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
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Rheumatoid Arthritis
Keywords: rheumatoid arthritis
ABT-494
Japanese
Antirheumatic agents
Lead sponsor: AbbVie
Sponsor class: INDUSTRY
First posted: 2016-03-28
Enrollment: 197
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

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)

Eligibility criteria: 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.

Primary outcomes:
measure: Percentage of Participants With an American College of Rheumatology 20% (ACR20) Response at Week 12
timeFrame: Baseline and Week 12
Secondary outcomes:
measure: Change From Baseline in Disease Activity Score 28 (DAS28) (CRP) at Week 12
timeFrame: Baseline and Week 12
measure: Change From Baseline in Health Assessment Questionnaire - Disability Index (HAQ-DI) at Week 12
timeFrame: Baseline and Week 12
measure: Percentage of Participants With an American College of Rheumatology 50% (ACR50) Response at Week 12
timeFrame: Baseline and Week 12
measure: Percentage of Participants With an American College of Rheumatology 70% (ACR70) Response at Week 12
timeFrame: Baseline and Week 12
measure: Change From Baseline in Short-Form 36 (SF-36) Physical Component Score (PCS) at Week 12
timeFrame: Baseline and Week 12
measure: Percentage of Participants Achieving Low Disease Activity (LDA) Based on DAS28(CRP) at Week 12
timeFrame: Week 12
measure: Percentage of Participants Achieving Clinical Remission (CR) Based on DAS28(CRP) at Week 12
timeFrame: Week 12
measure: Percentage of Participants With an American College of Rheumatology 20% (ACR20) Response at Week 1
timeFrame: Baseline and Week 1
measure: Change From Baseline in in Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) at Week 12
timeFrame: Baseline and Week 12
measure: Change From Baseline in Rheumatoid Arthritis Work Instability Scale (RA-WIS) at Week 12
timeFrame: Baseline and Week 12
measure: Change From Baseline in the Severity of Morning Stiffness at Week 12
timeFrame: Baseline and Week 12
Other outcomes:
Locations:
city: Nagoya-shi
country: Japan
facility: Nagoya University Hospital /ID# 148005
state: Aichi
city: Fukuoka-shi
country: Japan
facility: Hamanomachi Hospital /ID# 147991
state: Fukuoka
city: Fukuoka-shi
country: Japan
facility: Kyushu University Hospital /ID# 148008
state: Fukuoka
city: Takasaki
country: Japan
facility: Inoue Hospital /ID# 147966
state: Gunma
city: Asahikawa
country: Japan
facility: National Hospital Organization Asahikawa Medical Center /ID# 147994
state: Hokkaido
city: Asahikawa
country: Japan
facility: Katayama Orthopedic Rheumatology Clinic /ID# 147976
state: Hokkaido
city: Nishinomiya-shi
country: Japan
facility: The Hospital of Hyogo College of Medicine /ID# 147978
state: Hyogo
city: Sagamihara-shi
country: Japan
facility: National Hospital Organization Sagamihara National Hospital /ID# 148221
state: Kanagawa
city: Osaka
country: Japan
facility: NHO Osaka Minami Med Ctr /ID# 147986
state: Kawachinagano-shi
city: Kumamoto-shi
country: Japan
facility: Kumamoto Orthopaedic Hospital /ID# 147972
state: Kumamoto
city: Sendai-shi
country: Japan
facility: Tohoku University Hospital /ID# 148435
state: Miyagi
city: Miyazaki-shi
country: Japan
facility: Medical Corporation Keiai Kai Clinic /ID# 147975
state: Miyazaki
city: Nagaoka-shi
country: Japan
facility: Nagaoka Red Cross Hospital /ID# 147974
state: Niigata
