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)

Rheumatoid Arthritis Clinical Trial

Official 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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02706951
• Other study ID #: M15-555
• Secondary ID: 2015-003376-75
• Status: Completed
• Phase: Phase 3
• Start date: March 23, 2016
• Est. completion date: August 10, 2022

Study information

• Verified date: January 2024
• Source: AbbVie
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

The study includes a 35-day screening period; a 14-week randomized, double-blind, parallel-group, controlled treatment period (Period 1); a 246-week blinded extension period (Period 2); and a 30-day follow-up visit.

Participants who met eligibility criteria were to be randomized in a 2:2:1:1 ratio to one of four treatment groups:

• Group 1: upadacitinib 30 mg QD (Period 1) → upadacitinib 30 mg QD (Period 2)

• Group 2: upadacitinib 15 mg QD (Period 1) → upadacitinib 15 mg QD (Period 2)

• Group 3: MTX (Period 1) → upadacitinib 30 mg QD (Period 2)

• Group 4: MTX (Period 1) → upadacitinib 15 mg QD (Period 2)

Starting with implementation of Protocol Amendment 5, all participants in the extension period will receive open-label upadacitinib 15 mg QD, including those currently on upadacitinib 30 mg QD.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 648
• Est. completion date: August 10, 2022
• Est. primary completion date: October 2, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 99 Years

Eligibility

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.

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.

Related Conditions & MeSH terms

• Arthritis
• Arthritis, Rheumatoid
• Rheumatoid Arthritis

Intervention

Drug:
• Methotrexate
Capsule; Oral
• Upadacitinib
Tablet; Oral
• Placebo Upadacitinib
Tablet; Oral
• Placebo Methotrexate
Capsule; Oral

