and got open label rescue therapy after the second flare. Participants demonstrating a clinical response per PMS (defined as a decrease in PMS ≥ 2 points and ≥ 30% from Baseline) at Week 8 randomized to adalimumab maintenance high dose (0.6 mg/kg [maximum dose of 40 mg] every week [ew]). Participants were to continue their blinded treatment during the maintenance period until Week 52 unless they had ≥ 2 flares and got open label rescue therapy after the second flare.
Period Title: Induction Period
Started 32 51 18 0 0 0
Enrolled in Main Study 30 47 16 0 0 0
Enrolled in Japan Sub-study 2 4 2 0 0 0
Completed 22 43 16 0 0 0
Not Completed 10 8 2 0 0 0
Reason Not Completed
Withdrawal by Subject             2             1             0             0             0             0
Lack of Efficacy             2             1             1             0             0             0
Requires Alternative/Prohibited Therapy             1             1             1             0             0             0
Non-Responder at Week 8             4             4             0             0             0             0
Adverse Event             1             1             0             0             0             0
Period Title: Maintenance Period
Started 0 0 0 12 33 36
Completed [1] 0 0 0 11 25 32
Not Completed 0 0 0 1 8 4
Reason Not Completed
Requires Alternative/Prohibited Therapy             0             0             0             1             1             0
Withdrawal by Subject             0             0             0             0             2             1
Lack of Efficacy             0             0             0             0             5             2
Subject Non-Compliance             0             0             0             0             0             1
[1]
Completed Week 52
Arm/Group Title Integrated Study (Main + Japan Sub- Study): I-SD Integrated Study (Main + Japan Sub- Study): I-HD Integrated Study (Main + Japan Sub- Study): I-HD-OL Total
Hide Arm/Group Description Participants randomized to receive adalimumab 2.4 mg/kg (maximum dose of 160 mg) at Baseline and matching placebo at Week 1, 1.2 mg/kg (maximum dose of 80 mg) at Week 2, followed by 0.6 mg/kg (maximum dose of 40 mg) at Week 4 and Week 6. Participants randomized to receive adalimumab 2.4 mg/kg (maximum dose of 160 mg) at Baseline and at Week 1, 1.2 mg/kg (maximum dose of 80 mg) at Week 2, followed by 0.6 mg/kg (maximum dose of 40 mg) at Week 4 and Week 6. (After Amendment 4) participants assigned to open-label adalimumab 2.4 mg/kg (maximum dose of 160 mg) at Baseline and at Week 1, 1.2 mg/kg (maximum dose of 80 mg) at Week 2, followed by 0.6 mg/kg (maximum dose of 40 mg) at Week 4 and Week 6. Total of all reporting groups
Overall Number of Baseline Participants 32 51 18 101
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 32 participants 51 participants 18 participants 101 participants
14.7  (2.66) 13.8  (3.06) 13.8  (2.82) 14.1  (2.90)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 32 participants 51 participants 18 participants 101 participants
Female
15
  46.9%
23
  45.1%
13
  72.2%
51
  50.5%
Male
17
  53.1%
28
  54.9%
5
  27.8%
50
  49.5%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
 Number Analyzed 32 participants 51 participants 18 participants 101 participants
White
28
  87.5%
45
  88.2%
15
  83.3%
88
  87.1%
Black
1
   3.1%
2
   3.9%
0
   0.0%
3
   3.0%
Asian
3
   9.4%
4
   7.8%
2
  11.1%
9
   8.9%
Multiple
0
   0.0%
0
   0.0%
1
   5.6%
1
   1.0%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
 Number Analyzed 32 participants 51 participants 18 participants 101 participants
Hispanic or Latino
1
   3.1%
2
   3.9%
1
   5.6%
4
   4.0%
Japanese
2
   6.3%
4
   7.8%
2
  11.1%
8
   7.9%
No Ethnicity
29
  90.6%
45
  88.2%
15
  83.3%
89
  88.1%
Full Mayo Score (FMS)   [1] 
Mean (Standard Deviation)
Unit of measure:  Score on a scale
Number Analyzed 32 participants 51 participants 18 participants 101 participants
7.8  (1.22) 7.7  (1.25) 7.7  (1.09) 7.8  (1.20)
[1]
Measure Description: The Mayo score is a tool designed to measure disease activity for ulcerative colitis. The FMS ranges from 0 (normal or inactive disease) to 12 (severe disease) and is calculated as the sum of 4 subscores (stool frequency, rectal bleeding, endoscopy, and physician's global assessment), each of which ranges from 0 (normal) to 3 (severe disease).
Partial Mayo Score (PMS)   [1] 
Mean (Standard Deviation)
Unit of measure:  Score on a scale
Number Analyzed 32 participants 51 participants 18 participants 101 participants
5.7  (1.14) 5.5  (1.24) 5.5  (1.06) 5.6  (1.17)
[1]
Measure Description: The PMS (Mayo score without endoscopy) ranges from 0 (normal or inactive disease) to 9 (severe disease) and is calculated as the sum of 3 subscores (stool frequency, rectal bleeding and physician's global assessment), each of which ranges from 0 (normal) to 3 (severe disease).
Endoscopy Subscore   [1] 
Mean (Standard Deviation)
Unit of measure:  Score on a scale
Number Analyzed 32 participants 51 participants 18 participants 101 participants
2.1  (0.34) 2.2  (0.40) 2.2  (0.43) 2.2  (0.38)
[1]
Measure Description: The endoscopy subscore of the FMS ranges from 0 (normal) to 3 (severe disease).
Rectal Bleeding Subscore   [1] 
Mean (Standard Deviation)
Unit of measure:  Score on a scale
Number Analyzed 32 participants 51 participants 18 participants 101 participants
1.4  (0.93) 1.5  (0.88) 1.4  (0.97) 1.5  (0.91)
[1]
Measure Description: The rectal bleeding subscore of the FMS ranges from 0 (normal) to 3 (severe disease).
Physicians Global Assessment Subscore   [1] 
Mean (Standard Deviation)
Unit of measure:  Score on a scale
Number Analyzed 32 participants 51 participants 18 participants 101 participants
2.2  (0.40) 2.2  (0.43) 2.2  (0.38) 2.2  (0.41)
[1]
Measure Description: The physicians global assessment subscore of the FMS ranges from 0 (normal) to 3 (severe disease).
Stool Frequency Subscore   [1] 
Mean (Standard Deviation)
Unit of measure:  Score on a scale
Number Analyzed 32 participants 51 participants 18 participants 101 participants
2.1  (0.78) 1.8  (0.88) 1.9  (0.73) 1.9  (0.83)
[1]
Measure Description: The stool frequency subscore of the FMS ranges from 0 (normal) to 3 (severe disease).
1.Primary Outcome
Title Co-Primary Endpoint 1: Percentage of Participants Who Achieved Clinical Remission as Measured by Partial Mayo Score (PMS) at Week 8 - Induction Period
Hide Description The Mayo score is a tool designed to measure disease activity for ulcerative colitis. The PMS (Mayo score without endoscopy) ranges from 0 (normal or inactive disease) to 9 (severe disease) and is calculated as the sum of 3 sub scores (stool frequency, rectal bleeding and physician's global assessment), each of which ranges from 0 (normal) to 3 (severe disease). A negative change in PMS indicates improvement. Clinical remission was defined as a PMS ≤ 2 and no individual subscore > 1.
Time Frame Week 8
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-Treat (ITT): all participants who received at least 1 dose of study drug during the Induction period; analyzed as enrolled/randomized. Non-responder imputation (NRI): missing data is imputed as not having met the endpoint.
Arm/Group Title Main Study: I-SD Main Study: I-HD Main Study: I-SD + I-HD Main Study: I-HD-OL Integrated Study (Main + Japan Sub-Study): I-SD Integrated Study (Main + Japan Sub-Study): I-HD Integrated Study (Main + Japan Sub-Study): I-SD + I-HD Integrated Study (Main + Japan Sub-Study): I-HD-OL
Hide Arm/Group Description:
Participants randomized to receive adalimumab 2.4 mg/kg (maximum dose of 160 mg) at Baseline and matching placebo at Week 1, 1.2 mg/kg (maximum dose of 80 mg) at Week 2, followed by 0.6 mg/kg (maximum dose of 40 mg) at Week 4 and Week 6.
Participants randomized to receive adalimumab 2.4 mg/kg (maximum dose of 160 mg) at Baseline and at Week 1, 1.2 mg/kg (maximum dose of 80 mg) at Week 2, followed by 0.6 mg/kg (maximum dose of 40 mg) at Week 4 and Week 6.
Combined I-SD + I-HD arms (see above).
(After Amendment 4) participants assigned to open-label adalimumab 2.4 mg/kg (maximum dose of 160 mg) at Baseline and at Week 1, 1.2 mg/kg (maximum dose of 80 mg) at Week 2, followed by 0.6 mg/kg (maximum dose of 40 mg) at Week 4 and Week 6.
Participants randomized to receive adalimumab 2.4 mg/kg (maximum dose of 160 mg) at Baseline and matching placebo at Week 1, 1.2 mg/kg (maximum dose of 80 mg) at Week 2, followed by 0.6 mg/kg (maximum dose of 40 mg) at Week 4 and Week 6.
Participants randomized to receive adalimumab 2.4 mg/kg (maximum dose of 160 mg) at Baseline and at Week 1, 1.2 mg/kg (maximum dose of 80 mg) at Week 2, followed by 0.6 mg/kg (maximum dose of 40 mg) at Week 4 and Week 6.
Combined I-SD + I-HD arms (see above).
(After Amendment 4) participants assigned to open-label adalimumab 2.4 mg/kg (maximum dose of 160 mg) at Baseline and at Week 1, 1.2 mg/kg (maximum dose of 80 mg) at Week 2, followed by 0.6 mg/kg (maximum dose of 40 mg) at Week 4 and Week 6.
Overall Number of Participants Analyzed 30 47 77 16 32 51 83 18
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
43.3
(25.46 to 62.57)
59.6
(44.27 to 73.63)
53.2
(41.52 to 64.71)
68.8
(41.34 to 88.98)
40.6
(23.70 to 59.36)
58.8
(44.17 to 72.42)
51.8
(40.56 to 62.92)
66.7
(40.99 to 86.66)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Main Study: I-SD + I-HD
Comments Efficacy analysis was based on the Intent-To-Treat-Efficacy (ITT-E) population for the induction period. The ITT-E population was a subpopulation of the ITT population, which consisted of all participants who received at least one SC injection of the study medication during the induction period. Participants who received open-label high induction dose, because they enrolled after Protocol Amendment 4 was released, were excluded from the ITT-E population.
Type of Statistical Test Superiority
Comments one-sample two-sided Chi-square test
Statistical Test of Hypothesis P-Value < 0.001
Comments Adjusted p-value from a sequentially rejective multiple test procedure, testing co-primary and ranked secondary endpoints 1st for I-SD+I-HD, then for individual adalimumab dose groups (I-HD, I-SD) against the respective external placebo rate (19.83%)
Method rejective multiple test procedure
Comments controlling familywise Type I error of 5% in a strong sense
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Main Study: I-HD
Comments Efficacy analysis was based on the Intent-To-Treat-Efficacy (ITT-E) population for the induction period. The ITT-E population was a subpopulation of the ITT population, which consisted of all participants who received at least one SC injection of the study medication during the induction period. Participants who received open-label high induction dose, because they enrolled after Protocol Amendment 4 was released, were excluded from the ITT-E population.
Type of Statistical Test Superiority
Comments one-sample two-sided Chi-square test
Statistical Test of Hypothesis P-Value < 0.001
Comments Adjusted p-value from a sequentially rejective multiple test procedure, testing co-primary and ranked secondary endpoints 1st for I-SD+I-HD, then for individual adalimumab dose groups (I-HD, I-SD) against the respective external placebo rate (19.83%)
Method rejective multiple test procedure
Comments controlling familywise Type I error of 5% in a strong sense
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Main Study: I-SD
Comments Efficacy analysis was based on the Intent-To-Treat-Efficacy (ITT-E) population for the induction period. The ITT-E population was a subpopulation of the ITT population, which consisted of all participants who received at least one SC injection of the study medication during the induction period. Participants who received open-label high induction dose, because they enrolled after Protocol Amendment 4 was released, were excluded from the ITT-E population.
Type of Statistical Test Superiority
Comments one-sample two-sided Chi-square test
Statistical Test of Hypothesis P-Value 0.382
Comments Adjusted p-value from a sequentially rejective multiple test procedure, testing co-primary and ranked secondary endpoints 1st for I-SD+I-HD, then for individual adalimumab dose groups (I-HD, I-SD) against the respective external placebo rate (19.83%)
Method rejective multiple test procedure
Comments controlling familywise Type I error of 5% in a strong sense
