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A Study Investigating the Efficacy and Safety of ABT-494 Given With Methotrexate in Subjects With Rheumatoid Arthritis Who Failed Anti-Tumor Necrosis Factor (TNF) Biologic Therapy

Primary Purpose

Rheumatoid Arthritis

Status
Completed
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
ABT-494
Placebo
Sponsored by
AbbVie
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Rheumatoid Arthritis focused on measuring anti-inflammatory agents, Joint Diseases, Arthritis, Musculoskeletal Disease, antirheumatic agents

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Diagnosed with rheumatoid arthritis (RA) based on either the 1987-revised American College of Rheumatology (ACR) classification criteria or the 2010 American College of Rheumatology/European League against Rheumatism (ACR/EULAR) criteria for ≥ 3 months.
  • Subjects must have been receiving oral or parenteral methotrexate (MTX) therapy ≥ 3 months and on a stable prescription of 7.5 to 25 mg/week for at least 4 weeks prior to initiating the study drug. Subjects should also be on a stable dose of folic acid (or equivalent) for at least 4 weeks prior to initiating the study drug. Subjects should continue with their stable doses of MTX and folic acid throughout the study
  • Subjects have been treated with 1 or more anti-tumor necrosis factor (TNF) biologics (no maximum cap) for ≥ 3 months but continue to exhibit active RA, or had to discontinue due to intolerability or toxicity. In addition, subjects with prior exposure to non-anti-TNF biologic(s) (no maximum cap) (e.g., abatacept, rituximab, anakinra, or tocilizumab) are allowed.
  • Have active RA as defined by the following minimum disease activity criteria: ≥ 6 swollen joints (based on 66 joint counts) at Screening and Baseline, ≥ 6 tender joints (based on 68 joint counts) at Screening and Baseline, high sensitivity C reactive protein (hs-CRP) > Upper Limit of Normal (ULN) OR positive for both rheumatoid factor and anti-cyclic citrullinated peptide (anti-CCP) antibody.

Exclusion Criteria:

  • Prior exposure to Janus Activated Kinase (JAK) inhibitor (e.g. tofacitinib, baricitinib)
  • Pregnant or breastfeeding female
  • Ongoing or active infection.

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm 3

    Arm 4

    Arm 5

    Arm Type

    Placebo Comparator

    Experimental

    Experimental

    Experimental

    Experimental

    Arm Label

    Placebo BID

    ABT-494 3 mg BID

    ABT-494 6 mg BID

    ABT-494 12 mg BID

    ABT-494 18 mg BID

    Arm Description

    Placebo twice daily (BID) for 12 weeks.

    ABT-494 3 mg twice daily (BID) for 12 weeks.

    ABT-494 6 mg twice daily (BID) for 12 weeks.

    ABT-494 12 mg twice daily (BID) for 12 weeks.

    ABT-494 18 mg twice daily (BID) for 12 weeks.

    Outcomes

    Primary Outcome Measures

    Number of Subjects Achieving American College of Rheumatology 20% (ACR20) Response at Week 12
    Response defined as at least 20% reduction (improvement) compared with baseline in tender joint count (TJC68), swollen joint count (SJC66), and at least 3 of the 5 remaining ACR core set measures: patient's assessment of pain, patient's global assessment of disease activity (PtGA); physician's global assessment of disease activity (PGA), Health Assessment Questionnaire - Disability Index (HAQ-DI), and high-sensitivity C-reactive protein (hs CRP). Last observation carried forward (LOCF) was used for missing data.

    Secondary Outcome Measures

    Number of Subjects Achieving American College of Rheumatology 50% (ACR50) Response at Week 12
    Response defined as at least 50% reduction (improvement) compared with baseline in tender joint count (TJC68), swollen joint count (SJC66), and at least 3 of the 5 remaining ACR core set measures: patient's assessment of pain, PtGA; PGA, HAQ-DI, and hs CRP. LOCF was used.
    Number of Subjects Achieving American College of Rheumatology 70% (ACR70) Response at Week 12
    Response defined as at least 70% reduction (improvement) compared with baseline in tender joint count (TJC68), swollen joint count (SJC66), and at least 3 of the 5 remaining ACR core set measures: patient's assessment of pain, PtGA; PGA, HAQ-DI, and hs CRP. LOCF was used.
    Number of Subjects Achieving Low Disease Activity (LDA) Based on Disease Activity Score (DAS28) or Clinical Remission (CR) Based on (DAS28) at Week 12
    LDA is defined as DAS28 from 2.6 to < 3.2 at Week 12. CR is defined as DAS28 (CRP) < 2.6 at Week 12. The DAS28 is a validated index of rheumatoid arthritis disease activity. Twenty-eight tender joint counts, 28 swollen joint counts, hs CRP, and general health are included in the DAS28 score. Scores on the DAS28 range from 0 to 10. A DAS28 score >5.1 indicates high disease activity, a DAS28 score <3.2 indicates low disease activity, and a DAS28 score <2.6 indicates clinical remission. LOCF was used.
    Number of Subjects Achieving CR Based on DAS28 at Week 12
    The DAS28 is a validated index of rheumatoid arthritis disease activity. Twenty-eight tender joint counts, 28 swollen joint counts, hs CRP, and general health are included in the DAS28 score. Scores on the DAS28 range from 0 to 10. A DAS28 score >5.1 indicates high disease activity, a DAS28 score <3.2 indicates low disease activity, and a DAS28 score <2.6 indicates clinical remission. LOCF was used.