Locations

Country	Name	City	State
Argentina	Centro de Educación Médica e Investigaciones Clínicas "Norberto Quimo" - CEMIC /ID# 149176	Buenos Aires
Argentina	Consultorio Reumatologic Pampa /ID# 145979	Buenos Aires
Argentina	Ctr Privado Med Familiar /ID# 149183	Buenos Aires
Argentina	Mautalen Salud e Investigacion /ID# 145980	Buenos Aires
Argentina	Cordis S.A. /Id# 152621	Salta
Argentina	Centro de Enfermedades /ID# 153543	Santa Fe
Australia	Royal Prince Alfred Hospital /ID# 146028	Camperdown	New South Wales
Austria	Rheuma-Zentrum Wien-Oberlaa /ID# 144728	Wien
Belgium	Algemeen Stedelijk Ziekenhuis /ID# 148720	Aalst	Oost-Vlaanderen
Belgium	ReumaClinic Genk /ID# 146030	Genk
Bulgaria	Diag Consult Ctr 17 Sofia EOOD /ID# 144730	Sofia
Bulgaria	UMHAT Sv. Ivan Rilski /ID# 147351	Sofia
Chile	Reg. Clinical Hosptial Concepcion /ID# 151267	Concepcion
Chile	Quantum Research LTDA. /ID# 145984	Puerto Varas
Chile	Quantum Research Stgo. /ID# 145983	Santiago
Czechia	RHEUMA s.r.o. /ID# 144737	Breclav
Czechia	CTCenter MaVe, s.r.o. /ID# 144823	Olomouc	Olomoucky Kraj
Czechia	Nuselská poliklinika, Revmatologie /ID# 145986	Prague 4	Praha 4
Czechia	Thomayerova nemocnice /ID# 144736	Prague 4	Praha 4
Czechia	Medical Plus, s.r.o. /ID# 144821	Uherské Hradište
Estonia	North Estonian Medical Centre /ID# 145455	Tallinn
Estonia	MediTrials /ID# 159745	Tartu	Tartumaa
Greece	General Hospital of Athens "Ippokratio" /ID# 144739	Athens
Hungary	Magyar Honvedseg Egeszsegugyi Kozpont /ID# 144743	Budapest
Hungary	Pest Megyei Flor Ferenc Korhaz /ID# 144742	Kistarcsa
Hungary	Fejer Megyei Szent Gyorgy Korh /ID# 144741	Szekesfehervar
Hungary	Vital Medical Center Orvosi es /ID# 144740	Veszprém	Veszprem
Israel	Barzilai Medical Center /ID# 144744	Ashkelon
Israel	Bnai Zion Medical Center /ID# 144745	Haifa
Israel	The Lady Davis Carmel MC /ID# 147174	Haifa
Israel	Sheba Medical Center /ID# 144824	Ramat Gan
Italy	Universita di Catanzaro Magna Graecia /ID# 144747	Catanzaro	Calabria
Italy	A.O.U.I. di Verona Policlinico /ID# 144746	Verona
Japan	Kondo Clinic for Rheum & Ortho /ID# 148268	Fukuoka-shi	Fukuoka
Japan	NHO Kyushu Medical Center /ID# 148279	Fukuoka-shi	Fukuoka
Japan	NHO Kyushu Medical Center /ID# 148280	Fukuoka-shi	Fukuoka
Japan	Seirei Hamamatsu General Hosp /ID# 148270	Hamamatsu
Japan	Ohira Orthopaedic Hospital /ID# 157944	Hyuga
Japan	Aso Iizuka Hospital /ID# 148272	Iizuka-shi	Fukuoka
Japan	Bay Side Misato Medical Center /ID# 148281	Kochi-shi	Kochi
Japan	Center for Arthritis and Clinical Rheumatology Matsubara Clinic /ID# 148269	Kumamoto-shi	Kumamoto
Japan	Kumamoto Shinto General Hospital /ID# 148286	Kumamoto-shi	Kumamoto
Japan	Nagasaki University Hospital /ID# 149859	Nagasaki-shi	Nagasaki
Japan	Shirahama Hamayu Hospital /ID# 148277	Nishimura
Japan	Osaka Red Cross Hospital /ID# 148267	Osaka-shi	Osaka
Japan	Sanuki Municipal Hospital /ID# 158080	Sanuki
Japan	Hokkaido Medical Center for Rheumatic Diseases /ID# 148274	Sapporo
Japan	Hokkaido University Hospital /ID# 148285	Sapporo
Japan	Sasebo Chuo Hospital /ID# 148275	Sasebo-city	Nagasaki
Japan	Miyasato Clinic /ID# 148271	Shunan
Japan	Takaoka Rheumatic Orthopedic Clinic /ID# 148068	Takaoka
Japan	Inoue Hospital /ID# 148069	Takasaki	Gunma
Japan	Matsuta Clinic /ID# 148278	Tokyo
Japan	National Hospital Organization Shimoshizu National Hospital /ID# 148273	Yotsukaido
Mexico	Cryptex Investigación Clínica S.A de C.V /ID# 147095	Mexico City
Mexico	Desarrollos Biomedicos y Biotc /ID# 147379	Monterrey	Nuevo LEON
Poland	Osteo-Medic spolka cywilna /ID# 144753	Bialystok	Podlaskie
Poland	NZOZ Centrum Reumatologiczne /ID# 144749	Elblag	Warminsko-mazurskie
Poland	Centrum Badan Klinicznych Pi-House /ID# 149520	Gdansk	Pomorskie
Poland	REUMED Sp.z o.o. Filia nr 1 /ID# 144752	Lublin	Lubelskie
Poland	Medyczne Centrum Hetmanska /ID# 144751	Poznan	Wielkopolskie
Poland	Centralny Szpital Kliniczny MSWiA w Warszawie /ID# 149521	Warszawa	Mazowieckie
Poland	WroMedica I. Bielicka, A. Strzalkowska s.c. /ID# 157622	Wroclaw	Dolnoslaskie
Portugal	Centro Hospitalar Lisboa Norte, EPE /ID# 146035	Lisboa
Portugal	Instituto Portugues De Reumatologia /ID# 149281	Lisbon	Lisboa
Portugal	Centro Hospitalar Baixo Vouga /ID# 152916	Porto
Portugal	Centro Hospitalar De Vila Nova /ID# 146036	Vila Nova De Gaia	Porto
Puerto Rico	Dr. Ramon L. Ortega-Colon, MD /ID# 145989	Carolina
Puerto Rico	Ponce School of Medicine /ID# 145990	Ponce
Romania	Spitalul Municipal Ploiesti /ID# 144756	Ploiesti
Russian Federation	?ity Clinical Hospital 4 /ID# 145994	Ivanovo
Russian Federation	City Clinical Hospital Botkina /ID# 145995	Moscow
Russian Federation	Clinical Hospital No.1 n.a. N.I.Pirogov /ID# 147255	Moscow	Moskva
Russian Federation	City Clinical Hospital #5 /ID# 149832	Nizhnij Novgorod
Russian Federation	LLC Medical Center /ID# 144758	Novosibirsk	Novosibirskaya Oblast
Russian Federation	Orenburg State Medical Academy /ID# 145992	Orenburg
Russian Federation	Perm Clinical Center of FMBA /ID# 145993	Perm	Permskiy Kray
Russian Federation	Republican Clin Hos n.a. Baran /ID# 147251	Petrozavodsk
Russian Federation	Samara Regional Clinical Hosp /ID# 150934	Samara
Russian Federation	Tver Regional Clinical Hosp. /ID# 147254	Tver	Tverskaya Oblast
