A Study of Guselkumab in Participants With Active Psoriatic Arthritis and an Inadequate Response to Anti-Tumor Necrosis Factor Alpha (Anti-TNF Alpha) Therapy
- Registration Number
- NCT03796858
- Lead Sponsor
- Janssen Pharmaceutica N.V., Belgium
- Brief Summary
The purpose of this study is to evaluate guselkumab efficacy versus placebo in participants with active psoriatic arthritis (PsA) and an inadequate response to Anti-Tumor Necrosis Factor Alpha (TNF-alpha) therapy by assessing the reduction in signs and symptoms of joint disease.
- Detailed Description
Psoriatic arthritis is a multi-faceted disease that impacts the joints, soft tissues, and skin, all of which not only results in functional disability and impaired quality of life, but participants with this disease also have increased mortality. Guselkumab is a monoclonal antibody that binds to human interleukin 23 (IL-23) and inhibits IL-23 specific intracellular signaling and subsequent activation and cytokine production. Investigation of guselkumab in this Phase 3b PsA clinical study is supported by the favorable efficacy and safety results from Phase 2 study of guselkumab in PsA and Phase 2 and Phase 3 studies in psoriasis including the subset of participants with PsA. The primary hypothesis is that guselkumab 100 milligram (mg) at Weeks 0, 4, and every 8 weeks (q8w) thereafter is superior to placebo which will be assessed by the proportion of participants achieving an American College of Rheumatology (ACR 20) response at Week 24. The study includes 2 periods: A 24-week double-blind, placebo-controlled period for the primary analysis of the efficacy and safety of guselkumab, compared with placebo and a 32-week active-treatment and safety follow-up period for additional analysis of the efficacy and safety of guselkumab. Safety will be monitored throughout the study (Up to Week 56).
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 285
- Have a diagnosis of psoriatic arthritis (PsA) for at least 6 months before the first administration of study intervention and meet classification criteria for Psoriatic Arthritis (CASPAR) at screening
- Have active PsA as defined by at least 3 swollen joints and at least 3 tender joints at screening and at baseline
- Have at least 1 of the PsA subsets: distal interphalangeal joint involvement, polyarticular arthritis with absence of rheumatoid nodules, arthritis mutilans, asymmetric peripheral arthritis, or spondylitis with peripheral arthritis
- Have an inadequate response to anti-TNF alpha therapy, defined as presence of active PsA despite previous treatment with either 1 or 2 anti-TNF alpha agents and either of the following: a) Lack of benefit of an anti-TNF alpha therapy, as documented in the participant history by the treating physician, after at least 12 weeks of etanercept, adalimumab, golimumab, or certolizumab pegol therapy (or biosimilars) and/or at least a 14-week dosage regimen (i.e., at least 4 doses) of infliximab (or biosimilars). Documented lack of benefit may include inadequate improvement in joint counts, skin response, physical function, or disease activity, b) Intolerance to an anti-TNF alpha therapy, as documented in the patient history by the treating physician, to etanercept, adalimumab, golimumab, certolizumab pegol, or infliximab (or biosimilars, if available)
- Be willing to refrain from the use of complementary therapies for PsA or psoriasis including ayurvedic medicine, traditional Taiwanese, Korean, or Chinese medications and acupuncture within 2 weeks before the first study intervention administration and through Week 48
- Has other inflammatory diseases that might confound the evaluations of benefit of guselkumab therapy, including but not limited to rheumatoid arthritis (RA), axial spondyloarthritis (this does not include a primary diagnosis of PsA with spondylitis), systemic lupus erythematosus, or Lyme disease
- Has ever received more than 2 different anti-TNF alpha agents
- Has previously received any biologic treatment (other than anti-TNF Alpha agents), including, but not limited to ustekinumab, abatacept, secukinumab, tildrakizumab, ixekizumab, brodalumab, risankizumab, or other investigative biologic treatment
- Has previously received tofacitinib, baricitinib, filgotinib, peficitinib (ASP015K), decernotinib (VX 509), or any other a Janus kinase (JAK) inhibitor
- Has previously received any systemic immunosuppressants (for example, azathioprine, cyclosporine, 6 thioguanine, mercaptopurine, mycophenolate mofetil, hydroxyurea, tacrolimus) within 4 weeks of the first administration of study intervention
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Group 1: Guselkumab Guselkumab 100 mg Participants will receive guselkumab 100 milligram (mg) Subcutaneous (SC) injection at Weeks 0, 4, 12, 20, 28, 36, and 44 and placebo SC at Week 24 to maintain the blind. At Week 16, Participants who meet the early escape criteria will receive placebo at Week 16 and guselkumab at Week 20, then guselkumab every 8 weeks (q8w). Group 1: Guselkumab Placebo Participants will receive guselkumab 100 milligram (mg) Subcutaneous (SC) injection at Weeks 0, 4, 12, 20, 28, 36, and 44 and placebo SC at Week 24 to maintain the blind. At Week 16, Participants who meet the early escape criteria will receive placebo at Week 16 and guselkumab at Week 20, then guselkumab every 8 weeks (q8w). Group 2: Placebo followed by Guselkumab Guselkumab 100 mg Participants will receive placebo SC injection at Weeks 0, 4, 12, and 20, and will crossover to receive guselkumab 100 mg SC injection at Weeks 24, 28, 36, and 44. At Week 16, Participants who meet the early escape criteria will receive guselkumab at Weeks 16 and 20, then guselkumab q8w. Group 2: Placebo followed by Guselkumab Placebo Participants will receive placebo SC injection at Weeks 0, 4, 12, and 20, and will crossover to receive guselkumab 100 mg SC injection at Weeks 24, 28, 36, and 44. At Week 16, Participants who meet the early escape criteria will receive guselkumab at Weeks 16 and 20, then guselkumab q8w.
- Primary Outcome Measures
Name Time Method Percentage of Participants who Achieve an American College of Rheumatology (ACR) 20 Response at Week 24 Week 24 The ACR 20 Response is defined as greater than or equal to (\>=) 20 percent (%) improvement in swollen joint count (66 joints) and tender joint count (68 joints) and \>=20 percent improvement in 3 of following 5 assessments: participant's assessment of pain using Visual Analog Scale (VAS; 0-10 millimeter \[mm\], 0 mm=no pain and 10 mm=worst possible pain), participant's global assessment of disease activity by using VAS (scale ranges from 0 mm to 100 mm, \[0 mm=no pain to 100 mm=worst possible pain\]), physician's global assessment of disease activity using VAS, participant's assessment of physical function measured by Health Assessment Questionnaire-Disability Index (HAQ-DI, defined as a 20-question instrument assessing 8 functional areas. The derived HAQ-DI ranges from 0, indicating no difficulty, to 3, indicating inability to perform a task in that area) and C-reactive protein (CRP).
- Secondary Outcome Measures
Name Time Method Change from Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) Score at Week 24 Baseline, Week 24 The HAQ-DI is a 20-question instrument that assesses the degree of difficulty a person has in accomplishing tasks in 8 functional areas (dressing, arising, eating, walking, hygiene, reaching, gripping and activities of daily living). Responses in each functional area are scored from 0 to 3 (0=no difficulty and 3=inability to perform a task in that area). Overall score is computed as the sum of domain scores and divided by the number of domains answered. Total possible score range 0-3 where 0 = least difficulty and 3 = extreme difficulty.
Percentage of Participants who Achieve an ACR 50 Response at Week 24 Week 24 The ACR 50 Response is defined as greater than or equal to (\>=) 50 percent improvement in swollen joint count (66 joints) and tender joint count (68 joints) and \>=50 percent improvement in 3 of following 5 assessments: participant's assessment of pain using Visual Analog Scale (VAS; 0-10 millimeter \[mm\], 0 mm=no pain and 10 mm=worst possible pain), participant's global assessment of disease activity by using VAS (scale ranges from 0 mm to 100 mm, \[0 mm=no pain to 100 mm=worst possible pain\]), physician's global assessment of disease activity using VAS, participant's assessment of physical function measured by Health Assessment Questionnaire-Disability Index (HAQ-DI, defined as a 20-question instrument assessing 8 functional areas. The derived HAQ-DI ranges from 0, indicating no difficulty, to 3, indicating inability to perform a task in that area) and C-reactive protein (CRP).
Percentage of Participants who Achieve Psoriatic Area and Severity Index (PASI) 100 Response at Week 24 Among Participants with >=3% body Surface area Psoriatic Involvement and an Investigator's Global Assessment (IGA) Score of >=2 (Mild) at Baseline Week 24 PASI 100 response is defined as 100% improvement in PASI score from baseline (PASI score of 0). The PASI is a system used for assessing and grading the severity of psoriatic lesions and their response to therapy. In the PASI scoring system, the body is divided into 4 regions: the head, trunk, upper extremities, and lower extremities. Each of these areas is assessed separately for the percentage of the area involved, which translates to a numeric score that ranges from 0 (indicates no involvement) to 6 (90%-100% involvement), and for erythema, induration, and scaling, which are each rated on a scale of 0 to 4. The PASI produces a numeric score that could range from 0 (no psoriasis) to 72. A higher score indicates more severe disease.
Change from Baseline in 36-Item Short form Health Survey (SF-36) Physical Component Summary (PCS) Score at Week 24 Baseline, Week 24 The SF-36 is a generic health survey with 36 items that measure functional health and well-being from the participant's perspective. The survey is summarized into 8 dimensions/scales: physical functioning (PF), role-physical (RP), bodily pain (BP), general health (GH), vitality (VT), social functioning (SF), role-emotional (RE), and mental health (MH). The physical component summary measure is derived from 4 of the 8 health dimensions (aggregate of PF, RP, BP, and GH scales). The minimum score is 0 and the maximum score is 100. A higher score indicates a better health state.
Trial Locations
- Locations (117)
Centrum Terapii Wspolczesnej J M Jasnorzewska Spolka Komandytowo Akcyjna
🇵🇱Lodz, Poland
NZOZ Lecznica MAK MED S C
🇵🇱Nadarzyn, Poland
WroMedica I Bielicka A Strzalkowska s c
🇵🇱Wroclaw, Poland
Uls Almada Seixal - Hosp. Garcia de Orta
🇵🇹Almada, Portugal
Uls Regiao Aveiro - Hosp. Infante D. Pedro
🇵🇹Aveiro, Portugal
Uls Braga - Hosp. Braga
🇵🇹Braga, Portugal
Ipr Inst Port de Reumatologia
🇵🇹Lisboa, Portugal
Uls Lisboa Ocidental - Hosp. Egas Moniz
🇵🇹Lisboa, Portugal
Uls Santa Maria - Hosp. Santa Maria
🇵🇹Lisboa, Portugal
Hosp Univ A Coruna
🇪🇸A Coruna, Spain
Hosp Reina Sofia
🇪🇸Cordoba, Spain
Hosp Regional Univ de Malaga
🇪🇸Málaga, Spain
Communal Noncommercial Enterprise Cherkasy Regional Hospital of Cherkasy Regional Council
🇺🇦Cherkasy, Ukraine
SI National Scientific Center Institute of Cardiology of M.D. Strazhesko of NAMS of Ukraine
🇺🇦Kyiv, Ukraine
ME Poltava Regional Clinical Hospital named after M.V. Sklifosovsky of Poltava Regional Consuil
🇺🇦Poltava, Ukraine
Diagnostic Consulting Center No 17
🇧🇬Sofia, Bulgaria
Military Medical Academy
🇧🇬Sofia, Bulgaria
Hopital Pellegrin Tripode - CHU de Bordeaux
🇫🇷Bordeaux, France
Szpital Uniwersytecki Nr 2 w Bydgoszczy
🇵🇱Bydgoszcz, Poland
Centrum Kliniczno Badawcze
🇵🇱Elblag, Poland
Medycyna Kliniczna
🇵🇱Warsaw, Poland
Mazowieckie Centrum Reumatologii i Osteoporozy
🇵🇱Warszawa, Poland
Ulsam - Hosp. Conde de Bertiandos
🇵🇹Ponte de Lima, Portugal
Orenburg State Medical Academy
🇷🇺Orenburg, Russian Federation
Rostov Regional Clinical Dermatovenerological Dispensary
🇷🇺Rostov, Russian Federation
Ryazan Regional Clinical Dermatovenerological Dispensary
🇷🇺Ryazan, Russian Federation
Samara Regional Clinical Hospital Named After V.D.Seredavin
🇷🇺Samara, Russian Federation
Sararov Regional Clinical Hospital
🇷🇺Saratov, Russian Federation
Smolensk regional hospital on Smolensk railway station
🇷🇺Smolensk, Russian Federation
Leningrad region clinical hospital
🇷🇺St-Petersburg, Russian Federation
Tula Regional Clinical Dermatovenerological Dispensary
🇷🇺Tula, Russian Federation
Republican Clinical Hospital - G.G. Kuvatov
🇷🇺Ufa, Russian Federation
Ulyanovsk Regional Clinical Hospital
🇷🇺Ulyanovsk, Russian Federation
Regional Clinical Hospital
🇷🇺Velikiy Novgorod, Russian Federation
Clinical Emergency Hospital n.a. N.V. Solovyev
🇷🇺Yaroslavl, Russian Federation
Clinical Hospital #3
🇷🇺Yaroslavl, Russian Federation
Kyiv City Clinical Hospital #3, National Medical University
🇺🇦Kyiv, Ukraine
Medical Center 'Consylium Medical'
🇺🇦Kyiv, Ukraine
Kyiv Railway Station Clinical Hospital #2
🇺🇦Kyiv, Ukraine
Municipal Institution of Sumy Regional Council Sumy Regional Clinical Hospital
🇺🇦Sumy, Ukraine
Medical Center LTD Health Clinic Department of Cardiology and Rheumatology
🇺🇦Vinnytsya, Ukraine
VNMUn.af.Pyrogova,CNE Vinnytsia Regional Clinical Hospital n.af.Pyrogova Vinnytsia Regional Council
🇺🇦Vinnytsya, Ukraine
Municipal institution Central Clinical Hospital #1 Zhytomir
🇺🇦Zhytomyr, Ukraine
Royal National Hospital for Rheumatic Diseases
🇬🇧Bath, United Kingdom
Cambridge University Hospitals NHS Foundation Trust
🇬🇧Cambridge, United Kingdom
Cannock Chase Hospital
🇬🇧Cannock, United Kingdom
Chapel Allerton Hospital
🇬🇧Leeds, United Kingdom
Barts Health NHS Trust Whipps Cross University Hospital NHS Trust
🇬🇧London, United Kingdom
Guy's and St Thomas' NHS Foundation Trust - Rheumatoid Arthritis (RA) Clinic
🇬🇧London, United Kingdom
Complesso Integrato Columbus
🇮🇹Rome, Italy
Humanitas Hospital
🇮🇹Rozzano (MI), Italy
Multiprofile Hospital for Active Treatment Plovdiv
🇧🇬Plovdiv, Bulgaria
Medical Center Teodora
🇧🇬Ruse, Bulgaria
Universitatsklinikum Dusseldorf
🇩🇪Dusseldorf, Germany
Betegapolo Irgalmas Rend Budai Irgalmasrendi Korhaz
ðŸ‡ðŸ‡ºBudapest, Hungary
Fejer Varmegyei Szent Gyorgy Egyetemi Oktatokorhaz
ðŸ‡ðŸ‡ºSzékesfehérvár, Hungary
Dermed Centrum Medyczne Sp z o o
🇵🇱Lodz, Poland
Municipal Non-commercial Enterprise Ternopil University Hospital of Ternopil Regional Council
🇺🇦Ternopil, Ukraine
CHU Saint Pierre BXL
🇧🇪Brussels, Belgium
Reuma Clinic
🇧🇪Genk, Belgium
Universitair Ziekenhuis Gent
🇧🇪Gent, Belgium
UZ Leuven
🇧🇪Leuven, Belgium
Diagnostic - Consulting Center II-Pleven
🇧🇬Pleven, Bulgaria
Medical Center Medconsult-Pleven
🇧🇬Pleven, Bulgaria
Multiprofile Hosptal for Active Treatment Eurohospital Plovdiv
🇧🇬Plovdiv, Bulgaria
CHU Lapeyronie
🇫🇷Montpellier, France
Centre Hospitalier Regional d'Orleans (CHRO) - Hopital La Source
🇫🇷Orleans, France
Hopital Lariboisiere
🇫🇷Paris, France
Hôpital Pitié-Salpétrière
🇫🇷Paris, France
Hopital Cochin
🇫🇷Paris, France
Centre Hospitalier Universitaire de Toulouse - Hopital Purpan
🇫🇷Toulouse, France
CHU Trousseau - Service de Rhumatologie
🇫🇷Tours, France
Hamburger Rheuma Forschungszentrum II
🇩🇪Hamburg, Germany
Medizinische Hochschule Hannover
🇩🇪Hannover, Germany
Rheumazentrum Ruhrgebiet
🇩🇪Herne, Germany
Rheumatologische Schwerpunktpraxis
🇩🇪Rendsburg, Germany
Krankenhaus St. Josef
🇩🇪Wuppertal, Germany
424 Military Hospital of Thessaloniki
🇬🇷Thessaloniki, Greece
Bekes Megyei Kozponti Korhaz Pandy Kalman Tagkorhaz
ðŸ‡ðŸ‡ºGyula, Hungary
Szabolcs-Szatmar-Bereg Megyei Korhazak es Egyetemi Oktatokorhaz
ðŸ‡ðŸ‡ºNyiregyhaza, Hungary
MAV Korhaz es Rendelointezet
ðŸ‡ðŸ‡ºSzolnok, Hungary
Vital Medical Center Orvosi es Fogaszati Kozpont
ðŸ‡ðŸ‡ºVeszprem, Hungary
Barzilai Medical Center
🇮🇱Ashkelon, Israel
Bnai Zion Medical Center
🇮🇱Hifa, Israel
Carmel Medical Center
🇮🇱Hifa, Israel
Hadassah Medical Center
🇮🇱Jerusalem, Israel
Sheba Medical Center
🇮🇱Ramat Gan, Israel
Tel Aviv Sourasky Medical Center
🇮🇱Tel Aviv, Israel
Azienda Ospedaliera Universitaria Federico II
🇮🇹Napoli, Italy
Azienda Ospedaliero Universitaria Policlinico Paolo Giaccone
🇮🇹Palermo, Italy
Policlinico Tor Vergata
🇮🇹Roma, Italy
Chelyabinck Regional Clinical Hospital
🇷🇺Chelyabinsk, Russian Federation
Kemerovo State Medical University
🇷🇺Kemerovo, Russian Federation
Krasnoyarsk State Medical University
🇷🇺Krasnoyarsk, Russian Federation
Medical Centre Maximum Health
🇷🇺Kemerovo, Russian Federation
Family polyclinic #4
🇷🇺Korolev, Russian Federation
Krasnodar Clinical Dermatovenerologic Dispensary
🇷🇺Krasnodar, Russian Federation
Hosp. Univ. de Cruces
🇪🇸Barakaldo, Spain
Hosp. Univ. Germans Trias I Pujol
🇪🇸Barcelona, Spain
Hosp. Univ. de Basurto
🇪🇸Bilbao, Spain
Hosp. Univ. Ramon Y Cajal
🇪🇸Madrid, Spain
Hosp. Univ. 12 de Octubre
🇪🇸Madrid, Spain
Hosp. Univ. de Getafe
🇪🇸Madrid, Spain
Hosp. Clinico Univ. de Santiago
🇪🇸Santiago de Compostela, Spain
Hosp. Virgen Macarena
🇪🇸Sevilla, Spain
Hosp. Infanta Luisa
🇪🇸Sevilla, Spain
Hosp. Virgen Del Rocio
🇪🇸Sevilla, Spain
Hosp. Ntra. Sra. de Valme
🇪🇸Sevilla, Spain
Hosp. Do Meixoeiro
🇪🇸Vigo, Spain
Ivano-Frankivsk National Medical University, Ivano-Frankivsk City Clinical Hospital
🇺🇦Ivano-Frankivsk, Ukraine
City Multifield Hospital #18, Mechnikov Institute of Microbiology and Immunology of NAMS
🇺🇦Kharkiv, Ukraine
Municipal non-commercial enterprise of Kharkiv Regional Council Regional Clinical Hospital
🇺🇦Kharkiv, Ukraine
Khmelnitckiy regional hospital
🇺🇦Khmelnytsky, Ukraine
North Tyneside General Hospital
🇬🇧Newcastle, United Kingdom
Peterborough City Hospital
🇬🇧Peterborough, United Kingdom
Haywood Hospital
🇬🇧Stoke on Trent, United Kingdom
Torbay Hospital-Devon
🇬🇧Torquay, United Kingdom