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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT02675426




Registration number
NCT02675426
Ethics application status
Date submitted
11/12/2015
Date registered
5/02/2016
Date last updated
5/03/2020

Titles & IDs
Public title
A Study Comparing Upadacitinib (ABT-494) to Placebo in Adults With Rheumatoid Arthritis on a Stable Dose of Conventional Synthetic Disease-Modifying Antirheumatic Drugs (csDMARDs) Who Have an Inadequate Response to csDMARDs Alone
Scientific title
A Phase 3, Randomized, Double-Blind Study Comparing Upadacitinib (ABT-494) to Placebo in 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
Secondary ID [1] 0 0
2015-003332-13
Secondary ID [2] 0 0
M13-549
Universal Trial Number (UTN)
Trial acronym
SELECT-NEXT
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Rheumatoid Arthritis 0 0
Condition category
Condition code
Musculoskeletal 0 0 0 0
Osteoarthritis
Inflammatory and Immune System 0 0 0 0
Rheumatoid arthritis

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Placebo
Treatment: Drugs - Upadacitinib

Experimental: Upadacitinib 15 mg - Period 1: Participants receive Upadacitinib 15 mg once daily for 12 weeks.
Period 2: Participants will continue on Upadacitinib 15 mg once daily.

Experimental: Upadacitinib 30 mg - Period 1: Participants receive Upadacitinib 30 mg once daily for 12 weeks.
Period 2: Participants will continue on Upadacitinib 30 mg once daily until participants begin to receive Upadacitinib 15 mg once daily.

Experimental: Placebo and Upadacitinib 15 mg - Period 1: Participants receive Placebo once daily for 12 weeks.
Period 2: Participants will receive Upadacitinib 15 mg once daily.

Experimental: Placebo and Upadacitinib 30 mg - Period 1: Participants receive Placebo once daily for 12 weeks.
Period 2: Participants will receive Upadacitinib 30 mg once daily until participants begin to receive Upadacitinib 15 mg once daily.


Treatment: Drugs: Placebo
Tablet; Oral

Treatment: Drugs: Upadacitinib
Tablet; Oral

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Percentage of Participants With an American College of Rheumatology 20% (ACR20) Response at Week 12 - The primary endpoint for United States (US)/Food and Drug Administration (FDA) regulatory purposes was ACR 20% response (ACR20) 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).
Timepoint [1] 0 0
Baseline and week 12
Primary outcome [2] 0 0
Percentage of Participants Achieving Low Disease Activity (LDA) Based on DAS28(CRP) at Week 12 - The primary endpoint for European Union (EU)/European Medicines Agency (EMA) regulatory purposes was low disease activity, based on a Disease Activity Score 28 (DAS28)-CRP score of = 3.2 at week 12.
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 approximately 10, where higher scores indicate more disease activity.
A DAS28 score less than or equal to 3.2 indicates low disease activity.
Timepoint [2] 0 0
Week 12
Secondary outcome [1] 0 0
Change From Baseline in in Disease Activity Score 28 (CRP) at Week 12 - 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 approximately 10, where higher scores indicate more disease activity. A negative change from baseline in DAS28 (CRP) indicates improvement in disease activity.
Timepoint [1] 0 0
Baseline and week 12
Secondary outcome [2] 0 0
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.
Timepoint [2] 0 0
Baseline and week 12
Secondary outcome [3] 0 0
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.
Timepoint [3] 0 0
Baseline and Week 12
Secondary outcome [4] 0 0
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) 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 approximately 10, where higher scores indicate more disease activity.
Timepoint [4] 0 0
Week 12
Secondary outcome [5] 0 0
Percentage of Participants Achieving Low Disease Activity Based on CDAI at Week 12 - Low disease activity based on the clinical disease activity index (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 78 with higher scores indicating higher disease activity.
Timepoint [5] 0 0
Week 12
Secondary outcome [6] 0 0
Change From Baseline in Duration of Morning Stiffness at Week 12 - Participants were asked to indicate the time it took for them to get as limber as possible after awakening with morning stiffness over the past 7 days.
Timepoint [6] 0 0
Baseline and week 12
Secondary outcome [7] 0 0
Change From Baseline in in Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) - The FACIT Fatigue scale is a 13-item tool that measures an individual's level of fatigue during their usual daily activities over the past 7 days. Each of the fatigue and impact of fatigue items are measured on a four point Likert scale. The FACIT Fatigue Scale is the sum of the individual 13 scores and ranges from 0 to 52 where higher scores indicate better the quality of life. A positive change from baseline indicates improvement.
Timepoint [7] 0 0
Baseline and week 12
Secondary outcome [8] 0 0
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).
Timepoint [8] 0 0
Baseline and week 12
Secondary outcome [9] 0 0
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).
Timepoint [9] 0 0
Baseline and week 12
Secondary outcome [10] 0 0
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).
Timepoint [10] 0 0
Baseline and week 1

Eligibility
Key inclusion criteria
- Adult male or female, at least 18 years old.

- Diagnosis of Rheumatoid Arthritis (RA) for greater than or equal to 3 months.

- Subjects have been receiving conventional synthetic DMARD (csDMARD) therapy for
greater than or equal to 3 months and on a stable dose for greater than or equal to 4
weeks prior to the first dose of study drug. The following csDMARDs are allowed:
Methotrexate (MTX), sulfasalazine, hydroxychloroquine, chloroquine, and leflunomide.

- Meets the following minimum disease activity criteria: greater than or equal to 6
swollen joints (based on 66 joint counts) and greater than or equal to 6 tender joints
(based on 68 joint counts) at Screening and Baseline Visits.

- Subjects with prior exposure to at most one biologic DMARD (bDMARD) may be enrolled
(up to 20% of study population) if they have documented evidence of intolerance to
bDMARDs or limited exposure (less than 3 months) and have satisfied required washout
periods.
Minimum age
18 Years
Maximum age
99 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Prior exposure to any Janus kinase (JAK) inhibitor (including but not limited to
tofacitinib, baricitinib, and filgotinib).

- History of inflammatory joint disease other than RA. History of secondary Sjogren's
Syndrome is permitted.

- Subjects who are considered inadequate responders to bDMARD therapy as determined by
the Investigator.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,VIC
Recruitment hospital [1] 0 0
Coffs Clinical Trials /ID# 138747 - Coffs Harbour
Recruitment hospital [2] 0 0
Optimus Clinical Research Pty. /ID# 138769 - Kogarah
Recruitment hospital [3] 0 0
Emeritus Research /ID# 138773 - Camberwell
Recruitment hospital [4] 0 0
Barwon Rheumatology /ID# 138772 - Geelong
Recruitment postcode(s) [1] 0 0
2450 - Coffs Harbour
Recruitment postcode(s) [2] 0 0
2217 - Kogarah
Recruitment postcode(s) [3] 0 0
3124 - Camberwell
Recruitment postcode(s) [4] 0 0
3220 - Geelong
Recruitment outside Australia
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Lviv
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Odesa
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Southampton
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United Kingdom
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Warrington

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
AbbVie
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
The primary objectives of this study are to compare the efficacy, safety, and tolerability of
upadacitinib 30 mg once daily (QD) and 15 mg QD versus placebo for the treatment of signs and
symptoms of adults with moderately to severely active rheumatoid arthritis who were on a
stable dose of csDMARDs and had an inadequate response to csDMARDs.
Trial website
https://clinicaltrials.gov/show/NCT02675426
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
AbbVie Inc.
Address 0 0
AbbVie
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
Other publications