Rheumatoid Arthritis (RA)
Conditions
Keywords
Elsubrutinib, ABBV-105, Upadacitinib, ABBV-599, Rheumatoid Arthritis
Brief summary
This was a phase 2 study to evaluate the safety and efficacy of elsubrutinib (ELS) and ABBV-599 (ELS plus upadacitinib \[UPA\]) vs placebo on a background of conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs) for the treatment of signs and symptoms of rheumatoid arthritis (RA) at 12 weeks in biological disease-modifying anti-rheumatic drugs (bDMARD)-inadequate response (bDMARD-IR) or bDMARD-intolerant participants with moderately to severely active RA and to define optimal dose for further development.
Detailed description
This was a 12-week, randomized, double-blind, parallel-group, Phase 2, dose exploratory, multicenter study. Participants who met eligibility criteria were randomized in a 3:2:2:2:2:1 ratio to 1 of 6 treatment groups: ABBV-599 \[UPA 15 mg/ELS 60 mg\]); ELS 60 mg/UPA placebo; ELS 20 mg/UPA placebo; ELS 5 mg/UPA placebo; UPA 15 mg/ELS placebo; and ELS placebo/UPA placebo. The study included a 35-day maximum screening period and a 12-week treatment period with 30-day follow-up.
Interventions
DRUGElsubrutinib
Elsubrutinib capsule will be administered orally.
DRUGUpadacitinib
Upadacitinib tablet will be administered orally.
Placebo capsule for elsubrutinib will be administered orally.
Placebo tablet for upadacitinib will be administered orally.
Sponsors
AbbVie
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Diagnosis of rheumatoid arthritis (RA) for ≥ 3 months based on the 2010 American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) classification criteria for RA * Participant meets the following minimum disease activity criteria: * ≥ 6 swollen joints (based on 66 joint counts) and ≥ 6 tender joints (based on 68 joint counts) at Screening and Baseline Visits * High-sensitivity C-reactive protein (hsCRP) ≥ 3 mg/L (central lab) at Screening Visit * Participants must have been treated for ≥ 3 months with ≥ 1 biologic disease-modifying anti-rheumatic drug (bDMARD) therapy but continue to exhibit active RA or had to discontinue due to intolerability or toxicity, irrespective of treatment duration * Participants must have been receiving conventional synthetic disease-modifying anti-rheumatic drug (csDMARD) therapy ≥ 3 months and on a stable dose for ≥ 4 weeks prior to the first dose of study drug * Participants must have discontinued all bDMARDs prior to the first dose of study drug
Exclusion criteria
\- Participant has prior exposure to any Janus Kinase (JAK) inhibitor for greater than 2 weeks (including but not limited to upadacitinib, tofacitinib, baricitinib, and filgotinib). A washout period of ≥ 30 days is required for any JAK inhibitor prior to the first dose of study drug.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Disease Activity Score 28 C-reactive Protein [DAS28-CRP]) at Week 12 | Baseline, Week 12 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Simplified Disease Activity Index (SDAI) | Baseline, Week 2, Week 4, Week 8, and Week 12 | 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. |
| Percentage of Participants Achieving Clinical Remission (CR) Based on Disease Activity Score 28 C-reactive Protein [DAS28-CRP]) at Week 12 | At Week 12 | 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. |
| Percentage of Participants Achieving Low Disease Activity (LDA) Based on Disease Activity Score 28 C-reactive Protein [DAS28-CRP]) at Week 12 | At Week 12 | 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. |
| Percentage of Participants Achieving Low Disease Activity (LDA) Based on Clinical Disease Activity Index (CDAI) Criteria | Week 2, Week 4, Week 8, and Week 12 | 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. |
| Percentage of Participants Achieving Complete Remission (CR) Based on Clinical Disease Activity Index (CDAI) Criteria | Week 2, Week 4, Week 8, and Week 12 | 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. |
| Percentage of Participants With an American College of Rheumatology 20% (ACR20) Response | Baseline, Week 2, Week 4, Week 8, and Week 12 | 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) |
| Percentage of Participants With an American College of Rheumatology 50% (ACR50) Response | Baseline, Week 2, Week 4, Week 8, and Week 12 | 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) |
| Percentage of Participants With an American College of Rheumatology 70% (ACR70) Response | Baseline, Week 2, Week 4, Week 8, and Week 12 | 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) |
| Change From Baseline in Tender Joint Count 68 (TJC68) | Baseline, Week 2, Week 4, Week 8, and Week 12 | 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. |
| Change From Baseline in Swollen Joint Count 66 (SJC66) | Baseline, Week 2, Week 4, Week 8, and Week 12 | 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. |
| Change From Baseline in Clinical Disease Activity Index (CDAI) | Baseline, Week 2, Week 4, Week 8, and Week 12 | 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. |
| Change From Baseline in Patient's Global Assessment of Disease Activity (PGA) | Baseline, Week 2, Week 4, Week 8, and Week 12 | 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. |
| Change From Baseline in Physician's Global Assessment of Disease Activity (PhGA) | Baseline, Week 2, Week 4, Week 8, and Week 12 | 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. |
| Change From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) | Baseline, Week 2, Week 4, Week 8, and Week 12 | 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. |
| Change From Baseline in High-Sensitivity C-reactive Protein (hsCRP) | Baseline, Week 2, Week 4, Week 8, and Week 12 | 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. |
| Change From Baseline in Disease Activity Score 28 C-reactive Protein [DAS28-CRP]) | Baseline, Week 2, Week 4, Week 8, and Week 12 | 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. |
| Change From Baseline in Disease Activity Score 28 Erythrocyte Sedimentation Rate (DAS28- ESR) | Baseline, Week 2, Week 4, Week 8, and Week 12 | 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. |
| Change From Baseline in Morning Stiffness Severity | Baseline, Week 2, Week 4, Week 8, and Week 12 | 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. |
| Percentage of Participants Achieving Minimal Clinically Important Difference (MCID) in Change From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) | Baseline, Week 2, Week 4, Week 8, and Week 12 | 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. |
| Percentage of Participants Achieving American College of Rheumatology/European League Against Rheumatism (EULAR) Boolean Remission | Baseline, Week 2, Week 4, Week 8, and Week 12 | 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). |
| Change From Baseline in Participant's Assessment of Pain (Visual Analog Scale [VAS]) | Baseline, Week 2, Week 4, Week 8, and Week 12 | 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. |
Countries
Belgium, Canada, Czechia, Hungary, Poland, Puerto Rico, Spain, United Kingdom, United States
Participant flow
Pre-assignment details
Full Analysis Set: all randomized participants who received at least 1 dose of randomized study drug
Participants by arm
| Arm | Count |
|---|---|
| ELS Placebo/UPA Placebo 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 | 19 |
| UPA 15 mg/ELS 60 mg 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 | 62 |
| ELS 60 mg/UPA Placebo 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 | 41 |
| ELS 20 mg/UPA Placebo 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 | 39 |
| ELS 5 mg/UPA Placebo 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 | 41 |
| UPA 15 mg/ELS Placebo 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 | 40 |
| Total | 242 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 1 | 1 | 1 | 0 | 1 | 1 |
| Overall Study | Lost to Follow-up | 0 | 0 | 0 | 0 | 3 | 0 |
| Overall Study | Other, not specified | 0 | 0 | 0 | 1 | 2 | 0 |
| Overall Study | Withdrawal by Subject | 1 | 3 | 2 | 4 | 0 | 1 |
Baseline characteristics
| Characteristic | 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 |
|---|---|---|---|---|---|---|---|
| Age, Continuous | 57.6 years STANDARD_DEVIATION 9.12 | 56.2 years STANDARD_DEVIATION 12.82 | 59.2 years STANDARD_DEVIATION 11.11 | 59.7 years STANDARD_DEVIATION 10.95 | 58.1 years STANDARD_DEVIATION 11.01 | 57.7 years STANDARD_DEVIATION 10.6 | 58.0 years STANDARD_DEVIATION 11.27 |
| Race/Ethnicity, Customized American Indian or Alaska Native | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 2 Participants |
| Race/Ethnicity, Customized Asian | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 2 Participants |
| Race/Ethnicity, Customized Black or African American | 0 Participants | 3 Participants | 4 Participants | 4 Participants | 3 Participants | 3 Participants | 17 Participants |
| Race/Ethnicity, Customized Multiple | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized White | 19 Participants | 58 Participants | 36 Participants | 35 Participants | 35 Participants | 37 Participants | 220 Participants |
| Sex: Female, Male Female | 17 Participants | 48 Participants | 36 Participants | 35 Participants | 33 Participants | 35 Participants | 204 Participants |
| Sex: Female, Male Male | 2 Participants | 14 Participants | 5 Participants | 4 Participants | 8 Participants | 5 Participants | 38 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 19 | 0 / 62 | 0 / 41 | 0 / 39 | 1 / 41 | 0 / 40 |
| other Total, other adverse events | 10 / 19 | 7 / 62 | 17 / 41 | 10 / 39 | 8 / 41 | 9 / 40 |
| serious Total, serious adverse events | 1 / 19 | 0 / 62 | 0 / 41 | 2 / 39 | 3 / 41 | 0 / 40 |
Outcome results
Primary
Change From Baseline in Disease Activity Score 28 C-reactive Protein [DAS28-CRP]) at Week 12
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
Population: 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 | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| ELS Placebo/UPA Placebo | Change From Baseline in Disease Activity Score 28 C-reactive Protein [DAS28-CRP]) at Week 12 | -1.12 units on a scale |
| UPA 15 mg/ELS 60 mg | Change From Baseline in Disease Activity Score 28 C-reactive Protein [DAS28-CRP]) at Week 12 | -2.56 units on a scale |
| ELS 60 mg/UPA Placebo | Change From Baseline in Disease Activity Score 28 C-reactive Protein [DAS28-CRP]) at Week 12 | -1.52 units on a scale |
| ELS 20 mg/UPA Placebo | Change From Baseline in Disease Activity Score 28 C-reactive Protein [DAS28-CRP]) at Week 12 | -1.32 units on a scale |
| ELS 5 mg/UPA Placebo | Change From Baseline in Disease Activity Score 28 C-reactive Protein [DAS28-CRP]) at Week 12 | -1.33 units on a scale |
| UPA 15 mg/ELS Placebo | Change From Baseline in Disease Activity Score 28 C-reactive Protein [DAS28-CRP]) at Week 12 | -2.87 units on a scale |
Comparison: 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.p-value: <0.00190% CI: [-2.03, -0.85]t-test, 2 sided
Secondary
