- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02720523
A Study to Compare Upadacitinib (ABT-494) to Placebo in Adults With Rheumatoid Arthritis (RA) Who Are on a Stable Dose of Conventional Synthetic Disease-Modifying Anti-Rheumatic Drugs (csDMARDs) and Have an Inadequate Response to csDMARDs (SELECTSUNRISE)
A Phase 2b/3, Randomized, Double-Blind Study Comparing Upadacitinib (ABT-494) to Placebo in Japanese 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
This is a randomized, double-blind study comparing ABT-494 to placebo in Japanese participants 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.
Following marketing approval of upadacitinib for rheumatoid arthritis in Japan, this study will become a post-marketing clinical study and include a long-term extension period.
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
This study consisted of a 35-day screening period; a 12-week randomized, double-blind, parallel-group, placebo-controlled treatment period (Period 1); a 248-week blinded long-term extension period (Period 2); and a 30-day follow-up period (call or visit).
Participants who met eligibility criteria were randomized in a 3:3:3:1:1:1 ratio to one of six treatment groups:
- Group 1: Upadacitinib 7.5 mg QD (Period 1) → upadacitinib 7.5 mg QD (Period 2)
- Group 2: Upadacitinib 15 mg QD (Period 1) → upadacitinib 15 mg QD (Period 2)
- Group 3: Upadacitinib 30 mg QD (Period 1) → upadacitinib 30 mg QD (Period 2)
- Group 4: Placebo (Period 1) → upadacitinib 7.5 mg QD (Period 2)
- Group 5: Placebo (Period 1) → upadacitinib 15 mg QD (Period 2)
- Group 6: Placebo (Period 1) → upadacitinib 30 mg QD (Period 2)
Study Type
Enrollment (Actual)
Phase
- Phase 2
- Phase 3
Contacts and Locations
Study Locations
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Chiba, Japan, 260-8712
- NHO Chiba-East-Hospital /ID# 147996
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Fukui, Japan, 910-0068
- Sugimoto Rheumatology and Internal Medicine Clinic /ID# 147989
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Fukuoka, Japan, 8078556
- Hopsital of the University of Occupational and Enviromental Health /ID# 147970
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Fukuoka, Japan, 814-0002
- Shono Rheumatism Clinic /ID# 147971
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Hiroshima-Shi, Japan, 730-0017
- Hiroshima Rheumatology Clinic /ID# 147981
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Kato, Japan, 673-1462
- Matsubara Mayflower Hospital /ID# 147967
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Kumamoto, Japan, 861-5515
- Kumamoto Rheumatology Clinic /ID# 147988
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Kurume, Japan, 830-8543
- St. Mary's Hospital /ID# 147979
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Kyoto, Japan, 615-8256
- Kagawa University Hospital /ID# 148001
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Matsumoto, Japan, 390-0841
- Marunouchi Hospital /ID# 147973
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Miyagi, Japan, 981-0112
- Yu Family Clinic /ID# 147990
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Nagoya, Japan, 453-8511
- JP Red Cross Nagoya Daiichi /ID# 147995
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Nagoya, Japan, 464-0071
- Kondo Clinic for Ortho & Rheum /ID# 147984
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Oita, Japan, 870-0823
- Oribe Clinic of Rheumatology and Internal Medicine /ID# 149308
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Okayama, Japan, 700-8557
- Okayama City Gen Med Ctr /ID# 148000
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Omura, Japan, 856-0836
- Miyashita Rheumatology Clinic /ID# 147997
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Sapporo, Japan, 060-0001
- Sagawa Akira Rheumatology Clin /ID# 147987
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Sapporo, Japan, 060-8604
- Sapporo City General Hospital /ID# 147968
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Sendai, Japan, 983-0833
- Hikarigaoka Spellman Hospital /ID# 147993
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Takaoka, Japan, 933-0874
- Honjo Rheumatism Clinic /ID# 147983
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Takikawa, Japan, 073-0022
- Takikawa Municipal Hospital /ID# 149309
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Tokyo, Japan, 113-8431
- Juntendo University Hospital /ID# 147999
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Tokyo, Japan, 152-8902
- National Hospital Organization Tokyo Medical Center /ID# 147998
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Tokyo, Japan, 173-0032
- Nihon University Itabashi Hosp /ID# 147977
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Tomakomai, Japan, 053-0018
- Oki Medical Clinic /ID# 147985
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Toyonaka, Japan, 560-8552
- Toneyama National Hospital /ID# 148006
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Aichi
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Nagoya-shi, Aichi, Japan, 466-8560
- Nagoya University Hospital /ID# 148005
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Fukuoka
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Fukuoka-shi, Fukuoka, Japan, 810-8539
- Hamanomachi Hospital /ID# 147991
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Fukuoka-shi, Fukuoka, Japan, 812-8582
- Kyushu University Hospital /ID# 148008
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Gunma
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Takasaki, Gunma, Japan, 3700053
- Inoue Hospital /ID# 147966
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Hokkaido
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Asahikawa, Hokkaido, Japan, 070-8644
- National Hospital Organization Asahikawa Medical Center /ID# 147994
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Asahikawa, Hokkaido, Japan, 078-8243
- Katayama Orthopedic Rheumatology Clinic /ID# 147976
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Hyogo
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Nishinomiya-shi, Hyogo, Japan, 663-8501
- The Hospital of Hyogo College of Medicine /ID# 147978
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Kanagawa
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Sagamihara-shi, Kanagawa, Japan, 252-0315
- National Hospital Organization Sagamihara National Hospital /ID# 148221
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Kawachinagano-shi
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Osaka, Kawachinagano-shi, Japan, 586-8521
- NHO Osaka Minami Med Ctr /ID# 147986
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Kumamoto
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Kumamoto-shi, Kumamoto, Japan, 862-0976
- Kumamoto Orthopaedic Hospital /ID# 147972
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Miyagi
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Sendai-shi, Miyagi, Japan, 980-8574
- Tohoku University Hospital /ID# 148435
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Miyazaki
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Miyazaki-shi, Miyazaki, Japan, 880-0053
- Medical Corporation Keiai Kai Clinic /ID# 147975
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Niigata
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Nagaoka-shi, Niigata, Japan, 940-2108
- Nagaoka Red Cross Hospital /ID# 147974
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Shibata-shi, Niigata, Japan, 957-0054
- Niigata Rheumatic Center /ID# 148002
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Saitama
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Kawagoe-shi, Saitama, Japan, 350-8550
- Saitama Medical Center, Saitama Medical University /ID# 147965
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Tochigi
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Shimotsuke-shi, Tochigi, Japan, 329-0498
- Jichi Medical University Hospital /ID# 148220
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Tokyo
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Chuo-ku, Tokyo, Japan, 104-8560
- St.Luke's International Hospital /ID# 147969
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Ichinomiya-shi, Tokyo, Japan, 491-8558
- Ichinomiya Municipal Hospital /ID# 147992
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Meguro-ku, Tokyo, Japan, 1538515
- Toho University Ohashi Medical Center /ID# 148003
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Setagaya-ku, Tokyo, Japan, 156-0052
- Setagaya Rheumatic Clinic /ID# 148009
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Shinjuku-ku, Tokyo, Japan, 160-8582
- Keio University Hospital /ID# 147982
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Shinjuku-ku, Tokyo, Japan, 162-8666
- Tokyo Women's Medical University Hospital /ID# 148007
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Sumida-ku, Tokyo, Japan, 130-0013
- Medical Corporation Uchida Clinic /ID# 148219
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Yamaguchi
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Shimonoseki-shi, Yamaguchi, Japan, 752-0976
- Tokito Clinic Rheumatology and Orthopaedics Surgery /ID# 147980
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
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.
- Subjects have been receiving conventional synthetic disease-modifying anti-rheumatic drug (csDMARD) therapy >= 3 months and on a stable dose for >= 4 weeks prior to the first dose of study drug.
- Subject has >= 6 swollen joints (based on 66 joint counts) and >= 6 tender joints (based on 68 joint counts) at Screening and Baseline Visits.
Subjects with prior exposure to at most one biological disease-modifying anti-rheumatic drug (bDMARD) may be enrolled (up to 20% of total number of subjects) after the required washout period. Specifically, prior to enrollment:
- Subjects with limited exposure to bDMARD (< 3 months) OR
- Subjects who are responding to bDMARD therapy but had to discontinue due to intolerability (regardless of treatment duration).
Exclusion Criteria:
- Prior exposure to any Janus kinase (JAK) inhibitor
- Subjects who are considered inadequate responders (lack of efficacy) to bDMARD therapy, after minimum 3 months treatment, as determined 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 [SpA] including ankylosing spondylitis and non-radiographic axial SpA, reactive arthritis, overlap connective tissue diseases, scleroderma, polymyositis, dermatomyositis, fibromyalgia [currently with active symptoms]). Current diagnosis of secondary Sjogren's Syndrome is permitted.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Quadruple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Placebo / Upadacitinib 7.5 mg
Period 1: Participants will receive placebo once daily for 12 weeks. Period 2: Participants will receive Upadacitinib 7.5 mg once daily for 248 weeks. |
Tablet; Oral
Other Names:
Tablet; Oral
|
Experimental: Placebo / Upadacitinib 15 mg
Period 1: Participants will receive placebo once daily for 12 weeks. Period 2: Participants will receive upadacitinib 15 mg once daily for 248 weeks. |
Tablet; Oral
Other Names:
Tablet; Oral
|
Experimental: Placebo / Upadacitinib 30 mg
Period 1: Participants will receive placebo once daily for 12 weeks. Period 2: Participants will receive upadacitinib 30 mg once daily until regulatory approval of RA indication in Japan at which point they will switch to receive upadacitinib 15 mg once daily. Participants will receive upadacitinib for 248 weeks. |
Tablet; Oral
Other Names:
Tablet; Oral
|
Experimental: Upadacitinib 7.5 mg / Upadacitinib 7.5 mg
Period 1: Participants will receive upadacitinib 7.5 mg once daily for 12 weeks. Period 2: Participants will receive upadacitinib 7.5 mg once daily for 248 weeks. |
Tablet; Oral
Other Names:
|
Experimental: Upadacitinib 15 mg / Upadacitinib 15 mg
Period 1: Participants will receive upadacitinib 15 mg once daily for 12 weeks. Period 2: Participants will receive upadacitinib 15 mg once daily for 248 weeks. |
Tablet; Oral
Other Names:
|
Experimental: Upadacitinib 30 mg / Upadacitinib 30 mg
Period 1: Participants will receive upadacitinib 30 mg once daily for 12 weeks. Period 2: Participants will receive upadacitinib 30 mg once daily until regulatory approval of RA indication in Japan at which point they will switch to receive upadacitinib 15 mg once daily. Participants will receive upadacitinib for 248 weeks. |
Tablet; Oral
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Percentage of Participants With an American College of Rheumatology 20% (ACR20) 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 ACR20 response criteria:
|
Baseline and Week 12
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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. |
Baseline and Week 12
|
Change From Baseline in Disease Activity Score 28 (DAS28) (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 mm), and hsCRP (in mg/L).
Scores on the DAS28 range from 0 to approximately 10, where higher scores indicate more disease activity.
|
Baseline and Week 12
|
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. |
Baseline and Week 12
|
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:
|
Baseline and Week 12
|
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:
|
Baseline and Week 12
|
Percentage of Participants Achieving Low Disease Activity (LDA) Based on DAS28(CRP) at Week 12
Time Frame: Week 12
|
Low disease activity.
was defined as a DAS28 score less than or equal to 3.2.
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 mm), and hsCRP (in mg/L).
