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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT02706873




Registration number
NCT02706873
Ethics application status
Date submitted
18/02/2016
Date registered
11/03/2016
Date last updated
11/03/2020

Titles & IDs
Public title
A Study to Compare Upadacitinib (ABT-494) Monotherapy to Methotrexate (MTX) Monotherapy in Adults With Rheumatoid Arthritis (RA) Who Have Not Previously Taken Methotrexate
Scientific title
A Phase 3, Randomized, Double-Blind Study Comparing Upadacitinib (ABT-494) Once Daily Monotherapy to Methotrexate (MTX) Monotherapy in MTX-Naïve Subjects With Moderately to Severely Active Rheumatoid Arthritis
Secondary ID [1] 0 0
2015-003334-27
Secondary ID [2] 0 0
M13-545
Universal Trial Number (UTN)
Trial acronym
SELECT-EARLY
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Rheumatoid Arthritis 0 0
Condition category
Condition code
Musculoskeletal 0 0 0 0
Osteoarthritis
Inflammatory and Immune System 0 0 0 0
Rheumatoid arthritis

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Upadacitinib Placebo
Treatment: Drugs - Methotrexate
Treatment: Drugs - Methotrexate Placebo
Treatment: Drugs - Upadacitinib

Active Comparator: Placebo Upadacitinib and Methotrexate - Period 1: Participants will receive Upadacitinib placebo once daily and methotrexate once weekly for 48 weeks.
Period 2: Participants will continue on Upadacitinib placebo once daily and methotrexate once weekly followed by methotrexate alone once weekly.

Experimental: Upadacitinib 7.5 mg and Placebo Methotrexate (Japan-only) - Period 1: Participants will receive Upadacitinib 7.5 mg once daily and methotrexate placebo once weekly for 48 weeks.
Period 2: Participants will continue on Upadacitinib 7.5 mg once daily and methotrexate placebo once weekly followed by Upadacitinib 7.5 mg once daily without methotrexate placebo once the treatment assignment is unblinded to sites and participants.

Experimental: Upadacitinib 15 mg and Placebo Methotrexate - Period 1: Participants will receive Upadacitinib 15 mg once daily and methotrexate placebo once weekly for 48 weeks.
Period 2: Participants will continue on Upadacitinib 15 mg once daily and methotrexate placebo once weekly followed by Upadacitinib 15 mg once daily without methotrexate placebo once the treatment assignment is unblinded to sites and participants.

Experimental: Upadacitinib 30 mg and Placebo Methotrexate - Period 1: Participants will receive Upadacitinib 30 mg once daily and methotrexate placebo once weekly for 48 weeks.
Period 2: Participants will continue on Upadacitinib 30 mg once daily and methotrexate placebo once weekly until participants begin to receive Upadacitinib 15 mg once daily without methotrexate placebo once the treatment assignment is unblinded to sites and participants.


