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A Study to Investigate the Safety and Efficacy of ABBV-105 Alone or in Combination With Upadacitinib (ABBV-599 Combination) in Participants With Active Rheumatoid Arthritis

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: NCT03682705
Recruitment Status : Completed
First Posted : September 25, 2018
Results First Posted : May 3, 2021
Last Update Posted : May 3, 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 Rheumatoid Arthritis (RA)
Interventions Drug: Elsubrutinib
Drug: Upadacitinib
Drug: Placebo for elsubrutinib
Drug: Placebo for upadacitinib
Enrollment 242
Recruitment Details  
Pre-assignment Details Full Analysis Set: all randomized participants who received at least 1 dose of randomized study drug
Arm/Group Title ELS Placebo/UPA Placebo UPA 15 mg/ELS 60 mg ELS 60 mg/UPA Placebo ELS 20 mg/UPA Placebo ELS 5 mg/UPA Placebo UPA 15 mg/ELS Placebo
Hide Arm/Group Description Placebo capsule for elsubrutinib once a day by mouth for 12 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 12 weeks 15 mg film-coated upadacitinib tablet once a day by mouth for 12 weeks; 60 mg elsubrutinib capsule once a day by mouth for 12 weeks 60 mg elsubrutinib capsule once a day by mouth for 12 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 12 weeks 20 mg elsubrutinib capsule once a day by mouth for 12 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 12 weeks 5 mg elsubrutinib capsule once a day by mouth for 12 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 12 weeks 15 mg film-coated upadacitinib tablet once a day by mouth for 12 weeks; placebo capsule for elsubrutinib once a day by mouth for 12 weeks
Period Title: Overall Study
Started 19 62 41 39 41 40
Completed 17 58 38 34 35 38
Not Completed 2 4 3 5 6 2
Reason Not Completed
Adverse Event             1             1             1             0             1             1
Withdrawal by Subject             1             3             2             4             0             1
Other, not specified             0             0             0             1             2             0
Lost to Follow-up             0             0             0             0             3             0
Arm/Group Title ELS Placebo/UPA Placebo UPA 15 mg/ELS 60 mg ELS 60 mg/UPA Placebo ELS 20 mg/UPA Placebo ELS 5 mg/UPA Placebo UPA 15 mg/ELS Placebo Total
Hide Arm/Group Description Placebo capsule for elsubrutinib once a day by mouth for 12 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 12 weeks 15 mg film-coated upadacitinib tablet once a day by mouth for 12 weeks; 60 mg elsubrutinib capsule once a day by mouth for 12 weeks 60 mg elsubrutinib capsule once a day by mouth for 12 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 12 weeks 20 mg elsubrutinib capsule once a day by mouth for 12 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 12 weeks 5 mg elsubrutinib capsule once a day by mouth for 12 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 12 weeks 15 mg film-coated upadacitinib tablet once a day by mouth for 12 weeks; placebo capsule for elsubrutinib once a day by mouth for 12 weeks Total of all reporting groups
Overall Number of Baseline Participants 19 62 41 39 41 40 242
Hide Baseline Analysis Population Description
Full Analysis Set: all randomized participants who received at least 1 dose of randomized study drug
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 19 participants 62 participants 41 participants 39 participants 41 participants 40 participants 242 participants
57.6  (9.12) 56.2  (12.82) 59.2  (11.11) 59.7  (10.95) 58.1  (11.01) 57.7  (10.60) 58.0  (11.27)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 19 participants 62 participants 41 participants 39 participants 41 participants 40 participants 242 participants
Female 17 48 36 35 33 35 204
Male 2 14 5 4 8 5 38
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 19 participants 62 participants 41 participants 39 participants 41 participants 40 participants 242 participants
White 19 58 36 35 35 37 220
Black or African American 0 3 4 4 3 3 17
American Indian or Alaska Native 0 0 1 0 1 0 2
Native Hawaiian or Other Pacific Islander 0 0 0 0 0 0 0
Asian 0 1 0 0 1 0 2
Multiple 0 0 0 0 1 0 1
1.Primary Outcome
Title Change From Baseline in Disease Activity Score 28 C-reactive Protein [DAS28-CRP]) at Week 12
Hide Description The DAS28-CRP is a composite index used to assess rheumatoid arthritis disease activity, calculated based on the tender joint count (out of 28 evaluated joints), swollen joint count (out of 28 evaluated joints), Patient's Global Assessment of Disease Activity (0-100 mm), and high-sensitivity C-reactive protein (hsCRP; in mg/L). Scores on the DAS28-CRP range from 0 to approximately 10, where higher scores indicate more disease activity. A negative change from baseline indicates improvement in disease activity.
Time Frame Baseline, Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set: all randomized participants who received at least 1 dose of randomized study drug, had non-missing baseline values, and at least one post-baseline value. Baseline is defined as the last non-missing value prior to the first dose of study drug.
Arm/Group Title ELS Placebo/UPA Placebo UPA 15 mg/ELS 60 mg ELS 60 mg/UPA Placebo ELS 20 mg/UPA Placebo ELS 5 mg/UPA Placebo UPA 15 mg/ELS Placebo
Hide Arm/Group Description:
Placebo capsule for elsubrutinib once a day by mouth for 12 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 12 weeks
15 mg film-coated upadacitinib tablet once a day by mouth for 12 weeks; 60 mg elsubrutinib capsule once a day by mouth for 12 weeks
60 mg elsubrutinib capsule once a day by mouth for 12 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 12 weeks
20 mg elsubrutinib capsule once a day by mouth for 12 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 12 weeks
5 mg elsubrutinib capsule once a day by mouth for 12 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 12 weeks
15 mg film-coated upadacitinib tablet once a day by mouth for 12 weeks; placebo capsule for elsubrutinib once a day by mouth for 12 weeks
Overall Number of Participants Analyzed 18 54 35 29 34 37
Least Squares Mean (90% Confidence Interval)
Unit of Measure: units on a scale
-1.12
(-1.64 to -0.60)
-2.56
(-2.86 to -2.26)
-1.52
(-1.89 to -1.15)
-1.32
(-1.71 to -0.93)
-1.33
(-1.70 to -0.97)
-2.87
(-3.23 to -2.51)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection ELS Placebo/UPA Placebo, UPA 15 mg/ELS 60 mg
Comments Mixed-Effect Model Repeated Measure (MMRM) analysis was conducted, testing the superiority of the combination of upadacitinib 15 mg and elsubrutinib 60 mg compared to placebo at Week 12. Data collected after a participant discontinued study drug was considered as missing. The mixed model included the categorical fixed effects of treatment, visit and treatment-by-visit interaction, prior bDMARD use, and baseline DAS28 (CRP) measurement.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -1.44
Confidence Interval (2-Sided) 90%
-2.03 to -0.85
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.36
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Change From Baseline in Clinical Disease Activity Index (CDAI)
Hide Description The CDAI is a composite index for assessing disease activity based on the summation of the total tender joint count (out of 28 evaluated joints), swollen joint count (out of 28 evaluated joints), patient global assessment of disease activity measured on a VAS from 0 to 10 cm, and physician global assessment of disease activity measured on a VAS from 0 to 10 cm. The total CDAI score ranges from 0 to 78 with higher scores indicating higher disease activity. A negative change from baseline indicates improvement in disease activity.
Time Frame Baseline, Week 2, Week 4, Week 8, and Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set: all randomized participants who received at least 1 dose of randomized study drug, had non-missing baseline values, and at least one post-baseline value. Baseline is defined as the last non-missing value prior to the first dose of study drug.
Arm/Group Title ELS Placebo/UPA Placebo UPA 15 mg/ELS 60 mg ELS 60 mg/UPA Placebo ELS 20 mg/UPA Placebo ELS 5 mg/UPA Placebo UPA 15 mg/ELS Placebo
Hide Arm/Group Description:
Placebo capsule for elsubrutinib once a day by mouth for 12 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 12 weeks
15 mg film-coated upadacitinib tablet once a day by mouth for 12 weeks; 60 mg elsubrutinib capsule once a day by mouth for 12 weeks
60 mg elsubrutinib capsule once a day by mouth for 12 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 12 weeks
20 mg elsubrutinib capsule once a day by mouth for 12 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 12 weeks
5 mg elsubrutinib capsule once a day by mouth for 12 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 12 weeks
15 mg film-coated upadacitinib tablet once a day by mouth for 12 weeks; placebo capsule for elsubrutinib once a day by mouth for 12 weeks
Overall Number of Participants Analyzed 18 57 38 35 37 37
Least Squares Mean (90% Confidence Interval)
Unit of Measure: units on a scale
Week 2 Number Analyzed 17 participants 56 participants 38 participants 35 participants 35 participants 37 participants
-6.08
(-10.48 to -1.67)
-16.00
(-18.53 to -13.47)
-8.95
(-11.99 to -5.91)
-7.36
(-10.44 to -4.27)
-8.38
(-11.48 to -5.28)
-14.03
(-17.04 to -11.02)
Week 4 Number Analyzed 17 participants 57 participants 37 participants 34 participants 37 participants 37 participants
-11.60
(-16.38 to -6.82)
-20.24
(-22.97 to -17.50)
-11.67
(-15.01 to -8.34)
-10.10
(-13.50 to -6.70)
-12.90
(-16.22 to -9.58)
-20.30
(-23.57 to -17.03)
Week 8 Number Analyzed 17 participants 56 participants 35 participants 31 participants 35 participants 37 participants
-12.46
(-17.52 to -7.40)
-24.95
(-27.86 to -22.05)
-15.07
(-18.65 to -11.49)
-17.10
(-20.83 to -13.38)
-14.84
(-18.42 to -11.26)
-23.72
(-27.20 to -20.24)
Week 12 Number Analyzed 18 participants 52 participants 35 participants 29 participants 33 participants 36 participants
-14.57
(-19.77 to -9.36)
-27.00
(-30.05 to -23.95)
-17.50
(-21.22 to -13.78)
-16.70
(-20.62 to -12.78)
-16.51
(-20.27 to -12.75)
-28.85
(-32.48 to -25.21)
3.Secondary Outcome
Title Change From Baseline in Simplified Disease Activity Index (SDAI)
Hide Description The SDAI is a validated measure of rheumatoid arthritis disease activity. Twenty-eight tender joint counts, 28 swollen joint counts, global disease activity assessed by the participant on a visual analogue scale from 0 to 10 (cm), global disease activity assessed by an investigator on a visual analogue scale from 0 to 10 (cm), and serum levels of C-reactive protein (CRP; mg/dL) were included in the SDAI score. Scores on the SDAI range from 0 to 86.with higher scores indicating higher disease activity. A negative change from baseline indicates improvement in disease activity.
Time Frame Baseline, Week 2, Week 4, Week 8, and Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set: all randomized participants who received at least 1 dose of randomized study drug, had non-missing baseline values, and at least one post-baseline value. Baseline is defined as the last non-missing value prior to the first dose of study drug.
Arm/Group Title ELS Placebo/UPA Placebo UPA 15 mg/ELS 60 mg ELS 60 mg/UPA Placebo ELS 20 mg/UPA Placebo ELS 5 mg/UPA Placebo UPA 15 mg/ELS Placebo
Hide Arm/Group Description:
Placebo capsule for elsubrutinib once a day by mouth for 12 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 12 weeks
15 mg film-coated upadacitinib tablet once a day by mouth for 12 weeks; 60 mg elsubrutinib capsule once a day by mouth for 12 weeks
60 mg elsubrutinib capsule once a day by mouth for 12 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 12 weeks
20 mg elsubrutinib capsule once a day by mouth for 12 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 12 weeks
5 mg elsubrutinib capsule once a day by mouth for 12 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 12 weeks
15 mg film-coated upadacitinib tablet once a day by mouth for 12 weeks; placebo capsule for elsubrutinib once a day by mouth for 12 weeks
Overall Number of Participants Analyzed 18 57 38 35 37 37
Least Squares Mean (90% Confidence Interval)
Unit of Measure: units on a scale
Week 2 Number Analyzed 17 participants 56 participants 38 participants 35 participants 35 participants 37 participants
-6.17
(-10.67 to -1.67)
-17.01
(-19.60 to -14.43)
-8.79
(-11.89 to -5.68)
-7.42
(-10.57 to -4.26)
-8.54
(-11.71 to -5.38)
-15.30
(-18.37 to -12.22)
Week 4 Number Analyzed 17 participants 57 participants 37 participants 34 participants 37 participants 37 participants
-11.80
(-16.67 to -6.93)
-21.24
(-24.02 to -18.45)
-11.46
(-14.85 to -8.06)
-10.15
(-13.61 to -6.68)
-12.87
(-16.25 to -9.49)
-21.59
(-24.92 to -18.26)
Week 8 Number Analyzed 17 participants 56 participants 35 participants 30 participants 35 participants 37 participants
-12.15
(-17.35 to -6.95)
-25.96
(-28.95 to -22.98)
-15.26
(-18.94 to -11.57)
-17.32
(-21.17 to -13.46)
-15.21
(-18.89 to -11.53)
-25.07
(-28.65 to -21.49)
Week 12 Number Analyzed 18 participants 52 participants 35 participants 29 participants 32 participants 36 participants
-14.44
(-19.84 to -9.04)
-28.06
(-31.22 to -24.89)
-18.01
(-21.86 to -14.15)
-17.12
(-21.20 to -13.05)
-16.73
(-20.65 to -12.81)
-29.65
(-33.42 to -25.88)
4.Secondary Outcome
Title Percentage of Participants Achieving Clinical Remission (CR) Based on Disease Activity Score 28 C-reactive Protein [DAS28-CRP]) at Week 12
Hide Description The DAS28-CRP is a composite index used to assess rheumatoid arthritis disease activity, calculated based on the tender joint count (out of 28 evaluated joints), swollen joint count (out of 28 evaluated joints), Patient's Global Assessment of Disease Activity (0-100 mm), and high-sensitivity C-reactive protein (hsCRP; in mg/L). Scores on the DAS28-CRP range from 0 to approximately 10, where higher scores indicate more disease activity. Clinical remission (CR) based on DAS28 (CRP) is defined as achieving a DAS28 (CRP) of less than 2.6.
Time Frame At Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set: all randomized participants who received at least 1 dose of randomized study drug, nonresponder imputation was used for missing data
Arm/Group Title ELS Placebo/UPA Placebo UPA 15 mg/ELS 60 mg ELS 60 mg/UPA Placebo ELS 20 mg/UPA Placebo ELS 5 mg/UPA Placebo UPA 15 mg/ELS Placebo
Hide Arm/Group Description:
Placebo capsule for elsubrutinib once a day by mouth for 12 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 12 weeks
15 mg film-coated upadacitinib tablet once a day by mouth for 12 weeks; 60 mg elsubrutinib capsule once a day by mouth for 12 weeks
60 mg elsubrutinib capsule once a day by mouth for 12 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 12 weeks
20 mg elsubrutinib capsule once a day by mouth for 12 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 12 weeks
5 mg elsubrutinib capsule once a day by mouth for 12 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 12 weeks
15 mg film-coated upadacitinib tablet once a day by mouth for 12 weeks; placebo capsule for elsubrutinib once a day by mouth for 12 weeks
Overall Number of Participants Analyzed 19 62 41 39 41 40
Measure Type: Number
Number (90% Confidence Interval)
Unit of Measure: percentage of participants
10.5
(3.55 to 27.35)
32.3
(23.41 to 42.59)
19.5
(11.36 to 31.44)
7.7
(3.12 to 17.76)
9.8
(4.46 to 20.04)
42.5
(30.52 to 55.43)
5.Secondary Outcome
Title Percentage of Participants Achieving Low Disease Activity (LDA) Based on Disease Activity Score 28 C-reactive Protein [DAS28-CRP]) at Week 12
Hide Description The DAS28-CRP is a composite index used to assess rheumatoid arthritis disease activity, calculated based on the tender joint count (out of 28 evaluated joints), swollen joint count (out of 28 evaluated joints), Patient's Global Assessment of Disease Activity (0-100 mm), and high-sensitivity C-reactive protein (hsCRP; in mg/L). Scores on the DAS28-CRP range from 0 to approximately 10, where higher scores indicate more disease activity. Low Disease Activity (LDA) based on DAS28 (CRP) is defined as achieving a DAS28 (CRP) of less than or equal to 3.2.
Time Frame At Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set: all randomized participants who received at least 1 dose of randomized study drug, nonresponder imputation was used for missing data
Arm/Group Title ELS Placebo/UPA Placebo UPA 15 mg/ELS 60 mg ELS 60 mg/UPA Placebo ELS 20 mg/UPA Placebo ELS 5 mg/UPA Placebo UPA 15 mg/ELS Placebo
Hide Arm/Group Description:
Placebo capsule for elsubrutinib once a day by mouth for 12 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 12 weeks
15 mg film-coated upadacitinib tablet once a day by mouth for 12 weeks; 60 mg elsubrutinib capsule once a day by mouth for 12 weeks
60 mg elsubrutinib capsule once a day by mouth for 12 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 12 weeks
20 mg elsubrutinib capsule once a day by mouth for 12 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 12 weeks
5 mg elsubrutinib capsule once a day by mouth for 12 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 12 weeks
15 mg film-coated upadacitinib tablet once a day by mouth for 12 weeks; placebo capsule for elsubrutinib once a day by mouth for 12 weeks
Overall Number of Participants Analyzed 19 62 41 39 41 40
Measure Type: Number
Number (90% Confidence Interval)
Unit of Measure: percentage of participants
21.1
(9.82 to 39.50)
41.9
(32.18 to 52.37)
22.0
(13.24 to 34.13)
10.3
(4.69 to 20.98)
14.6
(7.76 to 25.89)
55.0
(42.16 to 67.21)
6.Secondary Outcome
Title Percentage of Participants Achieving Low Disease Activity (LDA) Based on Clinical Disease Activity Index (CDAI) Criteria
Hide Description The CDAI is a composite index for assessing disease activity based on the summation of the total tender joint count (out of 28 evaluated joints), swollen joint count (out of 28 evaluated joints), patient global assessment of disease activity measured on a VAS from 0 to 10 cm, and physician global assessment of disease activity measured on a VAS from 0 to 10 cm. The total CDAI score ranges from 0 to 78 with higher scores indicating higher disease activity. Low Disease Activity (LDA) based on CDAI is defined as achieving a CDAI of less than or equal to 10.
Time Frame Week 2, Week 4, Week 8, and Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set: all randomized participants who received at least 1 dose of randomized study drug, nonresponder imputation was used for missing data
Arm/Group Title ELS Placebo/UPA Placebo UPA 15 mg/ELS 60 mg ELS 60 mg/UPA Placebo ELS 20 mg/UPA Placebo ELS 5 mg/UPA Placebo UPA 15 mg/ELS Placebo
Hide Arm/Group Description:
Placebo capsule for elsubrutinib once a day by mouth for 12 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 12 weeks
15 mg film-coated upadacitinib tablet once a day by mouth for 12 weeks; 60 mg elsubrutinib capsule once a day by mouth for 12 weeks
60 mg elsubrutinib capsule once a day by mouth for 12 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 12 weeks
20 mg elsubrutinib capsule once a day by mouth for 12 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 12 weeks
5 mg elsubrutinib capsule once a day by mouth for 12 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 12 weeks
15 mg film-coated upadacitinib tablet once a day by mouth for 12 weeks; placebo capsule for elsubrutinib once a day by mouth for 12 weeks
Overall Number of Participants Analyzed 19 62 41 39 41 40
Measure Type: Number
Number (90% Confidence Interval)
Unit of Measure: percentage of participants
Week 2
10.5
(3.55 to 27.35)
16.1
(9.89 to 25.20)
9.8
(4.46 to 20.04)
0
(0.00 to 6.49)
2.4
(0.55 to 10.22)
12.5
(6.22 to 23.53)
Week 4
10.5
(3.55 to 27.35)
29.0
(20.59 to 39.23)
12.2
(6.06 to 23.01)
7.7
(3.12 to 17.76)
12.2
(6.06 to 23.01)
22.5
(13.59 to 34.90)
Week 8
5.3
(1.18 to 20.50)
46.8
(36.71 to 57.11)
17.1
(9.53 to 28.69)
20.5
(11.96 to 32.89)
24.4
(15.17 to 36.78)
35.0
(23.91 to 47.99)
Week 12
26.3
(13.44 to 45.09)
37.1
(27.74 to 47.53)
34.1
(23.29 to 46.97)
17.9
(10.03 to 30.02)
17.1
(9.53 to 28.69)
57.5
(44.57 to 69.48)
7.Secondary Outcome
Title Percentage of Participants Achieving Complete Remission (CR) Based on Clinical Disease Activity Index (CDAI) Criteria
Hide Description The CDAI is a composite index for assessing disease activity based on the summation of the total tender joint count (out of 28 evaluated joints), swollen joint count (out of 28 evaluated joints), patient global assessment of disease activity measured on a VAS from 0 to 10 cm, and physician global assessment of disease activity measured on a VAS from 0 to 10 cm. The total CDAI score ranges from 0 to 78 with higher scores indicating higher disease activity. Complete Remission (CR) based on CDAI is defined as achieving a CDAI of less than or equal to 2.8.
