A Phase 3 Study to Compare Upadacitinib to Abatacept in Subjects With Rheumatoid Arthritis on Stable Dose of Conventional Synthetic Disease- Modifying Antirheumatic Drugs (csDMARDs) Who Have an Inadequate Response or Intolerance to Biologic DMARDs
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| ClinicalTrials.gov Identifier: NCT03086343 |
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Recruitment Status :
Active, not recruiting
First Posted : March 22, 2017
Results First Posted : June 4, 2020
Last Update Posted : July 19, 2022
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Sponsor:
AbbVie
Information provided by (Responsible Party):
AbbVie
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Brief Summary:
The study objective of Period 1 was to compare the safety and efficacy of upadacitinib 15 mg once daily (QD) to abatacept on a background of conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) for the treatment of signs and symptoms of rheumatoid arthritis (RA) in biologic disease-modifying antirheumatic drug (bDMARD)-inadequate response or bDMARD-intolerant participants with moderately to severely active RA. The study objective of Period 2 is to evaluate the long-term safety, tolerability, and efficacy of upadacitinib 15 mg QD in participants with RA who had completed Period 1.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Rheumatoid Arthritis (RA) | Drug: Abatacept Drug: Placebo for abatacept Drug: Upadacitinib Drug: Placebo for upadacitinib | Phase 3 |
This is a Phase 3 multicenter study with 2 periods. Period 1 was a 24-week, randomized, double-blind, parallel-group, active-controlled period designed to compare the safety and efficacy of upadacitinib 15 mg and abatacept for the treatment of signs and symptoms of participants with moderately to severely active rheumatoid RA who had an inadequate response to or intolerance to bDMARD therapy and were currently on a stable dose of csDMARD(s) and had never received abatacept. Period 2 is an open-label, long-term extension study to evaluate the long-term safety, tolerability, and efficacy of upadacitinib 15 mg once a day (QD) in participants with RA who had completed Period 1.
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 613 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor) |
| Primary Purpose: | Treatment |
| Official Title: | A Phase 3, Randomized, Active-Controlled, Double-Blind Study Comparing Upadacitinib (ABT-494) to Abatacept in Subjects With Moderately to Severely Active Rheumatoid Arthritis With Inadequate Response or Intolerance to Biologic DMARDs (bDMARDs) on Stable Conventional Synthetic Disease Modifying Anti-Rheumatic Drugs (csDMARDs) |
| Actual Study Start Date : | May 9, 2017 |
| Actual Primary Completion Date : | June 13, 2019 |
| Estimated Study Completion Date : | June 1, 2023 |
Resource links provided by the National Library of Medicine
MedlinePlus Genetics related topics:
Rheumatoid arthritis
| Arm | Intervention/treatment |
|---|---|
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Active Comparator: Abatacept
500 mg (for body weight <60 kg); 750 mg (for body weight 60-100 kg); and 1000 mg (for body weight >100 kg) intravenous (IV) infusion at Baseline, Week 2, Week 4, Week 8, Week 12, Week 16 and Week 20
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Drug: Abatacept
IV infusion Drug: Placebo for abatacept IV infusion |
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Experimental: Upadacitinib 15 mg
One 15 mg tablet taken once per day by mouth for 24 weeks
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Drug: Upadacitinib
15 mg extended release tablet
Other Name: ABT-494 Drug: Placebo for upadacitinib Film-coated tablet |
Primary Outcome Measures :
- Change From Baseline in Disease Activity Score (DAS) 28 C-Reactive Protein (CRP) at Week 12 (Non-inferiority) [ Time Frame: Baseline and Week 12 ]The Disease Activity Score (DAS) 28 is a composite index used to assess rheumatoid arthritis disease activity, calculated based on the tender joint count (out of 28 evaluated joints), swollen joint count (out of 28 evaluated joints), Patient's Global Assessment of Disease Activity (0-100 mm), and high-sensitivity C-reactive protein (hsCRP; in mg/L). Scores on the DAS28 range from 0 to approximately 10, where higher scores indicate more disease activity. A negative change from Baseline indicates improvement in disease activity.
Secondary Outcome Measures :
- Change From Baseline in Disease Activity Score (DAS) 28 C-Reactive Protein (CRP) at Week 12 (Superiority) [ Time Frame: Baseline and Week 12 ]The Disease Activity Score (DAS) 28 is a composite index used to assess rheumatoid arthritis disease activity, calculated based on the tender joint count (out of 28 evaluated joints), swollen joint count (out of 28 evaluated joints), Patient's Global Assessment of Disease Activity (0-100 mm), and high-sensitivity C-reactive protein (hsCRP; in mg/L). Scores on the DAS28 range from 0 to approximately 10, where higher scores indicate more disease activity. A negative change from Baseline indicates improvement in disease activity.
- Percentage of Participants Achieving Clinical Remission (CR) Based on Disease Activity Score (DAS) 28 C-Reactive Protein (CRP) at Week 12 (Superiority) [ Time Frame: At Week 12 ]The Disease Activity Score (DAS) 28 is a composite index used to assess rheumatoid arthritis disease activity, calculated based on the tender joint count (out of 28 evaluated joints), swollen joint count (out of 28 evaluated joints), Patient's Global Assessment of Disease Activity (0-100 mm), and high-sensitivity C-reactive protein (hsCRP; in mg/L). Scores on the DAS28 range from 0 to approximately 10, where higher scores indicate more disease activity. A DAS 28 score less than 2.6 indicates clinical remission.
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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
Main 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 treated for ≥ 3 months prior to the screening visit with ≥ 1 bDMARD therapy, but continue to exhibit active RA or had to discontinue due to intolerability or toxicity, irrespective of treatment duration and have never received abatacept prior to the first dose of study drug
- Participants have been receiving csDMARD therapy ≥ 3 months and on a stable dose for ≥ 4 weeks prior to the first dose of study drug. The following csDMARDs are allowed: methotrexate (MTX), sulfasalazine, hydroxychloroquine, chloroquine, and leflunomide. A combination of up to two background csDMARDs is allowed except the combination of MTX and leflunomide
- Meets the following criteria: ≥ 6 swollen joints (based on 66 joint counts) and ≥ 6 tender joints (based on 68 joint counts) at Screening and Baseline Visits and high-sensitivity C-reactive protein (hsCRP) ≥ 3 mg/L at Screening
Main Exclusion Criteria:
- Prior exposure to any Janus kinase (JAK) inhibitor (including but not limited to upadacitinib, tofacitinib, baricitinib and filgotinib)
- Prior exposure to abatacept
- History of any arthritis with onset prior to age 17 years or current diagnosis of inflammatory joint disease other than RA. Current diagnosis of secondary Sjogren's Syndrome is permitted
- Laboratory values meeting the following criteria within the Screening period prior to the first dose of study drug: serum aspartate transaminase > 2 × upper limit of normal (ULN); serum alanine transaminase > 2 × ULN; estimated glomerular filtration rate by simplified 4-variable Modification of Diet in Renal Disease formula < 40 mL/minute/1.73 meter (m)^2; total white blood cell count < 2,500/ μL; absolute neutrophil count < 1,500/μL; platelet count < 100,000/μL; absolute lymphocyte count < 800/μL; and hemoglobin < 10 g/dL
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): NCT03086343
Locations
Show 161 study locations
Sponsors and Collaborators
AbbVie
Investigators
| Study Director: | AbbVie Inc. | AbbVie |
Study Documents (Full-Text)
Documents provided by AbbVie:
Documents provided by AbbVie:
Study Protocol [PDF] October 12, 2017
Statistical Analysis Plan [PDF] June 4, 2019
Publications:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
| Responsible Party: | AbbVie |
| ClinicalTrials.gov Identifier: | NCT03086343 |
| Other Study ID Numbers: |
M15-925 2016-000933-37 ( EudraCT Number ) |
| First Posted: | March 22, 2017 Key Record Dates |
| Results First Posted: | June 4, 2020 |
| Last Update Posted: | July 19, 2022 |
| Last Verified: | July 2022 |
| 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 |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
| Product Manufactured in and Exported from the U.S.: | No |
Keywords provided by AbbVie:
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Musculoskeletal Disease Arthritis Joint Disease Anti-inflammatory agents Antirheumatic agents |
Additional relevant MeSH terms:
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Arthritis Arthritis, Rheumatoid Joint Diseases Musculoskeletal Diseases Rheumatic Diseases Connective Tissue Diseases Autoimmune Diseases Immune System Diseases Abatacept Upadacitinib |
Immune Checkpoint Inhibitors Molecular Mechanisms of Pharmacological Action Antineoplastic Agents Immunosuppressive Agents Immunologic Factors Physiological Effects of Drugs Antirheumatic Agents Janus Kinase Inhibitors Protein Kinase Inhibitors Enzyme Inhibitors |