A Study Comparing Upadacitinib (ABT-494) to Placebo in Participants With Active Psoriatic Arthritis Who Have a History of Inadequate Response to at Least One Biologic Disease Modifying Anti-Rheumatic Drug (bDMARD)

Psoriatic Arthritis Clinical Trial

— SELECT - PsA 2  

Official title:

A Phase 3, Randomized, Double-Blind Study Comparing Upadacitinib (ABT-494) to Placebo in Subjects With Active Psoriatic Arthritis Who Have a History of Inadequate Response to at Least One Biologic Disease Modifying Anti-Rheumatic Drug (bDMARD) - SELECT - PsA 2

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03104374
• Other study ID #: M15-554
• Secondary ID: 2016-004152-30
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: May 1, 2017
• Est. completion date: September 30, 2024

Study information

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

Clinical Trial Summary

The study objectives of Period 1 are to compare the efficacy, safety, and tolerability of upadacitinib 15 mg once daily (QD) and 30 mg QD versus placebo for the treatment of signs and symptoms in adults with moderately to severely active psoriatic arthritis (PsA) who have had an inadequate response or intolerance to biologic disease-modifying anti-rheumatic drug (bDMARD).

The objective of Period 2 is to evaluate the long-term safety, tolerability and efficacy of upadacitinib 15 mg QD and 30 mg QD in participants who have completed Period 1.

Description:

The study includes a 35-day screening period, a 56-week blinded period (Period 1), a long-term extension period of up to a total treatment duration of approximately 3 years (Period 2), and a 30-day follow-up call or visit.

Period 1 includes 24 weeks of randomized, double-blind, parallel-group, placebo-controlled treatment followed by an additional 32 weeks of blinded treatment where all participants were to receive upadacitinib; at Week 24 participants assigned to placebo will be switched to upadacitinib according to their randomization assignment.

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

• Group 1: Upadacitinib 15 mg

• Group 2: Upadacitinib 30 mg

• Group 3: Placebo for 24 weeks followed by upadacitinib 15 mg

• Group 4: Placebo for 24 weeks followed by upadacitinib 30 mg

Participants who complete the Week 56 visit (end of Period 1) will enter the long-term extension portion of the study, Period 2, and continue study treatment as assigned in Period 1 in a blinded manner until the last participant completes the last visit of Period 1 (Week 56), when study drug assignment in both periods will be unblinded and study drug will be dispensed in an open-label fashion until the completion of Period 2.

At Week 16, rescue therapy will be offered to participants classified as non-responders (defined as not achieving at least 20% improvement in tender joint count (TJC) and/or swollen joint count (SJC) at both Week 12 and Week 16). Starting at Week 36, participants who fail to demonstrate at least 20% improvement in either or both TJC and SJC compared to Baseline at 2 consecutive visits will be discontinued from study drug treatment. Additionally, in participants continuing on study drug, starting at the Week 36 visit, initiation of or change in background PsA medication(s) is allowed as per local label.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 642
• Est. completion date: September 30, 2024
• Est. primary completion date: July 23, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Clinical diagnosis of PsA with symptom onset at least 6 months prior to the Screening Visit and fulfillment of the Classification Criteria for PsA (CASPAR) criteria

• Participant has active disease at Baseline defined as >= 3 tender joints (based on 68 joint counts) and >= 3 swollen joints (based on 66 joint counts) at Screening and Baseline Visits

• Diagnosis of active plaque psoriasis or documented history of plaque psoriasis

• Participant has had an inadequate response (lack of efficacy after a minimum 12 week duration of therapy) or intolerance to treatment with at least 1 bDMARD.

Exclusion Criteria:

• Prior exposure to any Janus Kinase (JAK) inhibitor (including but not limited to ruxolitinib, tofacitinib, baricitinib, and filgotinib)

• Current treatment with > 2 non-biologic DMARDs or use of DMARDs other than methotrexate (MTX), sulfasalazine (SSZ), leflunomide (LEF), apremilast, hydroxychloroquine (HCQ), bucillamine or iguratimod or use of MTX in combination with LEF at Baseline.

