Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

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: NCT01960855
Recruitment Status : Completed
First Posted : October 11, 2013
Results First Posted : June 27, 2018
Last Update Posted : June 27, 2018
Sponsor:
Information provided by (Responsible Party):
AbbVie

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.

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 : 276 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 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
Actual Study Start Date : October 2013
Actual Primary Completion Date : July 2015
Actual Study Completion Date : July 2015

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Placebo Comparator: Placebo BID
Placebo twice daily (BID) for 12 weeks.
Drug: Placebo
Placebo for ABT-494 capsule administered orally twice daily (BID).

Experimental: ABT-494 3 mg BID
ABT-494 3 mg twice daily (BID) for 12 weeks.
Drug: ABT-494
ABT-494 capsule administered orally twice daily (BID).

Experimental: ABT-494 6 mg BID
ABT-494 6 mg twice daily (BID) for 12 weeks.
Drug: ABT-494
ABT-494 capsule administered orally twice daily (BID).

Experimental: ABT-494 12 mg BID
ABT-494 12 mg twice daily (BID) for 12 weeks.
Drug: ABT-494
ABT-494 capsule administered orally twice daily (BID).

Experimental: ABT-494 18 mg BID
ABT-494 18 mg twice daily (BID) for 12 weeks.
Drug: ABT-494
ABT-494 capsule administered orally twice daily (BID).




Primary Outcome Measures :
  1. Number of Subjects Achieving American College of Rheumatology 20% (ACR20) Response at Week 12 [ Time Frame: Baseline (Week 0) and 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 :
  1. Number of Subjects Achieving American College of Rheumatology 50% (ACR50) Response at Week 12 [ Time Frame: Baseline (Week 0) and 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.

  2. Number of Subjects Achieving American College of Rheumatology 70% (ACR70) Response at Week 12 [ Time Frame: Baseline (Week 0) and 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.

  3. Number of Subjects Achieving Low Disease Activity (LDA) Based on Disease Activity Score (DAS28) or Clinical Remission (CR) Based on (DAS28) at Week 12 [ Time Frame: Baseline (Week 0) and 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.

  4. Number of Subjects Achieving CR Based on DAS28 at Week 12 [ Time Frame: Baseline (Week 0) and 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.



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

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): NCT01960855


Sponsors and Collaborators
AbbVie
Investigators
Layout table for investigator information
Study Director: AbbVie Inc AbbVie

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Layout table for additonal information
Responsible Party: AbbVie
ClinicalTrials.gov Identifier: NCT01960855     History of Changes
Other Study ID Numbers: M13-550
2013-002358-57 ( EudraCT Number )
First Posted: October 11, 2013    Key Record Dates
Results First Posted: June 27, 2018
Last Update Posted: June 27, 2018
Last Verified: May 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes

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