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A Study Comparing Upadacitinib (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 : July 25, 2018
Sponsor:
Information provided by (Responsible Party):
AbbVie

Brief Summary:
This is 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.

Condition or disease Intervention/treatment Phase
Rheumatoid Arthritis Drug: Placebo for Adalimumab Drug: ABT-494 Drug: Adalimumab Drug: Placebo for ABT-494 Phase 3

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 1630 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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)
Actual Study Start Date : December 1, 2015
Actual Primary Completion Date : October 27, 2017
Estimated Study Completion Date : August 10, 2020

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
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).
Drug: Placebo for Adalimumab
Placebo subcutaneous Injection

Drug: ABT-494
ABT-494 Oral Tablet
Other Name: Upadacitinib

Drug: Placebo for ABT-494
Placebo Oral Tablet

Active Comparator: Adalimumab (ADA)
Subcutaneous injection once every two weeks
Drug: Adalimumab
Adalimumab subcutaneous injection

Experimental: ABT-494
Once daily
Drug: ABT-494
ABT-494 Oral Tablet
Other Name: Upadacitinib




Primary Outcome Measures :
  1. 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).

  2. 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


Secondary Outcome Measures :
  1. 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.

  2. 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.

  3. 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.

  4. 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".

  5. 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)

  6. 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.

  7. 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.

  8. 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.

  9. 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

  10. 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

  11. 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.

  12. 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.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02629159


  Show 369 Study Locations
Sponsors and Collaborators
AbbVie
Investigators
Study Director: AbbVie Inc. AbbVie

Responsible Party: AbbVie
ClinicalTrials.gov Identifier: NCT02629159     History of Changes
Other Study ID Numbers: M14-465
2015-003333-95 ( EudraCT Number )
First Posted: December 14, 2015    Key Record Dates
Last Update Posted: July 25, 2018
Last Verified: July 2018
Individual Participant Data (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 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
Statistical Analysis Plan (SAP)
Clinical Study Report (CSR)
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

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

Keywords provided by AbbVie:
Musculoskeletal disease
Arthritis
Joint disease
Anti-inflammatory agents
Antirheumatic agents

Additional relevant MeSH terms:
Arthritis
Arthritis, Rheumatoid
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases
Methotrexate
Adalimumab
Abortifacient Agents, Nonsteroidal
Abortifacient Agents
Reproductive Control Agents
Physiological Effects of Drugs
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Dermatologic Agents
Enzyme Inhibitors
Folic Acid Antagonists
Immunosuppressive Agents
Immunologic Factors
Antirheumatic Agents
Nucleic Acid Synthesis Inhibitors
Anti-Inflammatory Agents