Change From Baseline in Clinical Disease Activity Index (CDAI)
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
Population: 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 | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| ELS Placebo/UPA Placebo | Change From Baseline in Clinical Disease Activity Index (CDAI) | Week 2 | -6.08 units on a scale |
| ELS Placebo/UPA Placebo | Change From Baseline in Clinical Disease Activity Index (CDAI) | Week 12 | -14.57 units on a scale |
| ELS Placebo/UPA Placebo | Change From Baseline in Clinical Disease Activity Index (CDAI) | Week 8 | -12.46 units on a scale |
| ELS Placebo/UPA Placebo | Change From Baseline in Clinical Disease Activity Index (CDAI) | Week 4 | -11.60 units on a scale |
| UPA 15 mg/ELS 60 mg | Change From Baseline in Clinical Disease Activity Index (CDAI) | Week 8 | -24.95 units on a scale |
| UPA 15 mg/ELS 60 mg | Change From Baseline in Clinical Disease Activity Index (CDAI) | Week 4 | -20.24 units on a scale |
| UPA 15 mg/ELS 60 mg | Change From Baseline in Clinical Disease Activity Index (CDAI) | Week 2 | -16.00 units on a scale |
| UPA 15 mg/ELS 60 mg | Change From Baseline in Clinical Disease Activity Index (CDAI) | Week 12 | -27.00 units on a scale |
| ELS 60 mg/UPA Placebo | Change From Baseline in Clinical Disease Activity Index (CDAI) | Week 12 | -17.50 units on a scale |
| ELS 60 mg/UPA Placebo | Change From Baseline in Clinical Disease Activity Index (CDAI) | Week 2 | -8.95 units on a scale |
| ELS 60 mg/UPA Placebo | Change From Baseline in Clinical Disease Activity Index (CDAI) | Week 4 | -11.67 units on a scale |
| ELS 60 mg/UPA Placebo | Change From Baseline in Clinical Disease Activity Index (CDAI) | Week 8 | -15.07 units on a scale |
| ELS 20 mg/UPA Placebo | Change From Baseline in Clinical Disease Activity Index (CDAI) | Week 4 | -10.10 units on a scale |
| ELS 20 mg/UPA Placebo | Change From Baseline in Clinical Disease Activity Index (CDAI) | Week 2 | -7.36 units on a scale |
| ELS 20 mg/UPA Placebo | Change From Baseline in Clinical Disease Activity Index (CDAI) | Week 12 | -16.70 units on a scale |
| ELS 20 mg/UPA Placebo | Change From Baseline in Clinical Disease Activity Index (CDAI) | Week 8 | -17.10 units on a scale |
| ELS 5 mg/UPA Placebo | Change From Baseline in Clinical Disease Activity Index (CDAI) | Week 4 | -12.90 units on a scale |
| ELS 5 mg/UPA Placebo | Change From Baseline in Clinical Disease Activity Index (CDAI) | Week 2 | -8.38 units on a scale |
| ELS 5 mg/UPA Placebo | Change From Baseline in Clinical Disease Activity Index (CDAI) | Week 8 | -14.84 units on a scale |
| ELS 5 mg/UPA Placebo | Change From Baseline in Clinical Disease Activity Index (CDAI) | Week 12 | -16.51 units on a scale |
| UPA 15 mg/ELS Placebo | Change From Baseline in Clinical Disease Activity Index (CDAI) | Week 12 | -28.85 units on a scale |
| UPA 15 mg/ELS Placebo | Change From Baseline in Clinical Disease Activity Index (CDAI) | Week 2 | -14.03 units on a scale |
| UPA 15 mg/ELS Placebo | Change From Baseline in Clinical Disease Activity Index (CDAI) | Week 4 | -20.30 units on a scale |
| UPA 15 mg/ELS Placebo | Change From Baseline in Clinical Disease Activity Index (CDAI) | Week 8 | -23.72 units on a scale |
Secondary
Change From Baseline in Disease Activity Score 28 C-reactive Protein [DAS28-CRP])
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
Population: 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 | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| ELS Placebo/UPA Placebo | Change From Baseline in Disease Activity Score 28 C-reactive Protein [DAS28-CRP]) | Week 2 | -0.46 units on a scale |
| ELS Placebo/UPA Placebo | Change From Baseline in Disease Activity Score 28 C-reactive Protein [DAS28-CRP]) | Week 4 | -0.90 units on a scale |
| ELS Placebo/UPA Placebo | Change From Baseline in Disease Activity Score 28 C-reactive Protein [DAS28-CRP]) | Week 8 | -0.78 units on a scale |
| ELS Placebo/UPA Placebo | Change From Baseline in Disease Activity Score 28 C-reactive Protein [DAS28-CRP]) | Week 12 | -1.12 units on a scale |
| UPA 15 mg/ELS 60 mg | Change From Baseline in Disease Activity Score 28 C-reactive Protein [DAS28-CRP]) | Week 8 | -2.40 units on a scale |
| UPA 15 mg/ELS 60 mg | Change From Baseline in Disease Activity Score 28 C-reactive Protein [DAS28-CRP]) | Week 4 | -1.96 units on a scale |
| UPA 15 mg/ELS 60 mg | Change From Baseline in Disease Activity Score 28 C-reactive Protein [DAS28-CRP]) | Week 2 | -1.53 units on a scale |
| UPA 15 mg/ELS 60 mg | Change From Baseline in Disease Activity Score 28 C-reactive Protein [DAS28-CRP]) | Week 12 | -2.56 units on a scale |
| ELS 60 mg/UPA Placebo | Change From Baseline in Disease Activity Score 28 C-reactive Protein [DAS28-CRP]) | Week 12 | -1.52 units on a scale |
| ELS 60 mg/UPA Placebo | Change From Baseline in Disease Activity Score 28 C-reactive Protein [DAS28-CRP]) | Week 8 | -1.21 units on a scale |
| ELS 60 mg/UPA Placebo | Change From Baseline in Disease Activity Score 28 C-reactive Protein [DAS28-CRP]) | Week 4 | -0.87 units on a scale |
| ELS 60 mg/UPA Placebo | Change From Baseline in Disease Activity Score 28 C-reactive Protein [DAS28-CRP]) | Week 2 | -0.63 units on a scale |
| ELS 20 mg/UPA Placebo | Change From Baseline in Disease Activity Score 28 C-reactive Protein [DAS28-CRP]) | Week 2 | -0.44 units on a scale |
| ELS 20 mg/UPA Placebo | Change From Baseline in Disease Activity Score 28 C-reactive Protein [DAS28-CRP]) | Week 12 | -1.32 units on a scale |
| ELS 20 mg/UPA Placebo | Change From Baseline in Disease Activity Score 28 C-reactive Protein [DAS28-CRP]) | Week 4 | -0.68 units on a scale |
| ELS 20 mg/UPA Placebo | Change From Baseline in Disease Activity Score 28 C-reactive Protein [DAS28-CRP]) | Week 8 | -1.24 units on a scale |
| ELS 5 mg/UPA Placebo | Change From Baseline in Disease Activity Score 28 C-reactive Protein [DAS28-CRP]) | Week 8 | -1.11 units on a scale |
| ELS 5 mg/UPA Placebo | Change From Baseline in Disease Activity Score 28 C-reactive Protein [DAS28-CRP]) | Week 12 | -1.33 units on a scale |
| ELS 5 mg/UPA Placebo | Change From Baseline in Disease Activity Score 28 C-reactive Protein [DAS28-CRP]) | Week 4 | -0.82 units on a scale |
| ELS 5 mg/UPA Placebo | Change From Baseline in Disease Activity Score 28 C-reactive Protein [DAS28-CRP]) | Week 2 | -0.56 units on a scale |
| UPA 15 mg/ELS Placebo | Change From Baseline in Disease Activity Score 28 C-reactive Protein [DAS28-CRP]) | Week 4 | -1.98 units on a scale |
| UPA 15 mg/ELS Placebo | Change From Baseline in Disease Activity Score 28 C-reactive Protein [DAS28-CRP]) | Week 8 | -2.34 units on a scale |
| UPA 15 mg/ELS Placebo | Change From Baseline in Disease Activity Score 28 C-reactive Protein [DAS28-CRP]) | Week 12 | -2.87 units on a scale |
| UPA 15 mg/ELS Placebo | Change From Baseline in Disease Activity Score 28 C-reactive Protein [DAS28-CRP]) | Week 2 | -1.43 units on a scale |
Secondary
Change From Baseline in Disease Activity Score 28 Erythrocyte Sedimentation Rate (DAS28- ESR)
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
Population: 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 | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| ELS Placebo/UPA Placebo | Change From Baseline in Disease Activity Score 28 Erythrocyte Sedimentation Rate (DAS28- ESR) | Week 2 | -0.46 units on a scale |
| ELS Placebo/UPA Placebo | Change From Baseline in Disease Activity Score 28 Erythrocyte Sedimentation Rate (DAS28- ESR) | Week 4 | -0.86 units on a scale |
| ELS Placebo/UPA Placebo | Change From Baseline in Disease Activity Score 28 Erythrocyte Sedimentation Rate (DAS28- ESR) | Week 8 | -0.80 units on a scale |
| ELS Placebo/UPA Placebo | Change From Baseline in Disease Activity Score 28 Erythrocyte Sedimentation Rate (DAS28- ESR) | Week 12 | -1.18 units on a scale |
| UPA 15 mg/ELS 60 mg | Change From Baseline in Disease Activity Score 28 Erythrocyte Sedimentation Rate (DAS28- ESR) | Week 8 | -2.41 units on a scale |
| UPA 15 mg/ELS 60 mg | Change From Baseline in Disease Activity Score 28 Erythrocyte Sedimentation Rate (DAS28- ESR) | Week 4 | -1.93 units on a scale |
| UPA 15 mg/ELS 60 mg | Change From Baseline in Disease Activity Score 28 Erythrocyte Sedimentation Rate (DAS28- ESR) | Week 2 | -1.48 units on a scale |
| UPA 15 mg/ELS 60 mg | Change From Baseline in Disease Activity Score 28 Erythrocyte Sedimentation Rate (DAS28- ESR) | Week 12 | -2.53 units on a scale |
| ELS 60 mg/UPA Placebo | Change From Baseline in Disease Activity Score 28 Erythrocyte Sedimentation Rate (DAS28- ESR) | Week 12 | -1.41 units on a scale |
| ELS 60 mg/UPA Placebo | Change From Baseline in Disease Activity Score 28 Erythrocyte Sedimentation Rate (DAS28- ESR) | Week 8 | -1.07 units on a scale |
| ELS 60 mg/UPA Placebo | Change From Baseline in Disease Activity Score 28 Erythrocyte Sedimentation Rate (DAS28- ESR) | Week 4 | -0.79 units on a scale |
| ELS 60 mg/UPA Placebo | Change From Baseline in Disease Activity Score 28 Erythrocyte Sedimentation Rate (DAS28- ESR) | Week 2 | -0.52 units on a scale |
| ELS 20 mg/UPA Placebo | Change From Baseline in Disease Activity Score 28 Erythrocyte Sedimentation Rate (DAS28- ESR) | Week 2 | -0.46 units on a scale |
| ELS 20 mg/UPA Placebo | Change From Baseline in Disease Activity Score 28 Erythrocyte Sedimentation Rate (DAS28- ESR) | Week 12 | -1.24 units on a scale |
| ELS 20 mg/UPA Placebo | Change From Baseline in Disease Activity Score 28 Erythrocyte Sedimentation Rate (DAS28- ESR) | Week 4 | -0.59 units on a scale |
| ELS 20 mg/UPA Placebo | Change From Baseline in Disease Activity Score 28 Erythrocyte Sedimentation Rate (DAS28- ESR) | Week 8 | -1.15 units on a scale |
| ELS 5 mg/UPA Placebo | Change From Baseline in Disease Activity Score 28 Erythrocyte Sedimentation Rate (DAS28- ESR) | Week 8 | -1.20 units on a scale |
| ELS 5 mg/UPA Placebo | Change From Baseline in Disease Activity Score 28 Erythrocyte Sedimentation Rate (DAS28- ESR) | Week 12 | -1.44 units on a scale |
| ELS 5 mg/UPA Placebo | Change From Baseline in Disease Activity Score 28 Erythrocyte Sedimentation Rate (DAS28- ESR) | Week 4 | -0.92 units on a scale |
| ELS 5 mg/UPA Placebo | Change From Baseline in Disease Activity Score 28 Erythrocyte Sedimentation Rate (DAS28- ESR) | Week 2 | -0.57 units on a scale |
| UPA 15 mg/ELS Placebo | Change From Baseline in Disease Activity Score 28 Erythrocyte Sedimentation Rate (DAS28- ESR) | Week 4 | -1.90 units on a scale |
| UPA 15 mg/ELS Placebo | Change From Baseline in Disease Activity Score 28 Erythrocyte Sedimentation Rate (DAS28- ESR) | Week 8 | -2.31 units on a scale |
| UPA 15 mg/ELS Placebo | Change From Baseline in Disease Activity Score 28 Erythrocyte Sedimentation Rate (DAS28- ESR) | Week 12 | -2.88 units on a scale |
| UPA 15 mg/ELS Placebo | Change From Baseline in Disease Activity Score 28 Erythrocyte Sedimentation Rate (DAS28- ESR) | Week 2 | -1.32 units on a scale |
Secondary
Change From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI)
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
Population: 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 | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| ELS Placebo/UPA Placebo | Change From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) | Week 8 | -0.24 units on a scale |
| ELS Placebo/UPA Placebo | Change From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) | Week 4 | -0.36 units on a scale |
| ELS Placebo/UPA Placebo | Change From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) | Week 12 | -0.30 units on a scale |
| ELS Placebo/UPA Placebo | Change From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) | Week 2 | -0.22 units on a scale |
| UPA 15 mg/ELS 60 mg | Change From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) | Week 8 | -0.47 units on a scale |
| UPA 15 mg/ELS 60 mg | Change From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) | Week 2 | -0.34 units on a scale |
| UPA 15 mg/ELS 60 mg | Change From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) | Week 4 | -0.39 units on a scale |
| UPA 15 mg/ELS 60 mg | Change From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) | Week 12 | -0.52 units on a scale |
| ELS 60 mg/UPA Placebo | Change From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) | Week 4 | -0.11 units on a scale |
| ELS 60 mg/UPA Placebo | Change From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) | Week 8 | -0.29 units on a scale |
| ELS 60 mg/UPA Placebo | Change From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) | Week 2 | -0.13 units on a scale |
| ELS 60 mg/UPA Placebo | Change From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) | Week 12 | -0.31 units on a scale |
| ELS 20 mg/UPA Placebo | Change From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) | Week 8 | -0.15 units on a scale |
| ELS 20 mg/UPA Placebo | Change From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) | Week 4 | -0.14 units on a scale |
| ELS 20 mg/UPA Placebo | Change From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) | Week 2 | -0.06 units on a scale |
| ELS 20 mg/UPA Placebo | Change From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) | Week 12 | -0.12 units on a scale |
| ELS 5 mg/UPA Placebo | Change From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) | Week 4 | -0.21 units on a scale |
| ELS 5 mg/UPA Placebo | Change From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) | Week 2 | -0.16 units on a scale |
| ELS 5 mg/UPA Placebo | Change From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) | Week 8 | -0.15 units on a scale |
| ELS 5 mg/UPA Placebo | Change From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) | Week 12 | -0.18 units on a scale |
| UPA 15 mg/ELS Placebo | Change From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) | Week 4 | -0.33 units on a scale |
| UPA 15 mg/ELS Placebo | Change From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) | Week 2 | -0.22 units on a scale |
| UPA 15 mg/ELS Placebo | Change From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) | Week 12 | -0.54 units on a scale |
| UPA 15 mg/ELS Placebo | Change From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) | Week 8 | -0.47 units on a scale |
Secondary
Change From Baseline in High-Sensitivity C-reactive Protein (hsCRP)
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
Population: 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 | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| ELS Placebo/UPA Placebo | Change From Baseline in High-Sensitivity C-reactive Protein (hsCRP) | Week 12 | 1.45 mg/L |
| ELS Placebo/UPA Placebo | Change From Baseline in High-Sensitivity C-reactive Protein (hsCRP) | Week 8 | 3.23 mg/L |
| ELS Placebo/UPA Placebo | Change From Baseline in High-Sensitivity C-reactive Protein (hsCRP) | Week 2 | -0.51 mg/L |
| ELS Placebo/UPA Placebo | Change From Baseline in High-Sensitivity C-reactive Protein (hsCRP) | Week 4 | 1.54 mg/L |
| UPA 15 mg/ELS 60 mg | Change From Baseline in High-Sensitivity C-reactive Protein (hsCRP) | Week 8 | -9.97 mg/L |
| UPA 15 mg/ELS 60 mg | Change From Baseline in High-Sensitivity C-reactive Protein (hsCRP) | Week 12 | -10.95 mg/L |
| UPA 15 mg/ELS 60 mg | Change From Baseline in High-Sensitivity C-reactive Protein (hsCRP) | Week 4 | -10.08 mg/L |
| UPA 15 mg/ELS 60 mg | Change From Baseline in High-Sensitivity C-reactive Protein (hsCRP) | Week 2 | -9.29 mg/L |
| ELS 60 mg/UPA Placebo | Change From Baseline in High-Sensitivity C-reactive Protein (hsCRP) | Week 12 | -4.58 mg/L |
| ELS 60 mg/UPA Placebo | Change From Baseline in High-Sensitivity C-reactive Protein (hsCRP) | Week 4 | 2.71 mg/L |
| ELS 60 mg/UPA Placebo | Change From Baseline in High-Sensitivity C-reactive Protein (hsCRP) | Week 8 | -1.39 mg/L |
| ELS 60 mg/UPA Placebo | Change From Baseline in High-Sensitivity C-reactive Protein (hsCRP) | Week 2 | 2.26 mg/L |
| ELS 20 mg/UPA Placebo | Change From Baseline in High-Sensitivity C-reactive Protein (hsCRP) | Week 2 | -0.34 mg/L |
| ELS 20 mg/UPA Placebo | Change From Baseline in High-Sensitivity C-reactive Protein (hsCRP) | Week 12 | -5.78 mg/L |
| ELS 20 mg/UPA Placebo | Change From Baseline in High-Sensitivity C-reactive Protein (hsCRP) | Week 4 | -0.78 mg/L |
| ELS 20 mg/UPA Placebo | Change From Baseline in High-Sensitivity C-reactive Protein (hsCRP) | Week 8 | -2.58 mg/L |
| ELS 5 mg/UPA Placebo | Change From Baseline in High-Sensitivity C-reactive Protein (hsCRP) | Week 4 | 0.72 mg/L |
| ELS 5 mg/UPA Placebo | Change From Baseline in High-Sensitivity C-reactive Protein (hsCRP) | Week 2 | -0.72 mg/L |
| ELS 5 mg/UPA Placebo | Change From Baseline in High-Sensitivity C-reactive Protein (hsCRP) | Week 8 | -2.93 mg/L |
| ELS 5 mg/UPA Placebo | Change From Baseline in High-Sensitivity C-reactive Protein (hsCRP) | Week 12 | -0.81 mg/L |
| UPA 15 mg/ELS Placebo | Change From Baseline in High-Sensitivity C-reactive Protein (hsCRP) | Week 12 | -7.44 mg/L |
| UPA 15 mg/ELS Placebo | Change From Baseline in High-Sensitivity C-reactive Protein (hsCRP) | Week 2 | -12.27 mg/L |
| UPA 15 mg/ELS Placebo | Change From Baseline in High-Sensitivity C-reactive Protein (hsCRP) | Week 4 | -12.59 mg/L |
| UPA 15 mg/ELS Placebo | Change From Baseline in High-Sensitivity C-reactive Protein (hsCRP) | Week 8 | -13.13 mg/L |
Secondary
Change From Baseline in Morning Stiffness Severity
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
Population: 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 | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| ELS Placebo/UPA Placebo | Change From Baseline in Morning Stiffness Severity | Week 2 | -1.76 units on a scale |
| ELS Placebo/UPA Placebo | Change From Baseline in Morning Stiffness Severity | Week 4 | -1.76 units on a scale |
| ELS Placebo/UPA Placebo | Change From Baseline in Morning Stiffness Severity | Week 8 | -1.67 units on a scale |
| ELS Placebo/UPA Placebo | Change From Baseline in Morning Stiffness Severity | Week 12 | -1.61 units on a scale |
| UPA 15 mg/ELS 60 mg | Change From Baseline in Morning Stiffness Severity | Week 8 | -3.07 units on a scale |
| UPA 15 mg/ELS 60 mg | Change From Baseline in Morning Stiffness Severity | Week 4 | -2.71 units on a scale |
| UPA 15 mg/ELS 60 mg | Change From Baseline in Morning Stiffness Severity | Week 2 | -2.02 units on a scale |
| UPA 15 mg/ELS 60 mg | Change From Baseline in Morning Stiffness Severity | Week 12 | -3.23 units on a scale |
| ELS 60 mg/UPA Placebo | Change From Baseline in Morning Stiffness Severity | Week 12 | -1.27 units on a scale |
| ELS 60 mg/UPA Placebo | Change From Baseline in Morning Stiffness Severity | Week 8 | -1.30 units on a scale |
| ELS 60 mg/UPA Placebo | Change From Baseline in Morning Stiffness Severity | Week 4 | -0.82 units on a scale |
| ELS 60 mg/UPA Placebo | Change From Baseline in Morning Stiffness Severity | Week 2 | -0.91 units on a scale |
| ELS 20 mg/UPA Placebo | Change From Baseline in Morning Stiffness Severity | Week 2 | -0.68 units on a scale |
| ELS 20 mg/UPA Placebo | Change From Baseline in Morning Stiffness Severity | Week 12 | -1.30 units on a scale |
| ELS 20 mg/UPA Placebo | Change From Baseline in Morning Stiffness Severity | Week 4 | -0.83 units on a scale |
| ELS 20 mg/UPA Placebo | Change From Baseline in Morning Stiffness Severity | Week 8 | -0.97 units on a scale |
| ELS 5 mg/UPA Placebo | Change From Baseline in Morning Stiffness Severity | Week 8 | -1.50 units on a scale |
| ELS 5 mg/UPA Placebo | Change From Baseline in Morning Stiffness Severity | Week 12 | -1.66 units on a scale |
| ELS 5 mg/UPA Placebo | Change From Baseline in Morning Stiffness Severity | Week 4 | -1.08 units on a scale |
| ELS 5 mg/UPA Placebo | Change From Baseline in Morning Stiffness Severity | Week 2 | -0.59 units on a scale |
| UPA 15 mg/ELS Placebo | Change From Baseline in Morning Stiffness Severity | Week 4 | -2.51 units on a scale |
| UPA 15 mg/ELS Placebo | Change From Baseline in Morning Stiffness Severity | Week 8 | -3.07 units on a scale |
| UPA 15 mg/ELS Placebo | Change From Baseline in Morning Stiffness Severity | Week 12 | -3.36 units on a scale |
| UPA 15 mg/ELS Placebo | Change From Baseline in Morning Stiffness Severity | Week 2 | -1.84 units on a scale |
Secondary
Change From Baseline in Participant's Assessment of Pain (Visual Analog Scale [VAS])
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
Population: 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 | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| ELS Placebo/UPA Placebo | Change From Baseline in Participant's Assessment of Pain (Visual Analog Scale [VAS]) | Week 2 | -14.97 units on a scale |
| ELS Placebo/UPA Placebo | Change From Baseline in Participant's Assessment of Pain (Visual Analog Scale [VAS]) | Week 4 | -20.87 units on a scale |
| ELS Placebo/UPA Placebo | Change From Baseline in Participant's Assessment of Pain (Visual Analog Scale [VAS]) | Week 8 | -16.21 units on a scale |
| ELS Placebo/UPA Placebo | Change From Baseline in Participant's Assessment of Pain (Visual Analog Scale [VAS]) | Week 12 | -23.37 units on a scale |
| UPA 15 mg/ELS 60 mg | Change From Baseline in Participant's Assessment of Pain (Visual Analog Scale [VAS]) | Week 8 | -31.86 units on a scale |
| UPA 15 mg/ELS 60 mg | Change From Baseline in Participant's Assessment of Pain (Visual Analog Scale [VAS]) | Week 4 | -28.17 units on a scale |
| UPA 15 mg/ELS 60 mg | Change From Baseline in Participant's Assessment of Pain (Visual Analog Scale [VAS]) | Week 2 | -24.02 units on a scale |
| UPA 15 mg/ELS 60 mg | Change From Baseline in Participant's Assessment of Pain (Visual Analog Scale [VAS]) | Week 12 | -32.27 units on a scale |
| ELS 60 mg/UPA Placebo | Change From Baseline in Participant's Assessment of Pain (Visual Analog Scale [VAS]) | Week 12 | -19.52 units on a scale |
| ELS 60 mg/UPA Placebo | Change From Baseline in Participant's Assessment of Pain (Visual Analog Scale [VAS]) | Week 8 | -20.92 units on a scale |
| ELS 60 mg/UPA Placebo | Change From Baseline in Participant's Assessment of Pain (Visual Analog Scale [VAS]) | Week 4 | -12.95 units on a scale |
| ELS 60 mg/UPA Placebo | Change From Baseline in Participant's Assessment of Pain (Visual Analog Scale [VAS]) | Week 2 | -10.22 units on a scale |
| ELS 20 mg/UPA Placebo | Change From Baseline in Participant's Assessment of Pain (Visual Analog Scale [VAS]) | Week 2 | -8.78 units on a scale |
| ELS 20 mg/UPA Placebo | Change From Baseline in Participant's Assessment of Pain (Visual Analog Scale [VAS]) | Week 12 | -10.46 units on a scale |
| ELS 20 mg/UPA Placebo | Change From Baseline in Participant's Assessment of Pain (Visual Analog Scale [VAS]) | Week 4 | -8.41 units on a scale |
| ELS 20 mg/UPA Placebo | Change From Baseline in Participant's Assessment of Pain (Visual Analog Scale [VAS]) | Week 8 | -11.12 units on a scale |
| ELS 5 mg/UPA Placebo | Change From Baseline in Participant's Assessment of Pain (Visual Analog Scale [VAS]) | Week 8 | -13.90 units on a scale |
| ELS 5 mg/UPA Placebo | Change From Baseline in Participant's Assessment of Pain (Visual Analog Scale [VAS]) | Week 12 | -17.84 units on a scale |
| ELS 5 mg/UPA Placebo | Change From Baseline in Participant's Assessment of Pain (Visual Analog Scale [VAS]) | Week 4 | -9.91 units on a scale |
| ELS 5 mg/UPA Placebo | Change From Baseline in Participant's Assessment of Pain (Visual Analog Scale [VAS]) | Week 2 | -7.61 units on a scale |
| UPA 15 mg/ELS Placebo | Change From Baseline in Participant's Assessment of Pain (Visual Analog Scale [VAS]) | Week 4 | -25.58 units on a scale |
| UPA 15 mg/ELS Placebo | Change From Baseline in Participant's Assessment of Pain (Visual Analog Scale [VAS]) | Week 8 | -30.70 units on a scale |
| UPA 15 mg/ELS Placebo | Change From Baseline in Participant's Assessment of Pain (Visual Analog Scale [VAS]) | Week 12 | -38.34 units on a scale |
| UPA 15 mg/ELS Placebo | Change From Baseline in Participant's Assessment of Pain (Visual Analog Scale [VAS]) | Week 2 | -15.99 units on a scale |
Secondary
Change From Baseline in Patient's Global Assessment of Disease Activity (PGA)
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
Population: 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 | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| ELS Placebo/UPA Placebo | Change From Baseline in Patient's Global Assessment of Disease Activity (PGA) | Week 2 | -11.87 units on a scale |
| ELS Placebo/UPA Placebo | Change From Baseline in Patient's Global Assessment of Disease Activity (PGA) | Week 4 | -20.93 units on a scale |
| ELS Placebo/UPA Placebo | Change From Baseline in Patient's Global Assessment of Disease Activity (PGA) | Week 8 | -15.14 units on a scale |
| ELS Placebo/UPA Placebo | Change From Baseline in Patient's Global Assessment of Disease Activity (PGA) | Week 12 | -19.55 units on a scale |
| UPA 15 mg/ELS 60 mg | Change From Baseline in Patient's Global Assessment of Disease Activity (PGA) | Week 8 | -28.05 units on a scale |
| UPA 15 mg/ELS 60 mg | Change From Baseline in Patient's Global Assessment of Disease Activity (PGA) | Week 4 | -25.97 units on a scale |
| UPA 15 mg/ELS 60 mg | Change From Baseline in Patient's Global Assessment of Disease Activity (PGA) | Week 2 | -23.44 units on a scale |
| UPA 15 mg/ELS 60 mg | Change From Baseline in Patient's Global Assessment of Disease Activity (PGA) | Week 12 | -30.52 units on a scale |
| ELS 60 mg/UPA Placebo | Change From Baseline in Patient's Global Assessment of Disease Activity (PGA) | Week 12 | -19.47 units on a scale |
| ELS 60 mg/UPA Placebo | Change From Baseline in Patient's Global Assessment of Disease Activity (PGA) | Week 8 | -17.25 units on a scale |
| ELS 60 mg/UPA Placebo | Change From Baseline in Patient's Global Assessment of Disease Activity (PGA) | Week 4 | -12.79 units on a scale |
| ELS 60 mg/UPA Placebo | Change From Baseline in Patient's Global Assessment of Disease Activity (PGA) | Week 2 | -11.16 units on a scale |
| ELS 20 mg/UPA Placebo | Change From Baseline in Patient's Global Assessment of Disease Activity (PGA) | Week 2 | -6.47 units on a scale |
| ELS 20 mg/UPA Placebo | Change From Baseline in Patient's Global Assessment of Disease Activity (PGA) | Week 12 | -8.45 units on a scale |
| ELS 20 mg/UPA Placebo | Change From Baseline in Patient's Global Assessment of Disease Activity (PGA) | Week 4 | -7.15 units on a scale |
| ELS 20 mg/UPA Placebo | Change From Baseline in Patient's Global Assessment of Disease Activity (PGA) | Week 8 | -6.27 units on a scale |
| ELS 5 mg/UPA Placebo | Change From Baseline in Patient's Global Assessment of Disease Activity (PGA) | Week 8 | -14.25 units on a scale |
| ELS 5 mg/UPA Placebo | Change From Baseline in Patient's Global Assessment of Disease Activity (PGA) | Week 12 | -16.40 units on a scale |
| ELS 5 mg/UPA Placebo | Change From Baseline in Patient's Global Assessment of Disease Activity (PGA) | Week 4 | -8.73 units on a scale |
| ELS 5 mg/UPA Placebo | Change From Baseline in Patient's Global Assessment of Disease Activity (PGA) | Week 2 | -5.95 units on a scale |
| UPA 15 mg/ELS Placebo | Change From Baseline in Patient's Global Assessment of Disease Activity (PGA) | Week 4 | -23.02 units on a scale |
| UPA 15 mg/ELS Placebo | Change From Baseline in Patient's Global Assessment of Disease Activity (PGA) | Week 8 | -26.79 units on a scale |
| UPA 15 mg/ELS Placebo | Change From Baseline in Patient's Global Assessment of Disease Activity (PGA) | Week 12 | -33.53 units on a scale |
| UPA 15 mg/ELS Placebo | Change From Baseline in Patient's Global Assessment of Disease Activity (PGA) | Week 2 | -14.76 units on a scale |
Secondary
Change From Baseline in Physician's Global Assessment of Disease Activity (PhGA)
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
Population: 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 | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| ELS Placebo/UPA Placebo | Change From Baseline in Physician's Global Assessment of Disease Activity (PhGA) | Week 2 | -16.31 units on a scale |
| ELS Placebo/UPA Placebo | Change From Baseline in Physician's Global Assessment of Disease Activity (PhGA) | Week 4 | -25.20 units on a scale |
| ELS Placebo/UPA Placebo | Change From Baseline in Physician's Global Assessment of Disease Activity (PhGA) | Week 8 | -24.47 units on a scale |
| ELS Placebo/UPA Placebo | Change From Baseline in Physician's Global Assessment of Disease Activity (PhGA) | Week 12 | -23.19 units on a scale |
| UPA 15 mg/ELS 60 mg | Change From Baseline in Physician's Global Assessment of Disease Activity (PhGA) | Week 8 | -40.00 units on a scale |
| UPA 15 mg/ELS 60 mg | Change From Baseline in Physician's Global Assessment of Disease Activity (PhGA) | Week 4 | -33.54 units on a scale |
| UPA 15 mg/ELS 60 mg | Change From Baseline in Physician's Global Assessment of Disease Activity (PhGA) | Week 2 | -22.35 units on a scale |
| UPA 15 mg/ELS 60 mg | Change From Baseline in Physician's Global Assessment of Disease Activity (PhGA) | Week 12 | -46.98 units on a scale |
| ELS 60 mg/UPA Placebo | Change From Baseline in Physician's Global Assessment of Disease Activity (PhGA) | Week 12 | -30.15 units on a scale |
| ELS 60 mg/UPA Placebo | Change From Baseline in Physician's Global Assessment of Disease Activity (PhGA) | Week 8 | -30.06 units on a scale |
| ELS 60 mg/UPA Placebo | Change From Baseline in Physician's Global Assessment of Disease Activity (PhGA) | Week 4 | -25.33 units on a scale |
| ELS 60 mg/UPA Placebo | Change From Baseline in Physician's Global Assessment of Disease Activity (PhGA) | Week 2 | -19.01 units on a scale |
| ELS 20 mg/UPA Placebo | Change From Baseline in Physician's Global Assessment of Disease Activity (PhGA) | Week 2 | -16.12 units on a scale |
| ELS 20 mg/UPA Placebo | Change From Baseline in Physician's Global Assessment of Disease Activity (PhGA) | Week 12 | -31.68 units on a scale |
| ELS 20 mg/UPA Placebo | Change From Baseline in Physician's Global Assessment of Disease Activity (PhGA) | Week 4 | -19.59 units on a scale |
| ELS 20 mg/UPA Placebo | Change From Baseline in Physician's Global Assessment of Disease Activity (PhGA) | Week 8 | -33.93 units on a scale |
| ELS 5 mg/UPA Placebo | Change From Baseline in Physician's Global Assessment of Disease Activity (PhGA) | Week 8 | -25.21 units on a scale |
| ELS 5 mg/UPA Placebo | Change From Baseline in Physician's Global Assessment of Disease Activity (PhGA) | Week 12 | -24.55 units on a scale |
| ELS 5 mg/UPA Placebo | Change From Baseline in Physician's Global Assessment of Disease Activity (PhGA) | Week 4 | -18.31 units on a scale |
| ELS 5 mg/UPA Placebo | Change From Baseline in Physician's Global Assessment of Disease Activity (PhGA) | Week 2 | -11.64 units on a scale |
| UPA 15 mg/ELS Placebo | Change From Baseline in Physician's Global Assessment of Disease Activity (PhGA) | Week 4 | -34.17 units on a scale |
| UPA 15 mg/ELS Placebo | Change From Baseline in Physician's Global Assessment of Disease Activity (PhGA) | Week 8 | -41.02 units on a scale |
| UPA 15 mg/ELS Placebo | Change From Baseline in Physician's Global Assessment of Disease Activity (PhGA) | Week 12 | -50.89 units on a scale |
| UPA 15 mg/ELS Placebo | Change From Baseline in Physician's Global Assessment of Disease Activity (PhGA) | Week 2 | -24.71 units on a scale |
Secondary
Change From Baseline in Simplified Disease Activity Index (SDAI)
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
Population: 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 | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| ELS Placebo/UPA Placebo | Change From Baseline in Simplified Disease Activity Index (SDAI) | Week 2 | -6.17 units on a scale |
| ELS Placebo/UPA Placebo | Change From Baseline in Simplified Disease Activity Index (SDAI) | Week 4 | -11.80 units on a scale |
| ELS Placebo/UPA Placebo | Change From Baseline in Simplified Disease Activity Index (SDAI) | Week 8 | -12.15 units on a scale |
| ELS Placebo/UPA Placebo | Change From Baseline in Simplified Disease Activity Index (SDAI) | Week 12 | -14.44 units on a scale |
| UPA 15 mg/ELS 60 mg | Change From Baseline in Simplified Disease Activity Index (SDAI) | Week 8 | -25.96 units on a scale |
| UPA 15 mg/ELS 60 mg | Change From Baseline in Simplified Disease Activity Index (SDAI) | Week 4 | -21.24 units on a scale |
| UPA 15 mg/ELS 60 mg | Change From Baseline in Simplified Disease Activity Index (SDAI) | Week 2 | -17.01 units on a scale |
| UPA 15 mg/ELS 60 mg | Change From Baseline in Simplified Disease Activity Index (SDAI) | Week 12 | -28.06 units on a scale |
| ELS 60 mg/UPA Placebo | Change From Baseline in Simplified Disease Activity Index (SDAI) | Week 12 | -18.01 units on a scale |
| ELS 60 mg/UPA Placebo | Change From Baseline in Simplified Disease Activity Index (SDAI) | Week 8 | -15.26 units on a scale |
| ELS 60 mg/UPA Placebo | Change From Baseline in Simplified Disease Activity Index (SDAI) | Week 4 | -11.46 units on a scale |
| ELS 60 mg/UPA Placebo | Change From Baseline in Simplified Disease Activity Index (SDAI) | Week 2 | -8.79 units on a scale |
| ELS 20 mg/UPA Placebo | Change From Baseline in Simplified Disease Activity Index (SDAI) | Week 2 | -7.42 units on a scale |
| ELS 20 mg/UPA Placebo | Change From Baseline in Simplified Disease Activity Index (SDAI) | Week 12 | -17.12 units on a scale |
| ELS 20 mg/UPA Placebo | Change From Baseline in Simplified Disease Activity Index (SDAI) | Week 4 | -10.15 units on a scale |
| ELS 20 mg/UPA Placebo | Change From Baseline in Simplified Disease Activity Index (SDAI) | Week 8 | -17.32 units on a scale |
| ELS 5 mg/UPA Placebo | Change From Baseline in Simplified Disease Activity Index (SDAI) | Week 8 | -15.21 units on a scale |
| ELS 5 mg/UPA Placebo | Change From Baseline in Simplified Disease Activity Index (SDAI) | Week 12 | -16.73 units on a scale |
| ELS 5 mg/UPA Placebo | Change From Baseline in Simplified Disease Activity Index (SDAI) | Week 4 | -12.87 units on a scale |
| ELS 5 mg/UPA Placebo | Change From Baseline in Simplified Disease Activity Index (SDAI) | Week 2 | -8.54 units on a scale |
| UPA 15 mg/ELS Placebo | Change From Baseline in Simplified Disease Activity Index (SDAI) | Week 4 | -21.59 units on a scale |
| UPA 15 mg/ELS Placebo | Change From Baseline in Simplified Disease Activity Index (SDAI) | Week 8 | -25.07 units on a scale |
| UPA 15 mg/ELS Placebo | Change From Baseline in Simplified Disease Activity Index (SDAI) | Week 12 | -29.65 units on a scale |
| UPA 15 mg/ELS Placebo | Change From Baseline in Simplified Disease Activity Index (SDAI) | Week 2 | -15.30 units on a scale |
Secondary
Change From Baseline in Swollen Joint Count 66 (SJC66)
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
Population: 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 | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| ELS Placebo/UPA Placebo | Change From Baseline in Swollen Joint Count 66 (SJC66) | Week 4 | -4.70 swollen joint counts |
| ELS Placebo/UPA Placebo | Change From Baseline in Swollen Joint Count 66 (SJC66) | Week 2 | -3.12 swollen joint counts |
| ELS Placebo/UPA Placebo | Change From Baseline in Swollen Joint Count 66 (SJC66) | Week 12 | -5.58 swollen joint counts |
| ELS Placebo/UPA Placebo | Change From Baseline in Swollen Joint Count 66 (SJC66) | Week 8 | -4.32 swollen joint counts |
| UPA 15 mg/ELS 60 mg | Change From Baseline in Swollen Joint Count 66 (SJC66) | Week 2 | -6.06 swollen joint counts |
| UPA 15 mg/ELS 60 mg | Change From Baseline in Swollen Joint Count 66 (SJC66) | Week 12 | -10.86 swollen joint counts |
| UPA 15 mg/ELS 60 mg | Change From Baseline in Swollen Joint Count 66 (SJC66) | Week 4 | -7.96 swollen joint counts |
| UPA 15 mg/ELS 60 mg | Change From Baseline in Swollen Joint Count 66 (SJC66) | Week 8 | -10.28 swollen joint counts |
| ELS 60 mg/UPA Placebo | Change From Baseline in Swollen Joint Count 66 (SJC66) | Week 8 | -6.15 swollen joint counts |
| ELS 60 mg/UPA Placebo | Change From Baseline in Swollen Joint Count 66 (SJC66) | Week 4 | -5.11 swollen joint counts |
| ELS 60 mg/UPA Placebo | Change From Baseline in Swollen Joint Count 66 (SJC66) | Week 12 | -6.68 swollen joint counts |
| ELS 60 mg/UPA Placebo | Change From Baseline in Swollen Joint Count 66 (SJC66) | Week 2 | -3.61 swollen joint counts |
| ELS 20 mg/UPA Placebo | Change From Baseline in Swollen Joint Count 66 (SJC66) | Week 2 | -3.30 swollen joint counts |
| ELS 20 mg/UPA Placebo | Change From Baseline in Swollen Joint Count 66 (SJC66) | Week 8 | -8.08 swollen joint counts |
| ELS 20 mg/UPA Placebo | Change From Baseline in Swollen Joint Count 66 (SJC66) | Week 4 | -4.67 swollen joint counts |
| ELS 20 mg/UPA Placebo | Change From Baseline in Swollen Joint Count 66 (SJC66) | Week 12 | -7.85 swollen joint counts |
| ELS 5 mg/UPA Placebo | Change From Baseline in Swollen Joint Count 66 (SJC66) | Week 4 | -6.05 swollen joint counts |
| ELS 5 mg/UPA Placebo | Change From Baseline in Swollen Joint Count 66 (SJC66) | Week 2 | -4.13 swollen joint counts |
| ELS 5 mg/UPA Placebo | Change From Baseline in Swollen Joint Count 66 (SJC66) | Week 8 | -7.58 swollen joint counts |
| ELS 5 mg/UPA Placebo | Change From Baseline in Swollen Joint Count 66 (SJC66) | Week 12 | -8.59 swollen joint counts |
| UPA 15 mg/ELS Placebo | Change From Baseline in Swollen Joint Count 66 (SJC66) | Week 4 | -8.81 swollen joint counts |
| UPA 15 mg/ELS Placebo | Change From Baseline in Swollen Joint Count 66 (SJC66) | Week 2 | -6.02 swollen joint counts |
| UPA 15 mg/ELS Placebo | Change From Baseline in Swollen Joint Count 66 (SJC66) | Week 12 | -11.14 swollen joint counts |
| UPA 15 mg/ELS Placebo | Change From Baseline in Swollen Joint Count 66 (SJC66) | Week 8 | -10.11 swollen joint counts |
Secondary
Change From Baseline in Tender Joint Count 68 (TJC68)
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
Population: 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 | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| ELS Placebo/UPA Placebo | Change From Baseline in Tender Joint Count 68 (TJC68) | Week 2 | -2.47 tender joint counts |
| ELS Placebo/UPA Placebo | Change From Baseline in Tender Joint Count 68 (TJC68) | Week 4 | -9.21 tender joint counts |
| ELS Placebo/UPA Placebo | Change From Baseline in Tender Joint Count 68 (TJC68) | Week 8 | -8.82 tender joint counts |
| ELS Placebo/UPA Placebo | Change From Baseline in Tender Joint Count 68 (TJC68) | Week 12 | -8.47 tender joint counts |
| UPA 15 mg/ELS 60 mg | Change From Baseline in Tender Joint Count 68 (TJC68) | Week 8 | -15.44 tender joint counts |
| UPA 15 mg/ELS 60 mg | Change From Baseline in Tender Joint Count 68 (TJC68) | Week 4 | -11.86 tender joint counts |
| UPA 15 mg/ELS 60 mg | Change From Baseline in Tender Joint Count 68 (TJC68) | Week 2 | -8.42 tender joint counts |
| UPA 15 mg/ELS 60 mg | Change From Baseline in Tender Joint Count 68 (TJC68) | Week 12 | -16.33 tender joint counts |
| ELS 60 mg/UPA Placebo | Change From Baseline in Tender Joint Count 68 (TJC68) | Week 12 | -9.14 tender joint counts |
| ELS 60 mg/UPA Placebo | Change From Baseline in Tender Joint Count 68 (TJC68) | Week 8 | -8.43 tender joint counts |
| ELS 60 mg/UPA Placebo | Change From Baseline in Tender Joint Count 68 (TJC68) | Week 4 | -5.16 tender joint counts |
| ELS 60 mg/UPA Placebo | Change From Baseline in Tender Joint Count 68 (TJC68) | Week 2 | -3.65 tender joint counts |
| ELS 20 mg/UPA Placebo | Change From Baseline in Tender Joint Count 68 (TJC68) | Week 2 | -3.86 tender joint counts |
| ELS 20 mg/UPA Placebo | Change From Baseline in Tender Joint Count 68 (TJC68) | Week 12 | -9.33 tender joint counts |
| ELS 20 mg/UPA Placebo | Change From Baseline in Tender Joint Count 68 (TJC68) | Week 4 | -5.39 tender joint counts |
| ELS 20 mg/UPA Placebo | Change From Baseline in Tender Joint Count 68 (TJC68) | Week 8 | -10.83 tender joint counts |
| ELS 5 mg/UPA Placebo | Change From Baseline in Tender Joint Count 68 (TJC68) | Week 8 | -9.08 tender joint counts |
| ELS 5 mg/UPA Placebo | Change From Baseline in Tender Joint Count 68 (TJC68) | Week 12 | -12.58 tender joint counts |
| ELS 5 mg/UPA Placebo | Change From Baseline in Tender Joint Count 68 (TJC68) | Week 4 | -8.08 tender joint counts |
| ELS 5 mg/UPA Placebo | Change From Baseline in Tender Joint Count 68 (TJC68) | Week 2 | -4.88 tender joint counts |
| UPA 15 mg/ELS Placebo | Change From Baseline in Tender Joint Count 68 (TJC68) | Week 4 | -12.76 tender joint counts |
| UPA 15 mg/ELS Placebo | Change From Baseline in Tender Joint Count 68 (TJC68) | Week 8 | -14.76 tender joint counts |
| UPA 15 mg/ELS Placebo | Change From Baseline in Tender Joint Count 68 (TJC68) | Week 12 | -17.56 tender joint counts |
| UPA 15 mg/ELS Placebo | Change From Baseline in Tender Joint Count 68 (TJC68) | Week 2 | -8.57 tender joint counts |
Secondary
Percentage of Participants Achieving American College of Rheumatology/European League Against Rheumatism (EULAR) Boolean Remission
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
Population: Full Analysis Set: all randomized participants who received at least 1 dose of randomized study drug, nonresponder imputation was used for missing data
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| ELS Placebo/UPA Placebo | Percentage of Participants Achieving American College of Rheumatology/European League Against Rheumatism (EULAR) Boolean Remission | Week 2 | 0 percentage of participants |
| ELS Placebo/UPA Placebo | Percentage of Participants Achieving American College of Rheumatology/European League Against Rheumatism (EULAR) Boolean Remission | Week 4 | 0 percentage of participants |
| ELS Placebo/UPA Placebo | Percentage of Participants Achieving American College of Rheumatology/European League Against Rheumatism (EULAR) Boolean Remission | Week 8 | 0 percentage of participants |
| ELS Placebo/UPA Placebo | Percentage of Participants Achieving American College of Rheumatology/European League Against Rheumatism (EULAR) Boolean Remission | Week 12 | 0 percentage of participants |
| UPA 15 mg/ELS 60 mg | Percentage of Participants Achieving American College of Rheumatology/European League Against Rheumatism (EULAR) Boolean Remission | Week 8 | 6.5 percentage of participants |
| UPA 15 mg/ELS 60 mg | Percentage of Participants Achieving American College of Rheumatology/European League Against Rheumatism (EULAR) Boolean Remission | Week 4 | 6.5 percentage of participants |
| UPA 15 mg/ELS 60 mg | Percentage of Participants Achieving American College of Rheumatology/European League Against Rheumatism (EULAR) Boolean Remission | Week 2 | 1.6 percentage of participants |
| UPA 15 mg/ELS 60 mg | Percentage of Participants Achieving American College of Rheumatology/European League Against Rheumatism (EULAR) Boolean Remission | Week 12 | 11.3 percentage of participants |
| ELS 60 mg/UPA Placebo | Percentage of Participants Achieving American College of Rheumatology/European League Against Rheumatism (EULAR) Boolean Remission | Week 12 | 9.8 percentage of participants |
| ELS 60 mg/UPA Placebo | Percentage of Participants Achieving American College of Rheumatology/European League Against Rheumatism (EULAR) Boolean Remission | Week 8 | 2.4 percentage of participants |
| ELS 60 mg/UPA Placebo | Percentage of Participants Achieving American College of Rheumatology/European League Against Rheumatism (EULAR) Boolean Remission | Week 4 | 2.4 percentage of participants |
| ELS 60 mg/UPA Placebo | Percentage of Participants Achieving American College of Rheumatology/European League Against Rheumatism (EULAR) Boolean Remission | Week 2 | 0 percentage of participants |
| ELS 20 mg/UPA Placebo | Percentage of Participants Achieving American College of Rheumatology/European League Against Rheumatism (EULAR) Boolean Remission | Week 2 | 0 percentage of participants |
| ELS 20 mg/UPA Placebo | Percentage of Participants Achieving American College of Rheumatology/European League Against Rheumatism (EULAR) Boolean Remission | Week 12 | 2.6 percentage of participants |
| ELS 20 mg/UPA Placebo | Percentage of Participants Achieving American College of Rheumatology/European League Against Rheumatism (EULAR) Boolean Remission | Week 4 | 0 percentage of participants |
