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

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ClinicalTrials.gov Identifier: NCT02629159
Recruitment Status : Active, not recruiting
First Posted : December 14, 2015
Last Update Posted : February 15, 2019
Sponsor:
Information provided by (Responsible Party):
AbbVie

Tracking Information
First Submitted Date  ICMJE December 10, 2015
First Posted Date  ICMJE December 14, 2015
Last Update Posted Date February 15, 2019
Actual Study Start Date  ICMJE December 1, 2015
Actual Primary Completion Date October 27, 2017   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 7, 2016)
  • 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 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
Original Primary Outcome Measures  ICMJE
 (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.
Change History Complete list of historical versions of study NCT02629159 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: February 21, 2018)
  • 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 subjects achieving Low Disease Activity (LDA) based on Clinical Disease Activity Index (CDAI) [ Time Frame: At week 12 ]
    Proportion of participants achieving low disease activity as defined by Clinical Disease Activity Index (CDAI) is assessed.
  • Proportion of subjects with no radiographic progression [ Time Frame: At week 26 ]
    Radiographic progression is defined as a change from baseline Modified Total Sharp Score (mTSS) that is greater than 0.
  • 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".
  • Change in Disease Activity Score (DAS) 28 (CRP). [ 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 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.
  • 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 modified Total Sharp Score (mTSS) [ Time Frame: From Day 1 to Week 26 ]
    For mTSS, the erosion score and the narrowing score are added to determine the total score, which ranges from 0 (no damage) to 448.
  • 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 subjects achieving Low Disease Activity (LDA) based on Disease Activity 28 (DAS28) C-Reactive Protein (CRP) [ Time Frame: At week 12 ]
    Proportion of participants achieving low disease activity as defined by a clinical response (DAS28[CRP] less than or equal to 3.2). The DAS28 is a validated index of rheumatoid arthritis disease activity. Twenty-eight tender joint counts, 28 swollen joint counts, C-reactive protein, and general health are included in the DAS28 score. Scores on the DAS28 range from 0 to 10. A DAS28 score greater than 5.1 indicates high disease activity, a DAS28 score less than or equal to 3.2 indicates low disease activity, and a DAS28 score less than 2.6 indicates clinical remission.
  • Change from baseline in Patient's Assessment of Pain at Week 12 (superiority of upadacitinib vs.ADA) [ Time Frame: At Week 12 ]
    Change from baseline in Patient's Assessment of Pain is assessed.
Original Secondary Outcome Measures  ICMJE
 (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  ICMJE A Study Comparing ABT-494 to Placebo and to Adalimumab in Subjects With Rheumatoid Arthritis Who Are on a Stable Dose of Methotrexate and Who Have an Inadequate Response to Methotrexate
Official Title  ICMJE 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 This is a phase 3, randomized, double-blind study comparing 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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Rheumatoid Arthritis
Intervention  ICMJE
  • Drug: Placebo for Adalimumab
    Placebo subcutaneous Injection
  • Drug: ABT-494
    ABT-494 Oral Tablet
    Other Name: Upadacitinib
  • Drug: Adalimumab
    Adalimumab subcutaneous injection
  • Drug: Placebo for ABT-494
    Placebo Oral Tablet
Study Arms  ICMJE
  • Placebo Comparator: Placebo followed by ABT-494
    Placebo once every two weeks for subcutaneous injection and once daily for oral tablet for 26 weeks (Period 1) followed by ABT-494 once daily for up to 5 years (Period 2).
    Interventions:
    • Drug: Placebo for Adalimumab
    • Drug: ABT-494
    • Drug: Placebo for ABT-494
  • Active Comparator: Adalimumab (ADA)
    Subcutaneous injection once every two weeks
    Intervention: Drug: Adalimumab
  • Experimental: ABT-494
    Once daily
    Intervention: Drug: ABT-494
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: February 13, 2019)
1629
Original Estimated Enrollment  ICMJE
 (submitted: December 10, 2015)
1500
Estimated Study Completion Date  ICMJE May 20, 2022
Actual Primary Completion Date October 27, 2017   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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 greater than or equal to 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 ADA) 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  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE 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  ICMJE NCT02629159
Other Study ID Numbers  ICMJE M14-465
2015-003333-95 ( EudraCT Number )
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  ICMJE
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 and 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: Data requests can be submitted at any time and the data will be accessible for 12 months, with possible extensions considered.
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 (SAP) and execution of a Data Sharing Agreement (DSA). For more information on the process, or to submit a request, visit the following link.
URL: https://www.abbvie.com/our-science/clinical-trials/clinical-trials-data-and-information-sharing/data-and-information-sharing-with-qualified-researchers.html
Responsible Party AbbVie
Study Sponsor  ICMJE AbbVie
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: AbbVie Inc. AbbVie
PRS Account AbbVie
Verification Date February 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP