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

Rheumatoid Arthritis Clinical Trial

— SELECTSUNRISE  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02720523
• Other study ID #: M14-663
• Status: Completed
• Phase: Phase 2/Phase 3
• Start date: March 22, 2016
• Est. completion date: June 7, 2022

Study information

• Verified date: June 2023
• Source: AbbVie
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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)

Recruitment information / eligibility

• Status: Completed
• Enrollment: 197
• Est. completion date: June 7, 2022
• Est. primary completion date: August 3, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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:

1. Subjects with limited exposure to bDMARD (< 3 months) OR

2. 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.

Related Conditions & MeSH terms

• Arthritis
• Arthritis, Rheumatoid
• Rheumatoid Arthritis

Intervention

Drug:
• Placebo
Tablet; Oral
• Upadacitinib
Tablet; Oral

Locations

Country	Name	City	State
Japan	Katayama Orthopedic Rheumatology Clinic /ID# 147976	Asahikawa	Hokkaido
Japan	National Hospital Organization Asahikawa Medical Center /ID# 147994	Asahikawa	Hokkaido
Japan	NHO Chiba-East-Hospital /ID# 147996	Chiba
Japan	St.Luke's International Hospital /ID# 147969	Chuo-ku	Tokyo
Japan	Sugimoto Rheumatology and Internal Medicine Clinic /ID# 147989	Fukui
Japan	Hopsital of the University of Occupational and Enviromental Health /ID# 147970	Fukuoka
Japan	Shono Rheumatism Clinic /ID# 147971	Fukuoka
Japan	Hamanomachi Hospital /ID# 147991	Fukuoka-shi	Fukuoka
Japan	Kyushu University Hospital /ID# 148008	Fukuoka-shi	Fukuoka
Japan	Hiroshima Rheumatology Clinic /ID# 147981	Hiroshima-Shi
Japan	Ichinomiya Municipal Hospital /ID# 147992	Ichinomiya-shi	Tokyo
Japan	Matsubara Mayflower Hospital /ID# 147967	Kato
Japan	Saitama Medical Center, Saitama Medical University /ID# 147965	Kawagoe-shi	Saitama
Japan	Kumamoto Rheumatology Clinic /ID# 147988	Kumamoto
Japan	Kumamoto Orthopaedic Hospital /ID# 147972	Kumamoto-shi	Kumamoto
Japan	St. Mary's Hospital /ID# 147979	Kurume
Japan	Kagawa University Hospital /ID# 148001	Kyoto
Japan	Marunouchi Hospital /ID# 147973	Matsumoto
Japan	Toho University Ohashi Medical Center /ID# 148003	Meguro-ku	Tokyo
Japan	Yu Family Clinic /ID# 147990	Miyagi
Japan	Medical Corporation Keiai Kai Clinic /ID# 147975	Miyazaki-shi	Miyazaki
Japan	Nagaoka Red Cross Hospital /ID# 147974	Nagaoka-shi	Niigata
Japan	JP Red Cross Nagoya Daiichi /ID# 147995	Nagoya
Japan	Kondo Clinic for Ortho & Rheum /ID# 147984	Nagoya
Japan	Nagoya University Hospital /ID# 148005	Nagoya-shi	Aichi
Japan	The Hospital of Hyogo College of Medicine /ID# 147978	Nishinomiya-shi	Hyogo
Japan	Oribe Clinic of Rheumatology and Internal Medicine /ID# 149308	Oita
Japan	Okayama City Gen Med Ctr /ID# 148000	Okayama
Japan	Miyashita Rheumatology Clinic /ID# 147997	Omura
Japan	NHO Osaka Minami Med Ctr /ID# 147986	Osaka	Kawachinagano-shi
Japan	National Hospital Organization Sagamihara National Hospital /ID# 148221	Sagamihara-shi	Kanagawa
Japan	Sagawa Akira Rheumatology Clin /ID# 147987	Sapporo
Japan	Sapporo City General Hospital /ID# 147968	Sapporo
Japan	Hikarigaoka Spellman Hospital /ID# 147993	Sendai
Japan	Tohoku University Hospital /ID# 148435	Sendai-shi	Miyagi
Japan	Setagaya Rheumatic Clinic /ID# 148009	Setagaya-ku	Tokyo
Japan	Niigata Rheumatic Center /ID# 148002	Shibata-shi	Niigata
Japan	Tokito Clinic Rheumatology and Orthopaedics Surgery /ID# 147980	Shimonoseki-shi	Yamaguchi
Japan	Jichi Medical University Hospital /ID# 148220	Shimotsuke-shi	Tochigi
Japan	Keio University Hospital /ID# 147982	Shinjuku-ku	Tokyo
Japan	Tokyo Women's Medical University Hospital /ID# 148007	Shinjuku-ku	Tokyo
Japan	Medical Corporation Uchida Clinic /ID# 148219	Sumida-ku	Tokyo
Japan	Honjo Rheumatism Clinic /ID# 147983	Takaoka
Japan	Inoue Hospital /ID# 147966	Takasaki	Gunma
Japan	Takikawa Municipal Hospital /ID# 149309	Takikawa
Japan	Juntendo University Hospital /ID# 147999	Tokyo
Japan	National Hospital Organization Tokyo Medical Center /ID# 147998	Tokyo
Japan	Nihon University Itabashi Hosp /ID# 147977	Tokyo
Japan	Oki Medical Clinic /ID# 147985	Tomakomai
Japan	Toneyama National Hospital /ID# 148006	Toyonaka

Sponsors (1)

Lead Sponsor	Collaborator
AbbVie

Country where clinical trial is conducted

Japan, 

References & Publications (1)

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants With an American College of Rheumatology 20% (ACR20) Response 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; = 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).	Baseline and Week 12
Secondary	Change From Baseline in Disease Activity Score 28 (DAS28) (CRP) 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 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
Secondary	Change From Baseline in Health Assessment Questionnaire - Disability Index (HAQ-DI) at 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
Secondary	Percentage of Participants With an American College of Rheumatology 50% (ACR50) Response at 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; = 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).	Baseline and Week 12
Secondary	Percentage of Participants With an American College of Rheumatology 70% (ACR70) Response at 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; = 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).	Baseline and Week 12
Secondary	Change From Baseline in Short-Form 36 (SF-36) Physical Component Score (PCS) at 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
Secondary	Percentage of Participants Achieving Low Disease Activity (LDA) Based on DAS28(CRP) at 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
Secondary	Percentage of Participants Achieving Clinical Remission (CR) Based on DAS28(CRP) at 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
Secondary	Percentage of Participants With an American College of Rheumatology 20% (ACR20) Response at 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).	Baseline and Week 1
Secondary	Change From Baseline in in Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) at 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
Secondary	Change From Baseline in Rheumatoid Arthritis Work Instability Scale (RA-WIS) at 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
Secondary	Change From Baseline in the Severity of Morning Stiffness at 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

External Links

•   clinical study report synopsis