Treatment: Drugs: Upadacitinib Placebo
Tablet; Oral

Treatment: Drugs: Methotrexate
Capsule or Tablet; Oral

Treatment: Drugs: Methotrexate Placebo
Capsule or Tablet; Oral

Treatment: Drugs: Upadacitinib
Tablet; Oral

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Percentage of Participants With an American College of Rheumatology 50% (ACR50) Response at Week 12 - Global Analysis - The primary endpoint for United States (US)/Food and Drug Administration (FDA) regulatory purposes was ACR 50% response (ACR50) at Week 12. Participants who met the following 3 conditions for improvement from baseline were classified as meeting the ACR50 response criteria:
= 50% improvement in 68-tender joint count;
= 50% improvement in 66-swollen joint count; and
= 50% improvement in at least 3 of the 5 following parameters:
Physician global assessment of disease activity
Patient global assessment of disease activity
Patient assessment of pain
Health Assessment Questionnaire - Disability Index (HAQ-DI)
High-sensitivity C-reactive protein (hsCRP).
Timepoint [1] 0 0
Baseline and Week 12
Primary outcome [2] 0 0
Percentage of Participants Achieving Clinical Remission (CR) Based on DAS28(CRP) at Week 24 - Global Analysis - The primary endpoint for European Union (EU)/European Medicines Agency (EMA) regulatory purposes was clinical remission, based on a Disease Activity Score 28 (DAS28)-CRP score of < 2.6 at Week 24.
The DAS28 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 hsCRP (in mg/L). Scores on the DAS28 range from 0 to approximately 10, where higher scores indicate more disease activity.
A DAS28 score less than 2.6 indicates clinical remission.
Timepoint [2] 0 0
Week 24
Primary outcome [3] 0 0
Percentage of Participants With an American College of Rheumatology 20% (ACR20) Response at Week 12 - Global Analysis - The primary endpoint for Japan/Pharmaceuticals and Medical Devices Agency (PMDA) regulatory purposes was ACR 20% response (ACR20) at Week 12. Participants who met the following 3 conditions for improvement from baseline were classified as meeting the ACR20 response criteria:
= 20% improvement in 68-tender joint count;
= 20% improvement in 66-swollen joint count; and
= 20% improvement in at least 3 of the 5 following parameters:
Physician global assessment of disease activity
Patient global assessment of disease activity
Patient assessment of pain
Health Assessment Questionnaire - Disability Index (HAQ-DI)
High-sensitivity C-reactive protein (hsCRP).
Timepoint [3] 0 0
Baseline and Week 12
Primary outcome [4] 0 0
Change From Baseline in Modified Total Sharp Score (mTSS) at Week 24 - Global Analysis - The 2nd primary endpoint for Japan/PMDA regulatory purposes was change from baseline in mTSS at Week 24.
The mTSS measures the level of joint damage from radiographs of the hands and feet, assessed by 2 independent, blinded readers. mTSS is calculated as the sum of the total joint erosion score and total joint space narrowing (JSN) score.
Joint erosion was assessed in 16 joints in each hand/wrist and 6 joints in each foot. Each joint was scored from 0 (no erosion) to 5 for hands/wrists or to 10 for feet (complete collapse). The total erosion score ranges from 0 to 280 (worst).
JSN was assessed in 15 joints of each hand and wrist, and 6 joints of each foot, including subluxation, from 0 (normal) to 4 (complete loss of joint space, bony ankylosis, or luxation). The total JSN score ranges from 0 to 168 (worst).
The mTSS is the sum of the joint erosion and JSN scores and ranges from 0 (normal) to 448 (worst). A change from Baseline greater than 0 indicates progression.
Timepoint [4] 0 0
Baseline to Week 24
Secondary outcome [1] 0 0
Change From Baseline in DAS28 (CRP) at Week 12 - Global Analysis - The DAS28 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 hsCRP (in mg/L). Scores on the DAS28 range from 0 to approximately 10, where higher scores indicate more disease activity. A negative change from Baseline in DAS28 (CRP) indicates improvement in disease activity.
Timepoint [1] 0 0
Baseline to Week 12
Secondary outcome [2] 0 0
Change From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) at Week 12 - Global Analysis - 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.
Timepoint [2] 0 0
Baseline to week 12
Secondary outcome [3] 0 0
Percentage of Participants Achieving Low Disease Activity (LDA) Based on DAS28(CRP) at Week 12 - Global Analysis - 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 hsCRP (in mg/L). Scores on the DAS28 range from 0 to approximately 10, where higher scores indicate more disease activity.
A DAS28(CRP) score less than or equal to 3.2 indicates low disease activity.
Timepoint [3] 0 0
Week 12
Secondary outcome [4] 0 0
Change From Baseline in Short-Form 36 (SF-36) Physical Component Score (PCS) at Week 12 - Global Analysis - The Short Form 36-Item Health Survey (SF-36) Version 2 is a self-administered questionnaire that measures the impact of disease on overall quality of life during the past 4 weeks. The SF-36 consists of 36 questions in eight domains (physical function, pain, general and mental health, vitality, social function, physical and emotional health).
The physical component score is a weighted combination of the 8 subscales with positive weighting for physical functioning, role-physical, bodily pain, and general health. The PCS was calculated using norm-based scoring so that 50 is the average score and the standard deviation equals 10. Higher scores are associated with better functioning/quality of life; a positive change from baseline score indicates an improvement.
Timepoint [4] 0 0
Baseline to week 12
Secondary outcome [5] 0 0
Change From Baseline in DAS28 (CRP) at Week 24 - Global Analysis - The DAS28 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 hsCRP (in mg/L). Scores on the DAS28 range from 0 to approximately 10, where higher scores indicate more disease activity. A negative change from Baseline in DAS28 (CRP) indicates improvement in disease activity.