• History of fibromyalgia, any arthritis with onset prior to age 17 years, or current diagnosis of inflammatory joint disease other than PsA (including, but not limited to rheumatoid arthritis, gout, overlap connective tissue diseases, scleroderma, polymyositis, dermatomyositis, systemic lupus erythematosus). Prior history of reactive arthritis or axial spondyloarthritis including ankylosing spondylitis and non-radiographic axial spondyloarthritis is permitted if documentation of change in diagnosis to PsA or additional diagnosis of PsA is made. Prior history of fibromyalgia is permitted if documentation of change in diagnosis to PsA or documentation that the diagnosis of fibromyalgia was made incorrectly.

Related Conditions & MeSH terms

• Arthritis
• Arthritis, Psoriatic
• Psoriatic Arthritis
• Rheumatic Diseases

Intervention

Drug:
• Upadacitinib
Oral tablet
• Placebo
Oral tablet

Locations

Country	Name	City	State
Belgium	Reuma clinic /ID# 164214	Genk
Belgium	UZ Ghent /ID# 164210	Ghent	Oost-Vlaanderen
Brazil	CIP - Centro Internacional de Pesquisa /ID# 161808	Goiânia	Goias
Brazil	Hospital de Clinicas de Porto Alegre /ID# 161795	Porto Alegre	Rio Grande Do Sul
Brazil	LMK Sevicos Medicos S/S /ID# 161806	Porto Alegre	Rio Grande Do Sul
Brazil	Hospital das Clinicas da Faculdade de Medicina de Ribeirão Preto - USP /ID# 163317	Ribeirao Preto	Sao Paulo
Brazil	Faculdade de Medicina do ABC /ID# 163489	Santo André	Sao Paulo
Brazil	Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo - HC /ID# 161793	São Paulo	Sao Paulo
Brazil	Hospital de Clínicas da Universidade Federal de Uberlândia /ID# 161794	Uberlândia	Minas Gerais
Canada	The Waterside Clinic /ID# 157838	Barrie	Ontario
Canada	Groupe de Recherche en Maladies Osseuses Inc /ID# 157836	Sainte-foy	Quebec
Canada	Ctr. de Recherche Musculo-Sque /ID# 163557	Trois-rivières	Quebec
Canada	Percuro Clinical Research, Ltd /ID# 157835	Victoria	British Columbia
Canada	Ciads /Id# 157843	Winnipeg	Manitoba
Chile	CTR Estudios SpA /ID# 206038	Providencia
Chile	Centro Inter Estud Clin CIEC /ID# 169543	Santiago
Chile	Prosalud Ltda. /ID# 169542	Santiago
Chile	Clinica Dermacross S.A /ID# 169537	Vitacura Santiago
Czechia	Revmatologie Bruntal, s.r.o /ID# 159632	Bruntál
Czechia	Medical Plus, s.r.o. /ID# 159631	Uherské Hradište
France	Hopital Saint Joseph /ID# 163755	Marseille CEDEX 08	Bouches-du-Rhone
France	Hopital Lariboisiere /ID# 163773	Paris
France	CHU Toulouse /ID# 163743	Toulouse CEDEX 3	Occitanie
France	Hopital Trousseau /ID# 163772	Tours
Greece	General Hospital of Athens Laiko /ID# 163474	Athens	Attiki
Greece	Naval Hospital of Athens /ID# 163495	Athens
Hungary	Betegapolo Irgalmas Rend - Budai Irgalmasrendi Korhaz /ID# 170911	Budapest
Hungary	Revita Reumatologiai Rendelo /ID# 162575	Budapest
Hungary	Debreceni Egyetem Kenezy Gyula /ID# 162572	Debrecen
Hungary	MAV Korhaz ess Rendelointezet /ID# 162574	Szolnok
Hungary	Vital Medical Center Orvosi-es Fogaszati Kozpont /ID# 162571	Veszprem
Italy	A.O. Univ. Ospedali Riuniti /ID# 162748	Ancona	Marche
Italy	Azienda Ospedaliera Universitaria Policlinico "G. Rodolico - San Marco" /Id# 164126	Catania
Italy	ASST G. Pini /ID# 164125	Milan
Italy	Azienda Unita Sanitaria Locale/IRCCS c/o Arcispedale Santa Maria Nuova /ID# 162751	Reggio Emilia	Emilia-Romagna
Japan	Asahikawa Medical University Hospital /ID# 200684	Asahikawa-shi	Hokkaido
Japan	Juntendo University Hospital /ID# 162089	Bunkyo-ku	Tokyo
Japan	St.Luke's International Hospital /ID# 162013	Chuo-ku	Tokyo
Japan	Fukuoka University Hospital /ID# 161774	Fukuoka-shi	Fukuoka
Japan	Kansai Medical University Hospital /ID# 162081	Hirakata-shi	Osaka
Japan	National Hospital Organization Osaka Minami Medical Center /ID# 162589	Kawachinagano-shi	Osaka
Japan	Kitakyushu Municipal Medical Center /ID# 163516	Kitakyushu-shi	Fukuoka
Japan	Daido Hospital /ID# 163639	Nagoya
Japan	Nagoya City University Hospital /ID# 162563	Nagoya-shi	Aichi
Japan	Oribe Clinic of Rheumatism and Medicine /ID# 163704	Oita-shi	Oita
Japan	Nippon Life Saiseikai Public Interest Foundation Nippon Life Hospital /ID# 161773	Osaka-shi	Osaka
Japan	Osaka City University Hospital /ID# 162082	Osaka-shi	Osaka
Japan	Tohoku University Hospital /ID# 164035	Sendai-shi	Miyagi
Japan	Keio University Hospital /ID# 162130	Shinjuku-ku	Tokyo
Japan	Mie University Hospital /ID# 162085	Tsu-shi	Mie
Netherlands	Erasmus Medisch Centrum /ID# 163052	Rotterdam
Netherlands	Maasstad Ziekenhuis /ID# 163050	Rotterdam
New Zealand	Middlemore Hospital /ID# 166411	Auckland
New Zealand	Waikato Hospital /ID# 166412	Hamilton	Waikato
New Zealand	Porter Rheumatology Ltd /ID# 200422	Nelson
New Zealand	Timaru Rheumatology Studies /ID# 166410	Timaru
Portugal	Centro Hospitalar Lisboa Norte, EPE /ID# 165895	Lisboa
Portugal	Centro Hospitalar Lisboa Ocidental, EPE /ID# 165896	Lisbon	Lisboa
Portugal	Instituto Portugues De Reumatologia /ID# 165894	Lisbon	Lisboa
Portugal	Unidade Local De Saude Do Alto Minho /ID# 165898	Viana Do Castelo
Portugal	Centro Hospitalar de Vila Nova Gaia/Espinho, EPE /ID# 165897	Vila Nova De Gaia	Porto
Puerto Rico	Ponce School of Medicine /ID# 163918	Ponce
Puerto Rico	GCM Medical Group, PSC /ID# 163716	San Juan
Spain	Hospital Universitario A Coruña - CHUAC /ID# 161019	A Coruña	A Coruna
Spain	Hospital Universitario Reina Sofia /ID# 170764	Cordoba
Spain	Hospital Clinico Universitario Virgen de la Arrixaca /ID# 163138	El Palmar	Murcia
United Kingdom	Royal United Hospitals Bath /ID# 161054	Bath	Bath And North East Somerset
United Kingdom	Whipps Cross Univ Hospital /ID# 161053	London	London, City Of
United Kingdom	Luton & Dunstable University Hospital /ID# 162713	Luton
United States	The Center for Rheumatology /ID# 167046	Albany	New York
United States	Tekton Research, Inc. /ID# 160008	Austin	Texas
United States	Arthritis & Rheumatic Disease Specialties /ID# 161409	Aventura	Florida
United States	Diagnostic Group Integrated He /ID# 161406	Beaumont	Texas
United States	DJL Clinical Research, PLLC /ID# 161414	Charlotte	North Carolina
United States	Great Lakes Clinical Trials /ID# 163438	Chicago	Illinois
United States	Clinical Res of West FL, Inc. /ID# 159840	Clearwater	Florida
United States	Adriana Pop-Moody MD Clinic PA /ID# 160009	Corpus Christi	Texas
United States	Covina Arthritis Clinic /ID# 159919	Covina	California
United States	Metroplex Clinical Research /ID# 159818	Dallas	Texas
United States	International Medical Research - Daytona /ID# 160051	Daytona Beach	Florida
United States	Denver Arthritis Clinic /ID# 159899	Denver	Colorado
United States	Altoona Ctr Clinical Res /ID# 159861	Duncansville	Pennsylvania
United States	TriWest Research Associates /ID# 159915	El Cajon	California
United States	Saint Jude Heritage /ID# 160005	Fullerton	California
