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

NCT ID: NCT02720523

Last Updated: 2023-06-07

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 197 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-03-22
• Study Completion Date: 2022-06-07

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)

Conditions

Rheumatoid Arthritis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

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.

Group Type: EXPERIMENTAL

Placebo

Intervention Type: DRUG

Tablet; Oral

Upadacitinib

Intervention Type: DRUG

Tablet; Oral

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.

Group Type: EXPERIMENTAL

Placebo

Intervention Type: DRUG

Tablet; Oral

Upadacitinib

Intervention Type: DRUG

Tablet; Oral

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.

Group Type: EXPERIMENTAL

Placebo

Intervention Type: DRUG

Tablet; Oral

Upadacitinib

Intervention Type: DRUG

Tablet; Oral

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.

Group Type: EXPERIMENTAL

Upadacitinib

Intervention Type: DRUG

Tablet; Oral

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.

Group Type: EXPERIMENTAL

Upadacitinib

Intervention Type: DRUG

Tablet; Oral

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.

Group Type: EXPERIMENTAL

Upadacitinib

Intervention Type: DRUG

Tablet; Oral

Interventions

Placebo

Tablet; Oral

Intervention Type: DRUG

Upadacitinib

Tablet; Oral

Intervention Type: DRUG

Other Intervention Names

ABT-494; RINVOQ™

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

AbbVie

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

AbbVie Inc.

Role: STUDY_DIRECTOR

AbbVie

Locations

Nagoya University Hospital /ID# 148005

Nagoya, Aichi-ken, Japan

Hamanomachi Hospital /ID# 147991

Fukuoka, Fukuoka, Japan

Kyushu University Hospital /ID# 148008

Fukuoka, Fukuoka, Japan

Inoue Hospital /ID# 147966

Takasaki, Gunma, Japan

National Hospital Organization Asahikawa Medical Center /ID# 147994

Asahikawa, Hokkaido, Japan

Katayama Orthopedic Rheumatology Clinic /ID# 147976

Asahikawa, Hokkaido, Japan

The Hospital of Hyogo College of Medicine /ID# 147978

Nishinomiya-shi, Hyōgo, Japan

National Hospital Organization Sagamihara National Hospital /ID# 148221

Sagamihara-shi, Kanagawa, Japan

NHO Osaka Minami Med Ctr /ID# 147986

Osaka, Kawachinagano-shi, Japan

Kumamoto Orthopaedic Hospital /ID# 147972

Kumamoto, Kumamoto, Japan

Tohoku University Hospital /ID# 148435

Sendai, Miyagi, Japan

Medical Corporation Keiai Kai Clinic /ID# 147975

Miyazaki, Miyazaki, Japan

Nagaoka Red Cross Hospital /ID# 147974

Nagaoka-shi, Niigata, Japan

Niigata Rheumatic Center /ID# 148002

Shibata-shi, Niigata, Japan

Saitama Medical Center, Saitama Medical University /ID# 147965

Kawagoe-shi, Saitama, Japan

Jichi Medical University Hospital /ID# 148220

Shimotsuke-shi, Tochigi, Japan

St.Luke's International Hospital /ID# 147969

Chuo-ku, Tokyo, Japan

Ichinomiya Municipal Hospital /ID# 147992

Ichinomiya-shi, Tokyo, Japan

Toho University Ohashi Medical Center /ID# 148003

Meguro-ku, Tokyo, Japan

Setagaya Rheumatic Clinic /ID# 148009

Setagaya-ku, Tokyo, 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

Tokito Clinic Rheumatology and Orthopaedics Surgery /ID# 147980

Shimonoseki-shi, Yamaguchi, Japan

NHO Chiba-East-Hospital /ID# 147996

Chiba, , 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

Hiroshima Rheumatology Clinic /ID# 147981

Hiroshima, , Japan

Matsubara Mayflower Hospital /ID# 147967

Katō, , Japan

Kumamoto Rheumatology Clinic /ID# 147988

Kumamoto, , Japan

St. Mary's Hospital /ID# 147979

Kurume, , Japan

Kagawa University Hospital /ID# 148001

Kyoto, , Japan

Marunouchi Hospital /ID# 147973

Matsumoto, , Japan

Yu Family Clinic /ID# 147990

Miyagi, , Japan

JP Red Cross Nagoya Daiichi /ID# 147995

Nagoya, , Japan

Kondo Clinic for Ortho & Rheum /ID# 147984

Nagoya, , Japan

Okayama City Gen Med Ctr /ID# 148000

Okayama, , Japan

Oribe Clinic of Rheumatology and Internal Medicine /ID# 149308

Ōita, , Japan

Miyashita Rheumatology Clinic /ID# 147997

Ōmura, , Japan

Sagawa Akira Rheumatology Clin /ID# 147987

Sapporo, , Japan

Sapporo City General Hospital /ID# 147968

Sapporo, , Japan

Hikarigaoka Spellman Hospital /ID# 147993

Sendai, , Japan

Honjo Rheumatism Clinic /ID# 147983

Takaoka, , 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, , Japan

Countries

Japan

References

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.

Reference Type: BACKGROUND

PMID: 32277824 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 34041702 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 33407801 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

https://www.abbvieclinicaltrials.com/study/?id=M14-663#additional-resources-section

clinical study report synopsis

Other Identifiers

M14-663

Identifier Type: -

Identifier Source: org_study_id