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Integrated Study (Main + Japan Sub-Study): I-SD + I-HD
Comments Efficacy analysis was based on the Intent-To-Treat-Efficacy (ITT-E) population for the induction period. The ITT-E population was a subpopulation of the ITT population, which consisted of all participants who received at least one SC injection of the study medication during the induction period. Participants who received open-label high induction dose, because they enrolled after Protocol Amendment 4 was released, were excluded from the ITT-E population.
Type of Statistical Test Superiority
Comments one-sample two-sided Chi-square test
Statistical Test of Hypothesis P-Value < 0.001
Comments Adjusted p-value from a sequentially rejective multiple test procedure, testing co-primary and ranked secondary endpoints 1st for I-SD+I-HD, then for individual adalimumab dose groups (I-HD, I-SD) against the respective external placebo rate (19.83%)
Method rejective multiple test procedure
Comments controlling familywise Type I error of 5% in a strong sense
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Integrated Study (Main + Japan Sub-Study): I-HD
Comments Efficacy analysis was based on the Intent-To-Treat-Efficacy (ITT-E) population for the induction period. The ITT-E population was a subpopulation of the ITT population, which consisted of all participants who received at least one SC injection of the study medication during the induction period. Participants who received open-label high induction dose, because they enrolled after Protocol Amendment 4 was released, were excluded from the ITT-E population.
Type of Statistical Test Superiority
Comments one-sample two-sided Chi-square test
Statistical Test of Hypothesis P-Value < 0.001
Comments Adjusted p-value from a sequentially rejective multiple test procedure, testing co-primary and ranked secondary endpoints 1st for I-SD+I-HD, then for individual adalimumab dose groups (I-HD, I-SD) against the respective external placebo rate (19.83%)
Method rejective multiple test procedure
Comments controlling familywise Type I error of 5% in a strong sense
Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Integrated Study (Main + Japan Sub-Study): I-SD
Comments Efficacy analysis was based on the Intent-To-Treat-Efficacy (ITT-E) population for the induction period. The ITT-E population was a subpopulation of the ITT population, which consisted of all participants who received at least one SC injection of the study medication during the induction period. Participants who received open-label high induction dose, because they enrolled after Protocol Amendment 4 was released, were excluded from the ITT-E population.
Type of Statistical Test Superiority
Comments one-sample two-sided Chi-square test
Statistical Test of Hypothesis P-Value 0.344
Comments Adjusted p-value from a sequentially rejective multiple test procedure, testing co-primary and ranked secondary endpoints 1st for I-SD+I-HD, then for individual adalimumab dose groups (I-HD, I-SD) against the respective external placebo rate (19.83%)
Method rejective multiple test procedure
Comments controlling familywise Type I error of 5% in a strong sense
2.Primary Outcome
Title Co-Primary Endpoint 2: Percentage of Participants With Clinical Remission Per Full Mayo Score (FMS) at Week 52 in Week 8 Responders Per PMS - Maintenance Period
Hide Description The FMS ranges from 0 (normal or inactive disease) to 12 (severe disease) and is calculated as the sum of 4 subscores (stool frequency, rectal bleeding, endoscopy, and physician's global assessment), each of which ranges from 0 (normal) to 3 (severe disease). The PMS (Mayo score without endoscopy) ranges from 0 (normal or inactive disease) to 9 (severe disease) and is calculated as the sum of 3 subscores (stool frequency, rectal bleeding and physician's global assessment). Negative changes indicate improvement. PMS responders are defined as those with a decrease in PMS ≥ 2 points and ≥ 30% from Baseline. Clinical remission per FMS is defined as Mayo Score ≤ 2 and no individual subscore > 1.
Time Frame Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
Modified intent-to-treat (mITT): all Week 8 PMS responders who were re-randomized at Week 8 and received at least 1 dose of study drug during the Maintenance period; analyzed as randomized at the beginning of the Maintenance phase. NRI: missing data is imputed as not having met the endpoint.
Arm/Group Title Main Study: M-PL Main Study: M-SD Main Study: M-HD Main Study: M-SD + M-HD Integrated Study (Main + Japan Sub-Study): M-PL Integrated Study (Main + Japan Sub-Study): M-SD Integrated Study (Main + Japan Sub-Study): M-HD Integrated Study (Main + Japan Sub-Study): M-SD + M-HD
Hide Arm/Group Description:
(Prior to Amendment 4) participants demonstrating a clinical response per PMS (defined as a decrease in PMS ≥ 2 points and ≥ 30% from Baseline) at Week 8 randomized to maintenance placebo. Participants were to continue their blinded treatment during the maintenance period until Week 52 unless they had ≥ 2 flares and got open label adalimumab rescue therapy after the second flare.
Participants demonstrating a clinical response per PMS (defined as a decrease in PMS ≥ 2 points and ≥ 30% from Baseline) at Week 8 randomized to adalimumab maintenance standard dose (0.6 mg/kg [maximum dose of 40 mg] eow). Participants were to continue their blinded treatment during the maintenance period until Week 52 unless they had ≥ 2 flares and got open label rescue therapy after the second flare.
Participants demonstrating a clinical response per PMS (defined as a decrease in PMS ≥ 2 points and ≥ 30% from Baseline) at Week 8 randomized to adalimumab maintenance high dose (0.6 mg/kg [maximum dose of 40 mg] ew). Participants were to continue their blinded treatment during the maintenance period until Week 52 unless they had ≥ 2 flares and got open label rescue therapy after the second flare.
Combined M-SD + M-HD arms (see above).
(Prior to Amendment 4) participants demonstrating a clinical response per PMS (defined as a decrease in PMS ≥ 2 points and ≥ 30% from Baseline) at Week 8 randomized to maintenance placebo. Participants were to continue their blinded treatment during the maintenance period until Week 52 unless they had ≥ 2 flares and got open label adalimumab rescue therapy after the second flare.
Participants demonstrating a clinical response per PMS (defined as a decrease in PMS ≥ 2 points and ≥ 30% from Baseline) at Week 8 randomized to adalimumab maintenance standard dose (0.6 mg/kg [maximum dose of 40 mg] eow). Participants were to continue their blinded treatment during the maintenance period until Week 52 unless they had ≥ 2 flares and got open label rescue therapy after the second flare.
Participants demonstrating a clinical response per PMS (defined as a decrease in PMS ≥ 2 points and ≥ 30% from Baseline) at Week 8 randomized to adalimumab maintenance high dose (0.6 mg/kg [maximum dose of 40 mg] ew). Participants were to continue their blinded treatment during the maintenance period until Week 52 unless they had ≥ 2 flares and got open label rescue therapy after the second flare.
Combined M-SD + M-HD arms (see above).
Overall Number of Participants Analyzed 12 31 31 62 12 33 35 68
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
33.3
(9.92 to 65.11)
29.0
(14.22 to 48.04)
45.2
(27.32 to 63.97)
37.1
(25.16 to 50.31)
33.3
(9.92 to 65.11)
27.3
(13.30 to 45.52)
42.9
(26.32 to 60.65)
35.3
(24.08 to 47.83)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Main Study: M-SD + M-HD
Comments Efficacy analysis was based on the modified Intent-To-Treat-Efficacy (mITT-E) population for the maintenance period. The mITT-E population was a subpopulation of the mITT population, where participants in M-PL arm were excluded.
Type of Statistical Test Superiority
Comments one-sample two-sided Chi-square test
Statistical Test of Hypothesis P-Value < 0.001
Comments Adjusted p-value from a sequentially rejective multiple test procedure, testing co-primary and ranked secondary endpoints 1st for M-SD+M-HD, then for individual adalimumab dose groups (M-HD, M-SD) against the respective external placebo rate (18.37%)
Method rejective multiple test procedure
Comments controlling familywise Type I error of 5% in a strong sense
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Main Study: M-HD
Comments Efficacy analysis was based on the modified Intent-To-Treat-Efficacy (mITT-E) population for the maintenance period. The mITT-E population was a subpopulation of the mITT population, where participants in M-PL arm were excluded.
Type of Statistical Test Superiority
Comments one-sample two-sided Chi-square test
Statistical Test of Hypothesis P-Value < 0.001
Comments Adjusted p-value from a sequentially rejective multiple test procedure, testing co-primary and ranked secondary endpoints 1st for M-SD+M-HD, then for individual adalimumab dose groups (M-HD, M-SD) against the respective external placebo rate (18.37%)
Method rejective multiple test procedure
Comments controlling familywise Type I error of 5% in a strong sense
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Main Study: M-SD
Comments Efficacy analysis was based on the modified Intent-To-Treat-Efficacy (mITT-E) population for the maintenance period. The mITT-E population was a subpopulation of the mITT population, where participants in M-PL arm were excluded.
Type of Statistical Test Superiority
Comments one-sample two-sided Chi-square test
Statistical Test of Hypothesis P-Value 0.382
Comments Adjusted p-value from a sequentially rejective multiple test procedure, testing co-primary and ranked secondary endpoints 1st for M-SD+M-HD, then for individual adalimumab dose groups (M-HD, M-SD) against the respective external placebo rate (18.37%)
Method rejective multiple test procedure
Comments controlling familywise Type I error of 5% in a strong sense
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Integrated Study (Main + Japan Sub-Study): M-SD + M-HD
Comments Efficacy analysis was based on the modified Intent-To-Treat-Efficacy (mITT-E) population for the maintenance period. The mITT-E population was a subpopulation of the mITT population, where participants in M-PL arm were excluded.
Type of Statistical Test Superiority
Comments one-sample two-sided Chi-square test
Statistical Test of Hypothesis P-Value < 0.001
Comments Adjusted p-value from a sequentially rejective multiple test procedure, testing co-primary and ranked secondary endpoints 1st for M-SD+M-HD, then for individual adalimumab dose groups (M-HD, M-SD) against the respective external placebo rate (18.37%)
Method rejective multiple test procedure
Comments controlling familywise Type I error of 5% in a strong sense
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Integrated Study (Main + Japan Sub-Study): M-HD
Comments Efficacy analysis was based on the modified Intent-To-Treat-Efficacy (mITT-E) population for the maintenance period. The mITT-E population was a subpopulation of the mITT population, where participants in M-PL arm were excluded.
Type of Statistical Test Superiority
Comments one-sample two-sided Chi-square test
Statistical Test of Hypothesis P-Value < 0.001
Comments Adjusted p-value from a sequentially rejective multiple test procedure, testing co-primary and ranked secondary endpoints 1st for M-SD+M-HD, then for individual adalimumab dose groups (M-HD, M-SD) against the respective external placebo rate (18.37%)
Method rejective multiple test procedure
Comments controlling familywise Type I error of 5% in a strong sense
Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Integrated Study (Main + Japan Sub-Study): M-SD
Comments Efficacy analysis was based on the modified Intent-To-Treat-Efficacy (mITT-E) population for the maintenance period. The mITT-E population was a subpopulation of the mITT population, where participants in M-PL arm were excluded.
Type of Statistical Test Superiority
Comments one-sample two-sided Chi-square test
Statistical Test of Hypothesis P-Value 0.344
Comments Adjusted p-value from a sequentially rejective multiple test procedure, testing co-primary and ranked secondary endpoints 1st for M-SD+M-HD, then for individual adalimumab dose groups (M-HD, M-SD) against the respective external placebo rate (18.37%)
Method rejective multiple test procedure
Comments controlling familywise Type I error of 5% in a strong sense
3.Secondary Outcome
