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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT02706951




Registration number
NCT02706951
Ethics application status
Date submitted
18/02/2016
Date registered
11/03/2016
Date last updated
30/01/2024

Titles & IDs
Public title
A Study Comparing Upadacitinib (ABT-494) Monotherapy to Methotrexate (MTX) Monotherapy in Adults With Rheumatoid Arthritis (RA) Who Have an Inadequate Response to MTX (SELECT-MONOTHERAPY)
Scientific title
A Phase 3, Randomized, Double-Blind Study Comparing Upadacitinib (ABT-494) Monotherapy to Methotrexate (MTX) in Adults With Moderately to Severely Active Rheumatoid Arthritis With Inadequate Response to MTX
Secondary ID [1] 0 0
2015-003376-75
Secondary ID [2] 0 0
M15-555
Universal Trial Number (UTN)
Trial acronym
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 - Methotrexate
Treatment: Drugs - Upadacitinib
Treatment: Drugs - Placebo Upadacitinib
Treatment: Drugs - Placebo Methotrexate

Experimental: Upadacitinib 30 mg - Period 1: Participants receive upadacitnib 30 mg once daily and placebo to methotrexate once weekly for 14 weeks.

Period 2: Participants receive upadacitinib 30 mg once daily until implementation of Protocol Amendment 5 when participants begin to receive upadacitinib 15 mg once daily up to Week 260.

Experimental: Upadacitinib 15 mg - Period 1: Participants receive upadacitnib 15 mg once daily and placebo to methotrexate once weekly for 14 weeks.

Period 2: Participants receive upadacitinib 15 mg once daily up to Week 260.

Experimental: Methotrexate / Upadacitinib 30 mg - Period 1: Participants receive methotrexate once weekly and placebo to upadacitinib once daily for 14 weeks.

Period 2: Participants receive upadacitinib 30 mg once daily until implementation of Protocol Amendment 5 when participants begin to receive upadacitinib 15 mg once daily up to Week 260.

Experimental: Methotrexate / Upadacitinib 15 mg - Period 1: Participants receive methotrexate once weekly and placebo to upadacitinib for 14 weeks.

Period 2: Participants receive upadacitinib 15 mg once daily up to Week 260.


Treatment: Drugs: Methotrexate
Capsule; Oral

Treatment: Drugs: Upadacitinib
Tablet; Oral

Treatment: Drugs: Placebo Upadacitinib
Tablet; Oral

Treatment: Drugs: Placebo Methotrexate
Capsule; 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 14
Timepoint [1] 0 0
Baseline and week 14
Primary outcome [2] 0 0
Percentage of Participants Achieving Low Disease Activity (LDA) Based on DAS28(CRP) at Week 14
Timepoint [2] 0 0
Week 14
Secondary outcome [1] 0 0
Change From Baseline in in Disease Activity Score 28 (CRP) at Week 14
Timepoint [1] 0 0
Baseline to week 14
Secondary outcome [2] 0 0
Change From Baseline in Heath Assessment Questionnaire and Disability Index (HAQ-DI) at Week 14
Timepoint [2] 0 0
Baseline to week 14
Secondary outcome [3] 0 0
Change From Baseline in Short-Form 36 (SF-36) Physical Component Score (PCS) at Week 14
Timepoint [3] 0 0
Baseline to week 14
Secondary outcome [4] 0 0
Percentage of Participants Achieving Clinical Remission (CR) Based on DAS28(CRP) at Week 14
Timepoint [4] 0 0
Week 14
Secondary outcome [5] 0 0
Change From Baseline in Duration of Morning Stiffness at Week 14
Timepoint [5] 0 0
Baseline to week 14
Secondary outcome [6] 0 0
Percentage of Participants With an American College of Rheumatology 50% (ACR50) Response at Week 14
Timepoint [6] 0 0
Baseline and week 14
Secondary outcome [7] 0 0
Percentage of Participants With an American College of Rheumatology 70% (ACR70) Response at Week 14
Timepoint [7] 0 0
Baseline and week 14

Eligibility
Key inclusion criteria
* Diagnosis of RA for >= 3 months.
* Subjects must have been on oral or parenteral MTX therapy >= 3 months and on a stable dose for >= 4 weeks prior to first dose of study drug.
* Must have discontinued all conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs) (other than MTX) >= 4 weeks prior to first dose of study drug.
* Meets the following minimum disease activity criteria: >= 6 swollen joints (based on 66 joint counts) and >= 6 tender joints (based on 68 joint counts) at Screening and Baseline Visits.
Minimum age
18 Years
Maximum age
99 Years
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 tofacitinib, baricitinib, and filgotinib).
* Prior exposure to any biological disease-modifying anti-rheumatic drugs (bDMARDs).
* Current diagnosis of inflammatory joint disease other than RA. Current diagnosis of secondary Sjogren's Syndrome is permitted.