| ELS 20 mg/UPA Placebo | Percentage of Participants Achieving American College of Rheumatology/European League Against Rheumatism (EULAR) Boolean Remission | Week 8 | 5.1 percentage of participants |
| ELS 5 mg/UPA Placebo | Percentage of Participants Achieving American College of Rheumatology/European League Against Rheumatism (EULAR) Boolean Remission | Week 8 | 0 percentage of participants |
| ELS 5 mg/UPA Placebo | Percentage of Participants Achieving American College of Rheumatology/European League Against Rheumatism (EULAR) Boolean Remission | Week 12 | 2.4 percentage of participants |
| ELS 5 mg/UPA Placebo | Percentage of Participants Achieving American College of Rheumatology/European League Against Rheumatism (EULAR) Boolean Remission | Week 4 | 0 percentage of participants |
| ELS 5 mg/UPA Placebo | Percentage of Participants Achieving American College of Rheumatology/European League Against Rheumatism (EULAR) Boolean Remission | Week 2 | 0 percentage of participants |
| UPA 15 mg/ELS Placebo | Percentage of Participants Achieving American College of Rheumatology/European League Against Rheumatism (EULAR) Boolean Remission | Week 4 | 2.5 percentage of participants |
| UPA 15 mg/ELS Placebo | Percentage of Participants Achieving American College of Rheumatology/European League Against Rheumatism (EULAR) Boolean Remission | Week 8 | 12.5 percentage of participants |
| UPA 15 mg/ELS Placebo | Percentage of Participants Achieving American College of Rheumatology/European League Against Rheumatism (EULAR) Boolean Remission | Week 12 | 10.0 percentage of participants |
| UPA 15 mg/ELS Placebo | Percentage of Participants Achieving American College of Rheumatology/European League Against Rheumatism (EULAR) Boolean Remission | Week 2 | 0 percentage of participants |
Secondary
Percentage of Participants Achieving Clinical Remission (CR) Based on Disease Activity Score 28 C-reactive Protein [DAS28-CRP]) at Week 12
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
Population: Full Analysis Set: all randomized participants who received at least 1 dose of randomized study drug, nonresponder imputation was used for missing data
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| ELS Placebo/UPA Placebo | Percentage of Participants Achieving Clinical Remission (CR) Based on Disease Activity Score 28 C-reactive Protein [DAS28-CRP]) at Week 12 | 10.5 percentage of participants |
| UPA 15 mg/ELS 60 mg | Percentage of Participants Achieving Clinical Remission (CR) Based on Disease Activity Score 28 C-reactive Protein [DAS28-CRP]) at Week 12 | 32.3 percentage of participants |
| ELS 60 mg/UPA Placebo | Percentage of Participants Achieving Clinical Remission (CR) Based on Disease Activity Score 28 C-reactive Protein [DAS28-CRP]) at Week 12 | 19.5 percentage of participants |
| ELS 20 mg/UPA Placebo | Percentage of Participants Achieving Clinical Remission (CR) Based on Disease Activity Score 28 C-reactive Protein [DAS28-CRP]) at Week 12 | 7.7 percentage of participants |
| ELS 5 mg/UPA Placebo | Percentage of Participants Achieving Clinical Remission (CR) Based on Disease Activity Score 28 C-reactive Protein [DAS28-CRP]) at Week 12 | 9.8 percentage of participants |
| UPA 15 mg/ELS Placebo | Percentage of Participants Achieving Clinical Remission (CR) Based on Disease Activity Score 28 C-reactive Protein [DAS28-CRP]) at Week 12 | 42.5 percentage of participants |
Secondary
Percentage of Participants Achieving Complete Remission (CR) Based on Clinical Disease Activity Index (CDAI) Criteria
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
Population: Full Analysis Set: all randomized participants who received at least 1 dose of randomized study drug, nonresponder imputation was used for missing data
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| ELS Placebo/UPA Placebo | Percentage of Participants Achieving Complete Remission (CR) Based on Clinical Disease Activity Index (CDAI) Criteria | Week 2 | 0 percentage of participants |
| ELS Placebo/UPA Placebo | Percentage of Participants Achieving Complete Remission (CR) Based on Clinical Disease Activity Index (CDAI) Criteria | Week 4 | 0 percentage of participants |
| ELS Placebo/UPA Placebo | Percentage of Participants Achieving Complete Remission (CR) Based on Clinical Disease Activity Index (CDAI) Criteria | Week 8 | 0 percentage of participants |
| ELS Placebo/UPA Placebo | Percentage of Participants Achieving Complete Remission (CR) Based on Clinical Disease Activity Index (CDAI) Criteria | Week 12 | 5.3 percentage of participants |
| UPA 15 mg/ELS 60 mg | Percentage of Participants Achieving Complete Remission (CR) Based on Clinical Disease Activity Index (CDAI) Criteria | Week 8 | 12.9 percentage of participants |
| UPA 15 mg/ELS 60 mg | Percentage of Participants Achieving Complete Remission (CR) Based on Clinical Disease Activity Index (CDAI) Criteria | Week 4 | 6.5 percentage of participants |
| UPA 15 mg/ELS 60 mg | Percentage of Participants Achieving Complete Remission (CR) Based on Clinical Disease Activity Index (CDAI) Criteria | Week 2 | 3.2 percentage of participants |
| UPA 15 mg/ELS 60 mg | Percentage of Participants Achieving Complete Remission (CR) Based on Clinical Disease Activity Index (CDAI) Criteria | Week 12 | 14.5 percentage of participants |
| ELS 60 mg/UPA Placebo | Percentage of Participants Achieving Complete Remission (CR) Based on Clinical Disease Activity Index (CDAI) Criteria | Week 12 | 7.3 percentage of participants |
| ELS 60 mg/UPA Placebo | Percentage of Participants Achieving Complete Remission (CR) Based on Clinical Disease Activity Index (CDAI) Criteria | Week 8 | 7.3 percentage of participants |
| ELS 60 mg/UPA Placebo | Percentage of Participants Achieving Complete Remission (CR) Based on Clinical Disease Activity Index (CDAI) Criteria | Week 4 | 2.4 percentage of participants |
| ELS 60 mg/UPA Placebo | Percentage of Participants Achieving Complete Remission (CR) Based on Clinical Disease Activity Index (CDAI) Criteria | Week 2 | 0 percentage of participants |
| ELS 20 mg/UPA Placebo | Percentage of Participants Achieving Complete Remission (CR) Based on Clinical Disease Activity Index (CDAI) Criteria | Week 2 | 0 percentage of participants |
| ELS 20 mg/UPA Placebo | Percentage of Participants Achieving Complete Remission (CR) Based on Clinical Disease Activity Index (CDAI) Criteria | Week 12 | 5.1 percentage of participants |
| ELS 20 mg/UPA Placebo | Percentage of Participants Achieving Complete Remission (CR) Based on Clinical Disease Activity Index (CDAI) Criteria | Week 4 | 2.6 percentage of participants |
| ELS 20 mg/UPA Placebo | Percentage of Participants Achieving Complete Remission (CR) Based on Clinical Disease Activity Index (CDAI) Criteria | Week 8 | 2.6 percentage of participants |
| ELS 5 mg/UPA Placebo | Percentage of Participants Achieving Complete Remission (CR) Based on Clinical Disease Activity Index (CDAI) Criteria | Week 8 | 2.4 percentage of participants |
| ELS 5 mg/UPA Placebo | Percentage of Participants Achieving Complete Remission (CR) Based on Clinical Disease Activity Index (CDAI) Criteria | Week 12 | 0 percentage of participants |
| ELS 5 mg/UPA Placebo | Percentage of Participants Achieving Complete Remission (CR) Based on Clinical Disease Activity Index (CDAI) Criteria | Week 4 | 0 percentage of participants |
| ELS 5 mg/UPA Placebo | Percentage of Participants Achieving Complete Remission (CR) Based on Clinical Disease Activity Index (CDAI) Criteria | Week 2 | 0 percentage of participants |
| UPA 15 mg/ELS Placebo | Percentage of Participants Achieving Complete Remission (CR) Based on Clinical Disease Activity Index (CDAI) Criteria | Week 4 | 2.5 percentage of participants |
| UPA 15 mg/ELS Placebo | Percentage of Participants Achieving Complete Remission (CR) Based on Clinical Disease Activity Index (CDAI) Criteria | Week 8 | 12.5 percentage of participants |
| UPA 15 mg/ELS Placebo | Percentage of Participants Achieving Complete Remission (CR) Based on Clinical Disease Activity Index (CDAI) Criteria | Week 12 | 15.0 percentage of participants |
| UPA 15 mg/ELS Placebo | Percentage of Participants Achieving Complete Remission (CR) Based on Clinical Disease Activity Index (CDAI) Criteria | Week 2 | 0 percentage of participants |
Secondary
Percentage of Participants Achieving Low Disease Activity (LDA) Based on Clinical Disease Activity Index (CDAI) Criteria
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
Population: Full Analysis Set: all randomized participants who received at least 1 dose of randomized study drug, nonresponder imputation was used for missing data
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| ELS Placebo/UPA Placebo | Percentage of Participants Achieving Low Disease Activity (LDA) Based on Clinical Disease Activity Index (CDAI) Criteria | Week 12 | 26.3 percentage of participants |
| ELS Placebo/UPA Placebo | Percentage of Participants Achieving Low Disease Activity (LDA) Based on Clinical Disease Activity Index (CDAI) Criteria | Week 2 | 10.5 percentage of participants |
| ELS Placebo/UPA Placebo | Percentage of Participants Achieving Low Disease Activity (LDA) Based on Clinical Disease Activity Index (CDAI) Criteria | Week 4 | 10.5 percentage of participants |
| ELS Placebo/UPA Placebo | Percentage of Participants Achieving Low Disease Activity (LDA) Based on Clinical Disease Activity Index (CDAI) Criteria | Week 8 | 5.3 percentage of participants |
| UPA 15 mg/ELS 60 mg | Percentage of Participants Achieving Low Disease Activity (LDA) Based on Clinical Disease Activity Index (CDAI) Criteria | Week 8 | 46.8 percentage of participants |
| UPA 15 mg/ELS 60 mg | Percentage of Participants Achieving Low Disease Activity (LDA) Based on Clinical Disease Activity Index (CDAI) Criteria | Week 4 | 29.0 percentage of participants |
| UPA 15 mg/ELS 60 mg | Percentage of Participants Achieving Low Disease Activity (LDA) Based on Clinical Disease Activity Index (CDAI) Criteria | Week 2 | 16.1 percentage of participants |
| UPA 15 mg/ELS 60 mg | Percentage of Participants Achieving Low Disease Activity (LDA) Based on Clinical Disease Activity Index (CDAI) Criteria | Week 12 | 37.1 percentage of participants |
| ELS 60 mg/UPA Placebo | Percentage of Participants Achieving Low Disease Activity (LDA) Based on Clinical Disease Activity Index (CDAI) Criteria | Week 8 | 17.1 percentage of participants |
| ELS 60 mg/UPA Placebo | Percentage of Participants Achieving Low Disease Activity (LDA) Based on Clinical Disease Activity Index (CDAI) Criteria | Week 12 | 34.1 percentage of participants |
| ELS 60 mg/UPA Placebo | Percentage of Participants Achieving Low Disease Activity (LDA) Based on Clinical Disease Activity Index (CDAI) Criteria | Week 2 | 9.8 percentage of participants |
| ELS 60 mg/UPA Placebo | Percentage of Participants Achieving Low Disease Activity (LDA) Based on Clinical Disease Activity Index (CDAI) Criteria | Week 4 | 12.2 percentage of participants |
