A Study Comparing Upadacitinib (ABT-494) to Placebo and to Adalimumab in Adults With Rheumatoid Arthritis Who Are on a Stable Dose of Methotrexate and Who Have an Inadequate Response to Methotrexate (SELECT-COMPARE)

• ClinicalTrials.gov Identifier: NCT02629159
• Recruitment Status: Active, not recruiting
• First Posted: December 14, 2015
• Results First Posted: October 7, 2019
• Last Update Posted: April 24, 2023
• Sponsor: AbbVie
• Information provided by (Responsible Party): AbbVie

Tracking Information

• First Submitted Date: December 10, 2015
• First Posted Date: December 14, 2015
• Results First Submitted Date: September 13, 2019
• Results First Posted Date: October 7, 2019
• Last Update Posted Date: April 24, 2023
• Actual Study Start Date: December 1, 2015
• Actual Primary Completion Date: October 27, 2017 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: September 13, 2019)

• Percentage of Participants With an American College of Rheumatology 20% (ACR20) Response at Week 12 [ Time Frame: Baseline and Week 12 ]
  The primary endpoint for United States (US)/Food and Drug Administration (FDA) 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:

  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:
     • 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).
• Percentage of Participants Achieving Clinical Remission (CR) Based on DAS28(CRP) at Week 12 [ Time Frame: Week 12 ]
  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 12. 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.

Original Primary Outcome Measures (submitted: December 10, 2015)

• Proportion of participants achieving American College of Rheumatology (ACR) 20 Response [ Time Frame: At week 12 ]
  American College of Rheumatology (ACR) 20 response rate will be determined based on 20% or greater improvement in Tender Joint Count (TJC) and Swollen Joint Count (SJC) and greater than or equal to 3 of the 5 measures of Patient's Assessment of Pain (Visual Analog Scale [VAS]), Patient's Global Assessment of Disease Activity (VAS), Physician's Global Assessment of Disease Activity (VAS), Health Assessment Questionnaire Disability Index (HAQ-DI), or High Sensitivity - C Reactive Protein (hsCRP).
• Proportion of participants achieving Low Disease Activity (LDA) [ Time Frame: At Week 12 ]
  LDA is defined as Disease Activity Score (DAS)28 (C reactive protein [CRP]) less than or equal to 3.2. DAS28 (CRP) score will be determined based on a continuous scale of combined measures of TJC, SJC, Patient's Global Assessment of Disease Activity (PtGA) (in mm), and hsCRP (in mg/L) at Week 12.

Current Secondary Outcome Measures (submitted: September 13, 2019)

• Change From Baseline in DAS28 (CRP) at Week 12 [ Time Frame: Baseline and Week 12 ]
  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.
• Change From Baseline in Modified Total Sharp Score (mTSS) at Week 26 [ Time Frame: Baseline and Week 26 ]
  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 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). 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 negative change from Baseline in mTSS indicates improvement in joint damage whereas a change from Baseline greater than 0 indicates progression.
• Change From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) at Week 12 [ Time Frame: Baseline 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.
• Percentage of Participants With an American College of Rheumatology 50% (ACR50) Response at Week 12 [ Time Frame: Baseline and Week 12 ]
  Participants who met the following 3 conditions for improvement from baseline were classified as meeting the ACR50 response 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:
     • 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).
• Change From Baseline in Short-Form 36 (SF-36) Physical Component Score (PCS) at Week 12 [ Time Frame: Baseline and Week 12 ]
  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.
• Percentage of Participants Achieving Low Disease Activity (LDA) Based on DAS28(CRP) at Week 12 [ Time Frame: 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 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.
• Percentage of Participants Achieving Low Disease Activity Based on CDAI at Week 12 [ Time Frame: Week 12 ]
  Low disease activity based on the clinical disease activity index (CDAI) is defined as a CDAI score ≤ 10. 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.
• Change From Baseline in Duration of Morning Stiffness at Week 12 [ Time Frame: Baseline and Week 12 ]
  Participants were asked to indicate the time it took for them to get as limber as possible after awakening with morning stiffness over the past 7 days. A negative change from Baseline indicates improvement.
• Change From Baseline in in Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) [ Time Frame: Baseline and Week 12 ]
  The FACIT Fatigue scale is a 13-item tool that measures an individual's level of fatigue during their usual daily activities over the past 7 days. Each of the fatigue and impact of fatigue items are measured on a four point Likert scale. The FACIT Fatigue Scale is the sum of the individual 13 scores and ranges from 0 to 52 where higher scores indicate better the quality of life. A positive change from Baseline indicates improvement.
• Change From Baseline in Patient's Assessment of Pain at Week 12 [ Time Frame: Baseline and Week 12 ]
  Participants were asked to indicate the severity of their arthritis pain within the previous week on a visual analog scale (VAS) from 0 to 100. A score of 0 indicates "no pain" and a score of 100 indicates "worst possible pain." A negative change from Baseline indicates improvement.
• Percentage of Participants With No Radiographic Progression at Week 26 [ Time Frame: Baseline and Week 26 ]
  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 and ranges from 0 (normal) to 448 (worst). 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).
• Percentage of Participants With an American College of Rheumatology 70% (ACR70) Response at Week 12 [ Time Frame: Baseline and Week 12 ]
  Participants who met the following 3 conditions for improvement from baseline were classified as meeting the ACR70 response 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:
     • 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).