Title Ranked Secondary Endpoint 1: Percentage of Participants With Clinical Response Per FMS at Week 52 in Week 8 Responders Per PMS - Maintenance Period
Hide Description The FMS ranges from 0 (normal or inactive disease) to 12 (severe disease) and is calculated as the sum of 4 subscores (stool frequency, rectal bleeding, endoscopy, and physician's global assessment), each of which ranges from 0 (normal) to 3 (severe disease). The PMS (Mayo score without endoscopy) ranges from 0 (normal or inactive disease) to 9 (severe disease) and is calculated as the sum of 3 subscores (stool frequency, rectal bleeding and physician's global assessment). Negative changes indicate improvement. PMS responders are defined as those with a decrease in PMS ≥ 2 points and ≥ 30% from Baseline. Clinical response per FMS is defined as a decrease in FMS ≥ 3 points and ≥ 30% from Baseline.
Time Frame Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
Modified intent-to-treat (mITT): all Week 8 PMS responders who were re-randomized at Week 8 and received at least 1 dose of study drug during the Maintenance period; analyzed as randomized at the beginning of the Maintenance phase. NRI: missing data is imputed as not having met the endpoint.
Arm/Group Title Main Study: M-PL Main Study: M-SD Main Study: M-HD Main Study: M-SD + M-HD Integrated Study (Main + Japan Sub-Study): M-PL Integrated Study (Main + Japan Sub-Study): M-SD Integrated Study (Main + Japan Sub-Study): M-HD Integrated Study (Main + Japan Sub-Study): M-SD + M-HD
Hide Arm/Group Description:
(Prior to Amendment 4) participants demonstrating a clinical response per PMS (defined as a decrease in PMS ≥ 2 points and ≥ 30% from Baseline) at Week 8 randomized to maintenance placebo. Participants were to continue their blinded treatment during the maintenance period until Week 52 unless they had ≥ 2 flares and got open label adalimumab rescue therapy after the second flare.
Participants demonstrating a clinical response per PMS (defined as a decrease in PMS ≥ 2 points and ≥ 30% from Baseline) at Week 8 randomized to adalimumab maintenance standard dose (0.6 mg/kg [maximum dose of 40 mg] eow). Participants were to continue their blinded treatment during the maintenance period until Week 52 unless they had ≥ 2 flares and got open label rescue therapy after the second flare.
Participants demonstrating a clinical response per PMS (defined as a decrease in PMS ≥ 2 points and ≥ 30% from Baseline) at Week 8 randomized to adalimumab maintenance high dose (0.6 mg/kg [maximum dose of 40 mg] ew). Participants were to continue their blinded treatment during the maintenance period until Week 52 unless they had ≥ 2 flares and got open label rescue therapy after the second flare.
Combined M-SD + M-HD arms (see above).
(Prior to Amendment 4) participants demonstrating a clinical response per PMS (defined as a decrease in PMS ≥ 2 points and ≥ 30% from Baseline) at Week 8 randomized to maintenance placebo. Participants were to continue their blinded treatment during the maintenance period until Week 52 unless they had ≥ 2 flares and got open label adalimumab rescue therapy after the second flare.
Participants demonstrating a clinical response per PMS (defined as a decrease in PMS ≥ 2 points and ≥ 30% from Baseline) at Week 8 randomized to adalimumab maintenance standard dose (0.6 mg/kg [maximum dose of 40 mg] eow). Participants were to continue their blinded treatment during the maintenance period until Week 52 unless they had ≥ 2 flares and got open label rescue therapy after the second flare.
Participants demonstrating a clinical response per PMS (defined as a decrease in PMS ≥ 2 points and ≥ 30% from Baseline) at Week 8 randomized to adalimumab maintenance high dose (0.6 mg/kg [maximum dose of 40 mg] ew). Participants were to continue their blinded treatment during the maintenance period until Week 52 unless they had ≥ 2 flares and got open label rescue therapy after the second flare.
Combined M-SD + M-HD arms (see above).
Overall Number of Participants Analyzed 12 31 31 62 12 33 35 68
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
33.3
(9.92 to 65.11)
61.3
(42.19 to 78.15)
67.7
(48.63 to 83.32)
64.5
(51.34 to 76.26)
33.3
(9.92 to 65.11)
57.6
(39.22 to 74.52)
65.7
(47.79 to 80.87)
61.8
(49.18 to 73.29)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Main Study: M-SD + M-HD
Comments Efficacy analysis was based on the modified Intent-To-Treat-Efficacy (mITT-E) population for the maintenance period. The mITT-E population was a subpopulation of the mITT population, where participants in M-PL arm were excluded.
Type of Statistical Test Superiority
Comments one-sample two-sided Chi-square test
Statistical Test of Hypothesis P-Value < 0.001
Comments Adjusted p-value from a sequentially rejective multiple test procedure, testing co-primary and ranked secondary endpoints 1st for M-SD+M-HD, then for individual adalimumab dose groups (M-HD, M-SD) against the respective external placebo rate (26.10%)
Method rejective multiple test procedure
Comments controlling familywise Type I error of 5% in a strong sense
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Main Study: M-HD
Comments Efficacy analysis was based on the modified Intent-To-Treat-Efficacy (mITT-E) population for the maintenance period. The mITT-E population was a subpopulation of the mITT population, where participants in M-PL arm were excluded.
Type of Statistical Test Superiority
Comments one-sample two-sided Chi-square test
Statistical Test of Hypothesis P-Value < 0.001
Comments Adjusted p-value from a sequentially rejective multiple test procedure, testing co-primary and ranked secondary endpoints 1st for M-SD+M-HD, then for individual adalimumab dose groups (M-HD, M-SD) against the respective external placebo rate (26.10%)
Method Chi-squared
Comments controlling familywise Type I error of 5% in a strong sense
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Main Study: M-SD
Comments Efficacy analysis was based on the modified Intent-To-Treat-Efficacy (mITT-E) population for the maintenance period. The mITT-E population was a subpopulation of the mITT population, where participants in M-PL arm were excluded.
Type of Statistical Test Superiority
Comments one-sample two-sided Chi-square test
Statistical Test of Hypothesis P-Value 0.008
Comments Adjusted p-value from a sequentially rejective multiple test procedure, testing co-primary and ranked secondary endpoints 1st for M-SD+M-HD, then for individual adalimumab dose groups (M-HD, M-SD) against the respective external placebo rate (26.10%)
Method Chi-squared
Comments controlling familywise Type I error of 5% in a strong sense
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Integrated Study (Main + Japan Sub-Study): M-SD + M-HD
Comments Efficacy analysis was based on the modified Intent-To-Treat-Efficacy (mITT-E) population for the maintenance period. The mITT-E population was a subpopulation of the mITT population, where participants in M-PL arm were excluded.
Type of Statistical Test Superiority
Comments one-sample two-sided Chi-square test
Statistical Test of Hypothesis P-Value < 0.001
Comments Adjusted p-value from a sequentially rejective multiple test procedure, testing co-primary and ranked secondary endpoints 1st for M-SD+M-HD, then for individual adalimumab dose groups (M-HD, M-SD) against the respective external placebo rate (26.10%)
Method rejective multiple test procedure
Comments controlling familywise Type I error of 5% in a strong sense
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Integrated Study (Main + Japan Sub-Study): M-HD
Comments Efficacy analysis was based on the modified Intent-To-Treat-Efficacy (mITT-E) population for the maintenance period. The mITT-E population was a subpopulation of the mITT population, where participants in M-PL arm were excluded.
Type of Statistical Test Superiority
Comments one-sample two-sided Chi-square test
Statistical Test of Hypothesis P-Value < 0.001
Comments Adjusted p-value from a sequentially rejective multiple test procedure, testing co-primary and ranked secondary endpoints 1st for M-SD+M-HD, then for individual adalimumab dose groups (M-HD, M-SD) against the respective external placebo rate (26.10%)
Method rejective multiple test procedure
Comments controlling familywise Type I error of 5% in a strong sense
Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Integrated Study (Main + Japan Sub-Study): M-SD
Comments Efficacy analysis was based on the modified Intent-To-Treat-Efficacy (mITT-E) population for the maintenance period. The mITT-E population was a subpopulation of the mITT population, where participants in M-PL arm were excluded.
Type of Statistical Test Superiority
Comments one-sample two-sided Chi-square test
Statistical Test of Hypothesis P-Value 0.038
Comments Adjusted p-value from a sequentially rejective multiple test procedure, testing co-primary and ranked secondary endpoints 1st for M-SD+M-HD, then for individual adalimumab dose groups (M-HD, M-SD) against the respective external placebo rate (26.10%)
Method rejective multiple test procedure
Comments controlling familywise Type I error of 5% in a strong sense
4.Secondary Outcome
Title Ranked Secondary Endpoint 2: Percentage of Participants With Mucosal Healing at Week 52 in Week 8 Responders Per PMS - Maintenance Period
Hide Description The FMS ranges from 0 (normal or inactive disease) to 12 (severe disease) and is calculated as the sum of 4 subscores (stool frequency, rectal bleeding, endoscopy, and physician's global assessment), each of which ranges from 0 (normal) to 3 (severe disease). The PMS (Mayo score without endoscopy) ranges from 0 (normal or inactive disease) to 9 (severe disease) and is calculated as the sum of 3 subscores (stool frequency, rectal bleeding and physician's global assessment). Negative changes indicate improvement. PMS responders are defined as those participants with a decrease in PMS ≥ 2 points and ≥ 30% from Baseline. Mucosal healing per Mayo endoscopy subscore is defined as a subscore of ≤ 1.
Time Frame Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
Modified intent-to-treat (mITT): all Week 8 PMS responders who were re-randomized at Week 8 and received at least 1 dose of study drug during the Maintenance period; analyzed as randomized at the beginning of the Maintenance phase. NRI: missing data is imputed as not having met the endpoint.
Arm/Group Title Main Study: M-PL Main Study: M-SD Main Study: M-HD Main Study: M-SD + M-HD Integrated Study (Main + Japan Sub-Study): M-PL Integrated Study (Main + Japan Sub-Study): M-SD Integrated Study (Main + Japan Sub-Study): M-HD Integrated Study (Main + Japan Sub-Study): M-SD + M-HD
Hide Arm/Group Description:
(Prior to Amendment 4) participants demonstrating a clinical response per PMS (defined as a decrease in PMS ≥ 2 points and ≥ 30% from Baseline) at Week 8 randomized to maintenance placebo. Participants were to continue their blinded treatment during the maintenance period until Week 52 unless they had ≥ 2 flares and got open label adalimumab rescue therapy after the second flare.
Participants demonstrating a clinical response per PMS (defined as a decrease in PMS ≥ 2 points and ≥ 30% from Baseline) at Week 8 randomized to adalimumab maintenance standard dose (0.6 mg/kg [maximum dose of 40 mg] eow). Participants were to continue their blinded treatment during the maintenance period until Week 52 unless they had ≥ 2 flares and got open label rescue therapy after the second flare.
Participants demonstrating a clinical response per PMS (defined as a decrease in PMS ≥ 2 points and ≥ 30% from Baseline) at Week 8 randomized to adalimumab maintenance high dose (0.6 mg/kg [maximum dose of 40 mg] ew). Participants were to continue their blinded treatment during the maintenance period until Week 52 unless they had ≥ 2 flares and got open label rescue therapy after the second flare.
Combined M-SD + M-HD arms (see above).
(Prior to Amendment 4) participants demonstrating a clinical response per PMS (defined as a decrease in PMS ≥ 2 points and ≥ 30% from Baseline) at Week 8 randomized to maintenance placebo. Participants were to continue their blinded treatment during the maintenance period until Week 52 unless they had ≥ 2 flares and got open label adalimumab rescue therapy after the second flare.
Participants demonstrating a clinical response per PMS (defined as a decrease in PMS ≥ 2 points and ≥ 30% from Baseline) at Week 8 randomized to adalimumab maintenance standard dose (0.6 mg/kg [maximum dose of 40 mg] eow). Participants were to continue their blinded treatment during the maintenance period until Week 52 unless they had ≥ 2 flares and got open label rescue therapy after the second flare.
Participants demonstrating a clinical response per PMS (defined as a decrease in PMS ≥ 2 points and ≥ 30% from Baseline) at Week 8 randomized to adalimumab maintenance high dose (0.6 mg/kg [maximum dose of 40 mg] ew). Participants were to continue their blinded treatment during the maintenance period until Week 52 unless they had ≥ 2 flares and got open label rescue therapy after the second flare.
Combined M-SD + M-HD arms (see above).
Overall Number of Participants Analyzed 12 31 31 62 12 33 35 68
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
33.3
(9.92 to 65.11)
38.7
(21.85 to 57.81)
51.6
(33.06 to 69.85)
45.2
(32.48 to 58.32)
33.3
(9.92 to 65.11)
36.4
(20.40 to 54.88)
48.6
(31.38 to 66.01)
42.6
(30.72 to 55.23)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Main Study: M-SD + M-HD
Comments Efficacy analysis was based on the modified Intent-To-Treat-Efficacy (mITT-E) population for the maintenance period. The mITT-E population was a subpopulation of the mITT population, where participants in M-PL arm were excluded.
Type of Statistical Test Superiority
Comments one-sample two-sided Chi-square test
Statistical Test of Hypothesis P-Value < 0.001
Comments Adjusted p-value from a sequentially rejective multiple test procedure, testing co-primary and ranked secondary endpoints 1st for M-SD+M-HD, then for individual adalimumab dose groups (M-HD, M-SD) against the respective external placebo rate (22.03%)
Method rejective multiple test procedure
Comments controlling familywise Type I error of 5% in a strong sense
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Main Study: M-HD
Comments Efficacy analysis was based on the modified Intent-To-Treat-Efficacy (mITT-E) population for the maintenance period. The mITT-E population was a subpopulation of the mITT population, where participants in M-PL arm were excluded.
Type of Statistical Test Superiority
Comments one-sample two-sided Chi-square test
Statistical Test of Hypothesis P-Value < 0.001
Comments Adjusted p-value from a sequentially rejective multiple test procedure, testing co-primary and ranked secondary endpoints 1st for M-SD+M-HD, then for individual adalimumab dose groups (M-HD, M-SD) against the respective external placebo rate (22.03%)
Method rejective multiple test procedure
Comments controlling familywise Type I error of 5% in a strong sense
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Main Study: M-SD
Comments Efficacy analysis was based on the modified Intent-To-Treat-Efficacy (mITT-E) population for the maintenance period. The mITT-E population was a subpopulation of the mITT population, where participants in M-PL arm were excluded.
Type of Statistical Test Superiority
Comments one-sample two-sided Chi-square test
Statistical Test of Hypothesis P-Value 0.382
Comments Adjusted p-value from a sequentially rejective multiple test procedure, testing co-primary and ranked secondary endpoints 1st for M-SD+M-HD, then for individual adalimumab dose groups (M-HD, M-SD) against the respective external placebo rate (22.03%)
Method rejective multiple test procedure
Comments controlling familywise Type I error of 5% in a strong sense
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Integrated Study (Main + Japan Sub-Study): M-SD + M-HD
Comments Efficacy analysis was based on the modified Intent-To-Treat-Efficacy (mITT-E) population for the maintenance period. The mITT-E population was a subpopulation of the mITT population, where participants in M-PL arm were excluded.
Type of Statistical Test Superiority
Comments one-sample two-sided Chi-square test
Statistical Test of Hypothesis P-Value < 0.001
Comments Adjusted p-value from a sequentially rejective multiple test procedure, testing co-primary and ranked secondary endpoints 1st for M-SD+M-HD, then for individual adalimumab dose groups (M-HD, M-SD) against the respective external placebo rate (22.03%)
Method rejective multiple test procedure
Comments controlling familywise Type I error of 5% in a strong sense
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Integrated Study (Main + Japan Sub-Study): M-HD
Comments Efficacy analysis was based on the modified Intent-To-Treat-Efficacy (mITT-E) population for the maintenance period. The mITT-E population was a subpopulation of the mITT population, where participants in M-PL arm were excluded.
Type of Statistical Test Superiority
Comments one-sample two-sided Chi-square test
Statistical Test of Hypothesis P-Value < 0.001
Comments Adjusted p-value from a sequentially rejective multiple test procedure, testing co-primary and ranked secondary endpoints 1st for M-SD+M-HD, then for individual adalimumab dose groups (M-HD, M-SD) against the respective external placebo rate (22.03%)
Method rejective multiple test procedure
Comments controlling familywise Type I error of 5% in a strong sense
Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Integrated Study (Main + Japan Sub-Study): M-SD
Comments Efficacy analysis was based on the modified Intent-To-Treat-Efficacy (mITT-E) population for the maintenance period. The mITT-E population was a subpopulation of the mITT population, where participants in M-PL arm were excluded.
Type of Statistical Test Superiority
Comments one-sample two-sided Chi-square test
Statistical Test of Hypothesis P-Value 0.344
Comments Adjusted p-value from a sequentially rejective multiple test procedure, testing co-primary and ranked secondary endpoints 1st for M-SD+M-HD, then for individual adalimumab dose groups (M-HD, M-SD) against the respective external placebo rate (22.03%)
Method rejective multiple test procedure
Comments controlling familywise Type I error of 5% in a strong sense
5.Secondary Outcome
Title Ranked Secondary Endpoint 3: Percentage of Participants With Clinical Remission Per FMS at Week 52 in Week 8 Remitters Per PMS - Maintenance Period
Hide Description The FMS ranges from 0 (normal or inactive disease) to 12 (severe disease) and is calculated as the sum of 4 subscores (stool frequency, rectal bleeding, endoscopy, and physician's global assessment), each of which ranges from 0 (normal) to 3 (severe disease). The PMS (Mayo score without endoscopy) ranges from 0 (normal or inactive disease) to 9 (severe disease) and is calculated as the sum of 3 subscores (stool frequency, rectal bleeding and physician's global assessment). Negative changes indicate improvement. PMS remitters are defined as those participants with a PMS ≤ 2 and no individual subscore > 1. Clinical remission per FMS is defined as Mayo Score ≤ 2 and no individual subscore > 1.
Time Frame Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
Modified intent-to-treat (mITT): all Week 8 PMS responders who were re-randomized at Week 8 and received at least 1 dose of study drug during the Maintenance period; analyzed as randomized at the beginning of the Maintenance phase. Participants who were also Week 8 remitters. NRI: missing data is imputed as not having met the endpoint.
Arm/Group Title Main Study: M-PL Main Study: M-SD Main Study: M-HD Main Study: M-SD + M-HD Integrated Study (Main + Japan Sub-Study): M-PL Integrated Study (Main + Japan Sub-Study): M-SD Integrated Study (Main + Japan Sub-Study): M-HD Integrated Study (Main + Japan Sub-Study): M-SD + M-HD
Hide Arm/Group Description:
(Prior to Amendment 4) participants demonstrating a clinical response per PMS (defined as a decrease in PMS ≥ 2 points and ≥ 30% from Baseline) at Week 8 randomized to maintenance placebo. Participants were to continue their blinded treatment during the maintenance period until Week 52 unless they had ≥ 2 flares and got open label adalimumab rescue therapy after the second flare.
Participants demonstrating a clinical response per PMS (defined as a decrease in PMS ≥ 2 points and ≥ 30% from Baseline) at Week 8 randomized to adalimumab maintenance standard dose (0.6 mg/kg [maximum dose of 40 mg] eow). Participants were to continue their blinded treatment during the maintenance period until Week 52 unless they had ≥ 2 flares and got open label rescue therapy after the second flare.
Participants demonstrating a clinical response per PMS (defined as a decrease in PMS ≥ 2 points and ≥ 30% from Baseline) at Week 8 randomized to adalimumab maintenance high dose (0.6 mg/kg [maximum dose of 40 mg] ew). Participants were to continue their blinded treatment during the maintenance period until Week 52 unless they had ≥ 2 flares and got open label rescue therapy after the second flare.
Combined M-SD + M-HD arms (see above).
(Prior to Amendment 4) participants demonstrating a clinical response per PMS (defined as a decrease in PMS ≥ 2 points and ≥ 30% from Baseline) at Week 8 randomized to maintenance placebo. Participants were to continue their blinded treatment during the maintenance period until Week 52 unless they had ≥ 2 flares and got open label adalimumab rescue therapy after the second flare.
Participants demonstrating a clinical response per PMS (defined as a decrease in PMS ≥ 2 points and ≥ 30% from Baseline) at Week 8 randomized to adalimumab maintenance standard dose (0.6 mg/kg [maximum dose of 40 mg] eow). Participants were to continue their blinded treatment during the maintenance period until Week 52 unless they had ≥ 2 flares and got open label rescue therapy after the second flare.
Participants demonstrating a clinical response per PMS (defined as a decrease in PMS ≥ 2 points and ≥ 30% from Baseline) at Week 8 randomized to adalimumab maintenance high dose (0.6 mg/kg [maximum dose of 40 mg] ew). Participants were to continue their blinded treatment during the maintenance period until Week 52 unless they had ≥ 2 flares and got open label rescue therapy after the second flare.
Combined M-SD + M-HD arms (see above).
Overall Number of Participants Analyzed 8 21 22 43 8 21 25 46
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
37.5
(8.52 to 75.51)
42.9
(21.82 to 65.98)
45.5
(24.39 to 67.79)
44.2
(29.08 to 60.12)
37.5
(8.52 to 75.51)
42.9
(21.82 to 65.98)
44.0
(24.40 to 65.07)
43.5
(28.93 to 58.89)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Main Study: M-SD + M-HD
Comments Efficacy analysis was based on the modified Intent-To-Treat-Efficacy (mITT-E) population for the maintenance period. The mITT-E population was a subpopulation of the mITT population, where participants in M-PL arm were excluded.
Type of Statistical Test Superiority
Comments one-sample two-sided Chi-square test
Statistical Test of Hypothesis P-Value < 0.001
Comments Adjusted p-value from a sequentially rejective multiple test procedure, testing co-primary and ranked secondary endpoints 1st for M-SD+M-HD, then for individual adalimumab dose groups (M-HD, M-SD) against the respective external placebo rate (14.79%)
Method rejective multiple test procedure
Comments controlling familywise Type I error of 5% in a strong sense
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Main Study: M-HD
Comments Efficacy analysis was based on the modified Intent-To-Treat-Efficacy (mITT-E) population for the maintenance period. The mITT-E population was a subpopulation of the mITT population, where participants in M-PL arm were excluded.
Type of Statistical Test Superiority
Comments one-sample two-sided Chi-square test
Statistical Test of Hypothesis P-Value < 0.001
Comments Adjusted p-value from a sequentially rejective multiple test procedure, testing co-primary and ranked secondary endpoints 1st for M-SD+M-HD, then for individual adalimumab dose groups (M-HD, M-SD) against the respective external placebo rate (14.79%)
Method rejective multiple test procedure
Comments controlling familywise Type I error of 5% in a strong sense
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Main Study: M-SD
Comments Efficacy analysis was based on the modified Intent-To-Treat-Efficacy (mITT-E) population for the maintenance period. The mITT-E population was a subpopulation of the mITT population, where participants in M-PL arm were excluded.
Type of Statistical Test Superiority
Comments one-sample two-sided Chi-square test
Statistical Test of Hypothesis P-Value 0.292
Comments Adjusted p-value from a sequentially rejective multiple test procedure, testing co-primary and ranked secondary endpoints 1st for M-SD+M-HD, then for individual adalimumab dose groups (M-HD, M-SD) against the respective external placebo rate (14.79%)
Method rejective multiple test procedure
Comments controlling familywise Type I error of 5% in a strong sense
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Integrated Study (Main + Japan Sub-Study): M-SD + M-HD
Comments Efficacy analysis was based on the modified Intent-To-Treat-Efficacy (mITT-E) population for the maintenance period. The mITT-E population was a subpopulation of the mITT population, where participants in M-PL arm were excluded.
Type of Statistical Test Superiority
Comments one-sample two-sided Chi-square test
Statistical Test of Hypothesis P-Value < 0.001
Comments Adjusted p-value from a sequentially rejective multiple test procedure, testing co-primary and ranked secondary endpoints 1st for M-SD+M-HD, then for individual adalimumab dose groups (M-HD, M-SD) against the respective external placebo rate (14.79%)
Method rejective multiple test procedure
Comments controlling familywise Type I error of 5% in a strong sense
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Integrated Study (Main + Japan Sub-Study): M-HD
Comments Efficacy analysis was based on the modified Intent-To-Treat-Efficacy (mITT-E) population for the maintenance period. The mITT-E population was a subpopulation of the mITT population, where participants in M-PL arm were excluded.
Type of Statistical Test Superiority
Comments one-sample two-sided Chi-square test
Statistical Test of Hypothesis P-Value < 0.001
Comments Adjusted p-value from a sequentially rejective multiple test procedure, testing co-primary and ranked secondary endpoints 1st for M-SD+M-HD, then for individual adalimumab dose groups (M-HD, M-SD) against the respective external placebo rate (14.79%)
Method rejective multiple test procedure
Comments controlling familywise Type I error of 5% in a strong sense
Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Integrated Study (Main + Japan Sub-Study): M-SD
Comments Efficacy analysis was based on the modified Intent-To-Treat-Efficacy (mITT-E) population for the maintenance period. The mITT-E population was a subpopulation of the mITT population, where participants in M-PL arm were excluded.
Type of Statistical Test Superiority
Comments one-sample two-sided Chi-square test
Statistical Test of Hypothesis P-Value 0.292
Comments Adjusted p-value from a sequentially rejective multiple test procedure, testing co-primary and ranked secondary endpoints 1st for M-SD+M-HD, then for individual adalimumab dose groups (M-HD, M-SD) against the respective external placebo rate (14.79%)
Method rejective multiple test procedure
Comments controlling familywise Type I error of 5% in a strong sense
6.Secondary Outcome
Title Ranked Secondary Endpoint 4: Percentage of Participants With Corticosteroid-Free Clinical Remission Per FMS at Week 52 in Week 8 Responders Per PMS - Maintenance Period
Hide Description The FMS ranges from 0 (normal or inactive disease) to 12 (severe disease) and is calculated as the sum of 4 subscores (stool frequency, rectal bleeding, endoscopy, and physician's global assessment), each of which ranges from 0 (normal) to 3 (severe disease). The PMS (Mayo score without endoscopy) ranges from 0 (normal or inactive disease) to 9 (severe disease) and is calculated as the sum of 3 subscores (stool frequency, rectal bleeding and physician's global assessment). Negative changes indicate improvement. PMS responders are defined as those with a decrease in PMS ≥ 2 points and ≥ 30% from baseline. Among participants receiving systemic corticosteroids at Baseline, corticosteroid-free clinical remission per FMS at Week 52 is defined as having discontinued systemic corticosteroids prior to Week 52 and being in FMS clinical remission at Week 52 (defined as Mayo Score ≤ 2 and no individual subscore > 1).
Time Frame Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
mITT: all Week 8 PMS responders who were re-randomized at Week 8 and received at least 1 dose of study drug during the Maintenance period; analyzed as randomized at the beginning of the Maintenance phase. Participants receiving systemic corticosteroids at baseline. NRI: missing data is imputed as not having met the endpoint.
Arm/Group Title Main Study: M-PL Main Study: M-SD Main Study: M-HD Main Study: M-SD + M-HD Integrated Study (Main + Japan Sub-Study): M-PL Integrated Study (Main + Japan Sub-Study): M-SD Integrated Study (Main + Japan Sub-Study): M-HD Integrated Study (Main + Japan Sub-Study): M-SD + M-HD
Hide Arm/Group Description:
(Prior to Amendment 4) participants demonstrating a clinical response per PMS (defined as a decrease in PMS ≥ 2 points and ≥ 30% from Baseline) at Week 8 randomized to maintenance placebo. Participants were to continue their blinded treatment during the maintenance period until Week 52 unless they had ≥ 2 flares and got open label adalimumab rescue therapy after the second flare.
Participants demonstrating a clinical response per PMS (defined as a decrease in PMS ≥ 2 points and ≥ 30% from Baseline) at Week 8 randomized to adalimumab maintenance standard dose (0.6 mg/kg [maximum dose of 40 mg] eow). Participants were to continue their blinded treatment during the maintenance period until Week 52 unless they had ≥ 2 flares and got open label rescue therapy after the second flare.
Participants demonstrating a clinical response per PMS (defined as a decrease in PMS ≥ 2 points and ≥ 30% from Baseline) at Week 8 randomized to adalimumab maintenance high dose (0.6 mg/kg [maximum dose of 40 mg] ew). Participants were to continue their blinded treatment during the maintenance period until Week 52 unless they had ≥ 2 flares and got open label rescue therapy after the second flare.
Combined M-SD + M-HD arms (see above).
(Prior to Amendment 4) participants demonstrating a clinical response per PMS (defined as a decrease in PMS ≥ 2 points and ≥ 30% from Baseline) at Week 8 randomized to maintenance placebo. Participants were to continue their blinded treatment during the maintenance period until Week 52 unless they had ≥ 2 flares and got open label adalimumab rescue therapy after the second flare.
Participants demonstrating a clinical response per PMS (defined as a decrease in PMS ≥ 2 points and ≥ 30% from Baseline) at Week 8 randomized to adalimumab maintenance standard dose (0.6 mg/kg [maximum dose of 40 mg] eow). Participants were to continue their blinded treatment during the maintenance period until Week 52 unless they had ≥ 2 flares and got open label rescue therapy after the second flare.
Participants demonstrating a clinical response per PMS (defined as a decrease in PMS ≥ 2 points and ≥ 30% from Baseline) at Week 8 randomized to adalimumab maintenance high dose (0.6 mg/kg [maximum dose of 40 mg] ew). Participants were to continue their blinded treatment during the maintenance period until Week 52 unless they had ≥ 2 flares and got open label rescue therapy after the second flare.
Combined M-SD + M-HD arms (see above).
Overall Number of Participants Analyzed 5 13 16 29 5 15 17 32
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
40.0
(5.27 to 85.34)
30.8
(9.09 to 61.43)
31.3
(11.02 to 58.66)
31.0
(15.28 to 50.83)
40.0
(5.27 to 85.34)
26.7
(7.79 to 55.10)
35.3
(14.21 to 61.67)
31.3
(16.12 to 50.01)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Main Study: M-SD + M-HD
Comments Efficacy analysis was based on the modified Intent-To-Treat-Efficacy (mITT-E) population for the maintenance period. The mITT-E population was a subpopulation of the mITT population, where participants in M-PL arm were excluded.
Type of Statistical Test Superiority
Comments one-sample two-sided Chi-square test
Statistical Test of Hypothesis P-Value 0.382
Comments Adjusted p-value from a sequentially rejective multiple test procedure, testing co-primary and ranked secondary endpoints 1st for M-SD+M-HD, then for individual adalimumab dose groups (M-HD, M-SD) against the respective external placebo rate (24.08%)
Method rejective multiple test procedure
Comments controlling familywise Type I error of 5% in a strong sense
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Main Study: M-HD
Comments Efficacy analysis was based on the modified Intent-To-Treat-Efficacy (mITT-E) population for the maintenance period. The mITT-E population was a subpopulation of the mITT population, where participants in M-PL arm were excluded.
Type of Statistical Test Superiority
Comments one-sample two-sided Chi-square test
Statistical Test of Hypothesis P-Value 1.000
Comments Adjusted p-value from a sequentially rejective multiple test procedure, testing co-primary and ranked secondary endpoints 1st for M-SD+M-HD, then for individual adalimumab dose groups (M-HD, M-SD) against the respective external placebo rate (24.08%)
Method rejective multiple test procedure
Comments controlling familywise Type I error of 5% in a strong sense
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Main Study: M-SD
Comments Efficacy analysis was based on the modified Intent-To-Treat-Efficacy (mITT-E) population for the maintenance period. The mITT-E population was a subpopulation of the mITT population, where participants in M-PL arm were excluded.
Type of Statistical Test Superiority
Comments one-sample two-sided Chi-square test
Statistical Test of Hypothesis P-Value 1.000
Comments Adjusted p-value from a sequentially rejective multiple test procedure, testing co-primary and ranked secondary endpoints 1st for M-SD+M-HD, then for individual adalimumab dose groups (M-HD, M-SD) against the respective external placebo rate (24.08%)
Method rejective multiple test procedure
Comments controlling familywise Type I error of 5% in a strong sense
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Integrated Study (Main + Japan Sub-Study): M-SD + M-HD
Comments Efficacy analysis was based on the modified Intent-To-Treat-Efficacy (mITT-E) population for the maintenance period. The mITT-E population was a subpopulation of the mITT population, where participants in M-PL arm were excluded.
Type of Statistical Test Superiority
Comments one-sample two-sided Chi-square test
Statistical Test of Hypothesis P-Value 0.344
Comments Adjusted p-value from a sequentially rejective multiple test procedure, testing co-primary and ranked secondary endpoints 1st for M-SD+M-HD, then for individual adalimumab dose groups (M-HD, M-SD) against the respective external placebo rate (24.08%)
Method rejective multiple test procedure
Comments controlling familywise Type I error of 5% in a strong sense
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Integrated Study (Main + Japan Sub-Study): M-HD
Comments Efficacy analysis was based on the modified Intent-To-Treat-Efficacy (mITT-E) population for the maintenance period. The mITT-E population was a subpopulation of the mITT population, where participants in M-PL arm were excluded.
Type of Statistical Test Superiority
Comments one-sample two-sided Chi-square test
Statistical Test of Hypothesis P-Value 0.559
Comments Adjusted p-value from a sequentially rejective multiple test procedure, testing co-primary and ranked secondary endpoints 1st for M-SD+M-HD, then for individual adalimumab dose groups (M-HD, M-SD) against the respective external placebo rate (24.08%)
Method rejective multiple test procedure
Comments controlling familywise Type I error of 5% in a strong sense
Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Integrated Study (Main + Japan Sub-Study): M-SD
Comments Efficacy analysis was based on the modified Intent-To-Treat-Efficacy (mITT-E) population for the maintenance period. The mITT-E population was a subpopulation of the mITT population, where participants in M-PL arm were excluded.
Type of Statistical Test Superiority
Comments one-sample two-sided Chi-square test
Statistical Test of Hypothesis P-Value 0.815
Comments Adjusted p-value from a sequentially rejective multiple test procedure, testing co-primary and ranked secondary endpoints 1st for M-SD+M-HD, then for individual adalimumab dose groups (M-HD, M-SD) against the respective external placebo rate (24.08%)
Method rejective multiple test procedure
Comments controlling familywise Type I error of 5% in a strong sense
Time Frame See time frame specifics detailed for each reporting group in their respective descriptions below.
Adverse Event Reporting Description Treatment-emergent adverse events (TEAEs) are presented.
 