| ELS 20 mg/UPA Placebo | Percentage of Participants Achieving Low Disease Activity (LDA) Based on Clinical Disease Activity Index (CDAI) Criteria | Week 12 | 17.9 percentage of participants |
| ELS 20 mg/UPA Placebo | Percentage of Participants Achieving Low Disease Activity (LDA) Based on Clinical Disease Activity Index (CDAI) Criteria | Week 4 | 7.7 percentage of participants |
| ELS 20 mg/UPA Placebo | Percentage of Participants Achieving Low Disease Activity (LDA) Based on Clinical Disease Activity Index (CDAI) Criteria | Week 2 | 0 percentage of participants |
| ELS 20 mg/UPA Placebo | Percentage of Participants Achieving Low Disease Activity (LDA) Based on Clinical Disease Activity Index (CDAI) Criteria | Week 8 | 20.5 percentage of participants |
| ELS 5 mg/UPA Placebo | Percentage of Participants Achieving Low Disease Activity (LDA) Based on Clinical Disease Activity Index (CDAI) Criteria | Week 12 | 17.1 percentage of participants |
| ELS 5 mg/UPA Placebo | Percentage of Participants Achieving Low Disease Activity (LDA) Based on Clinical Disease Activity Index (CDAI) Criteria | Week 4 | 12.2 percentage of participants |
| ELS 5 mg/UPA Placebo | Percentage of Participants Achieving Low Disease Activity (LDA) Based on Clinical Disease Activity Index (CDAI) Criteria | Week 8 | 24.4 percentage of participants |
| ELS 5 mg/UPA Placebo | Percentage of Participants Achieving Low Disease Activity (LDA) Based on Clinical Disease Activity Index (CDAI) Criteria | Week 2 | 2.4 percentage of participants |
| UPA 15 mg/ELS Placebo | Percentage of Participants Achieving Low Disease Activity (LDA) Based on Clinical Disease Activity Index (CDAI) Criteria | Week 12 | 57.5 percentage of participants |
| UPA 15 mg/ELS Placebo | Percentage of Participants Achieving Low Disease Activity (LDA) Based on Clinical Disease Activity Index (CDAI) Criteria | Week 8 | 35.0 percentage of participants |
| UPA 15 mg/ELS Placebo | Percentage of Participants Achieving Low Disease Activity (LDA) Based on Clinical Disease Activity Index (CDAI) Criteria | Week 4 | 22.5 percentage of participants |
| UPA 15 mg/ELS Placebo | Percentage of Participants Achieving Low Disease Activity (LDA) Based on Clinical Disease Activity Index (CDAI) Criteria | Week 2 | 12.5 percentage of participants |
Secondary
Percentage of Participants Achieving Low Disease Activity (LDA) Based on Disease Activity Score 28 C-reactive Protein [DAS28-CRP]) at Week 12
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
Population: Full Analysis Set: all randomized participants who received at least 1 dose of randomized study drug, nonresponder imputation was used for missing data
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| ELS Placebo/UPA Placebo | Percentage of Participants Achieving Low Disease Activity (LDA) Based on Disease Activity Score 28 C-reactive Protein [DAS28-CRP]) at Week 12 | 21.1 percentage of participants |
| UPA 15 mg/ELS 60 mg | Percentage of Participants Achieving Low Disease Activity (LDA) Based on Disease Activity Score 28 C-reactive Protein [DAS28-CRP]) at Week 12 | 41.9 percentage of participants |
| ELS 60 mg/UPA Placebo | Percentage of Participants Achieving Low Disease Activity (LDA) Based on Disease Activity Score 28 C-reactive Protein [DAS28-CRP]) at Week 12 | 22.0 percentage of participants |
| ELS 20 mg/UPA Placebo | Percentage of Participants Achieving Low Disease Activity (LDA) Based on Disease Activity Score 28 C-reactive Protein [DAS28-CRP]) at Week 12 | 10.3 percentage of participants |
| ELS 5 mg/UPA Placebo | Percentage of Participants Achieving Low Disease Activity (LDA) Based on Disease Activity Score 28 C-reactive Protein [DAS28-CRP]) at Week 12 | 14.6 percentage of participants |
| UPA 15 mg/ELS Placebo | Percentage of Participants Achieving Low Disease Activity (LDA) Based on Disease Activity Score 28 C-reactive Protein [DAS28-CRP]) at Week 12 | 55.0 percentage of participants |
Secondary
Percentage of Participants Achieving Minimal Clinically Important Difference (MCID) in Change From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI)
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
Population: Full Analysis Set: all randomized participants who received at least 1 dose of randomized study drug, nonresponder imputation was used for missing data
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| ELS Placebo/UPA Placebo | Percentage of Participants Achieving Minimal Clinically Important Difference (MCID) in Change From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) | Week 2 | 52.6 percentage of participants |
| ELS Placebo/UPA Placebo | Percentage of Participants Achieving Minimal Clinically Important Difference (MCID) in Change From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) | Week 4 | 68.4 percentage of participants |
| ELS Placebo/UPA Placebo | Percentage of Participants Achieving Minimal Clinically Important Difference (MCID) in Change From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) | Week 8 | 52.6 percentage of participants |
| ELS Placebo/UPA Placebo | Percentage of Participants Achieving Minimal Clinically Important Difference (MCID) in Change From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) | Week 12 | 47.4 percentage of participants |
| UPA 15 mg/ELS 60 mg | Percentage of Participants Achieving Minimal Clinically Important Difference (MCID) in Change From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) | Week 8 | 58.1 percentage of participants |
| UPA 15 mg/ELS 60 mg | Percentage of Participants Achieving Minimal Clinically Important Difference (MCID) in Change From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) | Week 4 | 54.8 percentage of participants |
| UPA 15 mg/ELS 60 mg | Percentage of Participants Achieving Minimal Clinically Important Difference (MCID) in Change From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) | Week 2 | 51.6 percentage of participants |
| UPA 15 mg/ELS 60 mg | Percentage of Participants Achieving Minimal Clinically Important Difference (MCID) in Change From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) | Week 12 | 58.1 percentage of participants |
| ELS 60 mg/UPA Placebo | Percentage of Participants Achieving Minimal Clinically Important Difference (MCID) in Change From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) | Week 12 | 53.7 percentage of participants |
| ELS 60 mg/UPA Placebo | Percentage of Participants Achieving Minimal Clinically Important Difference (MCID) in Change From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) | Week 8 | 51.2 percentage of participants |
| ELS 60 mg/UPA Placebo | Percentage of Participants Achieving Minimal Clinically Important Difference (MCID) in Change From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) | Week 4 | 34.1 percentage of participants |
| ELS 60 mg/UPA Placebo | Percentage of Participants Achieving Minimal Clinically Important Difference (MCID) in Change From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) | Week 2 | 36.6 percentage of participants |
| ELS 20 mg/UPA Placebo | Percentage of Participants Achieving Minimal Clinically Important Difference (MCID) in Change From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) | Week 2 | 30.8 percentage of participants |
| ELS 20 mg/UPA Placebo | Percentage of Participants Achieving Minimal Clinically Important Difference (MCID) in Change From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) | Week 12 | 43.6 percentage of participants |
| ELS 20 mg/UPA Placebo | Percentage of Participants Achieving Minimal Clinically Important Difference (MCID) in Change From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) | Week 4 | 41.0 percentage of participants |
| ELS 20 mg/UPA Placebo | Percentage of Participants Achieving Minimal Clinically Important Difference (MCID) in Change From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) | Week 8 | 51.3 percentage of participants |
| ELS 5 mg/UPA Placebo | Percentage of Participants Achieving Minimal Clinically Important Difference (MCID) in Change From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) | Week 8 | 36.6 percentage of participants |
| ELS 5 mg/UPA Placebo | Percentage of Participants Achieving Minimal Clinically Important Difference (MCID) in Change From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) | Week 12 | 43.9 percentage of participants |
| ELS 5 mg/UPA Placebo | Percentage of Participants Achieving Minimal Clinically Important Difference (MCID) in Change From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) | Week 4 | 53.7 percentage of participants |
| ELS 5 mg/UPA Placebo | Percentage of Participants Achieving Minimal Clinically Important Difference (MCID) in Change From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) | Week 2 | 36.6 percentage of participants |
| UPA 15 mg/ELS Placebo | Percentage of Participants Achieving Minimal Clinically Important Difference (MCID) in Change From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) | Week 4 | 45.0 percentage of participants |
| UPA 15 mg/ELS Placebo | Percentage of Participants Achieving Minimal Clinically Important Difference (MCID) in Change From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) | Week 8 | 65.0 percentage of participants |
| UPA 15 mg/ELS Placebo | Percentage of Participants Achieving Minimal Clinically Important Difference (MCID) in Change From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) | Week 12 | 55.0 percentage of participants |
| UPA 15 mg/ELS Placebo | Percentage of Participants Achieving Minimal Clinically Important Difference (MCID) in Change From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) | Week 2 | 52.5 percentage of participants |
Secondary
Percentage of Participants With an American College of Rheumatology 20% (ACR20) Response
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
Population: Full Analysis Set: all randomized participants who received at least 1 dose of randomized study drug, nonresponder imputation was used for missing data
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| ELS Placebo/UPA Placebo | Percentage of Participants With an American College of Rheumatology 20% (ACR20) Response | Week 12 | 47.4 percentage of participants |
| ELS Placebo/UPA Placebo | Percentage of Participants With an American College of Rheumatology 20% (ACR20) Response | Week 8 | 36.8 percentage of participants |
| ELS Placebo/UPA Placebo | Percentage of Participants With an American College of Rheumatology 20% (ACR20) Response | Week 4 | 42.1 percentage of participants |
| ELS Placebo/UPA Placebo | Percentage of Participants With an American College of Rheumatology 20% (ACR20) Response | Week 2 | 21.1 percentage of participants |
| UPA 15 mg/ELS 60 mg | Percentage of Participants With an American College of Rheumatology 20% (ACR20) Response | Week 4 | 51.6 percentage of participants |
| UPA 15 mg/ELS 60 mg | Percentage of Participants With an American College of Rheumatology 20% (ACR20) Response | Week 12 | 64.5 percentage of participants |
| UPA 15 mg/ELS 60 mg | Percentage of Participants With an American College of Rheumatology 20% (ACR20) Response | Week 8 | 64.5 percentage of participants |