Original Secondary Outcome Measures (submitted: December 10, 2015)

• Change in Disease Activity Score (DAS) 28. [ Time Frame: From Day 1 to Week 12 ]
  DAS28(CRP) score will be determined based on a continuous scale of combined measures of TJC, SJC, Patient's Global Assessment of Disease Activity (PtGA) (in mm), and hsCRP (in mg/L)
• Change in mean modified Total Sharp Score (mTSS) [ Time Frame: From Day 1 to Week 24 ]
  For mTSS, x-rays of hand/wrist and feet joints are scored for erosions (0 to 5) and joint space narrowing (0 to 4). The erosion score and the narrowing score are added to determine the total score, which ranges from 0 (no damage) to 448.
• Change in Health Assessment Questionnaire (HAQ-DI) [ Time Frame: From Day 1 to Week 12 ]
  HAQ-DI is a participant questionnaire with questions regarding the participant's illness and how it affect their daily life activities.
• Proportion of participants achieving American College of Rheumatology (ACR) 50 [ Time Frame: At week 12 ]
  ACR 50 response rate will be determined based on 50% or greater improvement in TJC and SJC and greater than or equal to 3 of the 5 measures of Patient's Assessment of Pain (VAS), Patient's Global Assessment of Disease Activity (VAS), Physician's Global Assessment of Disease Activity (VAS), HAQ-DI, or hsCRP
• Proportion of participants achieving American College of Rheumatology (ACR) 70 [ Time Frame: At Week 12 ]
  ACR 70 response rate will be determined based on 70% or greater improvement in TJC and SJC and greater than or equal to 3 of the 5 measures of Patient's Assessment of Pain (VAS), Patient's Global Assessment of Disease Activity (VAS), Physician's Global Assessment of Disease Activity (VAS), HAQ-DI, or hsCRP
• Proportion of participants achieving American College of Rheumatology (ACR) 50 response at Week 24 (non-inferiority of ABT-494 vs ADA) [ Time Frame: At Week 24 ]
  ACR 50 response rate will be determined based on 50% or greater improvement in TJC and SJC and greater than or equal to 3 of the 5 measures of Patient's Assessment of Pain (VAS), Patient's Global Assessment of Disease Activity (VAS), Physician's Global Assessment of Disease Activity (VAS), HAQ-DI, or hsCRP
• Change in Short Form 36 (SF-36) Physical Component Score (PCS) [ Time Frame: From Day 1 to Week 12 ]
  SF-36 is a 36 item participant questionnaire with questions regarding participant health and daily activities.
• Proportion of subjects achieving Clinical remission (CR) based on Disease Activity 28 (DAS28) C-Reactive Protein (CRP) [ Time Frame: At Week 12 ]
  CR based on DAS28 (CRP) response rate is defined as DAS28 (CRP) less than 2.6
• Change in Functional Assessment of Chronic Illness Therapy (FACIT-F) [ Time Frame: From Day 1 to Week 12 ]
  FACIT-F is participant questionnaire with 13 indexes rated on a 5 point scale. The indexes generally relate to the participant's level of fatigue during the past 7 days.
• Change in Work Instability Score for Rheumatoid Arthritis (RA-WIS) [ Time Frame: From Day 1 to Week 12 ]
  RA-WIS is a participant questionnaire containing 23 questions relating to the participant's functioning in their work environment.
• Change in Morning Stiffness severity [ Time Frame: From Day 1 to Week 12 ]
  Morning Stiffness severity is determined by the Patient's Assessment of Severity and Duration of Morning Stiffness questionnaire. The severity score is based on a single 0 to 10 rating scale with 0 indicating "No morning stiffness" and 10 indicating "Worst possible morning stiffness".

