A Study With Upadacitinib (ABT-494) in Subjects From China and Selected Countries With Moderately to Severely Active Rheumatoid Arthritis Who Have Had an Inadequate Response to Conventional Synthetic Disease-Modifying Anti-Rheumatic Drugs (csDMARDs)

A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study With Upadacitinib (ABT-494) in Subjects From China and Selected Countries With Moderately to Severely Active Rheumatoid Arthritis Who Have Had an Inadequate Response to Conventional Synthetic Disease-Modifying Anti-Rheumatic Drugs (csDMARDs)

The study objectives of Period 1 of this study were to compare the efficacy, safety, and tolerability of upadacitinib versus placebo for the treatment of signs and symptoms of subjects from China and selected countries including Brazil and South Korea with moderately to severely active rheumatoid arthritis (RA) who are on a stable dose of csDMARDs and have an inadequate response to csDMARDs.

The study objective of Period 2 is to evaluate the long-term safety, tolerability, and efficacy of upadacitinib in subjects with RA who have completed Period 1.

Study Overview

• Status: Completed
• Conditions: Rheumatoid Arthritis (RA)
• Intervention / Treatment: Drug: Placebo; Drug: Upadacitinib

Detailed Description

This is a Phase 3 multicenter study that includes two periods. Period 1 is a 12-week, randomized, double-blind, parallel-group, placebo-controlled period designed to compare the safety and efficacy of upadacitinib versus placebo for the treatment of signs and symptoms of participants with moderately to severely active RA who are on a stable dose of csDMARDs and have an inadequate response to csDMARDs. Period 2 is an open label 52 week extension period to evaluate the long-term safety, tolerability, and efficacy of upadacitinib in participants with RA who have completed Period 1.