Timepoint [5] 0 0
Baseline to Week 24
Secondary outcome [6] 0 0
Change From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) at Week 24 - Global Analysis - 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.
Timepoint [6] 0 0
Baseline to Week 24
Secondary outcome [7] 0 0
Percentage of Participants With an ACR50 Response at Week 24 - Global Analysis - Participants who met the following 3 conditions for improvement from baseline were classified as meeting the ACR50 response criteria:
= 50% improvement in 68-tender joint count;
= 50% improvement in 66-swollen joint count; and
= 50% improvement in at least 3 of the 5 following parameters:
Physician global assessment of disease activity
Patient global assessment of disease activity
Patient assessment of pain
Health Assessment Questionnaire - Disability Index (HAQ-DI)
High-sensitivity C-reactive protein (hsCRP).
Timepoint [7] 0 0
Baseline and Week 24
Secondary outcome [8] 0 0
Percentage of Participants Achieving Low Disease Activity (LDA) Based on DAS28(CRP) at Week 24 - Global Analysis - 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 hsCRP (in mg/L). Scores on the DAS28 range from 0 to approximately 10, where higher scores indicate more disease activity.
A DAS28(CRP) score less than or equal to 3.2 indicates low disease activity.
Timepoint [8] 0 0
Week 24
Secondary outcome [9] 0 0
Change From Baseline in Short-Form 36 (SF-36) Physical Component Score (PCS) at Week 24 - Global Analysis - The Short Form 36-Item Health Survey (SF-36) Version 2 is a self-administered questionnaire that measures the impact of disease on overall quality of life during the past 4 weeks. The SF-36 consists of 36 questions in eight domains (physical function, pain, general and mental health, vitality, social function, physical and emotional health).
The physical component score is a weighted combination of the 8 subscales with positive weighting for physical functioning, role-physical, bodily pain, and general health. The PCS was calculated using norm-based scoring so that 50 is the average score and the standard deviation equals 10. Higher scores are associated with better functioning/quality of life; a positive change from baseline score indicates an improvement.
Timepoint [9] 0 0
Baseline to Week 24
Secondary outcome [10] 0 0
Percentage of Participants With No Radiographic Progression at Week 24 - Global Analysis - No radiographic progression is defined as a change from Baseline in mTSS = 0. The mTSS measures the level of joint damage from radiographs of the hands and feet, which were assessed by 2 independent, blinded readers. mTSS is calculated as the sum of the total joint erosion score and total joint space narrowing (JSN) score. Joint erosion severity was assessed in 16 joints in each hand and wrist and 6 joints in each foot. Each joint was scored from 0 (no erosion) to 5 for hands/wrists or to 10 for feet (complete collapse). The total erosion score ranges from 0 to 280 (worst).
Joint space narrowing (JSN) was assessed in 15 joints of each hand and wrist, and 6 joints of each foot, including subluxation, from 0 (normal) to 4 (complete loss of joint space, bony ankylosis, or luxation). The total JSN score ranges from 0 to 168 (worst).
The mTSS is the sum of the joint erosion and JSN scores and ranges from 0 (normal) to 448 (worst).
Timepoint [10] 0 0
Week 24
Secondary outcome [11] 0 0
Percentage of Participants With an American College of Rheumatology 70% (ACR70) Response at Week 12 - Global Analysis - Participants who met the following 3 conditions for improvement from baseline were classified as meeting the ACR70 response criteria:
= 70% improvement in 68-tender joint count;
= 70% improvement in 66-swollen joint count; and
= 70% improvement in at least 3 of the 5 following parameters:
Physician global assessment of disease activity
Patient global assessment of disease activity
Patient assessment of pain
Health Assessment Questionnaire - Disability Index (HAQ-DI)
High-sensitivity C-reactive protein (hsCRP).
Timepoint [11] 0 0
Baseline and Week 12
Secondary outcome [12] 0 0
Percentage of Participants With an ACR20 Response at Week 24 - Global Analysis - Participants who met the following 3 conditions for improvement from baseline were classified as meeting the ACR20 response criteria:
= 20% improvement in 68-tender joint count;
= 20% improvement in 66-swollen joint count; and
= 20% improvement in at least 3 of the 5 following parameters:
Physician global assessment of disease activity
Patient global assessment of disease activity
Patient assessment of pain
Health Assessment Questionnaire - Disability Index (HAQ-DI)
High-sensitivity C-reactive protein (hsCRP).
Timepoint [12] 0 0
Baseline and Week 24
Secondary outcome [13] 0 0
Percentage of Participants With an ACR70 Response at Week 24 - Global Analysis - Participants who met the following 3 conditions for improvement from baseline were classified as meeting the ACR70 response criteria:
= 70% improvement in 68-tender joint count;
= 70% improvement in 66-swollen joint count; and
= 70% improvement in at least 3 of the 5 following parameters:
Physician global assessment of disease activity
Patient global assessment of disease activity
Patient assessment of pain
Health Assessment Questionnaire - Disability Index (HAQ-DI)
High-sensitivity C-reactive protein (hsCRP).
Timepoint [13] 0 0
Baseline and Week 24
Secondary outcome [14] 0 0
Percentage of Participants With an ACR20 Response at Week 12 - Japan Sub-study - Participants who met the following 3 conditions for improvement from baseline were classified as meeting the ACR20 response criteria:
= 20% improvement in 68-tender joint count;
= 20% improvement in 66-swollen joint count; and
= 20% improvement in at least 3 of the 5 following parameters:
Physician global assessment of disease activity
Patient global assessment of disease activity
Patient assessment of pain
