Clinical trial NCT02955212: 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)
Official title: 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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Rheumatoid Arthritis (RA)
Keywords: Rheumatoid Arthritis
Conventional Synthetic Disease-Modifying Anti-Rheumatic Drugs (csDMARDs)
ABT-494
Lead sponsor: AbbVie
Sponsor class: INDUSTRY
First posted: 2016-11-04
Enrollment: 338
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: 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.

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.

Eligibility criteria: 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.

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 Based on CRP (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: 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 Based on DAS28 (CRP) at Week 12
timeFrame: Week 12
measure: Percentage of Participants Achieving Low Disease Activity Based on Clinical Disease Activity Index (CDAI) at Week 12
timeFrame: 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: Percentage of Participants With an American College of Rheumatology 20% (ACR20) Response at Week 1
timeFrame: Baseline and Week 1
Other outcomes:
Locations:
city: Curitiba
country: Brazil
facility: Ceti - Centro de Estudos Em Terapias Inovadoras Ltda /Id# 152964
state: Parana
city: Maringa
country: Brazil
facility: Parana Medical Research Center /ID# 153507
state: Parana
city: Porto Alegre
country: Brazil
facility: LMK Sevicos Medicos S/S /ID# 152963
state: Rio Grande Do Sul
city: Sao Jose Do Rio Preto
country: Brazil
facility: Fundacao Faculdade Regional de Medicina de Sao Jose do Rio Preto /ID# 152961
state: Sao Paulo
city: São Paulo
country: Brazil
facility: CEPIC - Centro Paulista de Investigação Clínica e Serviços Médicos Ltda /ID# 152966
state: Sao Paulo
city: Bengbu
country: China
facility: 1st Aff Hosp of Bengbu Med Col /ID# 162161
state: Anhui
city: Hefei
country: China
facility: Anhui Provincial Hospital /ID# 161117
state: Anhui
city: Shanghai
country: China
facility: Zhongshan Hosp. of Fudan Uni. /ID# 161108
state: Anhui
city: Xiamen
country: China
facility: The 1st Aff Hosp Xiamen Univ /ID# 162154
state: Fujian
city: Zhuzhou
country: China
facility: Zhuzhou Central Hospital /ID# 162153
state: Hunan
city: Baotou
country: China
facility: The First Affiliated Hospital /ID# 163747
state: Inner Mongolia
city: Changzhou
country: China
facility: The First People's Hospital /ID# 168462
state: Jiangsu
city: Jiujiang
country: China
facility: The First People's Hospital of Jiujiang /ID# 168461
state: Jiangxi
city: Changchun
country: China
facility: The First Hosp of Jilin Univ /ID# 161116
state: Jilin
city: Jining
country: China
facility: Jining No.1 People's Hospital /ID# 162158
state: Shandong
city: Shanghai
country: China
facility: Shanghai Changhai Hospital /ID# 161123
state: Shanghai
city: Chengdu
country: China
facility: West China Hospital /ID# 161119
state: Sichuan
city: Beijing
country: China
facility: Xuanwu Hosp Capital Med Univ /ID# 161118
city: Beijing
country: China
facility: Peking Union Med College Hosp /ID# 161107
city: Changsha
country: China
facility: The Second Xiangya Hospital of Central South University /ID# 162152
city: Kunming
country: China
facility: First Affiliated Hospital of Kunming Medical University /ID# 164637
city: Nanjing
country: China
facility: Jiangsu Province Hospital /ID# 161122
city: Pingxiang
country: China
facility: Pingxiang People's Hospital /ID# 162151
city: Shantou Guangdong
country: China
facility: 1st Aff Hosp of Shantou Univ /ID# 162165
city: Taiyuan
country: China
facility: The Second Hospital of Shanxi /ID# 162164
city: Tianjin
country: China
facility: Tianjin Med Univ General Hosp /ID# 162155
city: Urumqi
country: China
facility: People's Hospital of Xinjiang /ID# 162157
city: Xi'an
country: China
facility: First Affiliated Hospital of Xi'an Jiaotong University /ID# 162150
city: Cheonan-si
country: Korea, Republic of
facility: SoonChunHyang University CheonAn Hospital /ID# 209078
state: Chungcheongnamdo
city: Daegu
country: Korea, Republic of
facility: Kyungpook National Univ Hosp /ID# 166919
state: Daegu Gwang Yeogsi
city: Jung-gu
country: Korea, Republic of
facility: Chungnam National University Hospital /ID# 167727
state: Daejeon Gwang Yeogsi
city: Suwon-si
country: Korea, Republic of
facility: Ajou University Hospital /ID# 163912
state: Gyeonggido
city: Suwon
country: Korea, Republic of
facility: St. Vincent's Hospital /ID# 166918
state: Gyeonggido
city: Jung-gu
country: Korea, Republic of
facility: Inha University Hospital /ID# 163910
state: Incheon Gwang Yeogsi
city: Gwangju
country: Korea, Republic of
facility: Chonnam National University Hospital /ID# 167726
state: Jeonranamdo
city: Dongdaemun-gu
country: Korea, Republic of
facility: Kyung Hee University Medical Center /ID# 163908
state: Seoul Teugbyeolsi
city: Dongjak-gu
country: Korea, Republic of
facility: SMG-SNU Boramae Medical Center /ID# 163911
state: Seoul Teugbyeolsi
city: Seodaemun-gu
country: Korea, Republic of
facility: Yonsei University Health System, Severance Hospital /ID# 168421
state: Seoul Teugbyeolsi
city: Seongdong-gu
country: Korea, Republic of
facility: Hanyang University Seoul Hospi /ID# 163913
state: Seoul Teugbyeolsi
city: Seoul
country: Korea, Republic of
facility: Konkuk University Medical Ctr /ID# 206148
state: Seoul Teugbyeolsi
city: Seoul
country: Korea, Republic of
facility: The Catholic University of Korea, Yeouido St. Mary's Hospital /ID# 204224
state: Seoul Teugbyeolsi
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center /ID# 163909
city: Seoul
country: Korea, Republic of
facility: Chung-Ang University Hostipal /ID# 209076
Study officials:
affiliation: AbbVie
name: AbbVie Inc.
role: STUDY_DIRECTOR
References: