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

• ClinicalTrials.gov Identifier: NCT03086343
• Recruitment Status: Active, not recruiting
• First Posted: March 22, 2017
• Results First Posted: June 4, 2020
• Last Update Posted: July 19, 2022
• Sponsor: AbbVie
• Information provided by (Responsible Party): AbbVie

Tracking Information

• First Submitted Date: March 20, 2017
• First Posted Date: March 22, 2017
• Results First Submitted Date: May 8, 2020
• Results First Posted Date: June 4, 2020
• Last Update Posted Date: July 19, 2022
• Actual Study Start Date: May 9, 2017
• Actual Primary Completion Date: June 13, 2019 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: May 8, 2020)

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.

Original Primary Outcome Measures (submitted: March 20, 2017)

Change in Disease Activity Score (DAS) 28 C-Reactive Protein (CRP) (non-inferiority) [ Time Frame: At week 12 ]

The Disease Activity Score (DAS)28 is a validated index of rheumatoid arthritis disease activity. Scores on the DAS28 range from 0 to 10.

Current Secondary Outcome Measures (submitted: May 8, 2020)

• 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.

Original Secondary Outcome Measures (submitted: March 20, 2017)

• Change in Disease Activity Score (DAS) 28 C-Reactive Protein (CRP) (superiority) [ 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.
• Proportion of participants achieving Disease Activity Score (DAS) 28 based Clinical Remission (CR) [ Time Frame: At week 12 ]
  Proportion of participants achieving Clinical Remission (CR) as defined by a clinical response Disease Activity Score (DAS)28 C-Reactive Protein (CRP) less than 2.6. 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 CR.

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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
• 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)
• 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.
• Detailed Description: 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
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Rheumatoid Arthritis (RA)

Intervention

• Drug: Abatacept
  IV infusion
• Drug: Placebo for abatacept
  IV infusion
• Drug: Upadacitinib
  15 mg extended release tablet
  Other Name: ABT-494
• Drug: Placebo for upadacitinib
  Film-coated tablet

Study Arms

• 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
  Interventions:

  • Drug: Abatacept
  • Drug: Placebo for abatacept
• Experimental: Upadacitinib 15 mg
  One 15 mg tablet taken once per day by mouth for 24 weeks
  Interventions:

  • Drug: Upadacitinib
  • Drug: Placebo for upadacitinib

Publications *

• Rubbert-Roth A, Enejosa J, Pangan AL, Haraoui B, Rischmueller M, Khan N, Zhang Y, Martin N, Xavier RM. Trial of Upadacitinib or Abatacept in Rheumatoid Arthritis. N Engl J Med. 2020 Oct 15;383(16):1511-1521. doi: 10.1056/NEJMoa2008250.
• Bergman M, Tundia N, Martin N, Suboticki JL, Patel J, Goldschmidt D, Song Y, Wright GC. Patient-reported outcomes of upadacitinib versus abatacept in patients with rheumatoid arthritis and an inadequate response to biologic disease-modifying antirheumatic drugs: 12- and 24-week results of a phase 3 trial. Arthritis Res Ther. 2022 Jun 24;24(1):155. doi: 10.1186/s13075-022-02813-x. Erratum In: Arthritis Res Ther. 2022 Nov 3;24(1):248.

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: May 8, 2020): 613
• Original Estimated Enrollment (submitted: March 20, 2017): 550
• Estimated Study Completion Date: June 1, 2023
• Actual Primary Completion Date: June 13, 2019 (Final data collection date for primary outcome measure)

Eligibility 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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Argentina, Australia, Belgium, Brazil, Bulgaria, Canada, Czechia, Germany, Greece, Hungary, Ireland, Israel, Italy, Korea, Republic of, Latvia, Mexico, Netherlands, New Zealand, Poland, Portugal, Puerto Rico, Romania, Russian Federation, Slovakia, Spain, Sweden, Switzerland, Turkey, United Kingdom, United States
• Removed Location Countries: Chile, Colombia

Administrative Information

• NCT Number: NCT03086343
• Other Study ID Numbers: M15-925; 2016-000933-37 ( EudraCT Number )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• 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

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
• Supporting Materials: Statistical Analysis Plan (SAP)
• Supporting Materials: Clinical Study Report (CSR)
• Supporting Materials: 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

• Current Responsible Party: AbbVie
• Original Responsible Party: Same as current
• Current Study Sponsor: AbbVie
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: AbbVie Inc.; AbbVie

• PRS Account: AbbVie
• Verification Date: July 2022