Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu

A Study Investigating the Efficacy and Safety of ABT-494 Given With Methotrexate (MTX) in Subjects With Rheumatoid Arthritis Who Have Had an Inadequate Response to MTX Alone

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT02066389
Recruitment Status : Completed
First Posted : February 19, 2014
Last Update Posted : June 16, 2016
Sponsor:
Information provided by (Responsible Party):
AbbVie

Brief Summary:
This is a randomized, double-blind, parallel-group, placebo controlled, multicenter study to assess the safety and efficacy of ABT-494 in subjects with active rheumatoid arthritis who have failed Methotrexate alone.

Condition or disease Intervention/treatment Phase
Rheumatoid Arthritis Drug: ABT-494 Drug: Placebo Phase 2

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 300 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Randomized, Double-Blind, Placebo-Controlled, Phase 2 Study to Investigate the Safety and Efficacy of ABT-494 With Background Methotrexate (MTX) in Subjects With Active Rheumatoid Arthritis (RA) Who Have Had an Inadequate Response to MTX Alone
Study Start Date : March 2014
Actual Primary Completion Date : June 2015
Actual Study Completion Date : June 2015

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Group 1
ABT-494 orally twice daily, low dose
Drug: ABT-494
Experimental: Group 2
ABT-494 orally twice daily, mid-low dose
Drug: ABT-494
Experimental: Group 3
ABT-494 orally twice daily, mid-high dose
Drug: ABT-494
Experimental: Group 4
ABT-494 orally twice daily, high dose
Drug: ABT-494
Experimental: Group 5
ABT-494 once daily
Drug: ABT-494
Placebo Comparator: Group 6
Placebo, twice daily
Drug: Placebo



Primary Outcome Measures :
  1. American College Rheumatology (ACR) 20 Response Rate [ Time Frame: Week 12 ]
    ACR 20 response rate will be determined based on 20% or greater improvement of Tender Joint Count and Swollen Joint Counts and greater than or equal to 3 of the 5 measures of Patient's Assessment of Pain , Patient's Assessment of Global Assessment of Disease Activity, Heath Assessment Questionnaire and Disability Index and High Sensitivity C-reactive Protein.


Secondary Outcome Measures :
  1. ACR 70 Response Rate [ Time Frame: Week 12 ]
    ACR 70 response rate will be determined based on 70% or greater improvement of Tender Joint Count and Swollen Joint Counts and greater than or equal to 3 of the 5 measures of Patient's Assessment of Pain , Patient's Assessment of Global Assessment of Disease Activity, Heath Assessment Questionnaire and Disability Index and High Sensitivity C-reactive Protein.

  2. Proportion of subjects achieving low disease activity (LDA) based on Disease Activity Score (DAS) 28[CRP] and CDAI criteria [ Time Frame: Week 12 ]

    LDA=DAS28[CRP] in the range of 2.6 to 3.2 and CDAI in the range of greater than 2.8 to 10.

    DAS28=Disease Activity Score. CRP=C-reactive protein. CDAI=Clinical Disease Activity Index. DAS28[CRP] is based on tender and swollen joints counts, high sensitivity C-reactive protein, and Patient's Global Assessment of Disease Activity. CDAI is based on tender and swollen joint counts, Patient's Global Assessment of Disease Activity, and the Physician's Assessment of Disease Activity.


  3. Proportion of subjects achieving clinical remission (CR) based on DAS28[CRP] and CDAI criteria [ Time Frame: Week 12 ]
    CR=DAS28[CRP] less than 2.6 and CDAI less than or equal to 2.8. DAS28=Disease Activity Score. CRP=C-reactive protein. CDAI=Clinical Disease Activity Index. DAS28[CRP] is based on tender and swollen joints counts, high sensitivity C-reactive protein, and Patient's Global Assessment of Disease Activity. CDAI is based on tender and swollen joint counts, Patient's Global Assessment of Disease Activity, and the Physician's Assessment of Disease Activity.

  4. ACR 50 Response Rate [ Time Frame: Week 12 ]
    ACR 50 response rate will be determined based on 50% or greater improvement of Tender Joint Count and Swollen Joint Counts and greater than or equal to 3 of the 5 measures of Patient's Assessment of Pain , Patient's Assessment of Global Assessment of Disease Activity, Heath Assessment Questionnaire and Disability Index and High Sensitivity C-reactive Protein.


Other Outcome Measures:
  1. ACR 20 Response Rate [ Time Frame: Week 8 ]
    ACR 20 response rate will be determined based on 20% or greater improvement of Tender Joint Count and Swollen Joint Counts and greater than or equal to 3 of the 5 measures of Patient's Assessment of Pain , Patient's Assessment of Global Assessment of Disease Activity, Heath Assessment Questionnaire and Disability Index and High Sensitivity C-reactive Protein.