Time Frame Week 2, Week 4, Week 8, and Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set: all randomized participants who received at least 1 dose of randomized study drug, nonresponder imputation was used for missing data
Arm/Group Title ELS Placebo/UPA Placebo UPA 15 mg/ELS 60 mg ELS 60 mg/UPA Placebo ELS 20 mg/UPA Placebo ELS 5 mg/UPA Placebo UPA 15 mg/ELS Placebo
Hide Arm/Group Description:
Placebo capsule for elsubrutinib once a day by mouth for 12 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 12 weeks
15 mg film-coated upadacitinib tablet once a day by mouth for 12 weeks; 60 mg elsubrutinib capsule once a day by mouth for 12 weeks
60 mg elsubrutinib capsule once a day by mouth for 12 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 12 weeks
20 mg elsubrutinib capsule once a day by mouth for 12 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 12 weeks
5 mg elsubrutinib capsule once a day by mouth for 12 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 12 weeks
15 mg film-coated upadacitinib tablet once a day by mouth for 12 weeks; placebo capsule for elsubrutinib once a day by mouth for 12 weeks
Overall Number of Participants Analyzed 19 62 41 39 41 40
Measure Type: Number
Number (90% Confidence Interval)
Unit of Measure: percentage of participants
Week 2
0
(0.00 to 12.46)
3.2
(1.07 to 9.29)
0
(0.00 to 6.19)
0
(0.00 to 6.49)
0
(0.00 to 6.19)
0
(0.00 to 6.34)
Week 4
0
(0.00 to 12.46)
6.5
(2.93 to 13.62)
2.4
(0.55 to 10.22)
2.6
(0.57 to 10.71)
0
(0.00 to 6.19)
2.5
(0.56 to 10.46)
Week 8
0
(0.00 to 12.46)
12.9
(7.43 to 21.48)
7.3
(2.96 to 16.96)
2.6
(0.57 to 10.71)
2.4
(0.55 to 10.22)
12.5
(6.22 to 23.53)
Week 12
5.3
(1.18 to 20.50)
14.5
(8.65 to 23.35)
7.3
(2.96 to 16.96)
5.1
(1.71 to 14.37)
0
(0.00 to 6.19)
15.0
(7.96 to 26.47)
8.Secondary Outcome
Title Percentage of Participants With an American College of Rheumatology 20% (ACR20) Response
Hide Description

Participants who met the following 3 conditions for improvement from baseline were classified as meeting the American College of Rheumatology 20% response (ACR20) criteria:

  1. ≥ 20% improvement in 68-tender joint count
  2. ≥ 20% improvement in 66-swollen joint count and
  3. ≥ 20% improvement in at least 3 of the 5 following parameters:

    • Patient's Assessment of Pain (Visual Analog Scale [VAS])
    • Patient's Global Assessment of Disease Activity (PtGA)
    • Physician's Global Assessment of Disease Activity (PhGA)
    • Health Assessment Questionnaire Disability Index (HAQ-DI)
    • High-sensitivity C-reactive protein (hsCRP)
Time Frame Baseline, Week 2, Week 4, Week 8, and Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set: all randomized participants who received at least 1 dose of randomized study drug, nonresponder imputation was used for missing data
Arm/Group Title ELS Placebo/UPA Placebo UPA 15 mg/ELS 60 mg ELS 60 mg/UPA Placebo ELS 20 mg/UPA Placebo ELS 5 mg/UPA Placebo UPA 15 mg/ELS Placebo
Hide Arm/Group Description:
Placebo capsule for elsubrutinib once a day by mouth for 12 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 12 weeks
15 mg film-coated upadacitinib tablet once a day by mouth for 12 weeks; 60 mg elsubrutinib capsule once a day by mouth for 12 weeks
60 mg elsubrutinib capsule once a day by mouth for 12 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 12 weeks
20 mg elsubrutinib capsule once a day by mouth for 12 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 12 weeks
5 mg elsubrutinib capsule once a day by mouth for 12 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 12 weeks
15 mg film-coated upadacitinib tablet once a day by mouth for 12 weeks; placebo capsule for elsubrutinib once a day by mouth for 12 weeks
Overall Number of Participants Analyzed 19 62 41 39 41 40
Measure Type: Number
Number (90% Confidence Interval)
Unit of Measure: percentage of participants
Week 2
21.1
(9.82 to 39.50)
45.2
(35.19 to 55.54)
24.4
(15.17 to 36.78)
12.8
(6.38 to 24.08)
14.6
(7.76 to 25.89)
52.5
(39.77 to 64.91)
Week 4
42.1
(25.63 to 60.55)
51.6
(41.33 to 61.76)
29.3
(19.16 to 41.94)
23.1
(13.95 to 35.70)
22.0
(13.24 to 34.13)
55.0
(42.16 to 67.21)
Week 8
36.8
(21.37 to 55.59)
64.5
(54.11 to 73.71)
39.0
(27.55 to 51.86)
30.8
(20.20 to 43.84)
39.0
(27.55 to 51.86)
67.5
(54.55 to 78.23)
Week 12
47.4
(30.07 to 65.33)
64.5
(54.11 to 73.71)
41.5
(29.72 to 54.26)
30.8
(20.20 to 43.84)
34.1
(23.29 to 46.97)
72.5
(59.75 to 82.40)
9.Secondary Outcome
Title Percentage of Participants With an American College of Rheumatology 50% (ACR50) Response
Hide Description

Participants who met the following 3 conditions for improvement from baseline were classified as meeting the American College of Rheumatology 50% response (ACR50) criteria:

  1. ≥ 50% improvement in 68-tender joint count
  2. ≥ 50% improvement in 66-swollen joint count and
  3. ≥ 50% improvement in at least 3 of the 5 following parameters:

    • Patient's Assessment of Pain (Visual Analog Scale [VAS])
    • Patient's Global Assessment of Disease Activity (PtGA)
    • Physician's Global Assessment of Disease Activity (PhGA)
    • Health Assessment Questionnaire Disability Index (HAQ-DI)
    • High-sensitivity C-reactive protein (hsCRP)
Time Frame Baseline, Week 2, Week 4, Week 8, and Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set: all randomized participants who received at least 1 dose of randomized study drug, nonresponder imputation was used for missing data
Arm/Group Title ELS Placebo/UPA Placebo UPA 15 mg/ELS 60 mg ELS 60 mg/UPA Placebo ELS 20 mg/UPA Placebo ELS 5 mg/UPA Placebo UPA 15 mg/ELS Placebo
Hide Arm/Group Description:
Placebo capsule for elsubrutinib once a day by mouth for 12 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 12 weeks
15 mg film-coated upadacitinib tablet once a day by mouth for 12 weeks; 60 mg elsubrutinib capsule once a day by mouth for 12 weeks
60 mg elsubrutinib capsule once a day by mouth for 12 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 12 weeks
20 mg elsubrutinib capsule once a day by mouth for 12 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 12 weeks
5 mg elsubrutinib capsule once a day by mouth for 12 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 12 weeks
15 mg film-coated upadacitinib tablet once a day by mouth for 12 weeks; placebo capsule for elsubrutinib once a day by mouth for 12 weeks
Overall Number of Participants Analyzed 19 62 41 39 41 40
Measure Type: Number
Number (90% Confidence Interval)
Unit of Measure: percentage of participants
Week 2
0
(0.00 to 12.46)
16.1
(9.89 to 25.20)
4.9
(1.63 to 13.71)
0
(0.00 to 6.49)
0
(0.00 to 6.19)
12.5
(6.22 to 23.53)
Week 4
10.5
(3.55 to 27.35)
19.4
(12.46 to 28.82)
17.1
(9.53 to 28.69)
2.6
(0.57 to 10.71)
4.9
(1.63 to 13.71)
30.0
(19.66 to 42.87)
Week 8
5.3
(1.18 to 20.50)
41.9
(32.18 to 52.37)
19.5
(11.36 to 31.44)
12.8
(6.38 to 24.08)
7.3
(2.96 to 16.96)
40.0
(28.29 to 52.98)
Week 12
21.1
(9.82 to 39.50)
45.2
(35.19 to 55.54)
29.3
(19.16 to 41.94)
12.8
(6.38 to 24.08)
17.1
(9.53 to 28.69)
47.5
(35.09 to 60.23)
10.Secondary Outcome
Title Percentage of Participants With an American College of Rheumatology 70% (ACR70) Response
Hide Description

Participants who met the following 3 conditions for improvement from baseline were classified as meeting the American College of Rheumatology 70% response (ACR70) criteria:

  1. ≥ 70% improvement in 68-tender joint count
  2. ≥ 70% improvement in 66-swollen joint count and
  3. ≥ 70% improvement in at least 3 of the 5 following parameters:

    • Patient's Assessment of Pain (Visual Analog Scale [VAS])
    • Patient's Global Assessment of Disease Activity (PtGA)
    • Physician's Global Assessment of Disease Activity (PhGA)
    • Health Assessment Questionnaire Disability Index (HAQ-DI)
    • High-sensitivity C-reactive protein (hsCRP)
Time Frame Baseline, Week 2, Week 4, Week 8, and Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set: all randomized participants who received at least 1 dose of randomized study drug, nonresponder imputation was used for missing data
Arm/Group Title ELS Placebo/UPA Placebo UPA 15 mg/ELS 60 mg ELS 60 mg/UPA Placebo ELS 20 mg/UPA Placebo ELS 5 mg/UPA Placebo UPA 15 mg/ELS Placebo
Hide Arm/Group Description:
Placebo capsule for elsubrutinib once a day by mouth for 12 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 12 weeks
15 mg film-coated upadacitinib tablet once a day by mouth for 12 weeks; 60 mg elsubrutinib capsule once a day by mouth for 12 weeks
60 mg elsubrutinib capsule once a day by mouth for 12 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 12 weeks
20 mg elsubrutinib capsule once a day by mouth for 12 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 12 weeks
5 mg elsubrutinib capsule once a day by mouth for 12 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 12 weeks
15 mg film-coated upadacitinib tablet once a day by mouth for 12 weeks; placebo capsule for elsubrutinib once a day by mouth for 12 weeks
Overall Number of Participants Analyzed 19 62 41 39 41 40
Measure Type: Number
Number (90% Confidence Interval)
Unit of Measure: percentage of participants
Week 2
0
(0.00 to 12.46)
8.1
(3.98 to 15.66)
2.4
(0.55 to 10.22)
0
(0.00 to 6.49)
0
(0.00 to 6.19)
0
(0.00 to 6.34)
Week 4
0
(0.00 to 12.46)
9.7
(5.09 to 17.64)
4.9
(1.63 to 13.71)
2.6
(0.57 to 10.71)
0
(0.00 to 6.19)
15.0
(7.96 to 26.47)
Week 8
0
(0.00 to 12.46)
17.7
(11.16 to 27.02)
4.9
(1.63 to 13.71)
2.6
(0.57 to 10.71)
0
(0.00 to 6.19)
25.0
(15.57 to 37.60)
Week 12
15.8
(6.49 to 33.62)
25.8
(17.81 to 35.82)
14.6
(7.76 to 25.89)
5.1
(1.71 to 14.37)
9.8
(4.46 to 20.04)
27.5
(17.60 to 40.25)
11.Secondary Outcome
Title Change From Baseline in Tender Joint Count 68 (TJC68)
Hide Description Sixty-eight joints were assessed for tenderness by physical examination. Pain or tenderness of each joint was classified as present (1) or absent (0), for a total possible score of 0 (0 joints with tenderness) to 68 (worst possible score/68 joints with tenderness). Negative values indicate improvement from baseline.