Arm/Group Title Integrated Study (Main + Japan Sub- Study): I-SD Integrated Study (Main + Japan Sub- Study): I-HD Integrated Study (Main + Japan Sub- Study): I-HD-OL Integrated Study (Main + Japan Sub- Study): M-SD Integrated Study (Main + Japan Sub- Study): M-HD Integrated Study (Main + Japan Sub- Study): M-PL Integrated Study (Main + Japan Sub- Study): Any Adalimumab
Hide Arm/Group Description

Participants randomized to receive adalimumab 2.4 mg/kg (maximum dose of 160 mg) at Baseline and matching placebo at Week 1, 1.2 mg/kg (maximum dose of 80 mg) at Week 2, followed by 0.6 mg/kg (maximum dose of 40 mg) at Week 4 and Week 6.

TEAEs during induction period: events with an onset date on or after first dose date of study drug in induction period and up to 70 days after last dose date of the study drug in induction period and prior to first dose date of study drug in maintenance period. Mean duration of treatment was 52.8 days.

Participants randomized to receive adalimumab 2.4 mg/kg (maximum dose of 160 mg) at Baseline and at Week 1, 1.2 mg/kg (maximum dose of 80 mg) at Week 2, followed by 0.6 mg/kg (maximum dose of 40 mg) at Week 4 and Week 6.