| UPA 15 mg/ELS 60 mg | Percentage of Participants With an American College of Rheumatology 20% (ACR20) Response | Week 2 | 45.2 percentage of participants |
| ELS 60 mg/UPA Placebo | Percentage of Participants With an American College of Rheumatology 20% (ACR20) Response | Week 4 | 29.3 percentage of participants |
| ELS 60 mg/UPA Placebo | Percentage of Participants With an American College of Rheumatology 20% (ACR20) Response | Week 2 | 24.4 percentage of participants |
| ELS 60 mg/UPA Placebo | Percentage of Participants With an American College of Rheumatology 20% (ACR20) Response | Week 12 | 41.5 percentage of participants |
| ELS 60 mg/UPA Placebo | Percentage of Participants With an American College of Rheumatology 20% (ACR20) Response | Week 8 | 39.0 percentage of participants |
| ELS 20 mg/UPA Placebo | Percentage of Participants With an American College of Rheumatology 20% (ACR20) Response | Week 12 | 30.8 percentage of participants |
| ELS 20 mg/UPA Placebo | Percentage of Participants With an American College of Rheumatology 20% (ACR20) Response | Week 2 | 12.8 percentage of participants |
| ELS 20 mg/UPA Placebo | Percentage of Participants With an American College of Rheumatology 20% (ACR20) Response | Week 4 | 23.1 percentage of participants |
| ELS 20 mg/UPA Placebo | Percentage of Participants With an American College of Rheumatology 20% (ACR20) Response | Week 8 | 30.8 percentage of participants |
| ELS 5 mg/UPA Placebo | Percentage of Participants With an American College of Rheumatology 20% (ACR20) Response | Week 2 | 14.6 percentage of participants |
| ELS 5 mg/UPA Placebo | Percentage of Participants With an American College of Rheumatology 20% (ACR20) Response | Week 4 | 22.0 percentage of participants |
| ELS 5 mg/UPA Placebo | Percentage of Participants With an American College of Rheumatology 20% (ACR20) Response | Week 8 | 39.0 percentage of participants |
| ELS 5 mg/UPA Placebo | Percentage of Participants With an American College of Rheumatology 20% (ACR20) Response | Week 12 | 34.1 percentage of participants |
| UPA 15 mg/ELS Placebo | Percentage of Participants With an American College of Rheumatology 20% (ACR20) Response | Week 4 | 55.0 percentage of participants |
| UPA 15 mg/ELS Placebo | Percentage of Participants With an American College of Rheumatology 20% (ACR20) Response | Week 2 | 52.5 percentage of participants |
| UPA 15 mg/ELS Placebo | Percentage of Participants With an American College of Rheumatology 20% (ACR20) Response | Week 12 | 72.5 percentage of participants |
| UPA 15 mg/ELS Placebo | Percentage of Participants With an American College of Rheumatology 20% (ACR20) Response | Week 8 | 67.5 percentage of participants |
Secondary
Percentage of Participants With an American College of Rheumatology 50% (ACR50) Response
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
Population: Full Analysis Set: all randomized participants who received at least 1 dose of randomized study drug, nonresponder imputation was used for missing data
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| ELS Placebo/UPA Placebo | Percentage of Participants With an American College of Rheumatology 50% (ACR50) Response | Week 2 | 0 percentage of participants |
| ELS Placebo/UPA Placebo | Percentage of Participants With an American College of Rheumatology 50% (ACR50) Response | Week 4 | 10.5 percentage of participants |
| ELS Placebo/UPA Placebo | Percentage of Participants With an American College of Rheumatology 50% (ACR50) Response | Week 8 | 5.3 percentage of participants |
| ELS Placebo/UPA Placebo | Percentage of Participants With an American College of Rheumatology 50% (ACR50) Response | Week 12 | 21.1 percentage of participants |
| UPA 15 mg/ELS 60 mg | Percentage of Participants With an American College of Rheumatology 50% (ACR50) Response | Week 8 | 41.9 percentage of participants |
| UPA 15 mg/ELS 60 mg | Percentage of Participants With an American College of Rheumatology 50% (ACR50) Response | Week 4 | 19.4 percentage of participants |
| UPA 15 mg/ELS 60 mg | Percentage of Participants With an American College of Rheumatology 50% (ACR50) Response | Week 2 | 16.1 percentage of participants |
| UPA 15 mg/ELS 60 mg | Percentage of Participants With an American College of Rheumatology 50% (ACR50) Response | Week 12 | 45.2 percentage of participants |
| ELS 60 mg/UPA Placebo | Percentage of Participants With an American College of Rheumatology 50% (ACR50) Response | Week 12 | 29.3 percentage of participants |
| ELS 60 mg/UPA Placebo | Percentage of Participants With an American College of Rheumatology 50% (ACR50) Response | Week 8 | 19.5 percentage of participants |
| ELS 60 mg/UPA Placebo | Percentage of Participants With an American College of Rheumatology 50% (ACR50) Response | Week 4 | 17.1 percentage of participants |
| ELS 60 mg/UPA Placebo | Percentage of Participants With an American College of Rheumatology 50% (ACR50) Response | Week 2 | 4.9 percentage of participants |
| ELS 20 mg/UPA Placebo | Percentage of Participants With an American College of Rheumatology 50% (ACR50) Response | Week 2 | 0 percentage of participants |
| ELS 20 mg/UPA Placebo | Percentage of Participants With an American College of Rheumatology 50% (ACR50) Response | Week 12 | 12.8 percentage of participants |
| ELS 20 mg/UPA Placebo | Percentage of Participants With an American College of Rheumatology 50% (ACR50) Response | Week 4 | 2.6 percentage of participants |
| ELS 20 mg/UPA Placebo | Percentage of Participants With an American College of Rheumatology 50% (ACR50) Response | Week 8 | 12.8 percentage of participants |
| ELS 5 mg/UPA Placebo | Percentage of Participants With an American College of Rheumatology 50% (ACR50) Response | Week 8 | 7.3 percentage of participants |
| ELS 5 mg/UPA Placebo | Percentage of Participants With an American College of Rheumatology 50% (ACR50) Response | Week 12 | 17.1 percentage of participants |
| ELS 5 mg/UPA Placebo | Percentage of Participants With an American College of Rheumatology 50% (ACR50) Response | Week 4 | 4.9 percentage of participants |
| ELS 5 mg/UPA Placebo | Percentage of Participants With an American College of Rheumatology 50% (ACR50) Response | Week 2 | 0 percentage of participants |
| UPA 15 mg/ELS Placebo | Percentage of Participants With an American College of Rheumatology 50% (ACR50) Response | Week 4 | 30.0 percentage of participants |
| UPA 15 mg/ELS Placebo | Percentage of Participants With an American College of Rheumatology 50% (ACR50) Response | Week 8 | 40.0 percentage of participants |
| UPA 15 mg/ELS Placebo | Percentage of Participants With an American College of Rheumatology 50% (ACR50) Response | Week 12 | 47.5 percentage of participants |
| UPA 15 mg/ELS Placebo | Percentage of Participants With an American College of Rheumatology 50% (ACR50) Response | Week 2 | 12.5 percentage of participants |
Secondary
Percentage of Participants With an American College of Rheumatology 70% (ACR70) Response
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
Population: Full Analysis Set: all randomized participants who received at least 1 dose of randomized study drug, nonresponder imputation was used for missing data
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| ELS Placebo/UPA Placebo | Percentage of Participants With an American College of Rheumatology 70% (ACR70) Response | Week 8 | 0 percentage of participants |
| ELS Placebo/UPA Placebo | Percentage of Participants With an American College of Rheumatology 70% (ACR70) Response | Week 12 | 15.8 percentage of participants |
| ELS Placebo/UPA Placebo | Percentage of Participants With an American College of Rheumatology 70% (ACR70) Response | Week 2 | 0 percentage of participants |
| ELS Placebo/UPA Placebo | Percentage of Participants With an American College of Rheumatology 70% (ACR70) Response | Week 4 | 0 percentage of participants |
| UPA 15 mg/ELS 60 mg | Percentage of Participants With an American College of Rheumatology 70% (ACR70) Response | Week 12 | 25.8 percentage of participants |
| UPA 15 mg/ELS 60 mg | Percentage of Participants With an American College of Rheumatology 70% (ACR70) Response | Week 2 | 8.1 percentage of participants |
| UPA 15 mg/ELS 60 mg | Percentage of Participants With an American College of Rheumatology 70% (ACR70) Response | Week 4 | 9.7 percentage of participants |
| UPA 15 mg/ELS 60 mg | Percentage of Participants With an American College of Rheumatology 70% (ACR70) Response | Week 8 | 17.7 percentage of participants |
| ELS 60 mg/UPA Placebo | Percentage of Participants With an American College of Rheumatology 70% (ACR70) Response | Week 4 | 4.9 percentage of participants |
| ELS 60 mg/UPA Placebo | Percentage of Participants With an American College of Rheumatology 70% (ACR70) Response | Week 2 | 2.4 percentage of participants |
| ELS 60 mg/UPA Placebo | Percentage of Participants With an American College of Rheumatology 70% (ACR70) Response | Week 8 | 4.9 percentage of participants |
| ELS 60 mg/UPA Placebo | Percentage of Participants With an American College of Rheumatology 70% (ACR70) Response | Week 12 | 14.6 percentage of participants |
| ELS 20 mg/UPA Placebo | Percentage of Participants With an American College of Rheumatology 70% (ACR70) Response | Week 2 | 0 percentage of participants |
| ELS 20 mg/UPA Placebo | Percentage of Participants With an American College of Rheumatology 70% (ACR70) Response | Week 4 | 2.6 percentage of participants |
| ELS 20 mg/UPA Placebo | Percentage of Participants With an American College of Rheumatology 70% (ACR70) Response | Week 12 | 5.1 percentage of participants |
| ELS 20 mg/UPA Placebo | Percentage of Participants With an American College of Rheumatology 70% (ACR70) Response | Week 8 | 2.6 percentage of participants |
| ELS 5 mg/UPA Placebo | Percentage of Participants With an American College of Rheumatology 70% (ACR70) Response | Week 2 | 0 percentage of participants |
| ELS 5 mg/UPA Placebo | Percentage of Participants With an American College of Rheumatology 70% (ACR70) Response | Week 8 | 0 percentage of participants |
| ELS 5 mg/UPA Placebo | Percentage of Participants With an American College of Rheumatology 70% (ACR70) Response | Week 12 | 9.8 percentage of participants |
| ELS 5 mg/UPA Placebo | Percentage of Participants With an American College of Rheumatology 70% (ACR70) Response | Week 4 | 0 percentage of participants |
| UPA 15 mg/ELS Placebo | Percentage of Participants With an American College of Rheumatology 70% (ACR70) Response | Week 2 | 0 percentage of participants |
| UPA 15 mg/ELS Placebo | Percentage of Participants With an American College of Rheumatology 70% (ACR70) Response | Week 12 | 27.5 percentage of participants |
| UPA 15 mg/ELS Placebo | Percentage of Participants With an American College of Rheumatology 70% (ACR70) Response | Week 8 | 25.0 percentage of participants |
| UPA 15 mg/ELS Placebo | Percentage of Participants With an American College of Rheumatology 70% (ACR70) Response | Week 4 | 15.0 percentage of participants |