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
23/03/2016
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
10/08/2022
Sample size
Target
Accrual to date
Final
648
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 0 0
Royal Prince Alfred Hospital /ID# 146028 - Camperdown
Recruitment postcode(s) [1] 0 0
2050 - Camperdown
Recruitment outside Australia
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Kiev
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Zaporizhia

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 of this study is to compare the safety and efficacy (signs and symptoms) of upadacitinib 30 mg once daily (QD) alone and upadacitinib 15 mg QD alone versus continuing MTX alone adults with moderately to severely active rheumatoid arthritis (RA) with an inadequate response to MTX.

The study objective of Period 2 is to evaluate the long term safety, tolerability, and efficacy of upadacitinib 30 mg QD and 15 mg QD in adults with RA who had completed Period 1.
Trial website
https://clinicaltrials.gov/study/NCT02706951
Trial related presentations / publications
Smolen JS, Pangan AL, Emery P, Rigby W, Tanaka Y, Vargas JI, Zhang Y, Damjanov N, Friedman A, Othman AA, Camp HS, Cohen S. Upadacitinib as monotherapy in patients with active rheumatoid arthritis and inadequate response to methotrexate (SELECT-MONOTHERAPY): a randomised, placebo-controlled, double-blind phase 3 study. Lancet. 2019 Jun 8;393(10188):2303-2311. doi: 10.1016/S0140-6736(19)30419-2. Epub 2019 May 23. Erratum In: Lancet. 2019 Jun 29;393(10191):2590. doi: 10.1016/S0140-6736(19)31474-6.
Bergman M, Buch MH, Tanaka Y, Citera G, Bahlas S, Wong E, Song Y, Zueger P, Ali M, Strand V. Routine Assessment of Patient Index Data 3 (RAPID3) in Patients with Rheumatoid Arthritis Treated with Long-Term Upadacitinib Therapy in Five Randomized Controlled Trials. Rheumatol Ther. 2022 Dec;9(6):1517-1529. doi: 10.1007/s40744-022-00483-4. Epub 2022 Sep 20.
Bergman M, Tundia N, Yang M, Orvis E, Clewell J, Bensimon A. Economic Benefit from Improvements in Quality of Life with Upadacitinib: Comparisons with Tofacitinib and Methotrexate in Patients with Rheumatoid Arthritis. Adv Ther. 2021 Dec;38(12):5649-5661. doi: 10.1007/s12325-021-01930-4. Epub 2021 Oct 12.
Yamaoka K, Tanaka Y, Kameda H, Khan N, Sasaki N, Harigai M, Song Y, Zhang Y, Takeuchi T. The Safety Profile of Upadacitinib in Patients with Rheumatoid Arthritis in Japan. Drug Saf. 2021 Jun;44(6):711-722. doi: 10.1007/s40264-021-01067-x. Epub 2021 May 27.
Strand V, Tundia N, Wells A, Buch MH, Radominski SC, Camp HS, Friedman A, Suboticki JL, Dunlap K, Goldschmidt D, Bergman M. Upadacitinib monotherapy improves patient-reported outcomes in rheumatoid arthritis: results from SELECT-EARLY and SELECT-MONOTHERAPY. Rheumatology (Oxford). 2021 Jul 1;60(7):3209-3221. doi: 10.1093/rheumatology/keaa770.
Cohen SB, van Vollenhoven RF, Winthrop KL, Zerbini CAF, Tanaka Y, Bessette L, Zhang Y, Khan N, Hendrickson B, Enejosa JV, Burmester GR. Safety profile of upadacitinib in rheumatoid arthritis: integrated analysis from the SELECT phase III clinical programme. Ann Rheum Dis. 2021 Mar;80(3):304-311. doi: 10.1136/annrheumdis-2020-218510. Epub 2020 Oct 28. Erratum In: Ann Rheum Dis. 2021 May;80(5):e83. doi: 10.1136/annrheumdis-2020-218510corr1.
Nader A, Mohamed MF, Winzenborg I, Doelger E, Noertersheuser P, Pangan AL, Othman AA. Exposure-Response Analyses of Upadacitinib Efficacy and Safety in Phase II and III Studies to Support Benefit-Risk Assessment in Rheumatoid Arthritis. Clin Pharmacol Ther. 2020 Apr;107(4):994-1003. doi: 10.1002/cpt.1671. Epub 2019 Nov 30.
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/study/NCT02706951