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)

Rheumatoid Arthritis (RA) Clinical Trial

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02955212
• Other study ID #: M15-557
• Status: Completed
• Phase: Phase 3
• Start date: January 3, 2018
• Est. completion date: September 3, 2020

Study information

• Verified date: August 2021
• Source: AbbVie
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 338
• Est. completion date: September 3, 2020
• Est. primary completion date: August 14, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Arthritis
• Arthritis, Rheumatoid
• Rheumatic Diseases
• Rheumatoid Arthritis (RA)

Intervention

Drug:
• Upadacitinib
Tablets for oral administration
• Placebo
Tablets for oral administration

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
AbbVie

Countries where clinical trial is conducted

Brazil,  China,  Korea, Republic of, 

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 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
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	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 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
Secondary	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
Secondary	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
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	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