Scores on the DAS28 range from 0 to approximately 10, where higher scores indicate more disease activity.
|
Week 12
|
Percentage of Participants Achieving Clinical Remission (CR) Based on DAS28(CRP) at Week 12
Time Frame: Week 12
|
Clinical remission was defined as a DAS28 (CRP) score less than 2.6.
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 mm), and hsCRP (in mg/L).
Scores on the DAS28 range from 0 to approximately 10, where higher scores indicate more disease activity.
|
Week 12
|
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:
|
Baseline and Week 1
|
Change From Baseline in in Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) at Week 12
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 quality of life.
A positive change from Baseline indicates improvement.
|
Baseline and Week 12
|
Change From Baseline in Rheumatoid Arthritis Work Instability Scale (RA-WIS) at Week 12
Time Frame: Baseline and Week 12
|
RA-WIS is a simple validated tool to evaluate work instability (the consequence of a mismatch between an individual's functional ability and their work tasks). RA-WIS consists of 23 questions relating to the participant's functioning in their work environment, each answered as Yes or No. The total score is the number of questions answered Yes, and ranges from 0 to 23. A score < 10 means low risk and no action is needed, scores between 10 and 17 indicate medium risk and appropriate advice and information should be given. If the score is > 17, it means high risk and it could warrant referral. A negative change from Baseline indicates improvement. |
Baseline and Week 12
|
Change From Baseline in the Severity of Morning Stiffness at Week 12
Time Frame: Baseline and Week 12
|
Morning stiffness severity was determined by the Patient's Assessment of Severity and Duration of Morning Stiffness questionnaire.
Participants rated the severity of morning stiffness on awakening over the past 7 days on a scale from 0 (No morning stiffness) to 10 (Worst possible morning stiffness).
|
Baseline and Week 12
|
Collaborators and Investigators
Sponsor
Investigators
- Study Director: ABBVIE INC., AbbVie
Publications and helpful links
General Publications
- Yamaoka K, Tanaka Y, Kameda H, Khan N, Sasaki N, Harigai M, Song Y, Zhang Y, Takeuchi T. The Safety Profile of Upadacitinib in Patients with Rheumatoid Arthritis in Japan. Drug Saf. 2021 Jun;44(6):711-722. doi: 10.1007/s40264-021-01067-x. Epub 2021 May 27.
- Kameda H, Takeuchi T, Yamaoka K, Oribe M, Kawano M, Zhou Y, Othman AA, Pangan AL, Kitamura S, Meerwein S, Tanaka Y. Efficacy and safety of upadacitinib in Japanese patients with rheumatoid arthritis (SELECT-SUNRISE): a placebo-controlled phase IIb/III study. Rheumatology (Oxford). 2020 Nov 1;59(11):3303-3313. doi: 10.1093/rheumatology/keaa084.
- Kameda H, Takeuchi T, Yamaoka K, Oribe M, Kawano M, Yokoyama M, Pangan AL, Konishi Y, Meerwein S, Tanaka Y. Efficacy and safety of upadacitinib over 84 weeks in Japanese patients with rheumatoid arthritis (SELECT-SUNRISE). Arthritis Res Ther. 2021 Jan 6;23(1):9. doi: 10.1186/s13075-020-02387-6.
Helpful Links
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimated)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Immune System Diseases
- Autoimmune Diseases
- Joint Diseases
- Musculoskeletal Diseases
- Rheumatic Diseases
- Connective Tissue Diseases
- Arthritis
- Arthritis, Rheumatoid
- Molecular Mechanisms of Pharmacological Action
- Enzyme Inhibitors
- Antirheumatic Agents
- Protein Kinase Inhibitors
- Janus Kinase Inhibitors
- Upadacitinib
Other Study ID Numbers
- M14-663
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
IPD Plan Description
IPD Sharing Time Frame
IPD Sharing Access Criteria
IPD Sharing Supporting Information Type
- STUDY_PROTOCOL
- SAP
- CSR
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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