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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT03086343




Registration number
NCT03086343
Ethics application status
Date submitted
20/03/2017
Date registered
22/03/2017
Date last updated
3/07/2023

Titles & IDs
Public title
A Phase 3 Study to Compare Upadacitinib to Abatacept in Subjects With Rheumatoid Arthritis on Stable Dose of Conventional Synthetic Disease- Modifying Antirheumatic Drugs (csDMARDs) Who Have an Inadequate Response or Intolerance to Biologic DMARDs
Scientific title
A Phase 3, Randomized, Active-Controlled, Double-Blind Study Comparing Upadacitinib (ABT-494) to Abatacept in Subjects With Moderately to Severely Active Rheumatoid Arthritis With Inadequate Response or Intolerance to Biologic DMARDs (bDMARDs) on Stable Conventional Synthetic Disease Modifying Anti-Rheumatic Drugs (csDMARDs)
Secondary ID [1] 0 0
2016-000933-37
Secondary ID [2] 0 0
M15-925
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Rheumatoid Arthritis (RA) 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 - Abatacept
Treatment: Drugs - Placebo for abatacept
Treatment: Drugs - Upadacitinib
Treatment: Drugs - Placebo for upadacitinib

Active Comparator: Abatacept - 500 mg (for body weight <60 kg); 750 mg (for body weight 60-100 kg); and 1000 mg (for body weight >100 kg) intravenous (IV) infusion at Baseline, Week 2, Week 4, Week 8, Week 12, Week 16 and Week 20

Experimental: Upadacitinib 15 mg - One 15 mg tablet taken once per day by mouth for 24 weeks


Treatment: Drugs: Abatacept
IV infusion

Treatment: Drugs: Placebo for abatacept
IV infusion

Treatment: Drugs: Upadacitinib
15 mg extended release tablet

Treatment: Drugs: Placebo for upadacitinib
Film-coated tablet
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Change From Baseline in Disease Activity Score (DAS) 28 C-Reactive Protein (CRP) at Week 12 (Non-inferiority)
Timepoint [1] 0 0
Baseline and Week 12
Secondary outcome [1] 0 0
Change From Baseline in Disease Activity Score (DAS) 28 C-Reactive Protein (CRP) at Week 12 (Superiority)
Timepoint [1] 0 0
Baseline and Week 12
Secondary outcome [2] 0 0
Percentage of Participants Achieving Clinical Remission (CR) Based on Disease Activity Score (DAS) 28 C-Reactive Protein (CRP) at Week 12 (Superiority)
Timepoint [2] 0 0
At Week 12

Eligibility
Key inclusion criteria
Main

- 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

- Participants have been treated for = 3 months prior to the screening visit with = 1
bDMARD therapy, but continue to exhibit active RA or had to discontinue due to
intolerability or toxicity, irrespective of treatment duration and have never received
abatacept prior to the first dose of study drug

- Participants have been receiving csDMARD therapy = 3 months and on a stable dose for =
4 weeks prior to the first dose of study drug. The following csDMARDs are allowed:
methotrexate (MTX), sulfasalazine, hydroxychloroquine, chloroquine, and leflunomide. A
combination of up to two background csDMARDs is allowed except the combination of MTX
and leflunomide

- Meets the following criteria: = 6 swollen joints (based on 66 joint counts) and = 6
tender joints (based on 68 joint counts) at Screening and Baseline Visits and
high-sensitivity C-reactive protein (hsCRP) = 3 mg/L at Screening

Main
Minimum age
18 Years
Maximum age
No limit
Sex
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
upadacitinib, tofacitinib, baricitinib and filgotinib)

- Prior exposure to abatacept

- History of any arthritis with onset prior to age 17 years or current diagnosis of
inflammatory joint disease other than RA. Current diagnosis of secondary Sjogren's
Syndrome is permitted

- Laboratory values meeting the following criteria within the Screening period prior to
the first dose of study drug: serum aspartate transaminase > 2 × upper limit of normal
(ULN); serum alanine transaminase > 2 × ULN; estimated glomerular filtration rate by
simplified 4-variable Modification of Diet in Renal Disease formula < 40
mL/minute/1.73 meter (m)^2; total white blood cell count < 2,500/ µL; absolute
neutrophil count < 1,500/µL; platelet count < 100,000/µL; absolute lymphocyte count <
800/µL; and hemoglobin < 10 g/dL

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
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
9/05/2017
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
6/06/2023
Sample size
Target
Accrual to date
Final
613
Recruitment in Australia
Recruitment state(s)
QLD,SA,VIC
Recruitment hospital [1] 0 0
Rheumatology Research Unit /ID# 159174 - Maroochydore
Recruitment hospital [2] 0 0
The Queen Elizabeth Hospital /ID# 159175 - Woodville
Recruitment hospital [3] 0 0
Western Health Footscray Hospi /ID# 157968 - Footscray
Recruitment postcode(s) [1] 0 0
4558 - Maroochydore
Recruitment postcode(s) [2] 0 0
5011 - Woodville
Recruitment postcode(s) [3] 0 0
3011 - Footscray
Recruitment outside Australia
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Truro

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

Ethics approval
Ethics application status

Summary
Brief summary
The study objective of Period 1 was to compare the safety and efficacy of upadacitinib 15 mg
once daily (QD) to abatacept on a background of conventional synthetic disease-modifying
antirheumatic drugs (csDMARDs) for the treatment of signs and symptoms of rheumatoid
arthritis (RA) in biologic disease-modifying antirheumatic drug (bDMARD)-inadequate response
or bDMARD-intolerant participants with moderately to severely active RA. The study objective
of Period 2 is to evaluate the long-term safety, tolerability, and efficacy of upadacitinib
15 mg QD in participants with RA who had completed Period 1.
Trial website
https://clinicaltrials.gov/ct2/show/NCT03086343
Trial related presentations / publications
Rubbert-Roth A, Enejosa J, Pangan AL, Haraoui B, Rischmueller M, Khan N, Zhang Y, Martin N, Xavier RM. Trial of Upadacitinib or Abatacept in Rheumatoid Arthritis. N Engl J Med. 2020 Oct 15;383(16):1511-1521. doi: 10.1056/NEJMoa2008250.
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

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT03086343