    Full Information

    First Posted
    October 9, 2013
    Last Updated
    July 29, 2021
    Sponsor
    AbbVie
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    1. Study Identification

    Unique Protocol Identification Number
    NCT01960855
    Brief Title
    A Study Investigating the Efficacy and Safety of ABT-494 Given With Methotrexate in Subjects With Rheumatoid Arthritis Who Failed Anti-Tumor Necrosis Factor (TNF) Biologic Therapy
    Official Title
    A Randomized, Double-Blind, Placebo-Controlled, Phase 2 Study to Investigate the Safety and Efficacy of ABT-494 Given With Methotrexate (MTX) in Subjects With Moderately to Severely Active Rheumatoid Arthritis (RA) Who Have Had an Inadequate Response or Intolerance to Anti-TNF Biologic Therapy
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    July 2021
    Overall Recruitment Status
    Completed
    Study Start Date
    October 2013 (Actual)
    Primary Completion Date
    July 2015 (Actual)
    Study Completion Date
    July 2015 (Actual)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    AbbVie

    4. Oversight

    Studies a U.S. FDA-regulated Drug Product
    Yes
    Data Monitoring Committee
    No

    5. Study Description

    Brief Summary
    The primary objective is to compare the safety and efficacy of multiple doses of ABT-494 versus placebo in moderately to severely active RA subjects on stable background MTX therapy with inadequate response or intolerance to anti-TNF biologic therapy.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Rheumatoid Arthritis
    Keywords
    anti-inflammatory agents, Joint Diseases, Arthritis, Musculoskeletal Disease, antirheumatic agents

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 2
    Interventional Study Model
    Parallel Assignment
    Masking
    ParticipantCare ProviderInvestigatorOutcomes Assessor
    Allocation
    Randomized
    Enrollment
    276 (Actual)

    8. Arms, Groups, and Interventions

    Arm Title
    Placebo BID
    Arm Type
    Placebo Comparator
    Arm Description
    Placebo twice daily (BID) for 12 weeks.
    Arm Title
    ABT-494 3 mg BID
    Arm Type
    Experimental
    Arm Description
    ABT-494 3 mg twice daily (BID) for 12 weeks.
    Arm Title
    ABT-494 6 mg BID
    Arm Type
    Experimental
    Arm Description
    ABT-494 6 mg twice daily (BID) for 12 weeks.
    Arm Title
    ABT-494 12 mg BID
    Arm Type
    Experimental
    Arm Description
    ABT-494 12 mg twice daily (BID) for 12 weeks.
    Arm Title
    ABT-494 18 mg BID
    Arm Type
    Experimental
    Arm Description
    ABT-494 18 mg twice daily (BID) for 12 weeks.
    Intervention Type
    Drug
    Intervention Name(s)
    ABT-494
    Intervention Description
    ABT-494 capsule administered orally twice daily (BID).
    Intervention Type
    Drug
    Intervention Name(s)
    Placebo
    Intervention Description
    Placebo for ABT-494 capsule administered orally twice daily (BID).
    Primary Outcome Measure Information:
    Title
    Number of Subjects Achieving American College of Rheumatology 20% (ACR20) Response at Week 12
    Description
    Response defined as at least 20% reduction (improvement) compared with baseline in tender joint count (TJC68), swollen joint count (SJC66), and at least 3 of the 5 remaining ACR core set measures: patient's assessment of pain, patient's global assessment of disease activity (PtGA); physician's global assessment of disease activity (PGA), Health Assessment Questionnaire - Disability Index (HAQ-DI), and high-sensitivity C-reactive protein (hs CRP). Last observation carried forward (LOCF) was used for missing data.
    Time Frame
    Baseline (Week 0) and Week 12
    Secondary Outcome Measure Information:
    Title
    Number of Subjects Achieving American College of Rheumatology 50% (ACR50) Response at Week 12
    Description
    Response defined as at least 50% reduction (improvement) compared with baseline in tender joint count (TJC68), swollen joint count (SJC66), and at least 3 of the 5 remaining ACR core set measures: patient's assessment of pain, PtGA; PGA, HAQ-DI, and hs CRP. LOCF was used.
    Time Frame
    Baseline (Week 0) and Week 12
    Title
    Number of Subjects Achieving American College of Rheumatology 70% (ACR70) Response at Week 12
    Description
    Response defined as at least 70% reduction (improvement) compared with baseline in tender joint count (TJC68), swollen joint count (SJC66), and at least 3 of the 5 remaining ACR core set measures: patient's assessment of pain, PtGA; PGA, HAQ-DI, and hs CRP. LOCF was used.
    Time Frame
    Baseline (Week 0) and Week 12
    Title
    Number of Subjects Achieving Low Disease Activity (LDA) Based on Disease Activity Score (DAS28) or Clinical Remission (CR) Based on (DAS28) at Week 12
    Description
    LDA is defined as DAS28 from 2.6 to < 3.2 at Week 12. CR is defined as DAS28 (CRP) < 2.6 at Week 12. The DAS28 is a validated index of rheumatoid arthritis disease activity. Twenty-eight tender joint counts, 28 swollen joint counts, hs CRP, and general health are included in the DAS28 score. Scores on the DAS28 range from 0 to 10. A DAS28 score >5.1 indicates high disease activity, a DAS28 score <3.2 indicates low disease activity, and a DAS28 score <2.6 indicates clinical remission. LOCF was used.
    Time Frame
    Baseline (Week 0) and Week 12
    Title
    Number of Subjects Achieving CR Based on DAS28 at Week 12
    Description
    The DAS28 is a validated index of rheumatoid arthritis disease activity. Twenty-eight tender joint counts, 28 swollen joint counts, hs CRP, and general health are included in the DAS28 score. Scores on the DAS28 range from 0 to 10. A DAS28 score >5.1 indicates high disease activity, a DAS28 score <3.2 indicates low disease activity, and a DAS28 score <2.6 indicates clinical remission. LOCF was used.
    Time Frame
    Baseline (Week 0) and Week 12

