A Study Comparing Upadacitinib (ABT-494) to Placebo in Adults With Rheumatoid Arthritis on a Stable Dose of Conventional Synthetic Disease-Modifying Antirheumatic Drugs (csDMARDs) Who Have an Inadequate Response to csDMARDs Alone (SELECT-NEXT)
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| ClinicalTrials.gov Identifier: NCT02675426 |
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Recruitment Status :
Completed
First Posted : February 5, 2016
Results First Posted : October 7, 2019
Last Update Posted : March 31, 2022
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| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Rheumatoid Arthritis | Drug: Placebo Drug: Upadacitinib | Phase 3 |
This Phase 3 multicenter study included two periods. Period 1 was a 12-week, randomized, double-blind, parallel-group, placebo-controlled period designed to compare the safety and efficacy of upadacitinib 30 mg once daily and 15 mg once daily versus placebo for the treatment of signs and symptoms of adults with moderately to severely active rheumatoid arthritis (RA) who were on a stable dose of csDMARDs and had an inadequate response to csDMARDs.
Period 2 is a blinded long-term (up to 5 years) extension period to evaluate the long-term safety, tolerability, and efficacy of upadacitinib 30 mg once daily and 15 mg daily in participants who had completed Period 1 that is currently ongoing.
Participants were to be randomized in a 2:2:1:1 ratio using interactive response technology (IRT) to receive double-blind study drug in one of the following treatment groups:
- Group 1: Upadacitinib 30 mg QD in Period 1 → Upadacitinib 30 mg QD in Period 2
- Group 2: Upadacitinib 15 mg QD in Period 1 → Upadacitinib 15 mg QD in Period 2
- Group 3: Placebo in Period 1 → Upadacitinib 30 mg QD in Period 2
- Group 4: Placebo in Period 1 → Upadacitinib 15 mg QD in Period 2
Randomization was stratified by prior exposure to biological disease-modifying anti-rheumatic drug (bDMARD) (yes/no) and geographic region.
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 661 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 Study Comparing Upadacitinib (ABT-494) to Placebo in Subjects With Moderately to Severely Active Rheumatoid Arthritis Who Are on a Stable Dose of Conventional Synthetic Disease-Modifying Anti-Rheumatic Drugs (csDMARDs) and Have an Inadequate Response to csDMARDs |
| Actual Study Start Date : | December 17, 2015 |
| Actual Primary Completion Date : | April 21, 2017 |
| Actual Study Completion Date : | March 10, 2022 |
| Arm | Intervention/treatment |
|---|---|
|
Experimental: Upadacitinib 15 mg
Period 1: Participants receive Upadacitinib 15 mg once daily for 12 weeks. Period 2: Participants will continue on Upadacitinib 15 mg once daily. |
Drug: Upadacitinib
Tablet; Oral
Other Names:
|
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Experimental: Upadacitinib 30 mg
Period 1: Participants receive Upadacitinib 30 mg once daily for 12 weeks. Period 2: Participants will continue on Upadacitinib 30 mg once daily until participants begin to receive Upadacitinib 15 mg once daily. |
Drug: Upadacitinib
Tablet; Oral
Other Names:
|
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Experimental: Placebo and Upadacitinib 15 mg
Period 1: Participants receive Placebo once daily for 12 weeks. Period 2: Participants will receive Upadacitinib 15 mg once daily. |
Drug: Placebo
Tablet; Oral Drug: Upadacitinib Tablet; Oral
Other Names:
|
|
Experimental: Placebo and Upadacitinib 30 mg
Period 1: Participants receive Placebo once daily for 12 weeks. Period 2: Participants will receive Upadacitinib 30 mg once daily until participants begin to receive Upadacitinib 15 mg once daily. |
Drug: Placebo
Tablet; Oral Drug: Upadacitinib Tablet; Oral
Other Names:
|
- Percentage of Participants With an American College of Rheumatology 20% (ACR20) Response at Week 12 [ Time Frame: Baseline and week 12 ]
The primary endpoint for United States (US)/Food and Drug Administration (FDA) regulatory purposes was ACR 20% response (ACR20) at Week 12. Participants who met the following 3 conditions for improvement from baseline were classified as meeting the ACR20 response criteria:
- ≥ 20% improvement in 68-tender joint count;
- ≥ 20% improvement in 66-swollen joint count; and
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≥ 20% improvement in at least 3 of the 5 following parameters:
- Physician global assessment of disease activity
- Patient global assessment of disease activity
- Patient assessment of pain
- Health Assessment Questionnaire - Disability Index (HAQ-DI)
- High-sensitivity C-reactive protein (hsCRP).
- Percentage of Participants Achieving Low Disease Activity (LDA) Based on DAS28(CRP) at Week 12 [ Time Frame: Week 12 ]
The primary endpoint for European Union (EU)/European Medicines Agency (EMA) regulatory purposes was low disease activity, based on a Disease Activity Score 28 (DAS28)-CRP score of ≤ 3.2 at week 12.
The DAS28 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), and hsCRP (in mg/L). Scores on the DAS28 range from 0 to approximately 10, where higher scores indicate more disease activity.
A DAS28 score less than or equal to 3.2 indicates low disease activity.
- Change From Baseline in in Disease Activity Score 28 (CRP) at Week 12 [ Time Frame: Baseline and week 12 ]The DAS28 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), and 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 in DAS28 (CRP) indicates improvement in disease activity.
- Change From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) at Week 12 [ Time Frame: Baseline and week 12 ]
The Health Assessment Questionnaire - Disability Index is a patient-reported questionnaire that measures the degree of difficulty a person has in accomplishing tasks in 8 functional areas (dressing, arising, eating, walking, hygiene, reaching, gripping, and errands and chores) over the past week. Participants assessed their ability to do each task on a scale from 0 (without any difficulty) to 3 (unable to do). Scores were averaged to provide an overall score ranging from 0 to 3, where 0 represents no disability and 3 represents very severe, high-dependency disability.
A negative change from Baseline in the overall score indicates improvement.
- Change From Baseline in Short-Form 36 (SF-36) Physical Component Score (PCS) at Week 12 [ Time Frame: Baseline and Week 12 ]
The Short Form 36-Item Health Survey (SF-36) Version 2 is a self-administered questionnaire that measures the impact of disease on overall quality of life during the past 4 weeks. The SF-36 consists of 36 questions in eight domains (physical function, pain, general and mental health, vitality, social function, physical and emotional health).
The physical component score is a weighted combination of the 8 subscales with positive weighting for physical functioning, role-physical, bodily pain, and general health. The PCS was calculated using norm-based scoring so that 50 is the average score and the standard deviation equals 10. Higher scores are associated with better functioning/quality of life; a positive change from baseline score indicates an improvement.
- Percentage of Participants Achieving Clinical Remission Based on DAS28 (CRP) at Week 12 [ Time Frame: Week 12 ]
Clinical remission (CR) based on DAS28 (CRP) is defined as achieving a DAS28 (CRP) of less than 2.6.
DAS28 (CRP) 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), and hsCRP (in mg/L). Scores on the DAS28 range from 0 to approximately 10, where higher scores indicate more disease activity.
- Percentage of Participants Achieving Low Disease Activity Based on CDAI at Week 12 [ Time Frame: Week 12 ]
Low disease activity based on the clinical disease activity index (CDAI) is defined as a CDAI score ≤ 10.
CDAI is a composite index for assessing disease activity based on the summation of the total tender joint count (out of 28 evaluated joints), swollen joint count (out of 28 evaluated joints), patient global assessment of disease activity measured on a VAS from 0 to 10 cm, and physician global assessment of disease activity measured on a VAS from 0 to 10 cm. The total CDAI score ranges from 0 to 78 with higher scores indicating higher disease activity.
- Change From Baseline in Duration of Morning Stiffness at Week 12 [ Time Frame: Baseline and week 12 ]Participants were asked to indicate the time it took for them to get as limber as possible after awakening with morning stiffness over the past 7 days.
- Change From Baseline in in Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) [ Time Frame: Baseline and week 12 ]The FACIT Fatigue scale is a 13-item tool that measures an individual's level of fatigue during their usual daily activities over the past 7 days. Each of the fatigue and impact of fatigue items are measured on a four point Likert scale. The FACIT Fatigue Scale is the sum of the individual 13 scores and ranges from 0 to 52 where higher scores indicate better the quality of life. A positive change from baseline indicates improvement.
- Percentage of Participants With an American College of Rheumatology 50% (ACR50) Response at Week 12 [ Time Frame: Baseline and week 12 ]
Participants who met the following 3 conditions for improvement from baseline were classified as meeting the ACR50 response criteria:
- ≥ 50% improvement in 68-tender joint count;
- ≥ 50% improvement in 66-swollen joint count; and
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≥ 50% improvement in at least 3 of the 5 following parameters:
- Physician global assessment of disease activity
- Patient global assessment of disease activity
- Patient assessment of pain
- Health Assessment Questionnaire - Disability Index (HAQ-DI)
- High-sensitivity C-reactive protein (hsCRP).
- Percentage of Participants With an American College of Rheumatology 70% (ACR70) Response at Week 12 [ Time Frame: Baseline and week 12 ]
Participants who met the following 3 conditions for improvement from baseline were classified as meeting the ACR70 response criteria:
- ≥ 70% improvement in 68-tender joint count;
- ≥ 70% improvement in 66-swollen joint count; and
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≥ 70% improvement in at least 3 of the 5 following parameters:
- Physician global assessment of disease activity
- Patient global assessment of disease activity
- Patient assessment of pain
- Health Assessment Questionnaire - Disability Index (HAQ-DI)
- High-sensitivity C-reactive protein (hsCRP).
- Percentage of Participants With an American College of Rheumatology 20% (ACR20) Response at Week 1 [ Time Frame: Baseline and week 1 ]
Participants who met the following 3 conditions for improvement from baseline were classified as meeting the ACR20 response criteria:
- ≥ 20% improvement in 68-tender joint count;
- ≥ 20% improvement in 66-swollen joint count; and
-
≥ 20% improvement in at least 3 of the 5 following parameters:
- Physician global assessment of disease activity
- Patient global assessment of disease activity
- Patient assessment of pain
- Health Assessment Questionnaire - Disability Index (HAQ-DI)
- High-sensitivity C-reactive protein (hsCRP).
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
| Ages Eligible for Study: | 18 Years to 99 Years (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- Adult male or female, at least 18 years old.
- Diagnosis of Rheumatoid Arthritis (RA) for greater than or equal to 3 months.
- Subjects have been receiving conventional synthetic DMARD (csDMARD) therapy for greater than or equal to 3 months and on a stable dose for greater than or equal to 4 weeks prior to the first dose of study drug. The following csDMARDs are allowed: Methotrexate (MTX), sulfasalazine, hydroxychloroquine, chloroquine, and leflunomide.
- Meets the following minimum disease activity criteria: greater than or equal to 6 swollen joints (based on 66 joint counts) and greater than or equal to 6 tender joints (based on 68 joint counts) at Screening and Baseline Visits.
- Subjects with prior exposure to at most one biologic DMARD (bDMARD) may be enrolled (up to 20% of study population) if they have documented evidence of intolerance to bDMARDs or limited exposure (less than 3 months) and have satisfied required washout periods.
Exclusion Criteria:
- Prior exposure to any Janus kinase (JAK) inhibitor (including but not limited to tofacitinib, baricitinib, and filgotinib).
- History of inflammatory joint disease other than RA. History of secondary Sjogren's Syndrome is permitted.
- Subjects who are considered inadequate responders to bDMARD therapy as determined by the Investigator.
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): NCT02675426
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| Study Director: | AbbVie Inc. | AbbVie |
Documents provided by AbbVie:
Publications:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
| Responsible Party: | AbbVie |
| ClinicalTrials.gov Identifier: | NCT02675426 |
| Other Study ID Numbers: |
M13-549 2015-003332-13 ( EudraCT Number ) |
| First Posted: | February 5, 2016 Key Record Dates |
| Results First Posted: | October 7, 2019 |
| Last Update Posted: | March 31, 2022 |
| Last Verified: | March 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 |
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Musculoskeletal Disease Arthritis Joint Disease Anti-inflammatory agents |
Antirheumatic agents Upadacitinib ABT-494 |
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Arthritis Arthritis, Rheumatoid Joint Diseases Musculoskeletal Diseases Rheumatic Diseases Connective Tissue Diseases Autoimmune Diseases |
Immune System Diseases Upadacitinib Janus Kinase Inhibitors Protein Kinase Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Antirheumatic Agents |