• Study Type: Interventional
• Enrollment (Actual): 338
• Phase: Phase 3

Contacts and Locations

Study Locations

• Brazil
  • Parana
    • Curitiba, Parana, Brazil, 80030-110
      • Ceti - Centro de Estudos Em Terapias Inovadoras Ltda /Id# 152964
    • Maringa, Parana, Brazil, 87015-000
      • Parana Medical Research Center /ID# 153507
  • Rio Grande Do Sul
    • Porto Alegre, Rio Grande Do Sul, Brazil, 90480-000
      • LMK Sevicos Medicos S/S /ID# 152963
  • Sao Paulo
    • Sao Jose Do Rio Preto, Sao Paulo, Brazil, 15090-000
      • Fundacao Faculdade Regional de Medicina de Sao Jose do Rio Preto /ID# 152961
    • São Paulo, Sao Paulo, Brazil, 04266-010
      • CEPIC - Centro Paulista de Investigação Clínica e Serviços Médicos Ltda /ID# 152966
• China
  • Beijing, China, 100053
    • Xuanwu Hosp Capital Med Univ /ID# 161118
  • Beijing, China, 100730
    • Peking Union Med College Hosp /ID# 161107
  • Changsha, China, 410000
    • The Second Xiangya Hospital of Central South University /ID# 162152
  • Kunming, China, 650032
    • First Affiliated Hospital of Kunming Medical University /ID# 164637
  • Nanjing, China, 210029
    • Jiangsu Province Hospital /ID# 161122
  • Pingxiang, China, 337055
    • Pingxiang People's Hospital /ID# 162151
  • Shantou Guangdong, China, 515041
    • 1st Aff Hosp of Shantou Univ /ID# 162165
  • Taiyuan, China, 030001
    • The Second Hospital of Shanxi /ID# 162164
  • Tianjin, China, 300052
    • Tianjin Med Univ General Hosp /ID# 162155
  • Urumqi, China, 830001
    • People's Hospital of Xinjiang /ID# 162157
  • Xi'an, China, 710061
    • First Affiliated Hospital of Xi'an Jiaotong University /ID# 162150
  • Anhui
    • Bengbu, Anhui, China, 233099
      • 1st Aff Hosp of Bengbu Med Col /ID# 162161
    • Hefei, Anhui, China, 230001
      • Anhui Provincial Hospital /ID# 161117
    • Shanghai, Anhui, China, 200032
      • Zhongshan Hosp. of Fudan Uni. /ID# 161108
  • Fujian
    • Xiamen, Fujian, China, 361003
      • The 1st Aff Hosp Xiamen Univ /ID# 162154
  • Hunan
    • Zhuzhou, Hunan, China, 412007
      • Zhuzhou Central Hospital /ID# 162153
  • Inner Mongolia
    • Baotou, Inner Mongolia, China, 014016
      • The First Affiliated Hospital /ID# 163747
  • Jiangsu
    • Changzhou, Jiangsu, China, 213004
      • The First People's Hospital /ID# 168462
  • Jiangxi
    • Jiujiang, Jiangxi, China, 332000
      • The First People's Hospital of Jiujiang /ID# 168461
  • Jilin
    • Changchun, Jilin, China, 130021
      • The First Hosp of Jilin Univ /ID# 161116
  • Shandong
    • Jining, Shandong, China, 272001
      • Jining No.1 People's Hospital /ID# 162158
  • Shanghai
    • Shanghai, Shanghai, China, 200433
      • Shanghai Changhai Hospital /ID# 161123
  • Sichuan
    • Chengdu, Sichuan, China, 610041
      • West China Hospital /ID# 161119
• Korea, Republic of
  • Seoul, Korea, Republic of, 05505
    • Asan Medical Center /ID# 163909
  • Seoul, Korea, Republic of, 06973
    • Chung-Ang University Hostipal /ID# 209076
  • Chungcheongnamdo
    • Cheonan-si, Chungcheongnamdo, Korea, Republic of, 31151
      • SoonChunHyang University CheonAn Hospital /ID# 209078
  • Daegu Gwang Yeogsi
    • Daegu, Daegu Gwang Yeogsi, Korea, Republic of, 41944
      • Kyungpook National Univ Hosp /ID# 166919
  • Daejeon Gwang Yeogsi
    • Jung-gu, Daejeon Gwang Yeogsi, Korea, Republic of, 35015
      • Chungnam National University Hospital /ID# 167727
  • Gyeonggido
    • Suwon, Gyeonggido, Korea, Republic of, 16247
      • St. Vincent's Hospital /ID# 166918
    • Suwon-si, Gyeonggido, Korea, Republic of, 16499
      • Ajou University Hospital /ID# 163912
  • Incheon Gwang Yeogsi
    • Jung-gu, Incheon Gwang Yeogsi, Korea, Republic of, 22332
      • Inha University Hospital /ID# 163910
  • Jeonranamdo
    • Gwangju, Jeonranamdo, Korea, Republic of, 61469
      • Chonnam National University Hospital /ID# 167726
  • Seoul Teugbyeolsi
    • Dongdaemun-gu, Seoul Teugbyeolsi, Korea, Republic of, 02447
      • Kyung Hee University Medical Center /ID# 163908
    • Dongjak-gu, Seoul Teugbyeolsi, Korea, Republic of, 07061
      • SMG-SNU Boramae Medical Center /ID# 163911
    • Seodaemun-gu, Seoul Teugbyeolsi, Korea, Republic of, 03722
      • Yonsei University Health System, Severance Hospital /ID# 168421
    • Seongdong-gu, Seoul Teugbyeolsi, Korea, Republic of, 04763
      • Hanyang University Seoul Hospi /ID# 163913
    • Seoul, Seoul Teugbyeolsi, Korea, Republic of, 05030
      • Konkuk University Medical Ctr /ID# 206148
    • Seoul, Seoul Teugbyeolsi, Korea, Republic of, 07345
      • The Catholic University of Korea, Yeouido St. Mary's Hospital /ID# 204224

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Diagnosis of RA for ≥ 3 months who also fulfill the 2010 American College of Rheumatology (ACR)/ European League Against Rheumatism (EULAR) classification criteria for RA.

• Participants have been receiving csDMARD therapy ≥ 3 months and on a stable dose for ≥ 4 weeks prior to the first dose of study drug.

  1. Participants must have failed (lack of efficacy) at least one of the following: methotrexate (MTX), sulfasalazine, or leflunomide.
  2. The following csDMARDs are allowed: oral or parenteral MTX, sulfasalazine, hydroxychloroquine, chloroquine, and leflunomide.
  3. A combination of up to two background csDMARDs is allowed except the combination of MTX and leflunomide.

• Participant meets both of the following disease activity criteria:

  1. ≥ 6 swollen joints (based on 66 joint counts) and ≥ 6 tender joints (based on 68 joint counts) at Screening and Baseline Visits; and
  2. High-sensitivity C-Reactive Protein (hsCRP) ≥ 3 mg/L at Screening

• Participants with prior exposure to at most one biological disease-modifying anti-rheumatic drugs (bDMARD) may be enrolled (up to 20% of total number of subjects). Specifically, prior to enrollment:

  1. Participants with limited exposure to bDMARD (< 3 months) OR
  2. Participants who are responding to a bDMARD therapy but had to discontinue due to intolerability (regardless of treatment duration).
• Participants must have discontinued bDMARD therapy prior to the first dose of study drug.

