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

NCT01960855 | Completed Phase 2 Results FDA Drug

• 2 other identifiers: M13-5502013-002358-57
• Study Type: interventional
• Target: 276
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Rheumatoid Arthritis

Keywords

anti-inflammatory agents; Joint Diseases; Arthritis; Musculoskeletal Disease; antirheumatic agents

Outcome Measures

Primary Outcomes (1)

• 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.

  Baseline (Week 0) and Week 12

Secondary Outcomes (4)

• Number of Subjects Achieving American College of Rheumatology 50% (ACR50) Response at Week 12

  Baseline (Week 0) and Week 12

• Number of Subjects Achieving American College of Rheumatology 70% (ACR70) Response at Week 12

  Baseline (Week 0) and Week 12

• 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

• Number of Subjects Achieving CR Based on DAS28 at Week 12

  Baseline (Week 0) and Week 12

Study Arms (5)

Placebo BID

PLACEBO COMPARATOR

Placebo twice daily (BID) for 12 weeks.

Drug: Placebo

ABT-494 3 mg BID

EXPERIMENTAL

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

Drug: ABT-494

ABT-494 6 mg BID

EXPERIMENTAL

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

Drug: ABT-494

ABT-494 12 mg BID

EXPERIMENTAL

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

Drug: ABT-494

ABT-494 18 mg BID

EXPERIMENTAL

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

Drug: ABT-494

Interventions

ABT-494 DRUG

ABT-494 capsule administered orally twice daily (BID).

ABT-494 12 mg BID; ABT-494 18 mg BID; ABT-494 3 mg BID; ABT-494 6 mg BID

Placebo DRUG

Placebo for ABT-494 capsule administered orally twice daily (BID).

Placebo BID

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

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

Sponsors & Collaborators

• AbbVie: lead

Related Publications (5)

• 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.

  PMID: 27389975 BACKGROUND

• 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.

  PMID: 34041702 DERIVED

• 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.

  PMID: 31610021 DERIVED

• 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.

  PMID: 31194885 DERIVED

• 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.

  PMID: 29076110 DERIVED

MeSH Terms

Conditions

Arthritis, Rheumatoid; Joint Diseases; Arthritis; Musculoskeletal Diseases

Interventions

upadacitinib

Condition Hierarchy (Ancestors)

Rheumatic Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Results Point of Contact

• Title: Global Medical Services
• Organization: AbbVie

800-633-9110

Study Officials

• AbbVie Inc

  AbbVie

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 9, 2013
• First Posted: October 11, 2013
• Study Start: October 1, 2013
• Primary Completion: July 1, 2015
• Study Completion: July 1, 2015
• Last Updated: August 24, 2021
• Results First Posted: June 27, 2018

Record last verified: 2021-07