Time Frame Baseline, Week 2, Week 4, Week 8, and Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set: all randomized participants who received at least 1 dose of randomized study drug, had non-missing baseline values, and at least one post-baseline value. Baseline is defined as the last non-missing value prior to the first dose of study drug.
Arm/Group Title ELS Placebo/UPA Placebo UPA 15 mg/ELS 60 mg ELS 60 mg/UPA Placebo ELS 20 mg/UPA Placebo ELS 5 mg/UPA Placebo UPA 15 mg/ELS Placebo
Hide Arm/Group Description:
Placebo capsule for elsubrutinib once a day by mouth for 12 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 12 weeks
15 mg film-coated upadacitinib tablet once a day by mouth for 12 weeks; 60 mg elsubrutinib capsule once a day by mouth for 12 weeks
60 mg elsubrutinib capsule once a day by mouth for 12 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 12 weeks
20 mg elsubrutinib capsule once a day by mouth for 12 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 12 weeks
5 mg elsubrutinib capsule once a day by mouth for 12 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 12 weeks
15 mg film-coated upadacitinib tablet once a day by mouth for 12 weeks; placebo capsule for elsubrutinib once a day by mouth for 12 weeks
Overall Number of Participants Analyzed 19 61 39 37 40 40
Least Squares Mean (90% Confidence Interval)
Unit of Measure: tender joint counts
Week 2 Number Analyzed 19 participants 61 participants 39 participants 37 participants 39 participants 40 participants
-2.47
(-6.10 to 1.16)
-8.42
(-10.53 to -6.31)
-3.65
(-6.23 to -1.07)
-3.86
(-6.46 to -1.26)
-4.88
(-7.43 to -2.33)
-8.57
(-11.09 to -6.05)
Week 4 Number Analyzed 19 participants 61 participants 38 participants 36 participants 40 participants 39 participants
-9.21
(-13.08 to -5.34)
-11.86
(-14.10 to -9.62)
-5.16
(-7.93 to -2.39)
-5.39
(-8.18 to -2.60)
-8.08
(-10.77 to -5.39)
-12.76
(-15.46 to -10.06)
Week 8 Number Analyzed 18 participants 59 participants 36 participants 33 participants 38 participants 38 participants
-8.82
(-12.85 to -4.79)
-15.44
(-17.75 to -13.12)
-8.43
(-11.31 to -5.55)
-10.83
(-13.78 to -7.88)
-9.08
(-11.88 to -6.27)
-14.76
(-17.56 to -11.97)
Week 12 Number Analyzed 18 participants 56 participants 36 participants 31 participants 35 participants 37 participants
-8.47
(-12.81 to -4.12)
-16.33
(-18.84 to -13.83)
-9.14
(-12.23 to -6.05)
-9.33
(-12.55 to -6.12)
-12.58
(-15.64 to -9.52)
-17.56
(-20.58 to -14.53)
12.Secondary Outcome
Title Change From Baseline in Swollen Joint Count 66 (SJC66)
Hide Description Sixty-six joints were assessed for swelling by physical examination. Swelling of each joint was classified as present (1) or absent (0), for a total possible score of 0 (0 joints with swelling) to 66 (worst possible score/66 joints with swelling). Negative values indicate improvement from baseline.
Time Frame Baseline, Week 2, Week 4, Week 8, and Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set: all randomized participants who received at least 1 dose of randomized study drug, had non-missing baseline values, and at least one post-baseline value. Baseline is defined as the last non-missing value prior to the first dose of study drug.
Arm/Group Title ELS Placebo/UPA Placebo UPA 15 mg/ELS 60 mg ELS 60 mg/UPA Placebo ELS 20 mg/UPA Placebo ELS 5 mg/UPA Placebo UPA 15 mg/ELS Placebo
Hide Arm/Group Description:
Placebo capsule for elsubrutinib once a day by mouth for 12 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 12 weeks
15 mg film-coated upadacitinib tablet once a day by mouth for 12 weeks; 60 mg elsubrutinib capsule once a day by mouth for 12 weeks
60 mg elsubrutinib capsule once a day by mouth for 12 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 12 weeks
20 mg elsubrutinib capsule once a day by mouth for 12 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 12 weeks
5 mg elsubrutinib capsule once a day by mouth for 12 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 12 weeks
15 mg film-coated upadacitinib tablet once a day by mouth for 12 weeks; placebo capsule for elsubrutinib once a day by mouth for 12 weeks
Overall Number of Participants Analyzed 19 61 39 37 40 40
Least Squares Mean (90% Confidence Interval)
Unit of Measure: swollen joint counts
Week 2 Number Analyzed 19 participants 61 participants 39 participants 37 participants 39 participants 40 participants
-3.12
(-5.20 to -1.05)
-6.06
(-7.26 to -4.86)
-3.61
(-5.08 to -2.14)
-3.30
(-4.78 to -1.82)
-4.13
(-5.60 to -2.67)
-6.02
(-7.46 to -4.58)
Week 4 Number Analyzed 19 participants 61 participants 38 participants 36 participants 40 participants 39 participants
-4.70
(-6.92 to -2.49)
-7.96
(-9.24 to -6.68)
-5.11
(-6.69 to -3.53)
-4.67
(-6.27 to -3.07)
-6.05
(-7.60 to -4.51)
-8.81
(-10.35 to -7.26)
Week 8 Number Analyzed 18 participants 59 participants 36 participants 33 participants 38 participants 38 participants
-4.32
(-6.57 to -2.06)
-10.28
(-11.57 to -8.99)
-6.15
(-7.77 to -4.54)
-8.08
(-9.74 to -6.42)
-7.58
(-9.15 to -6.00)
-10.11
(-11.68 to -8.55)
Week 12 Number Analyzed 18 participants 56 participants 36 participants 31 participants 35 participants 37 participants
-5.58
(-8.05 to -3.11)
-10.86
(-12.29 to -9.44)
-6.68
(-8.44 to -4.92)
-7.85
(-9.70 to -6.01)
-8.59
(-10.35 to -6.83)
-11.14
(-12.86 to -9.42)
13.Secondary Outcome
Title Change From Baseline in Participant's Assessment of Pain (Visual Analog Scale [VAS])
Hide Description Participants rated their pain on a visual analogue scale (VAS) of 0 to 100 (mm), with 0 representing no pain and 100 representing the worst possible pain. Negative values indicate improvement from baseline.
Time Frame Baseline, Week 2, Week 4, Week 8, and Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set: all randomized participants who received at least 1 dose of randomized study drug, had non-missing baseline values, and at least one post-baseline value. Baseline is defined as the last non-missing value prior to the first dose of study drug.
Arm/Group Title ELS Placebo/UPA Placebo UPA 15 mg/ELS 60 mg ELS 60 mg/UPA Placebo ELS 20 mg/UPA Placebo ELS 5 mg/UPA Placebo UPA 15 mg/ELS Placebo
Hide Arm/Group Description:
Placebo capsule for elsubrutinib once a day by mouth for 12 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 12 weeks
15 mg film-coated upadacitinib tablet once a day by mouth for 12 weeks; 60 mg elsubrutinib capsule once a day by mouth for 12 weeks
60 mg elsubrutinib capsule once a day by mouth for 12 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 12 weeks
20 mg elsubrutinib capsule once a day by mouth for 12 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 12 weeks
5 mg elsubrutinib capsule once a day by mouth for 12 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 12 weeks
15 mg film-coated upadacitinib tablet once a day by mouth for 12 weeks; placebo capsule for elsubrutinib once a day by mouth for 12 weeks
Overall Number of Participants Analyzed 19 59 39 35 40 39
Least Squares Mean (90% Confidence Interval)
Unit of Measure: units on a scale
Week 2 Number Analyzed 19 participants 59 participants 39 participants 35 participants 38 participants 39 participants
-14.97
(-22.80 to -7.14)
-24.02
(-28.63 to -19.41)
-10.22
(-15.81 to -4.63)
-8.78
(-14.49 to -3.07)
-7.61
(-13.12 to -2.11)
-15.99
(-21.49 to -10.48)
Week 4 Number Analyzed 19 participants 59 participants 37 participants 34 participants 40 participants 39 participants
-20.87
(-29.60 to -12.14)
-28.17
(-33.28 to -23.07)
-12.95
(-19.27 to -6.63)
-8.41
(-14.85 to -1.97)
-9.91
(-15.93 to -3.88)
-25.58
(-31.69 to -19.48)
Week 8 Number Analyzed 18 participants 57 participants 35 participants 31 participants 38 participants 38 participants
-16.21
(-25.97 to -6.45)
-31.86
(-37.50 to -26.22)
-20.92
(-27.96 to -13.88)
-11.12
(-18.46 to -3.79)
-13.90
(-20.64 to -7.16)
-30.70
(-37.47 to -23.92)
Week 12 Number Analyzed 18 participants 54 participants 35 participants 29 participants 35 participants 37 participants
-23.37
(-33.74 to -13.01)
-32.27
(-38.32 to -26.23)
-19.52
(-26.97 to -12.06)
-10.46
(-18.38 to -2.55)
-17.84
(-25.13 to -10.55)
-38.34
(-45.57 to -31.12)
14.Secondary Outcome
Title Change From Baseline in Patient's Global Assessment of Disease Activity (PGA)
Hide Description Participants rated their disease activity for the past 24 hours using a Patient's Global Assessment of Disease Activity Global visual analogue scale (VAS). The range is 0 to 100 mm, with 0 representing no disease activity and 100 representing severe disease activity. Negative values indicate improvement from baseline.
Time Frame Baseline, Week 2, Week 4, Week 8, and Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set: all randomized participants who received at least 1 dose of randomized study drug, had non-missing baseline values, and at least one post-baseline value. Baseline is defined as the last non-missing value prior to the first dose of study drug.
Arm/Group Title ELS Placebo/UPA Placebo UPA 15 mg/ELS 60 mg ELS 60 mg/UPA Placebo ELS 20 mg/UPA Placebo ELS 5 mg/UPA Placebo UPA 15 mg/ELS Placebo
Hide Arm/Group Description:
Placebo capsule for elsubrutinib once a day by mouth for 12 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 12 weeks
15 mg film-coated upadacitinib tablet once a day by mouth for 12 weeks; 60 mg elsubrutinib capsule once a day by mouth for 12 weeks
60 mg elsubrutinib capsule once a day by mouth for 12 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 12 weeks
20 mg elsubrutinib capsule once a day by mouth for 12 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 12 weeks
5 mg elsubrutinib capsule once a day by mouth for 12 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 12 weeks
15 mg film-coated upadacitinib tablet once a day by mouth for 12 weeks; placebo capsule for elsubrutinib once a day by mouth for 12 weeks
Overall Number of Participants Analyzed 19 59 39 35 40 39
Least Squares Mean (90% Confidence Interval)
Unit of Measure: units on a scale
Week 2 Number Analyzed 19 participants 59 participants 39 participants 35 participants 38 participants 39 participants
-11.87
(-20.12 to -3.63)
-23.44
(-28.31 to -18.57)
-11.16
(-17.07 to -5.25)
-6.47
(-12.51 to -0.44)
-5.95
(-11.76 to -0.14)
-14.76
(-20.56 to -8.95)
Week 4 Number Analyzed 19 participants 59 participants 37 participants 34 participants 40 participants 39 participants
-20.93
(-29.91 to -11.94)
-25.97
(-31.24 to -20.70)
-12.79
(-19.32 to -6.26)
-7.15
(-13.79 to -0.50)
-8.73
(-14.94 to -2.51)
-23.02
(-29.31 to -16.73)
Week 8 Number Analyzed 18 participants 57 participants 35 participants 31 participants 38 participants 38 participants
-15.14
(-25.37 to -4.91)
-28.05
(-33.97 to -22.13)
-17.25
(-24.65 to -9.84)
-6.27
(-14.00 to 1.45)
-14.25
(-21.34 to -7.17)
-26.79
(-33.90 to -19.69)
Week 12 Number Analyzed 18 participants 54 participants 35 participants 29 participants 35 participants 37 participants
-19.55
(-30.15 to -8.95)
-30.52
(-36.72 to -24.32)
-19.47
(-27.13 to -11.81)
-8.45
(-16.58 to -0.33)
-16.40
(-23.89 to -8.92)
-33.53
(-40.94 to -26.13)
15.Secondary Outcome
Title Change From Baseline in Physician's Global Assessment of Disease Activity (PhGA)
Hide Description The physician assessed a participant's disease activity at the time of the visit using a Physician's Global Assessment of Disease visual analogue scale (VAS). The range is 0 to 100 mm, with 0 representing no disease activity and 100 representing severe disease activity. Negative values indicate improvement from baseline.
Time Frame Baseline, Week 2, Week 4, Week 8, and Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set: all randomized participants who received at least 1 dose of randomized study drug, had non-missing baseline values, and at least one post-baseline value. Baseline is defined as the last non-missing value prior to the first dose of study drug.
Arm/Group Title ELS Placebo/UPA Placebo UPA 15 mg/ELS 60 mg ELS 60 mg/UPA Placebo ELS 20 mg/UPA Placebo ELS 5 mg/UPA Placebo UPA 15 mg/ELS Placebo
Hide Arm/Group Description:
Placebo capsule for elsubrutinib once a day by mouth for 12 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 12 weeks
15 mg film-coated upadacitinib tablet once a day by mouth for 12 weeks; 60 mg elsubrutinib capsule once a day by mouth for 12 weeks
60 mg elsubrutinib capsule once a day by mouth for 12 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 12 weeks
20 mg elsubrutinib capsule once a day by mouth for 12 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 12 weeks
5 mg elsubrutinib capsule once a day by mouth for 12 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 12 weeks
15 mg film-coated upadacitinib tablet once a day by mouth for 12 weeks; placebo capsule for elsubrutinib once a day by mouth for 12 weeks
Overall Number of Participants Analyzed 18 58 38 35 37 38
Least Squares Mean (90% Confidence Interval)
Unit of Measure: units on a scale
Week 2 Number Analyzed 17 participants 57 participants 38 participants 35 participants 36 participants 38 participants
-16.31
(-24.67 to -7.96)
-22.35
(-27.10 to -17.60)
-19.01
(-24.74 to -13.27)
-16.12
(-21.97 to -10.26)
-11.64
(-17.44 to -5.84)
-24.71
(-30.37 to -19.05)
Week 4 Number Analyzed 17 participants 58 participants 37 participants 34 participants 37 participants 37 participants
-25.20
(-33.52 to -16.89)
-33.54
(-38.26 to -28.82)
-25.33
(-31.11 to -19.55)
-19.59
(-25.49 to -13.69)
-18.31
(-24.05 to -12.56)
-34.17
(-39.86 to -28.49)
Week 8 Number Analyzed 17 participants 57 participants 35 participants 31 participants 35 participants 37 participants
-24.47
(-32.71 to -16.22)
-40.00
(-44.71 to -35.29)
-30.06
(-35.91 to -24.22)
-33.93
(-39.99 to -27.87)
-25.21
(-31.03 to -19.40)
-41.02
(-46.69 to -35.36)
Week 12 Number Analyzed 18 participants 53 participants 35 participants 29 participants 33 participants 36 participants
-23.19
(-31.69 to -14.69)
-46.98
(-52.00 to -41.96)
-30.15
(-36.28 to -24.03)
-31.68
(-38.19 to -25.18)
-24.55
(-30.75 to -18.36)
-50.89
(-56.87 to -44.91)
16.Secondary Outcome
Title Change From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI)
Hide Description The Health Assessment Questionnaire - Disability Index is a patient-reported questionnaire that measures the degree of difficulty a person has in accomplishing tasks in 8 functional areas (dressing, arising, eating, walking, hygiene, reaching, gripping, and errands and chores) over the past week. Participants assessed their ability to do each task on a scale from 0 (without any difficulty) to 3 (unable to do). Scores were averaged to provide an overall score ranging from 0 to 3, where 0 represents no disability and 3 represents very severe, high-dependency disability. A negative change from baseline in the overall score indicates improvement.
Time Frame Baseline, Week 2, Week 4, Week 8, and Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set: all randomized participants who received at least 1 dose of randomized study drug, had non-missing baseline values, and at least one post-baseline value. Baseline is defined as the last non-missing value prior to the first dose of study drug.
