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 ( SELECT-CHOICE ) (SELECT-CHOICE)

• ClinicalTrials.gov Identifier: NCT03086343
• Recruitment Status: Active, not recruiting
• First Posted: March 22, 2017
• Last Update Posted: October 8, 2019
• Sponsor: AbbVie
• Information provided by (Responsible Party): AbbVie

Study Description

Brief Summary:

The comparison of safety and efficacy of upadacitinib versus abatacept in participants with rheumatoid arthritis on a stable background conventional synthetic Disease Modifying Anti-Rheumatic Drug (csDMARD) who have an inadequate response or intolerance to biologic DMARDs.

Condition or disease	Intervention/treatment	Phase
Rheumatoid Arthritis (RA)	Drug: Upadacitinib matching placebo; Drug: Abatacept matching placebo; Drug: Upadacitinib; Drug: Abatacept	Phase 3

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 657 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 5, 2022

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: Abatacept followed by upadacitinib; Intravenous (IV) infusion of abatacept at Baseline, Week 2, Week 4, Week 8, Week 12, Week 16 and Week 20 followed by upadacitinib starting at week 24 up to 5 years.	Drug: Upadacitinib matching placebo; Oral tablet; Drug: Abatacept; IV infusion
Experimental: Upadacitinib; Once daily for 24 weeks during Period 1 and up to 5 years during Period 2.	Drug: Abatacept matching placebo; IV infusion; Drug: Upadacitinib; Oral Tablet; Other Name: ABT-494

Outcome Measures

Primary Outcome Measures :

1. 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.

Secondary Outcome Measures :

1. 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.
2. 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.

Eligibility Criteria

• 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.
• Participants have been treated for >= 3 months 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 hsCRP >= 3 mg/L at Screening .

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 milli liter (mL)/minute/1.73 meter (m)^2; total white blood cell count < 2,500/micro liter (μL); absolute neutrophil count < 1,500/μL; platelet count < 100,000/μL; absolute lymphocyte count < 800/μL; and hemoglobin < 10 g/ deciliter (dL).

Contacts and Locations

  Show 161 Study Locations

Sponsors and Collaborators

AbbVie

Investigators

• Study Director: AbbVie Inc.; AbbVie

More Information

• Responsible Party: AbbVie
• ClinicalTrials.gov Identifier: NCT03086343 History of Changes
• Other Study ID Numbers: M15-925; 2016-000933-37 ( EudraCT Number )
• First Posted: March 22, 2017
• Last Update Posted: October 8, 2019
• Last Verified: October 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

• 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:

Musculoskeletal Disease; Arthritis; Joint Disease; Anti-inflammatory agents; Antirheumatic agents

Additional relevant MeSH terms:

Arthritis; Arthritis, Rheumatoid; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases; Abatacept; Upadacitinib; Antirheumatic Agents; Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs; Janus Kinase Inhibitors; Protein Kinase Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action