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Study Comparing Upadacitinib (ABT-494) to Placebo and to Adalimumab in Adults With Rheumatoid Arthritis Who Are on a Stable Dose of Methotrexate and Who Have an Inadequate Response to Methotrexate
• Official Title: A Phase 3, Randomized, Double-Blind Study Comparing Upadacitinib (ABT-494) to Placebo and to Adalimumab in Subjects With Moderately to Severely Active Rheumatoid Arthritis Who Are on a Stable Background of Methotrexate (MTX) and Who Have an Inadequate Response to MTX (MTX-IR)
• Brief Summary: The purpose of this study was to assess efficacy, including inhibition of radiographic progression, and safety with upadacitinib versus placebo and versus an active comparator, adalimumab, in adults with with moderately to severely active rheumatoid arthritis (RA) who are on a stable background of methotrexate (MTX and who have an inadequate response to MTX.

Detailed Description

This study consists of a 48-week double-blind treatment period (Period 1) and a long-term extension period (Period 2).

Period 1 is a 48-week randomized, double-blind, parallel-group, placebo-controlled and active comparator-controlled period designed to compare the safety and efficacy of upadacitinib versus placebo, and versus adalimumab. Participants will be randomized in a 2:2:1 ratio to one of three treatment groups:

• Placebo (up to Week 26)
• Upadacitinib 15 mg once daily (QD)
• Adalimumab 40 mg every other week (eow)

Participants randomized to placebo who do not achieve a ≥ 20% improvement in tender joint count (TJC) and swollen joint count (SJC) at Weeks 14, 18, or 22 compared to Baseline will be switched to blinded upadacitinib treatment. At Week 26, all participants still receiving placebo will be switched to blinded upadacitinib treatment regardless of clinical response.

Participants randomized to adalimumab who do not achieve a ≥ 20% improvement in TJC and SJC at Weeks 14, 18, or 22 compared to Baseline will be switched to blinded upadacitinib. Participants still receiving adalimumab at Week 26 who do not achieve low disease activity (LDA) according to Clinical Disease Activity Index (CDAI; LDA is defined as CDAI ≤ 10) will be switched to blinded upadacitinib treatment to Week 48.

Participants randomized to upadacitinib who do not achieve a ≥ 20% improvement in TJC and SJC at Weeks 14, 18, or 22 compared to Baseline will be switched to blinded adalimumab; participants still receiving upadacitinib at Week 26 who do not achieve LDA (CDAI ≤ 10) will be switched to blinded adalimumab treatment to Week 48.

Participants who complete the Week 48 visit (end of Period 1) will enter the long-term extension phase of the study (Period 2), for up to 5 years. Participants will continue study treatment as assigned at the end of Period 1. Starting at the Week 48 and thereafter, at least 20% improvement in both TJC and SJC compared to Baseline is required to remain on study drug. Anyone who does not fulfill this criterion at 2 consecutive visits (starting at Week 48) will be discontinued.

• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Rheumatoid Arthritis

Intervention

• Drug: Placebo for Adalimumab
  Administered by subcutaneous injection once every other week
• Drug: Adalimumab
  Administered by subcutaneous injection once every other week
  Other Name: Humira
• Drug: Placebo for Upadacitinib
  Tablets taken orally once a day
• Drug: Upadacitinib
  Tablets taken orally once a day
  Other Name: ABT-494

Study Arms

• Placebo Comparator: Placebo followed by ABT-494

  Participants were to receive placebo to upadacitinib orally once daily (QD) and placebo to adalimumab by subcutaneous injection once every two weeks (eow) for up to 26 weeks. Participants who did not achieve a ≥ 20% improvement in tender joint count (TJC) and swollen joint count (SJC) at Weeks 14, 18, or 22 compared to Baseline were to be switched to 15 mg upadacitinib orally QD. At Week 26, all remaining participants were to be switched to 15 mg upadacitinib QD until Week 48 (end of Period 1).

  Participants who complete Period 1 will continue to receive 15 mg upadacitinib orally QD for up to 5 years in Period 2.

  Interventions:

  • Drug: Placebo for Adalimumab
  • Drug: Placebo for Upadacitinib
  • Drug: Upadacitinib
• Active Comparator: Adalimumab

  Participants were to receive placebo to upadacitinib orally QD and 40 mg adalimumab by subcutaneous injection eow for up to 48 weeks in Period 1. Participants who did not achieve a ≥ 20% improvement in TJC and SJC at Weeks 14, 18, or 22 compared to Baseline were to be switched to 15 mg upadacitinib orally QD. At Week 26 remaining participants who did not achieve low disease activity (defined as Clinical Disease Activity Index [CDAI] ≤ 10) were to be switched to 15 mg upadacitinib orally QD until Week 48.

  Participants who complete Period 1 will continue to receive the same treatment assigned at the end of Period 1 (15 mg upadacitinib QD or 40 mg adalimumab eow) for up to 5 years in Period 2.

  Interventions:

  • Drug: Adalimumab
  • Drug: Placebo for Upadacitinib
  • Drug: Upadacitinib
• Experimental: Upadacitinib

  Participants were to receive 15 mg upadacitinib orally QD and placebo to adalimumab by subcutaneous injection eow for up to 48 weeks in Period 1. Participants who did not achieve a ≥ 20% improvement in TJC and SJC at Weeks 14, 18, or 22 compared to Baseline were to be switched to 40 mg adalimumab eow. At Week 26 remaining participants who did not achieve low disease activity (defined as CDAI ≤ 10) were to be switched to 40 mg adalimumab eow until Week 48.

  Participants who complete Period 1 will continue to receive the same treatment assigned at the end of Period 1 (15 mg upadacitinib QD or 40 mg adalimumab eow) for up to 5 years in Period 2.

  Interventions:

  • Drug: Placebo for Adalimumab
  • Drug: Adalimumab
  • Drug: Upadacitinib

Publications *

• Fleischmann R, Pangan AL, Song IH, Mysler E, Bessette L, Peterfy C, Durez P, Ostor AJ, Li Y, Zhou Y, Othman AA, Genovese MC. Upadacitinib Versus Placebo or Adalimumab in Patients With Rheumatoid Arthritis and an Inadequate Response to Methotrexate: Results of a Phase III, Double-Blind, Randomized Controlled Trial. Arthritis Rheumatol. 2019 Nov;71(11):1788-1800. doi: 10.1002/art.41032. Epub 2019 Aug 28.
• Bergman M, Buch MH, Tanaka Y, Citera G, Bahlas S, Wong E, Song Y, Zueger P, Ali M, Strand V. Routine Assessment of Patient Index Data 3 (RAPID3) in Patients with Rheumatoid Arthritis Treated with Long-Term Upadacitinib Therapy in Five Randomized Controlled Trials. Rheumatol Ther. 2022 Dec;9(6):1517-1529. doi: 10.1007/s40744-022-00483-4. Epub 2022 Sep 20.
• Mysler E, Tanaka Y, Kavanaugh A, Aletaha D, Taylor PC, Song IH, Shaw T, Song Y, DeMasi R, Ali M, Fleischmann R. Impact of initial therapy with upadacitinib or adalimumab on achievement of 48-week treatment goals in patients with rheumatoid arthritis: post hoc analysis of SELECT-COMPARE. Rheumatology (Oxford). 2023 May 2;62(5):1804-1813. doi: 10.1093/rheumatology/keac477.
• Peterfy CG, Strand V, Friedman A, Hall S, Mysler E, Durez P, Baraliakos X, Enejosa JV, Shaw T, Li Y, Chen S, Song IH. Inhibition of structural joint damage progression with upadacitinib in rheumatoid arthritis: 1-year outcomes from the SELECT phase 3 program. Rheumatology (Oxford). 2022 Aug 3;61(8):3246-3256. doi: 10.1093/rheumatology/keab861.
• Yamaoka K, Tanaka Y, Kameda H, Khan N, Sasaki N, Harigai M, Song Y, Zhang Y, Takeuchi T. The Safety Profile of Upadacitinib in Patients with Rheumatoid Arthritis in Japan. Drug Saf. 2021 Jun;44(6):711-722. doi: 10.1007/s40264-021-01067-x. Epub 2021 May 27.
• Strand V, Tundia N, Bergman M, Ostor A, Durez P, Song IH, Enejosa J, Schlacher C, Song Y, Fleischmann R. Upadacitinib improves patient-reported outcomes vs placebo or adalimumab in patients with rheumatoid arthritis: results from SELECT-COMPARE. Rheumatology (Oxford). 2021 Dec 1;60(12):5583-5594. doi: 10.1093/rheumatology/keab158.
• Fleischmann RM, Blanco R, Hall S, Thomson GTD, Van den Bosch FE, Zerbini C, Bessette L, Enejosa J, Li Y, Song Y, DeMasi R, Song IH. Switching between Janus kinase inhibitor upadacitinib and adalimumab following insufficient response: efficacy and safety in patients with rheumatoid arthritis. Ann Rheum Dis. 2021 Apr;80(4):432-439. doi: 10.1136/annrheumdis-2020-218412. Epub 2020 Nov 4.
• Cohen SB, van Vollenhoven RF, Winthrop KL, Zerbini CAF, Tanaka Y, Bessette L, Zhang Y, Khan N, Hendrickson B, Enejosa JV, Burmester GR. Safety profile of upadacitinib in rheumatoid arthritis: integrated analysis from the SELECT phase III clinical programme. Ann Rheum Dis. 2021 Mar;80(3):304-311. doi: 10.1136/annrheumdis-2020-218510. Epub 2020 Oct 28. Erratum In: Ann Rheum Dis. 2021 May;80(5):e83.
• Nader A, Mohamed MF, Winzenborg I, Doelger E, Noertersheuser P, Pangan AL, Othman AA. Exposure-Response Analyses of Upadacitinib Efficacy and Safety in Phase II and III Studies to Support Benefit-Risk Assessment in Rheumatoid Arthritis. Clin Pharmacol Ther. 2020 Apr;107(4):994-1003. doi: 10.1002/cpt.1671. Epub 2019 Nov 30.
• Fleischmann RM, Genovese MC, Enejosa JV, Mysler E, Bessette L, Peterfy C, Durez P, Ostor A, Li Y, Song IH. Safety and effectiveness of upadacitinib or adalimumab plus methotrexate in patients with rheumatoid arthritis over 48 weeks with switch to alternate therapy in patients with insufficient response. Ann Rheum Dis. 2019 Nov;78(11):1454-1462. doi: 10.1136/annrheumdis-2019-215764. Epub 2019 Jul 30.

