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

NCT ID: NCT01960855

Last Updated: 2021-08-24

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

276 participants

Study Classification

INTERVENTIONAL

Study Start Date

2013-10-31

Study Completion Date

2015-07-31

Brief Summary

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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

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Conditions

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Rheumatoid Arthritis

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Placebo BID

Placebo twice daily (BID) for 12 weeks.

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

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

ABT-494 3 mg BID

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

Group Type EXPERIMENTAL

ABT-494

Intervention Type DRUG

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

ABT-494 6 mg BID

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

Group Type EXPERIMENTAL

ABT-494

Intervention Type DRUG

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

ABT-494 12 mg BID

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

Group Type EXPERIMENTAL

ABT-494

Intervention Type DRUG

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

ABT-494 18 mg BID

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

Group Type EXPERIMENTAL

ABT-494

Intervention Type DRUG

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

Interventions

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ABT-494

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

Intervention Type DRUG

Placebo

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

Intervention Type DRUG

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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AbbVie

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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AbbVie Inc

Role: STUDY_DIRECTOR

AbbVie

References

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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.

Reference Type BACKGROUND
PMID: 27389975 (View on PubMed)

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.

Reference Type DERIVED
PMID: 34041702 (View on PubMed)

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.

Reference Type DERIVED
PMID: 31610021 (View on PubMed)

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.

Reference Type DERIVED
PMID: 31194885 (View on PubMed)

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.

Reference Type DERIVED
PMID: 29076110 (View on PubMed)

Other Identifiers

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2013-002358-57

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

M13-550

Identifier Type: -

Identifier Source: org_study_id

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