Health Assessment Questionnaire - Disability Index (HAQ-DI)
High-sensitivity C-reactive protein (hsCRP).
Timepoint [14] 0 0
Baseline and Week 12
Secondary outcome [15] 0 0
Percentage of Participants With an ACR50 Response at Week 12 - Japan Sub-study - Participants who met the following 3 conditions for improvement from baseline were classified as meeting the ACR50 response criteria:
= 50% improvement in 68-tender joint count;
= 50% improvement in 66-swollen joint count; and
= 50% improvement in at least 3 of the 5 following parameters:
Physician global assessment of disease activity
Patient global assessment of disease activity
Patient assessment of pain
Health Assessment Questionnaire - Disability Index (HAQ-DI)
High-sensitivity C-reactive protein (hsCRP).
Timepoint [15] 0 0
Baseline and Week 12
Secondary outcome [16] 0 0
Percentage of Participants With an ACR70 Response at Week 12 - Japan Sub-study - Participants who met the following 3 conditions for improvement from baseline were classified as meeting the ACR70 response criteria:
= 70% improvement in 68-tender joint count;
= 70% improvement in 66-swollen joint count; and
= 70% improvement in at least 3 of the 5 following parameters:
Physician global assessment of disease activity
Patient global assessment of disease activity
Patient assessment of pain
Health Assessment Questionnaire - Disability Index (HAQ-DI)
High-sensitivity C-reactive protein (hsCRP).
Timepoint [16] 0 0
Baseline and Week 12
Secondary outcome [17] 0 0
Change From Baseline in DAS28 (CRP) at Week 12 - Japan Sub-study - The DAS28 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 hsCRP (in mg/L). Scores on the DAS28 range from 0 to approximately 10, where higher scores indicate more disease activity. A negative change from Baseline in DAS28 (CRP) indicates improvement in disease activity.
Timepoint [17] 0 0
Baseline to Week 12
Secondary outcome [18] 0 0
Change From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) at Week 12 - Japan Sub-study - 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.
Timepoint [18] 0 0
Baseline to week 12
Secondary outcome [19] 0 0
Change From Baseline in Short-Form 36 (SF-36) Physical Component Score (PCS) at Week 12 - Japan Sub-study - The Short Form 36-Item Health Survey (SF-36) Version 2 is a self-administered questionnaire that measures the impact of disease on overall quality of life during the past 4 weeks. The SF-36 consists of 36 questions in eight domains (physical function, pain, general and mental health, vitality, social function, physical and emotional health).
The physical component score is a weighted combination of the 8 subscales with positive weighting for physical functioning, role-physical, bodily pain, and general health. The PCS was calculated using norm-based scoring so that 50 is the average score and the standard deviation equals 10. Higher scores are associated with better functioning/quality of life; a positive change from baseline score indicates an improvement.
Timepoint [19] 0 0
Baseline to Week 12
Secondary outcome [20] 0 0
Percentage of Participants Achieving Low Disease Activity (LDA) Based on DAS28(CRP) at Week 12 - Japan Sub-study - 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 hsCRP (in mg/L). Scores on the DAS28 range from 0 to approximately 10, where higher scores indicate more disease activity.
A DAS28(CRP) score less than or equal to 3.2 indicates low disease activity.
Timepoint [20] 0 0
Week 12
Secondary outcome [21] 0 0
Percentage of Participants Achieving Clinical Remission (CR) Based on DAS28(CRP) at Week 24 - Japan Sub-study - 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 hsCRP (in mg/L). Scores on the DAS28 range from 0 to approximately 10, where higher scores indicate more disease activity.
A DAS28 score less than 2.6 indicates clinical remission.
Timepoint [21] 0 0
Week 24
Secondary outcome [22] 0 0
Change From Baseline in Modified Total Sharp Score (mTSS) at Week 24 - Japan Sub-study - The mTSS measures the level of joint damage from radiographs of the hands and feet, assessed by 2 independent, blinded readers. mTSS is calculated as the sum of the total joint erosion score and total joint space narrowing (JSN) score.
Joint erosion was assessed in 16 joints in each hand/wrist and 6 joints in each foot. Each joint was scored from 0 (no erosion) to 5 for hands/wrists or to 10 for feet (complete collapse). The total erosion score ranges from 0 to 280 (worst).
JSN was assessed in 15 joints of each hand and wrist, and 6 joints of each foot, including subluxation, from 0 (normal) to 4 (complete loss of joint space, bony ankylosis, or luxation). The total JSN score ranges from 0 to 168 (worst).
The mTSS is the sum of the joint erosion and JSN scores and ranges from 0 (normal) to 448 (worst). A change from Baseline greater than 0 indicates progression.
Timepoint [22] 0 0
Baseline to Week 24
Secondary outcome [23] 0 0
Percentage of Participants With No Radiographic Progression at Week 24 - Japan Sub-study - No radiographic progression is defined as a change from Baseline in mTSS = 0. The mTSS measures the level of joint damage from radiographs of the hands and feet, which were assessed by 2 independent, blinded readers. mTSS is calculated as the sum of the total joint erosion score and total joint space narrowing (JSN) score. Joint erosion severity was assessed in 16 joints in each hand and wrist and 6 joints in each foot. Each joint was scored from 0 (no erosion) to 5 for hands/wrists or to 10 for feet (complete collapse). The total erosion score ranges from 0 to 280 (worst).
Joint space narrowing (JSN) was assessed in 15 joints of each hand and wrist, and 6 joints of each foot, including subluxation, from 0 (normal) to 4 (complete loss of joint space, bony ankylosis, or luxation). The total JSN score ranges from 0 to 168 (worst).
The mTSS is the sum of the joint erosion and JSN scores and ranges from 0 (normal) to 448 (worst).
Timepoint [23] 0 0
Week 24

