A 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 Failed Anti-TNF Biologic Therapy
- Conditions
- Moderately to Severely Active Rheumatoid Arthritis (RA)MedDRA version: 17.0Level: PTClassification code 10039073Term: Rheumatoid arthritisSystem Organ Class: 10028395 - Musculoskeletal and connective tissue disordersTherapeutic area: Diseases [C] - Immune System Diseases [C20]
- Registration Number
- EUCTR2013-002358-57-ES
- Lead Sponsor
- AbbVie Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 250
1. Adult male or female, at least 18 years old.
2. Diagnosed with RA based on the 2010 American College of Rheumatology (ACR)/European League against Rheumatism (EULAR) criteria for greater than or equal to 3 months.
3. Subjects must have been receiving oral or parenteral MTX therapy greater than or equal to 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.
4. Subjects have been treated with 1 or 2 anti-TNF biologics for greater than 3 months but less than 3 years but continue to exhibit active RA, or had to discontinue due to intolerability or toxicity within 1 year prior to initiating the study drug, provided that they did not exhibit, based on reported history, initial nonresponse to the agent (i.e., exclude subjects with no clinical response to initial treatment with anti-TNF biologic).
5. Have active RA as defined by the following minimum disease activity criteria: greater than or equal to 6 swollen joints (based on 66 joint counts) at Screening and Baseline Visits; greater than or equal to 6 tender joints (based on 68 joint counts) at Screening and Baseline Visits; hs-CRP greater than 7 mg/L.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 185
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 65
1. Reported history of no clinical response to initial treatment with anti-TNF biologic.
2. Receipt of prior biologic therapy other than an anti-TNF (e.g., tocilizumab, rituximab, anakinra, or abatacept).
3. Prior exposure to JAK inhibitor (e.g., tofacitinib, baricitinib).
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 initiating the study drug.
5. Current or expected need of other immunosuppressant medications, except MTX. Use of oral intake of greater than 10 mg prednisone/day or equivalent corticosteroid therapy.
6. Laboratory values meeting the following criteria within 4 weeks prior to initiating study drug: Serum aspartate transaminase (AST) or alanine transaminase (ALT) greater than 1.5 × ULN; Estimated glomerular filtration rate (eGRF) by simplified 4-variable Modification of Diet in Renal Disease (MDRD) formula less than 40 mL/min/1.73 m2; Total white blood cell count (WBC) less than 3,000/µL; Absolute neutrophil count (ANC) less than 1,200 /µL; Platelet count less than 100,000/µL; Absolute lymphocytes count less than 500/ µL; Hemoglobin less than 9 gm/dL
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: 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.;Secondary Objective: Not applicable;Primary end point(s): ACR20 response rate.;Timepoint(s) of evaluation of this end point: Week 12
- Secondary Outcome Measures
Name Time Method Secondary end point(s): ACR50/70 response rates, the proportion of subjects achieving low disease activity (LDA) (2.6 less or equal to DAS28 [CRP] less than 3.2) or clinical remission (CR) (DAS28 [CRP] less than 2.6), and the proportion of subjects achieving CR (DAS28 [CRP] less than 2.6);Timepoint(s) of evaluation of this end point: Week 12