  2. Change in DAS 28[CRP] [ Time Frame: From Week 0 to Week 12 ]
    DAS28[CRP] is based on tender and swollen joints counts, high sensitivity C-reactive protein, and Patient's Global Assessment of Disease Activity.

  3. Change in Clinical Disease Activity Index (CDAI) [ Time Frame: From Week 0 to Week 12 ]
    CDAI is based on tender and swollen joint counts, Patient's Global Assessment of Disease Activity, and the Physician's Assessment of Disease Activity.

  4. ACRn [ Time Frame: Week 12 ]

    ACRn is defined as the average of the following three variables:

    1. The percentage improvement in Tender joint count (TJC);
    2. The percentage improvement in Swollen joint count (SJC);
    3. The median percentage improvement in the following five remaining ACR core set measures: Patient's Assessment of Pain using Visual Analog Scale (VAS), Patient's Global Assessment of Disease Activity, Physician's Global Assessment of Disease Activity, Patient's Assessment of Physical Function by Heath Assessment Questionnaire - Disability Index (HAQ-DI), High sensitivity CRP

  5. Change in Tender Joint Count [ Time Frame: From Week 0 to Week 12 ]
  6. Change in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) [ Time Frame: From Week 0 to Week 12 ]
    FACIT-F is a patient questionnaire.

  7. Incidence of Adverse Events [ Time Frame: Up to 30 day follow-up visit (30 days after last dose of study) ]
  8. Changes in vital signs [ Time Frame: From Week 0 to 30 day follow-up visit (30 days after last dose study drug) ]
    Vital signs include blood pressure, pulse rate, respiratory rate, and body temperature

  9. ACR 50 Response Rate [ Time Frame: Week 8 ]
    ACR 50 response rate will be determined based on 50% or greater improvement of Tender Joint Count and Swollen Joint Counts and greater than or equal to 3 of the 5 measures of Patient's Assessment of Pain , Patient's Assessment of Global Assessment of Disease Activity, Heath Assessment Questionnaire and Disability Index and High Sensitivity C-reactive Protein.

  10. ACR 70 response rate [ Time Frame: Week 8 ]
    ACR 70 response rate will be determined based on 70% or greater improvement of Tender Joint Count and Swollen Joint Counts and greater than or equal to 3 of the 5 measures of Patient's Assessment of Pain , Patient's Assessment of Global Assessment of Disease Activity, Heath Assessment Questionnaire and Disability Index and High Sensitivity C-reactive Protein.

  11. Change in Work Instability Score for Rheumatoid Arthritis (RA-WIS) [ Time Frame: From Week 0 to Week 12 ]
    RA-WIS is a patient questionnaire.

  12. Change in EuroQoL-5D (EQ-5D) [ Time Frame: From Week 0 to Week 12 ]
    EQ-5D is a patient questionnaire.

  13. Change in Short Form-36 (SF-36) [ Time Frame: From Week 0 to Week 12 ]
    SF-36 is a patient questionnaire.

  14. Change in physical examination results [ Time Frame: From Week 0 to Week 12 ]
    A symptom directed physical exam will be performed when necessary, as per Investigator's judgement.

  15. Changes in clinical laboratory data [ Time Frame: From Week 0 to 30 day follow-up visit (30 days after last dose of study drug) ]
    Clinical laboratory data include hematology, chemistry, and urinalysis

  16. Change in Swollen Joint Count [ Time Frame: From Week 0 to Week 12 ]
  17. Change in Patient Assessment of Pain Visual Analog Scale (VAS) [ Time Frame: From Week 0 to Week 12 ]
    This Visual Analog Scale consists of a horizontal 100 mm line anchored at either end by No Pain and at the other end with Worst Possible Pain.

  18. Change in Patient's Global Assessment of Disease Activity Visual Analog Scale (VAS) [ Time Frame: From Week 0 to Week 12 ]
    This Visual Analog Scale consists of a horizontal 100 mm line anchored at either end by Very Well and at the other end with Very Poorly.

  19. Physician's Global Assessment of Disease Activity Visual Analog Scale (VAS) [ Time Frame: From Week 0 to Week 12 ]
    This Visual Analog Scale consists of a horizontal 100 mm line anchored at either end by Very Low and at the other end with Very High.

  20. Change in Heath Assessment Questionnaire and Disability Index (HAQ-DI) [ Time Frame: From Week 0 to Week 12 ]
    HAQ-DI is a patient questionnaire.