Arm/Group Title ELS Placebo/UPA Placebo UPA 15 mg/ELS 60 mg ELS 60 mg/UPA Placebo ELS 20 mg/UPA Placebo ELS 5 mg/UPA Placebo UPA 15 mg/ELS Placebo
Hide Arm/Group Description:
Placebo capsule for elsubrutinib once a day by mouth for 12 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 12 weeks
15 mg film-coated upadacitinib tablet once a day by mouth for 12 weeks; 60 mg elsubrutinib capsule once a day by mouth for 12 weeks
60 mg elsubrutinib capsule once a day by mouth for 12 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 12 weeks
20 mg elsubrutinib capsule once a day by mouth for 12 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 12 weeks
5 mg elsubrutinib capsule once a day by mouth for 12 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 12 weeks
15 mg film-coated upadacitinib tablet once a day by mouth for 12 weeks; placebo capsule for elsubrutinib once a day by mouth for 12 weeks
Overall Number of Participants Analyzed 19 59 39 35 40 38
Least Squares Mean (90% Confidence Interval)
Unit of Measure: units on a scale
Week 2 Number Analyzed 19 participants 59 participants 39 participants 35 participants 38 participants 38 participants
-0.22
(-0.37 to -0.06)
-0.34
(-0.43 to -0.25)
-0.13
(-0.24 to -0.02)
-0.06
(-0.17 to 0.05)
-0.16
(-0.27 to -0.05)
-0.22
(-0.33 to -0.11)
Week 4 Number Analyzed 19 participants 59 participants 37 participants 34 participants 40 participants 38 participants
-0.36
(-0.53 to -0.18)
-0.39
(-0.49 to -0.29)
-0.11
(-0.23 to 0.02)
-0.14
(-0.27 to -0.02)
-0.21
(-0.33 to -0.09)
-0.33
(-0.45 to -0.20)
Week 8 Number Analyzed 18 participants 57 participants 35 participants 31 participants 38 participants 37 participants
-0.24
(-0.44 to -0.05)
-0.47
(-0.59 to -0.36)
-0.29
(-0.43 to -0.15)
-0.15
(-0.30 to -0.00)
-0.15
(-0.29 to -0.02)
-0.47
(-0.61 to -0.33)
Week 12 Number Analyzed 18 participants 54 participants 35 participants 29 participants 35 participants 36 participants
-0.30
(-0.52 to -0.08)
-0.52
(-0.65 to -0.39)
-0.31
(-0.46 to -0.15)
-0.12
(-0.28 to 0.05)
-0.18
(-0.33 to -0.03)
-0.54
(-0.70 to -0.39)
17.Secondary Outcome
Title Change From Baseline in High-Sensitivity C-reactive Protein (hsCRP)
Hide Description C-reactive protein is a blood test marker for inflammation in the body, and levels rise in response to inflammation. A negative change from baseline in indicates improvement.
Time Frame Baseline, Week 2, Week 4, Week 8, and Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set: all randomized participants who received at least 1 dose of randomized study drug, had non-missing baseline values, and at least one post-baseline value. Baseline is defined as the last non-missing value prior to the first dose of study drug.
Arm/Group Title ELS Placebo/UPA Placebo UPA 15 mg/ELS 60 mg ELS 60 mg/UPA Placebo ELS 20 mg/UPA Placebo ELS 5 mg/UPA Placebo UPA 15 mg/ELS Placebo
Hide Arm/Group Description:
Placebo capsule for elsubrutinib once a day by mouth for 12 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 12 weeks
15 mg film-coated upadacitinib tablet once a day by mouth for 12 weeks; 60 mg elsubrutinib capsule once a day by mouth for 12 weeks
60 mg elsubrutinib capsule once a day by mouth for 12 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 12 weeks
20 mg elsubrutinib capsule once a day by mouth for 12 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 12 weeks
5 mg elsubrutinib capsule once a day by mouth for 12 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 12 weeks
15 mg film-coated upadacitinib tablet once a day by mouth for 12 weeks; placebo capsule for elsubrutinib once a day by mouth for 12 weeks
Overall Number of Participants Analyzed 19 61 39 37 40 40
Least Squares Mean (90% Confidence Interval)
Unit of Measure: mg/L
Week 2 Number Analyzed 19 participants 61 participants 39 participants 37 participants 39 participants 40 participants
-0.51
(-4.82 to 3.81)
-9.29
(-11.79 to -6.80)
2.26
(-0.81 to 5.33)
-0.34
(-3.43 to 2.74)
-0.72
(-3.74 to 2.30)
-12.27
(-15.26 to -9.27)
Week 4 Number Analyzed 19 participants 61 participants 38 participants 36 participants 40 participants 39 participants
1.54
(-3.72 to 6.79)
-10.08
(-13.08 to -7.08)
2.71
(-1.05 to 6.46)
-0.78
(-4.58 to 3.02)
0.72
(-2.91 to 4.35)
-12.59
(-16.27 to -8.92)
Week 8 Number Analyzed 18 participants 59 participants 36 participants 32 participants 38 participants 38 participants
3.23
(-1.56 to 8.03)
-9.97
(-12.70 to -7.24)
-1.39
(-4.83 to 2.05)
-2.58
(-6.15 to 1.00)
-2.93
(-6.26 to 0.39)
-13.13
(-16.46 to -9.81)
Week 12 Number Analyzed 18 participants 56 participants 36 participants 31 participants 34 participants 37 participants
1.45
(-5.10 to 8.00)
-10.95
(-14.73 to -7.18)
-4.58
(-9.26 to 0.09)
-5.78
(-10.77 to -0.78)
-0.81
(-5.58 to 3.97)
-7.44
(-12.03 to -2.86)
18.Secondary Outcome
Title Change From Baseline in Disease Activity Score 28 C-reactive Protein [DAS28-CRP])
Hide Description The DAS28-CRP is a composite index used to assess rheumatoid arthritis disease activity, calculated based on the tender joint count (out of 28 evaluated joints), swollen joint count (out of 28 evaluated joints), Patient's Global Assessment of Disease Activity (0-100 mm), and high-sensitivity C-reactive protein (hsCRP; in mg/L). Scores on the DAS28-CRP range from 0 to approximately 10, where higher scores indicate more disease activity. A negative change from baseline indicates improvement in disease activity.
Time Frame Baseline, Week 2, Week 4, Week 8, and Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set: all randomized participants who received at least 1 dose of randomized study drug, had non-missing baseline values, and at least one post-baseline value. Baseline is defined as the last non-missing value prior to the first dose of study drug.
Arm/Group Title ELS Placebo/UPA Placebo UPA 15 mg/ELS 60 mg ELS 60 mg/UPA Placebo ELS 20 mg/UPA Placebo ELS 5 mg/UPA Placebo UPA 15 mg/ELS Placebo
Hide Arm/Group Description:
Placebo capsule for elsubrutinib once a day by mouth for 12 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 12 weeks
15 mg film-coated upadacitinib tablet once a day by mouth for 12 weeks; 60 mg elsubrutinib capsule once a day by mouth for 12 weeks
60 mg elsubrutinib capsule once a day by mouth for 12 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 12 weeks
20 mg elsubrutinib capsule once a day by mouth for 12 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 12 weeks
5 mg elsubrutinib capsule once a day by mouth for 12 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 12 weeks
15 mg film-coated upadacitinib tablet once a day by mouth for 12 weeks; placebo capsule for elsubrutinib once a day by mouth for 12 weeks
Overall Number of Participants Analyzed 19 59 39 35 40 39
Least Squares Mean (90% Confidence Interval)
Unit of Measure: units on a scale
Week 2 Number Analyzed 19 participants 59 participants 39 participants 35 participants 38 participants 39 participants
-0.46
(-0.83 to -0.10)
-1.53
(-1.75 to -1.31)
-0.63
(-0.89 to -0.36)
-0.44
(-0.71 to -0.18)
-0.56
(-0.82 to -0.30)
-1.43
(-1.69 to -1.17)
Week 4 Number Analyzed 19 participants 59 participants 37 participants 34 participants 40 participants 39 participants
-0.90
(-1.33 to -0.47)
-1.96
(-2.21 to -1.71)
-0.87
(-1.18 to -0.56)
-0.68
(-1.00 to -0.36)
-0.82
(-1.11 to -0.52)
-1.98
(-2.28 to -1.67)
Week 8 Number Analyzed 18 participants 57 participants 35 participants 30 participants 38 participants 38 participants
-0.78
(-1.27 to -0.29)
-2.40
(-2.68 to -2.11)
-1.21
(-1.56 to -0.86)
-1.24
(-1.61 to -0.87)
-1.11
(-1.45 to -0.77)
-2.34
(-2.68 to -2.00)
Week 12 Number Analyzed 18 participants 54 participants 35 participants 29 participants 34 participants 37 participants
-1.12
(-1.64 to -0.60)
-2.56
(-2.86 to -2.26)
-1.52
(-1.89 to -1.15)
-1.32
(-1.71 to -0.93)
-1.33
(-1.70 to -0.97)
-2.87
(-3.23 to -2.51)
19.Secondary Outcome
Title Change From Baseline in Disease Activity Score 28 Erythrocyte Sedimentation Rate (DAS28- ESR)
Hide Description The DAS28-ESR is a validated index of rheumatoid arthritis disease activity. Twenty-eight tender joint counts, 28 swollen joint counts, the erythrocyte sedimentation rate (ESR; mm/hour), and the participant's assessment of global disease activity (on a visual analog scale [VAS] from 0 to 100 mm) are included in the DAS28 -ESR score. Scores on the DAS28-ESR range from 0 to 10; higher scores indicate more disease activity.
Time Frame Baseline, Week 2, Week 4, Week 8, and Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set: all randomized participants who received at least 1 dose of randomized study drug, had non-missing baseline values, and at least one post-baseline value. Baseline is defined as the last non-missing value prior to the first dose of study drug.