Eligibility
Key inclusion criteria
- Duration of symptoms consistent with RA for = 6 weeks who also fulfill the 2010
American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR)
classification criteria for RA.

- Naïve to Methotrexate (MTX) or, if already on MTX, have received no more than 3 weekly
MTX doses with requirement to complete a 4-week MTX washout before the first dose of
study drug.

- Participants with prior exposure to conventional synthetic disease-modifying
anti-rheumatic drugs(csDMARDs) other than MTX may be enrolled if completed the washout
period.

- Participant meets both of 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) = 5 mg/L (central lab, upper limit of
normal [ULN] 2.87 mg/L at Screening Visit.

- Greater than or equal to 1 bone erosion on x-ray (by local reading) OR in the absence
of documented bone erosion, both positive rheumatoid factor (RF) and positive
anti-cyclic citrullinated peptide (anti CCP) autoantibodies are required at Screening.

- Stable dose of non-steroidal anti-inflammatory drugs (NSAIDs), acetaminophen, oral
corticosteroids (equivalent to prednisone = 10 mg/day), or inhaled corticosteroids for
stable medical conditions are allowed but must have been at a stable dose = 1 week
prior to the first dose of study drug.
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Intolerant to Methotrexate (MTX).

- Prior exposure to any Janus kinase (JAK) inhibitor (including but not limited to
tofacitinib, baricitinib, and filgotinib).

- Prior exposure to any biologic disease-modifying anti-rheumatic drugs (bDMARDs).

- History of any arthritis with onset prior to age 17 years or current diagnosis,
inflammatory joint disease other than RA (including but not limited to gout, systemic
lupus erythematosus, psoriatic arthritis, axial spondyloarthritis including ankylosing
spondylitis and non-radiographic axial spondyloarthritis, reactive arthritis, overlap
connective tissue diseases, scleroderma, polymyositis, dermatomyositis, fibromyalgia
[currently with active symptoms]. Current diagnosis of secondary Sjogren's Syndrome is
permitted.

- Has been treated with intra-articular, intramuscular, intravenous, trigger point or
tender point, intra-bursa, or intra-tendon sheath corticosteroids in the preceding 8
weeks prior to the first dose of study drug.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,TAS,VIC
Recruitment hospital [1] 0 0
Royal Prince Alfred Hospital /ID# 143149 - Camperdown
Recruitment hospital [2] 0 0
Rheumatology Research Unit /ID# 143147 - Maroochydore
Recruitment hospital [3] 0 0
The Queen Elizabeth Hospital /ID# 143148 - Woodville
Recruitment hospital [4] 0 0
Southern Clinical Research Pty /ID# 143150 - Hobart
Recruitment hospital [5] 0 0
Emeritus Research /ID# 143146 - Camberwell
Recruitment postcode(s) [1] 0 0
2050 - Camperdown
Recruitment postcode(s) [2] 0 0
4558 - Maroochydore
Recruitment postcode(s) [3] 0 0
5011 - Woodville
Recruitment postcode(s) [4] 0 0
7000 - Hobart
Recruitment postcode(s) [5] 0 0
3124 - Camberwell
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Florida
Country [3] 0 0
United States of America
State/province [3] 0 0
Illinois
Country [4] 0 0
United States of America
State/province [4] 0 0
Kentucky
Country [5] 0 0
United States of America
State/province [5] 0 0
New Jersey
Country [6] 0 0
United States of America
State/province [6] 0 0
North Dakota
Country [7] 0 0
United States of America
State/province [7] 0 0
Ohio
Country [8] 0 0
United States of America
State/province [8] 0 0
Oklahoma
Country [9] 0 0
United States of America
State/province [9] 0 0
Pennsylvania
Country [10] 0 0
United States of America
State/province [10] 0 0
South Carolina
Country [11] 0 0
United States of America
State/province [11] 0 0
Tennessee
Country [12] 0 0
United States of America
State/province [12] 0 0
Texas
Country [13] 0 0
United States of America
State/province [13] 0 0
Virginia
Country [14] 0 0
Argentina
State/province [14] 0 0
Buenos Aires
Country [15] 0 0
Argentina
State/province [15] 0 0
Santa FE
Country [16] 0 0
Argentina
State/province [16] 0 0
Cordoba
Country [17] 0 0
Argentina
State/province [17] 0 0
San Miguel de Tucuman
Country [18] 0 0
Belarus
State/province [18] 0 0
Minsk
Country [19] 0 0
Belgium
State/province [19] 0 0
Hainaut
Country [20] 0 0
Belgium
State/province [20] 0 0
Oost-Vlaanderen
Country [21] 0 0
Belgium
State/province [21] 0 0
Genk
Country [22] 0 0
Belgium
State/province [22] 0 0
Mons
Country [23] 0 0
Bosnia and Herzegovina
State/province [23] 0 0
Republika Srpska
Country [24] 0 0
Bosnia and Herzegovina
State/province [24] 0 0
Sarajevo
Country [25] 0 0
Brazil
State/province [25] 0 0
Goias
Country [26] 0 0
Brazil
State/province [26] 0 0
Parana
Country [27] 0 0
Brazil
State/province [27] 0 0
Rio Grande Do Sul
Country [28] 0 0
Brazil
State/province [28] 0 0
Sao Paulo
Country [29] 0 0
Brazil
State/province [29] 0 0
Rio de Janeiro
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Japan
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Southampton

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
AbbVie
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
The objectives of Period 1 were the following:

To compare the safety and efficacy of upadacitinib 7.5 mg once daily (QD) monotherapy (for
participants in Japan only), 15 mg QD monotherapy, and 30 mg QD monotherapy versus weekly
methotrexate monotherapy for the treatment of signs and symptoms of RA in methotrexate-naïve
adults with moderately to severely active RA; To compare the efficacy of upadacitinib 15 mg
QD monotherapy and upadacitinib 30 mg QD monotherapy versus weekly methotrexate monotherapy
for prevention of structural progression in methotrexate-naïve adults with moderately to
severely active RA.

The objective of Period 2 is to evaluate the long-term safety, tolerability, and efficacy of
upadacitinib 7.5 mg QD (for participants in Japan only), 15 mg QD, and 30 mg QD in adults
with RA who have completed Period 1.
Trial website
https://clinicaltrials.gov/show/NCT02706873
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
AbbVie Inc.
Address 0 0
AbbVie
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
Other publications