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

Phase 2

Completed

• Conditions: Rheumatoid Arthritis
• Interventions: Drug: ABT-494; Drug: Placebo

• Registration Number: NCT01960855
• Lead Sponsor: 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.

Detailed Description

Not available

Study Timeline

• Study Start: 2013-10
• Study First Submitted: 2013-10-09
• Study First Submitted QC: 2013-10-09
• Study First Posted: 2013-10-11
• Primary Completion: 2015-07
• Study Completion: 2015-07
• Disposition First Submitted: 2016-06-30
• Disposition First Submitted QC: 2016-06-30
• Disposition First Posted: 2016-07-01
• Results First Submitted: 2018-05-30
• Results First Submitted QC: 2018-05-30
• Results First Posted: 2018-06-27
• Status Verified: 2021-07
• Last Update Submitted: 2021-07-29
• Last Update Posted: 2021-08-24

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 276

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
ABT-494 18 mg BID	ABT-494	ABT-494 18 mg twice daily (BID) for 12 weeks.
Placebo BID	Placebo	Placebo twice daily (BID) for 12 weeks.
ABT-494 3 mg BID	ABT-494	ABT-494 3 mg twice daily (BID) for 12 weeks.
ABT-494 6 mg BID	ABT-494	ABT-494 6 mg twice daily (BID) for 12 weeks.
ABT-494 12 mg BID	ABT-494	ABT-494 12 mg twice daily (BID) for 12 weeks.

Primary Outcome Measures

Name	Time	Method
Number of Subjects Achieving American College of Rheumatology 20% (ACR20) Response at Week 12	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

Name	Time	Method
Number of Subjects Achieving American College of Rheumatology 50% (ACR50) Response at Week 12	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.
Number of Subjects Achieving American College of Rheumatology 70% (ACR70) Response at Week 12	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.
Number of Subjects Achieving CR Based on DAS28 at Week 12	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.
Number of Subjects Achieving Low Disease Activity (LDA) Based on Disease Activity Score (DAS28) or Clinical Remission (CR) Based on (DAS28) at Week 12	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.