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: February 13, 2019): 1629
• Original Estimated Enrollment (submitted: December 10, 2015): 1500
• Estimated Study Completion Date: September 30, 2027
• Actual Primary Completion Date: October 27, 2017 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Adult male or female, at least 18 years old.
• Diagnosis of RA for greater than or equal to 3 months.
• Subjects must have been on oral or parenteral methotrexate (MTX) therapy greater than or equal to 3 months and on a stable prescription of greater than or equal to 15 to 25 mg/week (or greater than or equal to 10 mg/week in subjects intolerant of MTX at doses greater than or equal to 12.5 mg/week) for at least 4 weeks prior to the first dose of study drug. In addition all subjects should take a dietary supplement of folic acid or folinic acid throughout the study participation.
• Meets the following minimum disease activity criteria: greater than or equal to 6 swollen joints (based on 66 joint counts) and greater than or equal to 6 tender joints (based on 68 joint counts) at Screening and Baseline Visits.
• At least one of the following at Screening: greater than or equal to 3 bone erosions on x-ray OR greater than or equal to 1 bone erosion and a positive rheumatoid factor OR greater than or equal to 1 bone erosion and a positive anti-cyclic citrullinated peptide autoantibodies.
• Subjects with prior exposure to only one biological disease-modifying anti-rheumatic drugs (bDMARD) (except adalimumab) may be enrolled (up to 20% of total study population) if they have documented evidence of intolerance to the bDMARD or limited exposure (less than 3 months), but required washout periods need to be satisfied.
• Except for MTX, subject must have discontinued all conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs).

Exclusion Criteria:

• Prior exposure to any Janus kinase (JAK) inhibitor (including but not limited to tofacitinib, baricitinib, and filgotinib).
• Subjects who have been exposed to adalimumab or who are considered inadequate responders to bDMARD therapy as determined by the Investigator.
• History of inflammatory joint disease other than RA. History of secondary Sjogren's Syndrome is permitted.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Argentina, Australia, Austria, Belarus, Belgium, Bosnia and Herzegovina, Brazil, Bulgaria, Canada, Chile, Colombia, Croatia, Czechia, Denmark, Estonia, France, Germany, Greece, Hong Kong, Hungary, Ireland, Israel, Italy, Kazakhstan, Korea, Republic of, Latvia, Lithuania, Malaysia, Mexico, New Zealand, Poland, Portugal, Puerto Rico, Romania, Russian Federation, Serbia, Slovakia, South Africa, Spain, Taiwan, Turkey, Ukraine, United Kingdom, United States
• Removed Location Countries: Czech Republic, Finland, Netherlands

Administrative Information

• NCT Number: NCT02629159
• Other Study ID Numbers: M14-465; 2022-501017-31-00 ( Other Identifier: EU CT )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No

IPD Sharing Statement

• Plan to Share IPD: Yes
• Plan Description: AbbVie is committed to responsible data sharing regarding the clinical trials we sponsor. This includes access to anonymized, individual and trial-level data (analysis data sets), as well as other information (e.g., protocols, analyses plans, clinical study reports), as long as the trials are not part of an ongoing or planned regulatory submission. This includes requests for clinical trial data for unlicensed products and indications.
• Supporting Materials: Study Protocol
• Supporting Materials: Statistical Analysis Plan (SAP)
• Supporting Materials: Clinical Study Report (CSR)
• Supporting Materials: Analytic Code
• Time Frame: For details on when studies are available for sharing visit https://vivli.org/ourmember/abbvie/
• Access Criteria: Access to this clinical trial data can be requested by any qualified researchers who engage in rigorous independent scientific research, and will be provided following review and approval of a research proposal and statistical analysis plan and execution of a data sharing statement. Data requests can be submitted at any time after approval in the US and/or EU and a primary manuscript is accepted for publication. For more information on the process, or to submit a request, visit the following link https://www.abbvieclinicaltrials.com/hcp/data-sharing/
• URL: https://vivli.org/ourmember/abbvie/

• Current Responsible Party: AbbVie
• Original Responsible Party: Same as current
• Current Study Sponsor: AbbVie
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: AbbVie Inc.; AbbVie

• PRS Account: AbbVie
• Verification Date: April 2023