  21. Change in high sensitivity C-reactive protein (hsCRP) [ Time Frame: From Week 0 to Week 12 ]
    hsCRP is a laboratory value



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years to 100 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Diagnosed with RA based on either the 1987-revised ACR classification criteria or the 2010 American College of Rheumatology (ACR)/European League against Rheumatism (EULAR) criteria for ≥ 3 months.
  2. Have active RA as defined by the following minimum disease activity criteria:

    • ≥ 6 swollen joints (based on 66 joint counts) at Screening and Baseline Visits.
    • ≥ 6 tender joints (based on 68 joint counts) at Screening and Baseline Visits.
    • hsCRP > Upper Limit of Normal (ULN) OR positive for both rheumatoid factor and anti-Cyclic Citrullinated Peptide (CCP) at Screening.
  3. Subjects must have been receiving oral or parenteral methotrexate therapy ≥ 3 months and on a stable prescription of 7.5 to 25 mg/week for at least 4 weeks prior to Baseline Visit. Subjects should also be on a stable dose of folic acid (or equivalent) for at least 4 weeks prior to Baseline Visit. Subjects should continue with their stable doses of methotrexate and folic acid throughout the study.
  4. Except for MTX, subjects must have discontinued all oral Disease-Modifying Anti-Rheumatic drugs (DMARDs) prior to Baseline Visit as specified below or for at least five times the mean terminal elimination half-life of a drug, whichever is longer:

    • ≥ 4 weeks prior to Baseline Visit for minocycline, penicillamine, sulfasalazine, hydroxychloroquine, chloroquine, azathioprine, gold formulations, cyclophosphamide
    • ≥ 8 weeks prior to Baseline Visit for leflunomide if no elimination procedure was followed, or adhere to a washout procedure (i.e., 11 days washout with colestyramine, or 30 days washout with activated charcoal)
  5. Subject has a negative Tuberculosis (TB) Screening Assessment. If the subject has evidence of a latent TB infection, the subject must initiate and complete a minimum of 2 weeks (or per local guidelines, whichever is longer) of an ongoing TB prophylaxis or have documented completion of a full course of TB prophylaxis, prior to Baseline Visit.
  6. Subjects can be taking non-steroidal anti-inflammatory drugs (NSAIDS), acetaminophen, oral corticosteroids (equivalent to prednisone ≤ 10 mg), or inhaled corticosteroids at a stable dose for at least 4 weeks prior to Baseline Visit for stable medical conditions and should be kept at a stable dose throughout the study. NSAIDs, acetaminophen tramadol, codeine, hydrocodone and propoxyphene taken as needed are allowed but may not be taken 24 hours prior to any study visit. Oral and inhaled corticosteroids taken PRN are allowed but may not be taken 24 hours prior to any study visit.
  7. Subjects must have discontinued high potency opiates including (but not limited to): oxycodone, oxymorphone, fentanyl, levorphanol, buprenorphine, methadone, hydromorphone, and morphine at least 4 weeks prior to Baseline Visit.

Exclusion Criteria:

  1. Female who is pregnant or breastfeeding.
  2. Prior exposure to Janus Activated Kinase (JAK) inhibitor (e.g., tofacitinib, baricitinib).
  3. Prior exposure to any investigational or approved biologic RA therapy.
  4. Receipt of any investigational drug of chemical or biologic nature within a minimum of 30 days or 5 half-lives of the drug (whichever is longer) prior to Week 0 Visit.
  5. Current or expected need of other immunosuppressant medications, except methotrexate. Use of oral intake of > 10 mg prednisone/day or equivalent corticosteroid therapy (see inclusion criterion 7).
  6. Subject has been treated with intra-articular or parenteral administration of corticosteroids in the preceding 8 weeks prior to the Week 0 Visit.
  7. Screening laboratory values meeting the following criteria:

    • Serum aspartate transaminase (AST) or alanine transaminase (ALT) > 1.5 × ULN
    • Estimated glomerular filtration rate (eGRF) by simplified 4-variable Modification of Diet in Renal Disease (MDRD) formula < 40 mL/min/1.73 m2
    • Total white blood cell count (WBC) < 3,000/µL
    • Absolute neutrophil count (ANC) < 1,200/µL
    • Platelet count < 100,000/µL
    • Absolute lymphocytes count < 750/ µL
    • Hemoglobin < 9 gm/dL

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): NCT02066389


  Show 63 Study Locations
Sponsors and Collaborators
AbbVie
Investigators
Layout table for investigator information
Study Director: Steven Pulaski, MS AbbVie

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Layout table for additonal information
Responsible Party: AbbVie
ClinicalTrials.gov Identifier: NCT02066389     History of Changes
Other Study ID Numbers: M13-537
2013-003984-72 ( EudraCT Number )
First Posted: February 19, 2014    Key Record Dates
Last Update Posted: June 16, 2016
Last Verified: June 2016

Keywords provided by AbbVie:
anti-inflammatory agents
Joint Diseases
Arthritis
Musculoskeletal Disease
antirheumatic agents

Additional relevant MeSH terms:
Layout table for MeSH terms
Arthritis
Arthritis, Rheumatoid
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases
Methotrexate
Upadacitinib
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
Janus Kinase Inhibitors
Protein Kinase Inhibitors