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A Study With Upatacitinib (ABT-494) in Subjects From China and Selected Countries With Moderately to Severely Active Rheumatoid Arthritis Who Have Had an Inadequate Response to Conventional Synthetic Disease-Modifying Anti-Rheumatic Drugs (csDMARDs)

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ClinicalTrials.gov Identifier: NCT02955212
Recruitment Status : Recruiting
First Posted : November 4, 2016
Last Update Posted : March 5, 2019
Sponsor:
Information provided by (Responsible Party):
AbbVie

Brief Summary:
This is a Phase 3 multicenter study that includes two periods. Period 1 is a 12-week, randomized, double-blind, parallel-group, placebo-controlled period designed to compare the safety and efficacy of upadacitinib versus placebo for the treatment of signs and symptoms of participants with moderately to severely active RA who are on a stable dose of csDMARDs and have an inadequate response to csDMARDs. Period 2 is an open label 52 week extension period to evaluate the long-term safety, tolerability, and efficacy of upadacitinib in participants with RA who have completed Period 1.

Condition or disease Intervention/treatment Phase
Rheumatoid Arthritis (RA) Drug: Upadacitinib Drug: Placebo Phase 3

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 322 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study With Upadacitinib (ABT-494) in Subjects From China and Selected Countries With Moderately to Severely Active Rheumatoid Arthritis Who Have Had an Inadequate Response to Conventional Synthetic Disease-Modifying Anti-Rheumatic Drugs (csDMARDs)
Actual Study Start Date : January 3, 2018
Estimated Primary Completion Date : July 23, 2019
Estimated Study Completion Date : August 20, 2020

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Placebo Comparator: Placebo (Period 1) followed by Upadacitinib (Period 2)
Placebo will be administered in Period 1, followed by upadacitinib which will be administered in Period 2.
Drug: Upadacitinib
Oral formulation once daily

Drug: Placebo
Oral formulation once daily

Experimental: Upadacitinib (Period 1) followed by Upadacitinib (Period 2)
Upadacitinib will be administered in Periods 1 and 2.
Drug: Upadacitinib
Oral formulation once daily




Primary Outcome Measures :
  1. Proportion of participants achieving American College of Rheumatology (ACR) 20 response [ Time Frame: At Week 12 ]
    ACR20 response rate will be determined based on 20% or greater improvement in tender joint count (TJC) and swollen joint count (SJC) and >= 3 of the 5 measures of Patient's Assessment of Pain (VAS), Patient's Global Assessment of Disease Activity (VAS), Physician's Global Assessment of Disease Activity (VAS), Health Assessment Questionnaire - Disability Index (HAQ-DI), or high-sensitivity C-reactive protein (hsCRP).


Secondary Outcome Measures :
  1. Change from baseline in Short form-36 (SF-36) Physical Component Score (PCS) [ Time Frame: At Week 12 ]
    SF-36 is a 36 item participant questionnaire with questions regarding participant health and daily activities.

  2. Change from baseline in disease activity score (DAS) 28 C-reactive protein (CRP) (Period 1) [ Time Frame: At Week 12 ]
    The DAS28 is a validated index of rheumatoid arthritis disease activity. Scores on the DAS28 range from 0 to 10.

  3. Proportion of subjects achieving low disease activity (LDA) based on DAS28 (CRP) <= 3.2 [ Time Frame: At Week 12 ]
    Proportion of participants achieving low disease activity as defined by a clinical response DAS28[CRP] less than or equal to 3.2. The DAS28 is a validated index of rheumatoid arthritis disease activity. Scores on the DAS28 range from 0 to 10. A DAS28 score greater than 5.1 indicates high disease activity, a DAS28 score less than or equal to 3.2 indicates low disease activity, and a DAS28 score less than 2.6 indicates clinical remission.

  4. ACR 70 Response Rate [ Time Frame: At Week 12 ]
    ACR criteria measure improvements in tender and swollen joint counts, patient assessments of pain, global disease activity and physical function, physician global assessment of disease activity and acute phase reactant.

  5. Proportion of subjects achieving clinical remission (CR) [ Time Frame: At Week 12 ]
    CR based on DAS28 (CRP) response rate is defined as DAS28 (CRP) less than 2.6.

  6. Proportion of subjects achieving LDA based on CDAI ≤ 10 [ Time Frame: At Week 12 ]
    Clinical Disease Activity Index

  7. Change from baseline in Health Assessment Questionnaire - Disability Index (HAQ-DI) (Period 1) [ Time Frame: At Week 12 ]
    HAQ-DI is a participant questionnaire with questions regarding the participant's illness and how it affect their daily life activities.

  8. ACR 20 response rate [ Time Frame: At Week 1 ]
    Change from baseline in individual components of ACR response at Week 1

  9. ACR 50 Response Rate [ Time Frame: At Week 12 ]
    ACR criteria measure improvements in tender and swollen joint counts, patient assessments of pain, global disease activity and physical function, physician global assessment of disease activity and acute phase reactant.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Diagnosis of Rheumatoid Arthritis (RA) for >= 3 months who also fulfill the 2010 American College of Rheumatology (ACR)/ European League Against Rheumatism (EULAR) classification criteria for RA.
  • Participants have been receiving csDMARD therapy >= 3 months and on a stable dose for >= 4 weeks prior to the first dose of study drug.

    1. Participants must have failed (lack of efficacy) at least one of the following: methotrexate (MTX), sulfasalazine, or leflunomide.
    2. The following csDMARDs are allowed: oral or parenteral MTX, sulfasalazine, hydroxychloroquine, chloroquine, and leflunomide.
    3. A combination of up to two background csDMARDs is allowed except the combination of MTX and leflunomide.
  • Participant meets both of the following disease activity criteria:

    1. >= 6 swollen joints (based on 66 joint counts) and ≥ 6 tender joints (based on 68 joint counts) at Screening and Baseline Visits; and
    2. High-sensitivity C-Reactive Protein (hsCRP) >= upper limit of normal at Screening Visit
  • Participants with prior exposure to at most one bDMARD may be enrolled (up to 20% of total number of subjects). Specifically, prior to enrollment:

    1. Participants with limited exposure to Biological disease-modifying anti-rheumatic drugs (bDMARD) (< 3 months) OR
    2. Participants who are responding to a bDMARD therapy but had to discontinue due to intolerability (regardless of treatment duration).
  • Participants must have discontinued bDMARD therapy prior to the first dose of study drug.

The washout period for bDMARDs prior to the first dose of study is specified below or at least five times the mean terminal elimination half-life of a drug:

  • ≥ 4 weeks for etanercept;
  • ≥ 8 weeks for adalimumab, infliximab, certolizumab, golimumab, abatacept, and tocilizumab;
  • ≥ 1 year for rituximab OR ≥ 6 months if B cells have returned to pre-treatment level or normal reference range if pre-treatment levels are not available.
  • For all other bDMARDs, contact the TA MD for the washout period required prior to the first dose of study drug.

Exclusion Criteria:

  • Prior exposure to any Janus kinase (JAK) inhibitor (including but not limited to tofacitinib, baricitinib, and filgotinib).
  • Participants who are considered inadequate responders (lack of efficacy) to bDMARD therapy as defined by the Investigator.
  • History of any arthritis with onset prior to age 17 years or current diagnosis of inflammatory joint disease other than RA (including but not limited to gout, systemic lupus erythematosus, psoriatic arthritis, axial spondyloarthritis including ankylosing spondylitis and non-radiographic axial spondyloarthritis, reactive arthritis, overlap connective tissue diseases, scleroderma, polymyositis, dermatomyositis, fibromyalgia [currently with active symptoms]. Current diagnosis of secondary Sjogren's Syndrome is permitted.

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): NCT02955212


Contacts
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Contact: ABBVIE CALL CENTER 847.283.8955 abbvieclinicaltrials@abbvie.com

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Sponsors and Collaborators
AbbVie
Investigators
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Study Director: AbbVie Inc. AbbVie

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Responsible Party: AbbVie
ClinicalTrials.gov Identifier: NCT02955212     History of Changes
Other Study ID Numbers: M15-557
First Posted: November 4, 2016    Key Record Dates
Last Update Posted: March 5, 2019
Last Verified: March 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: AbbVie is committed to responsible data sharing regarding the clinical trials we sponsor. This includes access to anonymized, individual and trial-level data (analysis data sets), as well as other information (e.g., protocols and clinical study reports), as long as the trials are not part of an ongoing or planned regulatory submission. This includes requests for clinical trial data for unlicensed products and indications.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Clinical Study Report (CSR)
Analytic Code
Time Frame: Data requests can be submitted at any time and the data will be accessible for 12 months, with possible extensions considered.
Access Criteria: Access to this clinical trial data can be requested by any qualified researchers who engage in rigorous, independent scientific research, and will be provided following review and approval of a research proposal and Statistical Analysis Plan (SAP) and execution of a Data Sharing Agreement (DSA). For more information on the process, or to submit a request, visit the following link.
URL: https://www.abbvie.com/our-science/clinical-trials/clinical-trials-data-and-information-sharing/data-and-information-sharing-with-qualified-researchers.html

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No

Keywords provided by AbbVie:
Rheumatoid Arthritis
Conventional Synthetic Disease-Modifying Anti-Rheumatic Drugs (csDMARDs)
ABT-494

Additional relevant MeSH terms:
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Arthritis
Arthritis, Rheumatoid
Rheumatic Diseases
Joint Diseases
Musculoskeletal Diseases
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases
Upadacitinib
Antirheumatic Agents
Janus Kinase Inhibitors
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action