United States	C.V. Mehta MD, Med Corporation /ID# 161192	Hemet	California
United States	Accurate Clinical Research /ID# 160052	Houston	Texas
United States	Care Access Research, Huntingt /ID# 160049	Huntington Beach	California
United States	Rheumatology Consultants, PLLC /ID# 161408	Knoxville	Tennessee
United States	Kotha and Kotha /ID# 159834	La Mesa	California
United States	Arthritis and Osteo Assoc /ID# 160015	Las Cruces	New Mexico
United States	P&I Clinical Research /ID# 159837	Lufkin	Texas
United States	Atlanta Research Center for Rheumatology /ID# 161201	Marietta	Georgia
United States	Dr. Ramesh Gupta /ID# 160067	Memphis	Tennessee
United States	AZ Arthritis & Rheum Research /ID# 160047	Mesa	Arizona
United States	SW Rheumatology Res. LLC /ID# 160014	Mesquite	Texas
United States	Precision Research Org, LLC /ID# 161293	Miami Lakes	Florida
United States	Trinity Health Med Arts Clinic /ID# 159811	Minot	North Dakota
United States	Alabama Medical Group, PC /ID# 159836	Mobile	Alabama
United States	The Arthritis & Diabetes Clinic, Inc. /ID# 161294	Monroe	Louisiana
United States	Suncoast Clinical Research /ID# 161417	New Port Richey	Florida
United States	Health Research of Oklahoma /ID# 159913	Oklahoma City	Oklahoma
United States	Westroads Clinical Research /ID# 160004	Omaha	Nebraska
United States	Millennium Research /ID# 159833	Ormond Beach	Florida
United States	Arthritis Center, Inc. /ID# 163463	Palm Harbor	Florida
United States	Gulf Region Clinical Res Inst /ID# 159860	Pensacola	Florida
United States	SunValley Arthritis Center, Lt /ID# 161203	Peoria	Arizona
United States	AZ Arthritis and Rheumotology Research, PLLC /ID# 160006	Phoenix	Arizona
United States	St. Lawrence Health System /ID# 159857	Potsdam	New York
United States	BayCare Medical Group /ID# 161405	Saint Petersburg	Florida
United States	Sarasota Arthritis Center /ID# 159854	Sarasota	Florida
United States	Swedish Medical Center /ID# 159918	Seattle	Washington
United States	Clinical Investigation Specialists - Skokie /ID# 160068	Skokie	Illinois
United States	Clinvest Research LLC /ID# 161208	Springfield	Missouri
United States	Stanford University School of Med /ID# 161402	Stanford	California
United States	Articularis Healthcare Group, Inc d/b/a Low Country Rheumatology /ID# 163462	Summerville	South Carolina
United States	W. Broward Rheum Assoc Inc. /ID# 161412	Tamarac	Florida
United States	BayCare Medical Group, Inc. /ID# 159912	Tampa	Florida
United States	Clinical Research of West Florida, Inc /ID# 160069	Tampa	Florida
United States	USF Health Morsani Center for /ID# 161291	Tampa	Florida
United States	DM Clinical Research /ID# 161753	Tomball	Texas
United States	Atlantic Coast Research /ID# 159810	Toms River	New Jersey
United States	Inland Rheum Clin Trials Inc. /ID# 159839	Upland	California
United States	STAT Research, Inc. /ID# 161416	Vandalia	Ohio
United States	Deerbrook Medical Associates /ID# 159815	Vernon Hills	Illinois
United States	Arthritis & Osteoporosis Clinic /ID# 161400	Waco	Texas
United States	The Center for Rheumatology & Bone Research /ID# 159900	Wheaton	Maryland
United States	Medvin Clinical Research /ID# 160045	Whittier	California
United States	PMG Research of Wilmington LLC /ID# 161403	Wilmington	North Carolina
United States	Clinical Pharma Study Group /ID# 158712	Worcester	Massachusetts
United States	Florida Medical Clinic /ID# 160013	Zephyrhills	Florida

Sponsors (1)

Lead Sponsor	Collaborator
AbbVie

Countries where clinical trial is conducted

United States,  Belgium,  Brazil,  Canada,  Chile,  Czechia,  France,  Greece,  Hungary,  Italy,  Japan,  Netherlands,  New Zealand,  Portugal,  Puerto Rico,  Spain,  United Kingdom, 

References & Publications (1)

Mease PJ, Lertratanakul A, Anderson JK, Papp K, Van den Bosch F, Tsuji S, Dokoupilova E, Keiserman M, Wang X, Zhong S, McCaskill RM, Zueger P, Pangan AL, Tillett W. Upadacitinib for psoriatic arthritis refractory to biologics: SELECT-PsA 2. Ann Rheum Dis. — 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 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 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	Percentage of Participants Achieving a Static Investigator Global Assessment (sIGA) of Psoriasis of 0 or 1 and at Least a 2-point Improvement From Baseline (sIGA 0/1) at Week 16	The sIGA is a 5 point scale ranging from 0 to 4, based on the investigator's assessment of the average elevation, erythema, and scaling of all psoriatic lesions at the current visit. A lower score indicates less severe psoriasis (0 = clear, 1 = almost clear, 2 = mild, 3 = moderate and 4 = severe).	Baseline and Week 16
Secondary	Percentage of Participants Achieving Psoriasis Area Severity Index (PASI) 75 Response at Week 16	PASI is a composite score based on the percentage of the body surface area (BSA) affected by psoriasis and the intensity of erythema (reddening), induration (thickening or hardening of the skin), and desquamation (peeling of the skin) of lesions assessed at 4 anatomic sites (head, upper extremities, trunk, and lower extremities). At each location, the percentage of BSA involvement is assigned a score from 0 (no involvement) to 6 (90% to 100% involvement), and erythema, induration, and desquamation are scored on a scale from 0 (no symptoms) to 4 (very marked).; The PASI score ranges from 0 (no psoriasis) to 72 (very severe psoriasis). A PASI-75 response is the percentage of participants who achieved at least a 75% reduction (improvement) from Baseline in PASI score.	Baseline and Week 16
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	Change From Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Score at Week 12	The FACIT-Fatigue questionnaire is a self-administered patient questionnaire that consists of 13 questions designed to measure the degree of fatigue experienced by participants in the previous 7 days, including physical fatigue (e.g., I feel tired), functional fatigue (e.g., trouble finishing things), emotional fatigue (e.g., frustration), and social consequences of fatigue (e.g., limits social activity). Participants respond to the questions on a scale from 0 'not at all' to 4 'very much'. The FACIT Fatigue score is computed by summing the item scores, after reversing those items that are worded in the negative direction. The FACIT-Fatigue subscale score ranges from 0 to 52, where higher scores represent less fatigue. A positive change from Baseline indicates improvement.	Baseline and Week 12
Secondary	Percentage of Participants Achieving Minimal Disease Activity (MDA) at Week 24	A participant was classified as achieving MDA if 5 of the following 7 criteria were met: Tender joint count (out of 68 joints) = 1; Swollen joint count (out of 66 joints) = 1; PASI score = 1 (score ranges from 0 - 72) or percent BSA involved with psoriasis = 3%; Patient's assessment of pain = 1.5 (NRS from 0 to 10); Patient's Global Assessment of disease activity = 2 (NRS from 0 to 10); HAQ-DI score = 0.5 (index score ranges from 0 to 3); Leeds Enthesitis Index = 1 (assesses the presence or absence of enthesitis at 3 bilateral sites, with an overall score range from 0 to 6)	Week 24
Secondary	Change From Baseline in Self-Assessment of Psoriasis Symptoms (SAPS) Score at Week 16	The SAPS is an 11-item self-assessment of psoriasis symptoms that includes questions on: pain, itching, redness, scaling, flaking, bleeding, burning, stinging, tenderness, pain due to skin cracking, and joint pain. Each item is scored from 0 to 10, with 0 being least severe and 10 being most severe. The total score is generated by summing the 11 items and ranges from 0 to 110 (worst). A negative change from Baseline in the total score indicates improvement.	Baseline and Week 16
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 2	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 2