TEAEs during induction period: events with an onset date on or after first dose date of study drug in induction period and up to 70 days after last dose date of the study drug in induction period and prior to first dose date of study drug in maintenance period. Mean duration of treatment was 55.4 days.

(After Amendment 4) participants assigned to open-label adalimumab 2.4 mg/kg (maximum dose of 160 mg) at Baseline and at Week 1, 1.2 mg/kg (maximum dose of 80 mg) at Week 2, followed by 0.6 mg/kg (maximum dose of 40 mg) at Week 4 and Week 6.

TEAEs during induction period: events with an onset date on or after first dose date of study drug in induction period and up to 70 days after last dose date of the study drug in induction period and prior to first dose date of study drug in maintenance period. Mean duration of treatment was 53.8 days.

Participants demonstrating a clinical response per PMS (defined as a decrease in PMS ≥ 2 points and ≥ 30% from Baseline) at Week 8 randomized to adalimumab maintenance standard dose (0.6 mg/kg [maximum dose of 40 mg] eow). Participants were to continue their blinded treatment during the maintenance period until Week 52 unless they had ≥ 2 flares and got open label adalimumab rescue therapy after the second flare.

TEAEs during maintenance period: events with an onset date on or after first dose date of study drug in maintenance period and prior to re-randomization due to first disease flare if applicable and up to 70 days after the last dose date of the study drug in maintenance period. Events with an onset date on or after the first dose date in long-term follow-up study M10-870 (NCT02632175) are excluded. Mean duration of treatment was 226.8 days.

Participants demonstrating a clinical response per PMS (defined as a decrease in PMS ≥ 2 points and ≥ 30% from Baseline) at Week 8 randomized to adalimumab maintenance high dose (0.6 mg/kg [maximum dose of 40 mg] ew). Participants were to continue their blinded treatment during the maintenance period until Week 52 unless they had ≥ 2 flares and got open label adalimumab rescue therapy after the second flare.

TEAEs during maintenance period: events with an onset date on or after first dose date of study drug in maintenance period and prior to re-randomization due to first disease flare if applicable and up to 70 days after the last dose date of the study drug in maintenance period. Events with an onset date on or after the first dose date in long-term follow-up study M10-870 (NCT02632175) are excluded. Mean duration of treatment was 241.0 days.