Arm/Group Title ELS Placebo/UPA Placebo UPA 15 mg/ELS 60 mg ELS 60 mg/UPA Placebo ELS 20 mg/UPA Placebo ELS 5 mg/UPA Placebo UPA 15 mg/ELS Placebo
Hide Arm/Group Description:
Placebo capsule for elsubrutinib once a day by mouth for 12 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 12 weeks
15 mg film-coated upadacitinib tablet once a day by mouth for 12 weeks; 60 mg elsubrutinib capsule once a day by mouth for 12 weeks
60 mg elsubrutinib capsule once a day by mouth for 12 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 12 weeks
20 mg elsubrutinib capsule once a day by mouth for 12 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 12 weeks
5 mg elsubrutinib capsule once a day by mouth for 12 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 12 weeks
15 mg film-coated upadacitinib tablet once a day by mouth for 12 weeks; placebo capsule for elsubrutinib once a day by mouth for 12 weeks
Overall Number of Participants Analyzed 19 59 39 34 40 39
Least Squares Mean (90% Confidence Interval)
Unit of Measure: units on a scale
Week 2 Number Analyzed 19 participants 59 participants 39 participants 34 participants 38 participants 39 participants
-0.46
(-0.82 to -0.09)
-1.48
(-1.69 to -1.26)
-0.52
(-0.79 to -0.26)
-0.46
(-0.74 to -0.19)
-0.57
(-0.83 to -0.32)
-1.32
(-1.58 to -1.06)
Week 4 Number Analyzed 19 participants 58 participants 37 participants 34 participants 40 participants 39 participants
-0.86
(-1.30 to -0.43)
-1.93
(-2.19 to -1.68)
-0.79
(-1.11 to -0.48)
-0.59
(-0.91 to -0.26)
-0.92
(-1.23 to -0.62)
-1.90
(-2.20 to -1.59)
Week 8 Number Analyzed 18 participants 57 participants 35 participants 30 participants 37 participants 38 participants
-0.80
(-1.29 to -0.31)
-2.41
(-2.69 to -2.12)
-1.07
(-1.42 to -0.71)
-1.15
(-1.52 to -0.78)
-1.20
(-1.54 to -0.86)
-2.31
(-2.65 to -1.97)
Week 12 Number Analyzed 18 participants 54 participants 35 participants 29 participants 35 participants 37 participants
-1.18
(-1.71 to -0.64)
-2.53
(-2.84 to -2.22)
-1.41
(-1.80 to -1.03)
-1.24
(-1.65 to -0.83)
-1.44
(-1.82 to -1.06)
-2.88
(-3.25 to -2.50)
20.Secondary Outcome
Title Change From Baseline in Morning Stiffness Severity
Hide Description Morning stiffness severity was assessed by a numeric rating-scale (NRS). Participants rated the severity of morning stiffness during the past week from 0 to 10 with 0 representing "not severe" and 10 "very severe". Negative values indicate improvement from baseline.
Time Frame Baseline, Week 2, Week 4, Week 8, and Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set: all randomized participants who received at least 1 dose of randomized study drug, had non-missing baseline values, and at least one post-baseline value. Baseline is defined as the last non-missing value prior to the first dose of study drug.
Arm/Group Title ELS Placebo/UPA Placebo UPA 15 mg/ELS 60 mg ELS 60 mg/UPA Placebo ELS 20 mg/UPA Placebo ELS 5 mg/UPA Placebo UPA 15 mg/ELS Placebo
Hide Arm/Group Description:
Placebo capsule for elsubrutinib once a day by mouth for 12 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 12 weeks
15 mg film-coated upadacitinib tablet once a day by mouth for 12 weeks; 60 mg elsubrutinib capsule once a day by mouth for 12 weeks
60 mg elsubrutinib capsule once a day by mouth for 12 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 12 weeks
20 mg elsubrutinib capsule once a day by mouth for 12 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 12 weeks
5 mg elsubrutinib capsule once a day by mouth for 12 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 12 weeks
15 mg film-coated upadacitinib tablet once a day by mouth for 12 weeks; placebo capsule for elsubrutinib once a day by mouth for 12 weeks
Overall Number of Participants Analyzed 19 59 39 35 40 38
Least Squares Mean (90% Confidence Interval)
Unit of Measure: units on a scale
Week 2 Number Analyzed 19 participants 59 participants 39 participants 35 participants 38 participants 38 participants
-1.76
(-2.54 to -0.98)
-2.02
(-2.48 to -1.56)
-0.91
(-1.47 to -0.35)
-0.68
(-1.26 to -0.11)
-0.59
(-1.15 to -0.04)
-1.84
(-2.40 to -1.29)
Week 4 Number Analyzed 19 participants 59 participants 37 participants 34 participants 40 participants 38 participants
-1.76
(-2.63 to -0.90)
-2.71
(-3.22 to -2.21)
-0.82
(-1.45 to -0.20)
-0.83
(-1.47 to -0.19)
-1.08
(-1.67 to -0.48)
-2.51
(-3.13 to -1.90)
Week 8 Number Analyzed 18 participants 57 participants 35 participants 31 participants 38 participants 37 participants
-1.67
(-2.56 to -0.77)
-3.07
(-3.59 to -2.55)
-1.30
(-1.94 to -0.65)
-0.97
(-1.64 to -0.30)
-1.50
(-2.11 to -0.88)
-3.07
(-3.70 to -2.44)
Week 12 Number Analyzed 18 participants 54 participants 34 participants 29 participants 35 participants 36 participants
-1.61
(-2.60 to -0.63)
-3.23
(-3.81 to -2.65)
-1.27
(-1.99 to -0.56)
-1.30
(-2.06 to -0.55)
-1.66
(-2.36 to -0.97)
-3.36
(-4.06 to -2.67)
21.Secondary Outcome
Title Percentage of Participants Achieving Minimal Clinically Important Difference (MCID) in Change From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI)
Hide Description The Health Assessment Questionnaire - Disability Index is a patient-reported questionnaire that measures the degree of difficulty a person has in accomplishing tasks in 8 functional areas (dressing, arising, eating, walking, hygiene, reaching, gripping, and errands and chores) over the past week. Participants assessed their ability to do each task on a scale from 0 (without any difficulty) to 3 (unable to do). Scores were averaged to provide an overall score ranging from 0 to 3, where 0 represents no disability and 3 represents very severe, high-dependency disability. The minimal clinically important difference (MCID) in HAQ-DI is defined as change from Baseline ≤ -0.22 for rheumatoid arthritis.
Time Frame Baseline, Week 2, Week 4, Week 8, and Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set: all randomized participants who received at least 1 dose of randomized study drug, nonresponder imputation was used for missing data
Arm/Group Title ELS Placebo/UPA Placebo UPA 15 mg/ELS 60 mg ELS 60 mg/UPA Placebo ELS 20 mg/UPA Placebo ELS 5 mg/UPA Placebo UPA 15 mg/ELS Placebo
Hide Arm/Group Description:
Placebo capsule for elsubrutinib once a day by mouth for 12 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 12 weeks
15 mg film-coated upadacitinib tablet once a day by mouth for 12 weeks; 60 mg elsubrutinib capsule once a day by mouth for 12 weeks
60 mg elsubrutinib capsule once a day by mouth for 12 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 12 weeks
20 mg elsubrutinib capsule once a day by mouth for 12 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 12 weeks
5 mg elsubrutinib capsule once a day by mouth for 12 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 12 weeks
15 mg film-coated upadacitinib tablet once a day by mouth for 12 weeks; placebo capsule for elsubrutinib once a day by mouth for 12 weeks
Overall Number of Participants Analyzed 19 62 41 39 41 40
Measure Type: Number
Number (90% Confidence Interval)
Unit of Measure: percentage of participants
Week 2
52.6
(34.67 to 69.93)
51.6
(41.33 to 61.76)
36.6
(25.40 to 49.43)
30.8
(20.20 to 43.84)
36.6
(25.40 to 49.43)
52.5
(39.77 to 64.91)
Week 4
68.4
(49.55 to 82.70)
54.8
(44.46 to 64.81)
34.1
(23.29 to 46.97)
41.0
(29.07 to 54.15)
53.7
(41.02 to 65.84)
45.0
(32.79 to 57.84)
Week 8
52.6
(34.67 to 69.93)
58.1
(47.63 to 67.82)
51.2
(38.71 to 63.58)
51.3
(38.47 to 63.93)
36.6
(25.40 to 49.43)
65.0
(52.01 to 76.09)
Week 12
47.4
(30.07 to 65.33)
58.1
(47.63 to 67.82)
53.7
(41.02 to 65.84)
43.6
(31.37 to 56.64)
43.9
(31.93 to 56.63)
55.0
(42.16 to 67.21)
22.Secondary Outcome
Title Percentage of Participants Achieving American College of Rheumatology/European League Against Rheumatism (EULAR) Boolean Remission
Hide Description The EULAR Boolean-based definition of remission is as follows: at any time point, a participant must satisfy all of the following: tender joint count ≤1, swollen joint count ≤1, C-reactive protein ≤1 mg/dl and Patient Global Assessment (PGA) ≤1 (on a 0-10 scale).
Time Frame Baseline, Week 2, Week 4, Week 8, and Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set: all randomized participants who received at least 1 dose of randomized study drug, nonresponder imputation was used for missing data
Arm/Group Title ELS Placebo/UPA Placebo UPA 15 mg/ELS 60 mg ELS 60 mg/UPA Placebo ELS 20 mg/UPA Placebo ELS 5 mg/UPA Placebo UPA 15 mg/ELS Placebo
Hide Arm/Group Description:
Placebo capsule for elsubrutinib once a day by mouth for 12 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 12 weeks
15 mg film-coated upadacitinib tablet once a day by mouth for 12 weeks; 60 mg elsubrutinib capsule once a day by mouth for 12 weeks
60 mg elsubrutinib capsule once a day by mouth for 12 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 12 weeks
20 mg elsubrutinib capsule once a day by mouth for 12 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 12 weeks
5 mg elsubrutinib capsule once a day by mouth for 12 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 12 weeks
15 mg film-coated upadacitinib tablet once a day by mouth for 12 weeks; placebo capsule for elsubrutinib once a day by mouth for 12 weeks
Overall Number of Participants Analyzed 19 62 41 39 41 40
Measure Type: Number
Number (90% Confidence Interval)
Unit of Measure: percentage of participants
Week 2
0
(0.00 to 12.46)
1.6
(0.36 to 6.91)
0
(0.00 to 6.19)
0
(0.00 to 6.49)
0
(0.00 to 6.19)
0
(0.00 to 6.34)
Week 4
0
(0.00 to 12.46)
6.5
(2.93 to 13.62)
2.4
(0.55 to 10.22)
0
(0.00 to 6.49)
0
(0.00 to 6.19)
2.5
(0.56 to 10.46)
Week 8
0
(0.00 to 12.46)
6.5
(2.93 to 13.62)
2.4
(0.55 to 10.22)
5.1
(1.71 to 14.37)
0
(0.00 to 6.19)
12.5
(6.22 to 23.53)
Week 12
0
(0.00 to 12.46)
11.3
(6.24 to 19.58)
9.8
(4.46 to 20.04)
2.6
(0.57 to 10.71)
2.4
(0.55 to 10.22)
10.0
(4.57 to 20.50)
Time Frame Treatment-emergent adverse events (TEAEs) and serious adverse events (TESAEs) were collected from the first dose of study drug until 30 days after last study drug administration, up to 16 weeks. In addition, serious adverse events and protocol-related nonserious adverse events were collected from the time the participant signed the study-specific informed consent.
Adverse Event Reporting Description TEAEs and SAEs are defined as any AE or SAE with onset or worsening reported by a participant from the time that the first dose of study drug is administered until 30 days have elapsed following discontinuation of study drug. TEAEs were collected whether elicited or spontaneously reported by the participant.
 
Arm/Group Title ELS Placebo/UPA Placebo UPA 15 mg/ELS 60 mg ELS 60 mg/UPA Placebo ELS 20 mg/UPA Placebo ELS 5 mg/UPA Placebo UPA 15 mg/ELS Placebo
Hide Arm/Group Description Placebo capsule for elsubrutinib once a day by mouth for 12 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 12 weeks 15 mg film-coated upadacitinib tablet once a day by mouth for 12 weeks; 60 mg elsubrutinib capsule once a day by mouth for 12 weeks 60 mg elsubrutinib capsule once a day by mouth for 12 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 12 weeks 20 mg elsubrutinib capsule once a day by mouth for 12 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 12 weeks 5 mg elsubrutinib capsule once a day by mouth for 12 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 12 weeks 15 mg film-coated upadacitinib tablet once a day by mouth for 12 weeks; placebo capsule for elsubrutinib once a day by mouth for 12 weeks
All-Cause Mortality
ELS Placebo/UPA Placebo UPA 15 mg/ELS 60 mg ELS 60 mg/UPA Placebo ELS 20 mg/UPA Placebo ELS 5 mg/UPA Placebo UPA 15 mg/ELS Placebo
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/19 (0.00%)      0/62 (0.00%)      0/41 (0.00%)      0/39 (0.00%)      1/41 (2.44%)      0/40 (0.00%)    
Hide Serious Adverse Events
ELS Placebo/UPA Placebo UPA 15 mg/ELS 60 mg ELS 60 mg/UPA Placebo ELS 20 mg/UPA Placebo ELS 5 mg/UPA Placebo UPA 15 mg/ELS Placebo
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   1/19 (5.26%)      0/62 (0.00%)      0/41 (0.00%)      2/39 (5.13%)      3/41 (7.32%)      0/40 (0.00%)    
Cardiac disorders             
CARDIAC ARREST  1  0/19 (0.00%)  0 0/62 (0.00%)  0 0/41 (0.00%)  0 0/39 (0.00%)  0 1/41 (2.44%)  1 0/40 (0.00%)  0
CORONARY ARTERY DISEASE  1  0/19 (0.00%)  0 0/62 (0.00%)  0 0/41 (0.00%)  0 1/39 (2.56%)  1 0/41 (0.00%)  0 0/40 (0.00%)  0
Infections and infestations             
PYELONEPHRITIS  1  0/19 (0.00%)  0 0/62 (0.00%)  0 0/41 (0.00%)  0 0/39 (0.00%)  0 1/41 (2.44%)  1 0/40 (0.00%)  0
Injury, poisoning and procedural complications             
CLAVICLE FRACTURE  1  0/19 (0.00%)  0 0/62 (0.00%)  0 0/41 (0.00%)  0 0/39 (0.00%)  0 1/41 (2.44%)  1 0/40 (0.00%)  0
RIB FRACTURE  1  0/19 (0.00%)  0 0/62 (0.00%)  0 0/41 (0.00%)  0 0/39 (0.00%)  0 1/41 (2.44%)  1 0/40 (0.00%)  0
ROAD TRAFFIC ACCIDENT  1  0/19 (0.00%)  0 0/62 (0.00%)  0 0/41 (0.00%)  0 0/39 (0.00%)  0 1/41 (2.44%)  1 0/40 (0.00%)  0
Investigations             
PROSTATIC SPECIFIC ANTIGEN INCREASED  1  1/19 (5.26%)  1 0/62 (0.00%)  0 0/41 (0.00%)  0 0/39 (0.00%)  0 0/41 (0.00%)  0 0/40 (0.00%)  0
Nervous system disorders             
LUMBAR RADICULOPATHY  1  0/19 (0.00%)  0 0/62 (0.00%)  0 0/41 (0.00%)  0 1/39 (2.56%)  1 0/41 (0.00%)  0 0/40 (0.00%)  0
1
Term from vocabulary, MedDRA 22.1
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
ELS Placebo/UPA Placebo UPA 15 mg/ELS 60 mg ELS 60 mg/UPA Placebo ELS 20 mg/UPA Placebo ELS 5 mg/UPA Placebo UPA 15 mg/ELS Placebo
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   10/19 (52.63%)      7/62 (11.29%)      17/41 (41.46%)      10/39 (25.64%)      8/41 (19.51%)      9/40 (22.50%)    
Gastrointestinal disorders             
DIARRHOEA  1  0/19 (0.00%)  0 0/62 (0.00%)  0 3/41 (7.32%)  3 0/39 (0.00%)  0 0/41 (0.00%)  0 0/40 (0.00%)  0
General disorders             
PERIPHERAL SWELLING  1  1/19 (5.26%)  1 0/62 (0.00%)  0 1/41 (2.44%)  1 0/39 (0.00%)  0 0/41 (0.00%)  0 0/40 (0.00%)  0
Infections and infestations             
BRONCHITIS  1  1/19 (5.26%)  1 0/62 (0.00%)  0 1/41 (2.44%)  1 0/39 (0.00%)  0 1/41 (2.44%)  1 0/40 (0.00%)  0
SINUSITIS  1  1/19 (5.26%)  1 0/62 (0.00%)  0 1/41 (2.44%)  1 0/39 (0.00%)  0 0/41 (0.00%)  0 0/40 (0.00%)  0
TOOTH INFECTION  1  1/19 (5.26%)  1 0/62 (0.00%)  0 0/41 (0.00%)  0 1/39 (2.56%)  1 0/41 (0.00%)  0 1/40 (2.50%)  1
UPPER RESPIRATORY TRACT INFECTION  1  1/19 (5.26%)  1 4/62 (6.45%)  4 2/41 (4.88%)  2 3/39 (7.69%)  3 2/41 (4.88%)  2 2/40 (5.00%)  2
URINARY TRACT INFECTION  1  0/19 (0.00%)  0 0/62 (0.00%)  0 4/41 (9.76%)  5 2/39 (5.13%)  2 2/41 (4.88%)  2 3/40 (7.50%)  4
Injury, poisoning and procedural complications             
ANIMAL BITE  1  1/19 (5.26%)  1 0/62 (0.00%)  0 0/41 (0.00%)  0 0/39 (0.00%)  0 0/41 (0.00%)  0 0/40 (0.00%)  0
Investigations             
ALANINE AMINOTRANSFERASE INCREASED  1  0/19 (0.00%)  0 0/62 (0.00%)  0 0/41 (0.00%)  0 0/39 (0.00%)  0 0/41 (0.00%)  0 2/40 (5.00%)  2
BLOOD GLUCOSE INCREASED  1  1/19 (5.26%)  1 0/62 (0.00%)  0 0/41 (0.00%)  0 0/39 (0.00%)  0 0/41 (0.00%)  0 0/40 (0.00%)  0
Metabolism and nutrition disorders             
VITAMIN D DEFICIENCY  1  1/19 (5.26%)  1 0/62 (0.00%)  0 0/41 (0.00%)  0 0/39 (0.00%)  0 0/41 (0.00%)  0 0/40 (0.00%)  0
Musculoskeletal and connective tissue disorders             
ARTHRALGIA  1  1/19 (5.26%)  1 1/62 (1.61%)  1 0/41 (0.00%)  0 0/39 (0.00%)  0 0/41 (0.00%)  0 0/40 (0.00%)  0
ARTHRITIS  1  1/19 (5.26%)  1 0/62 (0.00%)  0 1/41 (2.44%)  1 0/39 (0.00%)  0 0/41 (0.00%)  0 0/40 (0.00%)  0
BONE DEFORMITY  1  1/19 (5.26%)  1 0/62 (0.00%)  0 0/41 (0.00%)  0 0/39 (0.00%)  0 0/41 (0.00%)  0 0/40 (0.00%)  0
PAIN IN EXTREMITY  1  1/19 (5.26%)  1 0/62 (0.00%)  0 0/41 (0.00%)  0 0/39 (0.00%)  0 0/41 (0.00%)  0 0/40 (0.00%)  0
RHEUMATOID ARTHRITIS  1  2/19 (10.53%)  2 0/62 (0.00%)  0 3/41 (7.32%)  3 3/39 (7.69%)  3 3/41 (7.32%)  3 0/40 (0.00%)  0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)             
ENDOMETRIAL ADENOCARCINOMA  1  1/19 (5.26%)  1 0/62 (0.00%)  0 0/41 (0.00%)  0 0/39 (0.00%)  0 0/41 (0.00%)  0 0/40 (0.00%)  0
Respiratory, thoracic and mediastinal disorders             
COUGH  1  0/19 (0.00%)  0 1/62 (1.61%)  1 2/41 (4.88%)  2 0/39 (0.00%)  0 0/41 (0.00%)  0 2/40 (5.00%)  2
Skin and subcutaneous tissue disorders             
ALOPECIA  1  0/19 (0.00%)  0 0/62 (0.00%)  0 0/41 (0.00%)  0 2/39 (5.13%)  2 0/41 (0.00%)  0 0/40 (0.00%)  0
ERYTHEMA  1  1/19 (5.26%)  1 1/62 (1.61%)  1 0/41 (0.00%)  0 0/39 (0.00%)  0 0/41 (0.00%)  0 0/40 (0.00%)  0
1
Term from vocabulary, MedDRA 22.1
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
Layout table for additonal information
Responsible Party: AbbVie
ClinicalTrials.gov Identifier: NCT03682705    
Other Study ID Numbers: M16-063
2018-000666-10 ( EudraCT Number )
First Submitted: September 21, 2018
First Posted: September 25, 2018
Results First Submitted: March 4, 2021
Results First Posted: May 3, 2021
Last Update Posted: May 3, 2021