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    Inclusion Criteria: Diagnosed with rheumatoid arthritis (RA) based on either the 1987-revised American College of Rheumatology (ACR) classification criteria or the 2010 American College of Rheumatology/European League against Rheumatism (ACR/EULAR) criteria for ≥ 3 months. Subjects must have been receiving oral or parenteral methotrexate (MTX) therapy ≥ 3 months and on a stable prescription of 7.5 to 25 mg/week for at least 4 weeks prior to initiating the study drug. Subjects should also be on a stable dose of folic acid (or equivalent) for at least 4 weeks prior to initiating the study drug. Subjects should continue with their stable doses of MTX and folic acid throughout the study Subjects have been treated with 1 or more anti-tumor necrosis factor (TNF) biologics (no maximum cap) for ≥ 3 months but continue to exhibit active RA, or had to discontinue due to intolerability or toxicity. In addition, subjects with prior exposure to non-anti-TNF biologic(s) (no maximum cap) (e.g., abatacept, rituximab, anakinra, or tocilizumab) are allowed. Have active RA as defined by the following minimum disease activity criteria: ≥ 6 swollen joints (based on 66 joint counts) at Screening and Baseline, ≥ 6 tender joints (based on 68 joint counts) at Screening and Baseline, high sensitivity C reactive protein (hs-CRP) > Upper Limit of Normal (ULN) OR positive for both rheumatoid factor and anti-cyclic citrullinated peptide (anti-CCP) antibody. Exclusion Criteria: Prior exposure to Janus Activated Kinase (JAK) inhibitor (e.g. tofacitinib, baricitinib) Pregnant or breastfeeding female Ongoing or active infection.
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    AbbVie Inc
    Organizational Affiliation
    AbbVie
    Official's Role
    Study Director

    12. IPD Sharing Statement

    Plan to Share IPD
    Undecided
    Citations:
    PubMed Identifier
    27389975
    Citation
    Kremer JM, Emery P, Camp HS, Friedman A, Wang L, Othman AA, Khan N, Pangan AL, Jungerwirth S, Keystone EC. A Phase IIb Study of ABT-494, a Selective JAK-1 Inhibitor, in Patients With Rheumatoid Arthritis and an Inadequate Response to Anti-Tumor Necrosis Factor Therapy. Arthritis Rheumatol. 2016 Dec;68(12):2867-2877. doi: 10.1002/art.39801.
    Results Reference
    background
    PubMed Identifier
    34041702
    Citation
    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.
    Results Reference
    derived
    PubMed Identifier
    31610021
    Citation
    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.
    Results Reference
    derived
    PubMed Identifier
    31194885
    Citation
    Mohamed MF, Klunder B, Camp HS, Othman AA. Exposure-Response Analyses of Upadacitinib Efficacy in Phase II Trials in Rheumatoid Arthritis and Basis for Phase III Dose Selection. Clin Pharmacol Ther. 2019 Dec;106(6):1319-1327. doi: 10.1002/cpt.1543. Epub 2019 Aug 23.
    Results Reference
    derived
    PubMed Identifier
    29076110
    Citation
    Klunder B, Mohamed MF, Othman AA. Population Pharmacokinetics of Upadacitinib in Healthy Subjects and Subjects with Rheumatoid Arthritis: Analyses of Phase I and II Clinical Trials. Clin Pharmacokinet. 2018 Aug;57(8):977-988. doi: 10.1007/s40262-017-0605-6.
    Results Reference
    derived

    Learn more about this trial

    A Study Investigating the Efficacy and Safety of ABT-494 Given With Methotrexate in Subjects With Rheumatoid Arthritis Who Failed Anti-Tumor Necrosis Factor (TNF) Biologic Therapy

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