(Prior to Amendment 4) participants demonstrating a clinical response per PMS (defined as a decrease in PMS ≥ 2 points and ≥ 30% from Baseline) at Week 8 randomized to maintenance placebo. Participants were to continue their blinded treatment during the maintenance period until Week 52 unless they had ≥ 2 flares and got open label adalimumab rescue therapy after the second flare.

TEAEs during maintenance period: events with an onset date on or after first dose date of study drug in maintenance period and prior to re-randomization due to first disease flare if applicable and up to 70 days after the last dose date of the study drug in maintenance period. Events with an onset date on or after the first dose date in long-term follow-up study M10-870 (NCT02632175) are excluded. Mean duration of treatment was 184.2 days.

Participants receiving any adalimumab during Induction or Maintenance Phase.

Any Adalimumab TEAEs: events with an onset date on or after first dose date of adalimumab and up to 70 days after the last dose date of adalimumab and prior to the first dose date in M10-870 if applicable, whichever comes first. For participants who received placebo during the maintenance period, TEAE collection period ends 70 days after last induction dose of adalimumab and re-starts with their next adalimumab dose, if applicable. Mean duration of treatment was 256.3 days.
All-Cause Mortality
Integrated Study (Main + Japan Sub- Study): I-SD Integrated Study (Main + Japan Sub- Study): I-HD Integrated Study (Main + Japan Sub- Study): I-HD-OL Integrated Study (Main + Japan Sub- Study): M-SD Integrated Study (Main + Japan Sub- Study): M-HD Integrated Study (Main + Japan Sub- Study): M-PL Integrated Study (Main + Japan Sub- Study): Any Adalimumab
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/32 (0.00%)      0/51 (0.00%)      0/18 (0.00%)      0/33 (0.00%)      0/36 (0.00%)      0/12 (0.00%)      0/101 (0.00%)    
Hide Serious Adverse Events
Integrated Study (Main + Japan Sub- Study): I-SD Integrated Study (Main + Japan Sub- Study): I-HD Integrated Study (Main + Japan Sub- Study): I-HD-OL Integrated Study (Main + Japan Sub- Study): M-SD Integrated Study (Main + Japan Sub- Study): M-HD Integrated Study (Main + Japan Sub- Study): M-PL Integrated Study (Main + Japan Sub- Study): Any Adalimumab
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   5/32 (15.63%)      4/51 (7.84%)      1/18 (5.56%)      5/33 (15.15%)      5/36 (13.89%)      1/12 (8.33%)      22/101 (21.78%)    
Blood and lymphatic system disorders               
ANAEMIA † 1  2/32 (6.25%)  2 0/51 (0.00%)  0 0/18 (0.00%)  0 1/33 (3.03%)  2 0/36 (0.00%)  0 0/12 (0.00%)  0 3/101 (2.97%)  4
Cardiac disorders               
PERICARDITIS † 1  1/32 (3.13%)  1 0/51 (0.00%)  0 0/18 (0.00%)  0 0/33 (0.00%)  0 0/36 (0.00%)  0 0/12 (0.00%)  0 1/101 (0.99%)  1
Gastrointestinal disorders               
COLITIS ULCERATIVE † 1  2/32 (6.25%)  2 2/51 (3.92%)  2 1/18 (5.56%)  1 3/33 (9.09%)  4 0/36 (0.00%)  0 0/12 (0.00%)  0 10/101 (9.90%)  11
DYSPEPSIA † 1  0/32 (0.00%)  0 0/51 (0.00%)  0 0/18 (0.00%)  0 0/33 (0.00%)  0 1/36 (2.78%)  1 0/12 (0.00%)  0 1/101 (0.99%)  1
ENTERITIS † 1  0/32 (0.00%)  0 0/51 (0.00%)  0 0/18 (0.00%)  0 1/33 (3.03%)  1 0/36 (0.00%)  0 0/12 (0.00%)  0 1/101 (0.99%)  1
PANCREATITIS † 1  0/32 (0.00%)  0 1/51 (1.96%)  1 0/18 (0.00%)  0 0/33 (0.00%)  0 0/36 (0.00%)  0 0/12 (0.00%)  0 1/101 (0.99%)  1
Infections and infestations               
ENTERITIS INFECTIOUS † 1  0/32 (0.00%)  0 0/51 (0.00%)  0 0/18 (0.00%)  0 1/33 (3.03%)  1 0/36 (0.00%)  0 0/12 (0.00%)  0 1/101 (0.99%)  1
GASTROENTERITIS † 1  0/32 (0.00%)  0 0/51 (0.00%)  0 0/18 (0.00%)  0 2/33 (6.06%)  2 0/36 (0.00%)  0 0/12 (0.00%)  0 2/101 (1.98%)  2
MENINGITIS ASEPTIC † 1  0/32 (0.00%)  0 0/51 (0.00%)  0 0/18 (0.00%)  0 0/33 (0.00%)  0 1/36 (2.78%)  1 0/12 (0.00%)  0 1/101 (0.99%)  1
PHARYNGITIS † 1  0/32 (0.00%)  0 0/51 (0.00%)  0 0/18 (0.00%)  0 0/33 (0.00%)  0 1/36 (2.78%)  1 0/12 (0.00%)  0 1/101 (0.99%)  1
URINARY TRACT INFECTION † 1  0/32 (0.00%)  0 0/51 (0.00%)  0 0/18 (0.00%)  0 0/33 (0.00%)  0 1/36 (2.78%)  1 0/12 (0.00%)  0 1/101 (0.99%)  1
Injury, poisoning and procedural complications               
HAND FRACTURE † 1  0/32 (0.00%)  0 0/51 (0.00%)  0 0/18 (0.00%)  0 0/33 (0.00%)  0 1/36 (2.78%)  1 0/12 (0.00%)  0 1/101 (0.99%)  1
WRIST FRACTURE † 1  0/32 (0.00%)  0 1/51 (1.96%)  1 0/18 (0.00%)  0 0/33 (0.00%)  0 0/36 (0.00%)  0 0/12 (0.00%)  0 1/101 (0.99%)  1
Nervous system disorders               
HEADACHE † 1  1/32 (3.13%)  1 0/51 (0.00%)  0 0/18 (0.00%)  0 0/33 (0.00%)  0 0/36 (0.00%)  0 0/12 (0.00%)  0 1/101 (0.99%)  1
LOSS OF CONSCIOUSNESS † 1  1/32 (3.13%)  1 0/51 (0.00%)  0 0/18 (0.00%)  0 0/33 (0.00%)  0 0/36 (0.00%)  0 0/12 (0.00%)  0 1/101 (0.99%)  1
Skin and subcutaneous tissue disorders               
ERYTHEMA NODOSUM † 1  0/32 (0.00%)  0 0/51 (0.00%)  0 0/18 (0.00%)  0 0/33 (0.00%)  0 1/36 (2.78%)  1 0/12 (0.00%)  0 1/101 (0.99%)  1
PSORIASIS † 1  0/32 (0.00%)  0 0/51 (0.00%)  0 0/18 (0.00%)  0 0/33 (0.00%)  0 0/36 (0.00%)  0 1/12 (8.33%)  1 0/101 (0.00%)  0
1
Term from vocabulary, MedDRA 22.0
†
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Integrated Study (Main + Japan Sub- Study): I-SD Integrated Study (Main + Japan Sub- Study): I-HD Integrated Study (Main + Japan Sub- Study): I-HD-OL Integrated Study (Main + Japan Sub- Study): M-SD Integrated Study (Main + Japan Sub- Study): M-HD Integrated Study (Main + Japan Sub- Study): M-PL Integrated Study (Main + Japan Sub- Study): Any Adalimumab
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   13/32 (40.63%)      16/51 (31.37%)      14/18 (77.78%)      15/33 (45.45%)      20/36 (55.56%)      10/12 (83.33%)      65/101 (64.36%)    
Blood and lymphatic system disorders               
ANAEMIA † 1  1/32 (3.13%)  1 3/51 (5.88%)  3 1/18 (5.56%)  1 2/33 (6.06%)  2 1/36 (2.78%)  1 1/12 (8.33%)  1 9/101 (8.91%)  9
NEUTROPENIA † 1  0/32 (0.00%)  0 0/51 (0.00%)  0 0/18 (0.00%)  0 0/33 (0.00%)  0 0/36 (0.00%)  0 1/12 (8.33%)  1 0/101 (0.00%)  0
THROMBOCYTOSIS † 1  0/32 (0.00%)  0 0/51 (0.00%)  0 1/18 (5.56%)  1 0/33 (0.00%)  0 0/36 (0.00%)  0 0/12 (0.00%)  0 1/101 (0.99%)  1
Eye disorders               
NONINFECTIVE CONJUNCTIVITIS † 1  0/32 (0.00%)  0 0/51 (0.00%)  0 0/18 (0.00%)  0 0/33 (0.00%)  0 0/36 (0.00%)  0 1/12 (8.33%)  1 1/101 (0.99%)  1
Gastrointestinal disorders               
ABDOMINAL PAIN † 1  0/32 (0.00%)  0 2/51 (3.92%)  2 2/18 (11.11%)  2 1/33 (3.03%)  3 1/36 (2.78%)  1 1/12 (8.33%)  1 6/101 (5.94%)  11
ABDOMINAL PAIN UPPER † 1  1/32 (3.13%)  1 2/51 (3.92%)  2 0/18 (0.00%)  0 0/33 (0.00%)  0 2/36 (5.56%)  2 0/12 (0.00%)  0 4/101 (3.96%)  5
COLITIS ULCERATIVE † 1  2/32 (6.25%)  2 0/51 (0.00%)  0 0/18 (0.00%)  0 3/33 (9.09%)  3 4/36 (11.11%)  4 2/12 (16.67%)  2 11/101 (10.89%)  14
CONSTIPATION † 1  0/32 (0.00%)  0 0/51 (0.00%)  0 1/18 (5.56%)  1 1/33 (3.03%)  1 0/36 (0.00%)  0 0/12 (0.00%)  0 2/101 (1.98%)  2
DIARRHOEA † 1  0/32 (0.00%)  0 0/51 (0.00%)  0 1/18 (5.56%)  1 0/33 (0.00%)  0 1/36 (2.78%)  1 0/12 (0.00%)  0 2/101 (1.98%)  2
GASTROOESOPHAGEAL REFLUX DISEASE † 1  0/32 (0.00%)  0 1/51 (1.96%)  1 1/18 (5.56%)  1 0/33 (0.00%)  0 1/36 (2.78%)  1 0/12 (0.00%)  0 2/101 (1.98%)  3
NAUSEA † 1  0/32 (0.00%)  0 3/51 (5.88%)  3 1/18 (5.56%)  1 0/33 (0.00%)  0 0/36 (0.00%)  0 0/12 (0.00%)  0 4/101 (3.96%)  4
VOMITING † 1  0/32 (0.00%)  0 1/51 (1.96%)  1 1/18 (5.56%)  1 0/33 (0.00%)  0 0/36 (0.00%)  0 0/12 (0.00%)  0 3/101 (2.97%)  3
General disorders               
FATIGUE † 1  0/32 (0.00%)  0 1/51 (1.96%)  1 0/18 (0.00%)  0 2/33 (6.06%)  2 0/36 (0.00%)  0 0/12 (0.00%)  0 3/101 (2.97%)  3
INFLAMMATION † 1  0/32 (0.00%)  0 0/51 (0.00%)  0 0/18 (0.00%)  0 0/33 (0.00%)  0 0/36 (0.00%)  0 1/12 (8.33%)  1 1/101 (0.99%)  1
PERIPHERAL SWELLING † 1  1/32 (3.13%)  1 0/51 (0.00%)  0 1/18 (5.56%)  1 0/33 (0.00%)  0 0/36 (0.00%)  0 0/12 (0.00%)  0 2/101 (1.98%)  2
PYREXIA † 1  2/32 (6.25%)  2 1/51 (1.96%)  1 0/18 (0.00%)  0 1/33 (3.03%)  1 0/36 (0.00%)  0 0/12 (0.00%)  0 5/101 (4.95%)  5
Infections and infestations               
BRONCHITIS † 1  0/32 (0.00%)  0 0/51 (0.00%)  0 1/18 (5.56%)  1 1/33 (3.03%)  1 0/36 (0.00%)  0 0/12 (0.00%)  0 2/101 (1.98%)  2
GASTROENTERITIS † 1  0/32 (0.00%)  0 0/51 (0.00%)  0 0/18 (0.00%)  0 0/33 (0.00%)  0 0/36 (0.00%)  0 1/12 (8.33%)  1 1/101 (0.99%)  1
INFLUENZA † 1  0/32 (0.00%)  0 0/51 (0.00%)  0 0/18 (0.00%)  0 0/33 (0.00%)  0 2/36 (5.56%)  2 0/12 (0.00%)  0 2/101 (1.98%)  2
NASOPHARYNGITIS † 1  2/32 (6.25%)  2 2/51 (3.92%)  2 1/18 (5.56%)  2 3/33 (9.09%)  4 4/36 (11.11%)  4 1/12 (8.33%)  1 12/101 (11.88%)  18
PHARYNGITIS † 1  2/32 (6.25%)  2 1/51 (1.96%)  1 1/18 (5.56%)  1 2/33 (6.06%)  2 1/36 (2.78%)  1 1/12 (8.33%)  3 9/101 (8.91%)  10
RESPIRATORY TRACT INFECTION VIRAL † 1  0/32 (0.00%)  0 0/51 (0.00%)  0 0/18 (0.00%)  0 0/33 (0.00%)  0 0/36 (0.00%)  0 1/12 (8.33%)  1 1/101 (0.99%)  1
STREPTOCOCCAL INFECTION † 1  0/32 (0.00%)  0 0/51 (0.00%)  0 1/18 (5.56%)  1 0/33 (0.00%)  0 0/36 (0.00%)  0 0/12 (0.00%)  0 1/101 (0.99%)  2
TOOTH ABSCESS † 1  0/32 (0.00%)  0 0/51 (0.00%)  0 0/18 (0.00%)  0 0/33 (0.00%)  0 0/36 (0.00%)  0 1/12 (8.33%)  1 1/101 (0.99%)  1
UPPER RESPIRATORY TRACT INFECTION † 1  0/32 (0.00%)  0 3/51 (5.88%)  4 0/18 (0.00%)  0 2/33 (6.06%)  3 4/36 (11.11%)  4 2/12 (16.67%)  2 10/101 (9.90%)  13
VIRAL INFECTION † 1  0/32 (0.00%)  0 0/51 (0.00%)  0 1/18 (5.56%)  1 0/33 (0.00%)  0 0/36 (0.00%)  0 0/12 (0.00%)  0 1/101 (0.99%)  1
VULVOVAGINAL MYCOTIC INFECTION † 1  0/32 (0.00%)  0 0/51 (0.00%)  0 1/18 (5.56%)  1 0/33 (0.00%)  0 0/36 (0.00%)  0 0/12 (0.00%)  0 1/101 (0.99%)  1
Injury, poisoning and procedural complications               
JOINT INJURY † 1  0/32 (0.00%)  0 0/51 (0.00%)  0 0/18 (0.00%)  0 0/33 (0.00%)  0 0/36 (0.00%)  0 1/12 (8.33%)  1 0/101 (0.00%)  0
Investigations               
C-REACTIVE PROTEIN INCREASED † 1  0/32 (0.00%)  0 1/51 (1.96%)  1 0/18 (0.00%)  0 3/33 (9.09%)  3 0/36 (0.00%)  0 0/12 (0.00%)  0 5/101 (4.95%)  5
HEPATIC ENZYME INCREASED † 1  0/32 (0.00%)  0 0/51 (0.00%)  0 1/18 (5.56%)  1 0/33 (0.00%)  0 0/36 (0.00%)  0 0/12 (0.00%)  0 1/101 (0.99%)  1
MONOCYTE COUNT DECREASED † 1  0/32 (0.00%)  0 0/51 (0.00%)  0 1/18 (5.56%)  1 0/33 (0.00%)  0 0/36 (0.00%)  0 0/12 (0.00%)  0 1/101 (0.99%)  1
NEUTROPHIL COUNT DECREASED † 1  0/32 (0.00%)  0 0/51 (0.00%)  0 1/18 (5.56%)  1 1/33 (3.03%)  1 0/36 (0.00%)  0 0/12 (0.00%)  0 2/101 (1.98%)  3
WHITE BLOOD CELL COUNT DECREASED † 1  0/32 (0.00%)  0 0/51 (0.00%)  0 1/18 (5.56%)  1 1/33 (3.03%)  1 0/36 (0.00%)  0 0/12 (0.00%)  0 2/101 (1.98%)  3
Musculoskeletal and connective tissue disorders               
ARTHRALGIA † 1  1/32 (3.13%)  1 0/51 (0.00%)  0 1/18 (5.56%)  1 0/33 (0.00%)  0 1/36 (2.78%)  1 0/12 (0.00%)  0 3/101 (2.97%)  3
MUSCULOSKELETAL PAIN † 1  0/32 (0.00%)  0 0/51 (0.00%)  0 0/18 (0.00%)  0 0/33 (0.00%)  0 0/36 (0.00%)  0 1/12 (8.33%)  1 0/101 (0.00%)  0
Nervous system disorders               
HEADACHE † 1  4/32 (12.50%)  4 5/51 (9.80%)  7 4/18 (22.22%)  6 6/33 (18.18%)  6 2/36 (5.56%)  2 2/12 (16.67%)  2 19/101 (18.81%)  28
TREMOR † 1  0/32 (0.00%)  0 1/51 (1.96%)  2 1/18 (5.56%)  1 0/33 (0.00%)  0 0/36 (0.00%)  0 0/12 (0.00%)  0 2/101 (1.98%)  3
Renal and urinary disorders               
GLYCOSURIA † 1  0/32 (0.00%)  0 0/51 (0.00%)  0 1/18 (5.56%)  1 0/33 (0.00%)  0 0/36 (0.00%)  0 0/12 (0.00%)  0 1/101 (0.99%)  1
Respiratory, thoracic and mediastinal disorders               
COUGH † 1  0/32 (0.00%)  0 1/51 (1.96%)  1 0/18 (0.00%)  0 0/33 (0.00%)  0 2/36 (5.56%)  2 0/12 (0.00%)  0 4/101 (3.96%)  6
EPISTAXIS † 1  0/32 (0.00%)  0 0/51 (0.00%)  0 0/18 (0.00%)  0 0/33 (0.00%)  0 0/36 (0.00%)  0 2/12 (16.67%)  2 2/101 (1.98%)  2
OROPHARYNGEAL PAIN † 1  1/32 (3.13%)  1 1/51 (1.96%)  1 2/18 (11.11%)  2 2/33 (6.06%)  2 1/36 (2.78%)  1 0/12 (0.00%)  0 7/101 (6.93%)  8
RHINITIS ALLERGIC † 1  0/32 (0.00%)  0 0/51 (0.00%)  0 0/18 (0.00%)  0 0/33 (0.00%)  0 2/36 (5.56%)  3 0/12 (0.00%)  0 2/101 (1.98%)  3
RHINORRHOEA † 1  0/32 (0.00%)  0 1/51 (1.96%)  1 1/18 (5.56%)  1 1/33 (3.03%)  1 0/36 (0.00%)  0 0/12 (0.00%)  0 3/101 (2.97%)  3
WHEEZING † 1  0/32 (0.00%)  0 0/51 (0.00%)  0 0/18 (0.00%)  0 0/33 (0.00%)  0 0/36 (0.00%)  0 1/12 (8.33%)  1 1/101 (0.99%)  1
Skin and subcutaneous tissue disorders               
DERMATITIS † 1  0/32 (0.00%)  0 0/51 (0.00%)  0 0/18 (0.00%)  0 0/33 (0.00%)  0 1/36 (2.78%)  1 1/12 (8.33%)  1 2/101 (1.98%)  2
HANGNAIL † 1  0/32 (0.00%)  0 0/51 (0.00%)  0 0/18 (0.00%)  0 0/33 (0.00%)  0 0/36 (0.00%)  0 1/12 (8.33%)  1 1/101 (0.99%)  1
RASH † 1  0/32 (0.00%)  0 0/51 (0.00%)  0 1/18 (5.56%)  1 1/33 (3.03%)  1 2/36 (5.56%)  2 0/12 (0.00%)  0 4/101 (3.96%)  4
1
Term from vocabulary, MedDRA 22.0
†
Indicates events were collected by systematic assessment
[Not Specified]
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
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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: NCT02065557    
Other Study ID Numbers: M11-290
2013-003032-77 ( EudraCT Number )
First Submitted: February 17, 2014
First Posted: February 19, 2014
Results First Submitted: September 10, 2020
Results First Posted: October 5, 2020
Last Update Posted: October 5, 2020