Exclusion Criteria:

• Prior exposure to any Janus kinase (JAK) inhibitor (including but not limited to tofacitinib, baricitinib, and filgotinib).
• Participants who are considered inadequate responders (lack of efficacy) to bDMARD therapy as defined 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 including ankylosing spondylitis and non-radiographic axial spondyloarthritis, 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
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
PLACEBO_COMPARATOR: Placebo / Upadacitinib 15 mg; Participants randomized to receive placebo once daily for 12 weeks in Period 1 followed by upadacitinib 15 mg once daily for up to 52 weeks in Period 2.	Drug: Placebo; Tablets for oral administration; Drug: Upadacitinib; Tablets for oral administration; Other Names: ABT-494; RINVOQ™
EXPERIMENTAL: Upadacitinib 15 mg; Participants randomized to receive upadacitinib 15 mg once daily for 12 weeks in Period 1 and up to an additional 52 weeks in Period 2.	Drug: Upadacitinib; Tablets for oral administration; Other Names: ABT-494; RINVOQ™

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	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 activityPatient global assessment of disease activityPatient assessment of painHealth Assessment Questionnaire - Disability Index (HAQ-DI)High-sensitivity C-reactive protein (hsCRP).	Baseline and Week 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 activityPatient global assessment of disease activityPatient assessment of painHealth Assessment Questionnaire - Disability Index (HAQ-DI)High-sensitivity C-reactive protein (hsCRP).	Baseline and Week 12
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
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
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 activityPatient global assessment of disease activityPatient assessment of painHealth Assessment Questionnaire - Disability Index (HAQ-DI)High-sensitivity C-reactive protein (hsCRP).	Baseline and Week 12
Change From Baseline in Disease Activity Score Based on CRP (DAS28 [CRP]) at Week 12	The 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 10, where higher scores indicate more disease activity. A negative change from Baseline in DAS28 (CRP) indicates improvement in disease activity.	Baseline and Week 12
Percentage of Participants Achieving Low Disease Activity (LDA) Based on DAS28 (CRP) at Week 12	Low disease activity based on DAS28 (CRP) is defined a DAS28 (CRP) score of ≤ 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), and hsCRP (in mg/L). Scores on the DAS28 range from 0 to 10, where higher scores indicate more disease activity. A DAS28 score less than or equal to 3.2 indicates low disease activity.	Week 12
Percentage of Participants Achieving Clinical Remission Based on DAS28 (CRP) at Week 12	Clinical remission (CR) based on DAS28 (CRP) is defined as achieving a DAS28 (CRP) score 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 10, where higher scores indicate more disease activity.	Week 12
Percentage of Participants Achieving Low Disease Activity Based on Clinical Disease Activity Index (CDAI) at Week 12	Low disease activity based on 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 76 with higher scores indicating higher disease activity.	Week 12
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 activityPatient global assessment of disease activityPatient assessment of painHealth Assessment Questionnaire - Disability Index (HAQ-DI)High-sensitivity C-reactive protein (hsCRP).	Baseline and Week 1

Collaborators and Investigators

• Sponsor: AbbVie

Study record dates

Study Major Dates

• Study Start (ACTUAL): January 3, 2018
• Primary Completion (ACTUAL): August 14, 2019
• Study Completion (ACTUAL): September 3, 2020

Study Registration Dates

• First Submitted: November 2, 2016
• First Submitted That Met QC Criteria: November 2, 2016
• First Posted (ESTIMATE): November 4, 2016

Study Record Updates

• Last Update Posted (ACTUAL): September 27, 2021
• Last Update Submitted That Met QC Criteria: August 30, 2021
• Last Verified: August 1, 2021

More Information

Terms related to this study

• Keywords: Rheumatoid Arthritis; ABT-494; Conventional Synthetic Disease-Modifying Anti-Rheumatic Drugs (csDMARDs)
• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Joint Diseases; Musculoskeletal Diseases; Connective Tissue Diseases; Arthritis; Arthritis, Rheumatoid; Rheumatic Diseases; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antirheumatic Agents; Protein Kinase Inhibitors; Janus Kinase Inhibitors; Upadacitinib
• Other Study ID Numbers: M15-557

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD 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.
• IPD Sharing Time Frame: Data requests can be submitted at any time and the data will be accessible for 12 months, with possible extensions considered.
• IPD Sharing 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.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; CSR

Drug and device information, study documents

• 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.: Yes