city: Shibata-shi
country: Japan
facility: Niigata Rheumatic Center /ID# 148002
state: Niigata
city: Kawagoe-shi
country: Japan
facility: Saitama Medical Center, Saitama Medical University /ID# 147965
state: Saitama
city: Shimotsuke-shi
country: Japan
facility: Jichi Medical University Hospital /ID# 148220
state: Tochigi
city: Chuo-ku
country: Japan
facility: St.Luke's International Hospital /ID# 147969
state: Tokyo
city: Ichinomiya-shi
country: Japan
facility: Ichinomiya Municipal Hospital /ID# 147992
state: Tokyo
city: Meguro-ku
country: Japan
facility: Toho University Ohashi Medical Center /ID# 148003
state: Tokyo
city: Setagaya-ku
country: Japan
facility: Setagaya Rheumatic Clinic /ID# 148009
state: Tokyo
city: Shinjuku-ku
country: Japan
facility: Keio University Hospital /ID# 147982
state: Tokyo
city: Shinjuku-ku
country: Japan
facility: Tokyo Women's Medical University Hospital /ID# 148007
state: Tokyo
city: Sumida-ku
country: Japan
facility: Medical Corporation Uchida Clinic /ID# 148219
state: Tokyo
city: Shimonoseki-shi
country: Japan
facility: Tokito Clinic Rheumatology and Orthopaedics Surgery /ID# 147980
state: Yamaguchi
city: Chiba
country: Japan
facility: NHO Chiba-East-Hospital /ID# 147996
city: Fukui
country: Japan
facility: Sugimoto Rheumatology and Internal Medicine Clinic /ID# 147989
city: Fukuoka
country: Japan
facility: Hopsital of the University of Occupational and Enviromental Health /ID# 147970
city: Fukuoka
country: Japan
facility: Shono Rheumatism Clinic /ID# 147971
city: Hiroshima-Shi
country: Japan
facility: Hiroshima Rheumatology Clinic /ID# 147981
city: Kato
country: Japan
facility: Matsubara Mayflower Hospital /ID# 147967
city: Kumamoto
country: Japan
facility: Kumamoto Rheumatology Clinic /ID# 147988
city: Kurume
country: Japan
facility: St. Mary's Hospital /ID# 147979
city: Kyoto
country: Japan
facility: Kagawa University Hospital /ID# 148001
city: Matsumoto
country: Japan
facility: Marunouchi Hospital /ID# 147973
city: Miyagi
country: Japan
facility: Yu Family Clinic /ID# 147990
city: Nagoya
country: Japan
facility: JP Red Cross Nagoya Daiichi /ID# 147995
city: Nagoya
country: Japan
facility: Kondo Clinic for Ortho & Rheum /ID# 147984
city: Oita
country: Japan
facility: Oribe Clinic of Rheumatology and Internal Medicine /ID# 149308
city: Okayama
country: Japan
facility: Okayama City Gen Med Ctr /ID# 148000
city: Omura
country: Japan
facility: Miyashita Rheumatology Clinic /ID# 147997
city: Sapporo
country: Japan
facility: Sagawa Akira Rheumatology Clin /ID# 147987
city: Sapporo
country: Japan
facility: Sapporo City General Hospital /ID# 147968
city: Sendai
country: Japan
facility: Hikarigaoka Spellman Hospital /ID# 147993
city: Takaoka
country: Japan
facility: Honjo Rheumatism Clinic /ID# 147983
city: Takikawa
country: Japan
facility: Takikawa Municipal Hospital /ID# 149309
city: Tokyo
country: Japan
facility: Juntendo University Hospital /ID# 147999
city: Tokyo
country: Japan
facility: National Hospital Organization Tokyo Medical Center /ID# 147998
city: Tokyo
country: Japan
facility: Nihon University Itabashi Hosp /ID# 147977
city: Tomakomai
country: Japan
facility: Oki Medical Clinic /ID# 147985
city: Toyonaka
country: Japan
facility: Toneyama National Hospital /ID# 148006
Study officials:
affiliation: AbbVie
name: AbbVie Inc.
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.
citation: 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.