Russian Federation	Reg Clin Hosp n.a. Kuvatova G. /ID# 144757	UFA
Russian Federation	Yaroslavi State Medical Univer /ID# 147253	Yaroslavl
Serbia	Institute for Rheumatology /ID# 144759	Belgrade	Beograd
Serbia	Institute for Rheumatology /ID# 144761	Belgrade	Beograd
Serbia	Institute for Rheumatology /ID# 144762	Belgrade	Beograd
Serbia	Special Hospital for Rheuma /ID# 144760	Novi Sad	Vojvodina
South Africa	Synexus Helderberg Clinical Tr /ID# 148724	Cape Town	Western Cape
South Africa	Tiervlei Trial Centre /ID# 153086	Cape Town	Western Cape
South Africa	Wits Clinical Research Site /ID# 149835	Johannesburg	Gauteng
South Africa	University of Pretoria /ID# 148740	Pretoria	Gauteng
Spain	Hospital Plató /ID# 145999	Barcelona
Spain	Hospital Univ Germans Trias I /ID# 146037	Barcelona
Spain	Hospital Infanta Luisa /ID# 144771	Sevilla
Spain	Hospital Universitario de Valm /ID# 144770	Sevilla
Spain	Hospital Universitario La Fe /ID# 158013	Valencia
Turkey	Uludag Üniversitesi Atatürk Rehabilitasyon Uygulama ve Arastirma Merkezi /ID# 144772	Osmangazi	Bursa
Ukraine	Regional Clinical Hospital /ID# 152007	Ivano-frankivsk
Ukraine	NSC-Strazhesko Ist Cardiology /ID# 152004	Kiev
Ukraine	Lviv Regional Clinical Hospita /ID# 154448	Lviv	Lvivska Oblast
Ukraine	Vinnytsia Regional Clinical Hospital n.a. M.I.Pyrogov /ID# 146002	Vinnytsia	Vinnytska Oblast
Ukraine	Zaporizhzhia Regional Clinical /ID# 146000	Zaporizhia
United States	Albuquerque Clinical Trials, Inc /ID# 147618	Albuquerque	New Mexico
United States	Tekton Research, Inc. /ID# 159554	Austin	Texas
United States	Ochsner Clinic Foundation /ID# 153573	Baton Rouge	Louisiana
United States	Diagnostic Group Integrated He /ID# 148725	Beaumont	Texas
United States	Trinity Universal Res Assoc /ID# 150138	Carrollton	Texas
United States	Ctr for Arth and Rheum Disease /ID# 143759	Chesapeake	Virginia
United States	Great Lakes Clinical Trials /ID# 150935	Chicago	Illinois
United States	Arth and Osteo Clin Brazo Valley /ID# 160810	College Station	Texas
United States	Arthritis Assoc & Osteo Ctr /ID# 147176	Colorado Springs	Colorado
United States	Adriana Pop-Moody MD Clinic PA /ID# 147627	Corpus Christi	Texas
United States	Jefrey D. Lieberman, MD, P.C. /ID# 151816	Decatur	Georgia
United States	Ctr Rheum, Immuno, Arthritis /ID# 143766	Fort Lauderdale	Florida
United States	Aurora Rheumatology and Immunotherapy Center /ID# 160811	Franklin	Wisconsin
United States	ArthroCare Arthritis Care & Re /ID# 143751	Gilbert	Arizona
United States	Innovative Clinical Research /ID# 143757	Greenville	South Carolina
United States	C.V. Mehta MD, Med Corporation /ID# 143762	Hemet	California
United States	Accurate Clinical Management /ID# 143768	Houston	Texas
United States	Accurate Clinical Research /ID# 143769	Houston	Texas
United States	Pioneer Research Solutions, Inc. /ID# 143765	Houston	Texas
United States	Rheum Assoc of North Alabama /ID# 146009	Huntsville	Alabama
United States	NEA Baptist Womens Clinic /ID# 148904	Jonesboro	Arkansas
United States	Arthritis and Osteo Assoc /ID# 147177	Las Cruces	New Mexico
United States	Dartmouth-Hitchcock Medical Center /ID# 146008	Lebanon	New Hampshire
United States	P&I Clinical Research /ID# 151358	Lufkin	Texas
United States	Mansfield Health Center /ID# 161627	Mansfield	Massachusetts
United States	SW Rheumatology Res. LLC /ID# 147620	Mesquite	Texas
United States	South Florida Research Ph I-IV /ID# 151983	Miami Springs	Florida
United States	Alabama Medical Group, PC /ID# 153941	Mobile	Alabama
United States	The Arthritis & Diabetes Clinic, Inc. /ID# 160809	Monroe	Louisiana
United States	Nashville Arthritis and Rheumatology /ID# 162641	Nashville	Tennessee
United States	Coastal Carolina Health Care /ID# 149275	New Bern	North Carolina
United States	Health Research Oklahoma /ID# 159550	Oklahoma City	Oklahoma
United States	Quality Clinical Research Inc. /ID# 156415	Omaha	Nebraska
United States	Elite Clinical Studies, LLC /ID# 143760	Phoenix	Arizona
United States	Advent Clinical Research /ID# 143767	Pinellas Park	Florida
United States	Sun Research Institute /ID# 159553	San Antonio	Texas
United States	Arthritis Clinic of Central TX /ID# 149266	San Marcos	Texas
United States	Sarasota Arthritis Center /ID# 146011	Sarasota	Florida
United States	Vanguard Medical Research, LLC /ID# 153124	Shreveport	Louisiana
United States	W. Broward Rheum Assoc Inc. /ID# 146010	Tamarac	Florida
United States	BayCare Medical Group, Inc. /ID# 151985	Tampa	Florida
United States	BayCare Medical Group, Inc. /ID# 163595	Tampa	Florida
United States	Clinical Research West FL /ID# 148726	Tampa	Florida
United States	SW FL Clin Res Ctr, Tampa, FL /ID# 143763	Tampa	Florida
United States	University of South Florida /ID# 146004	Tampa	Florida
United States	Adv Rheumatology of Houston /ID# 162609	The Woodlands	Texas
United States	DM Clinical Research /ID# 151359	Tomball	Texas
United States	University of Arizona Cancer Center - North Campus /ID# 147175	Tucson	Arizona
United States	Healthcare Research Consultant /ID# 147632	Tulsa	Oklahoma
United States	STAT Research, Inc. /ID# 143770	Vandalia	Ohio
United States	Arthritis & Osteoporosis Clinic /ID# 143752	Waco	Texas
United States	PRN Professional Research Network of Kansas, LLC /ID# 143761	Wichita	Kansas

Sponsors (1)

Lead Sponsor	Collaborator
AbbVie

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Austria,  Belgium,  Bulgaria,  Chile,  Czechia,  Estonia,  Greece,  Hungary,  Israel,  Italy,  Japan,  Mexico,  Poland,  Portugal,  Puerto Rico,  Romania,  Russian Federation,  Serbia,  South Africa,  Spain,  Turkey,  Ukraine, 

References & Publications (1)

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants With an American College of Rheumatology 20% (ACR20) Response at Week 14	The primary endpoint for United States (US)/Food and Drug Administration (FDA) regulatory purposes was ACR 20% response (ACR20) at Week 14. 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 14
Primary	Percentage of Participants Achieving Low Disease Activity (LDA) Based on DAS28(CRP) at Week 14	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 14.; 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 mm), 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.	Week 14
Secondary	Change From Baseline in in Disease Activity Score 28 (CRP) at Week 14	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 mm), 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.	Baseline to week 14
Secondary	Change From Baseline in Heath Assessment Questionnaire and Disability Index (HAQ-DI) at Week 14	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 to week 14
Secondary	Change From Baseline in Short-Form 36 (SF-36) Physical Component Score (PCS) at Week 14	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 to week 14
Secondary	Percentage of Participants Achieving Clinical Remission (CR) Based on DAS28(CRP) at Week 14	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 mm), 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 2.6 indicates clinical remission.	Week 14
Secondary	Change From Baseline in Duration of Morning Stiffness at Week 14	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. A negative change from Baseline indicates improvement.	Baseline to week 14
Secondary	Percentage of Participants With an American College of Rheumatology 50% (ACR50) Response at Week 14	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 14
Secondary	Percentage of Participants With an American College of Rheumatology 70% (ACR70) Response at Week 14	Participants who met the following 3 conditions for improvement from baseline were classified as meeting the ACR50 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 14

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