Clinical trial NCT03796858: A Study of Guselkumab in Participants With Active Psoriatic Arthritis and an Inadequate Response to Anti-Tumor Necrosis Factor Alpha (Anti-TNF Alpha) Therapy
Official title: Phase 3b, Multicenter, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Efficacy and Safety of Guselkumab Administered Subcutaneously in Participants With Active Psoriatic Arthritis and an Inadequate Response to Anti-Tumor Necrosis Factor Alpha (Anti-TNFα) Therapy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Arthritis, Psoriatic
Lead sponsor: Janssen Pharmaceutica N.V., Belgium
Sponsor class: INDUSTRY
First posted: 2019-01-08
Enrollment: 285
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).

Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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

Primary outcomes:
measure: Percentage of Participants who Achieve an American College of Rheumatology (ACR) 20 Response at Week 24
timeFrame: Week 24
Secondary outcomes:
measure: Change from Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) Score at Week 24
timeFrame: Baseline, Week 24
measure: Percentage of Participants who Achieve an ACR 50 Response at Week 24
timeFrame: Week 24
measure: Change from Baseline in 36-Item Short form Health Survey (SF-36) Physical Component Summary (PCS) Score at Week 24
timeFrame: Baseline, Week 24
measure: 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
timeFrame: Week 24
Other outcomes:
Locations:
city: Brussels
country: Belgium
facility: CHU Saint Pierre BXL
city: Genk
country: Belgium
facility: Reuma Clinic
city: Gent
country: Belgium
facility: Universitair Ziekenhuis Gent
city: Leuven
country: Belgium
facility: UZ Leuven
city: Pleven
country: Bulgaria
facility: Diagnostic - Consulting Center II-Pleven
city: Pleven
country: Bulgaria
facility: Medical Center Medconsult-Pleven
city: Plovdiv
country: Bulgaria
facility: Multiprofile Hospital for Active Treatment Plovdiv
city: Plovdiv
country: Bulgaria
facility: Multiprofile Hosptal for Active Treatment Eurohospital Plovdiv
city: Ruse
country: Bulgaria
facility: Medical Center Teodora
city: Sofia
country: Bulgaria
facility: Diagnostic Consulting Center No 17
city: Sofia
country: Bulgaria
facility: Military Medical Academy
city: Bordeaux
country: France
facility: Hopital Pellegrin Tripode - CHU de Bordeaux
city: Montpellier
country: France
facility: CHU Lapeyronie
city: Orleans
country: France
facility: Centre Hospitalier Regional d'Orleans (CHRO) - Hopital La Source
city: Paris
country: France
facility: Hopital Lariboisiere
city: Paris
country: France
facility: Hôpital Pitié-Salpétrière
city: Paris
country: France
facility: Hopital Cochin
city: Toulouse
country: France
facility: Centre Hospitalier Universitaire de Toulouse - Hopital Purpan
city: Tours
country: France
facility: CHU Trousseau - Service de Rhumatologie
city: Dusseldorf
country: Germany
facility: Universitatsklinikum Dusseldorf
city: Hamburg
country: Germany
facility: Hamburger Rheuma Forschungszentrum II
city: Hannover
country: Germany
facility: Medizinische Hochschule Hannover
city: Herne
country: Germany
facility: Rheumazentrum Ruhrgebiet
city: Rendsburg
country: Germany
facility: Rheumatologische Schwerpunktpraxis
city: Wuppertal
country: Germany
facility: Krankenhaus St. Josef
city: Thessaloniki
country: Greece
facility: 424 Military Hospital of Thessaloniki
city: Budapest
country: Hungary
facility: Betegapolo Irgalmas Rend Budai Irgalmasrendi Korhaz
city: Gyula
country: Hungary
facility: Bekes Megyei Kozponti Korhaz Pandy Kalman Tagkorhaz
city: Nyiregyhaza
country: Hungary
facility: Szabolcs-Szatmar-Bereg Megyei Korhazak es Egyetemi Oktatokorhaz
city: Szolnok
country: Hungary
facility: MAV Korhaz es Rendelointezet
city: Székesfehérvár
country: Hungary
facility: Fejer Varmegyei Szent Gyorgy Egyetemi Oktatokorhaz
city: Veszprem
country: Hungary
facility: Vital Medical Center Orvosi es Fogaszati Kozpont
city: Ashkelon
country: Israel
facility: Barzilai Medical Center
city: Hifa
country: Israel
facility: Bnai Zion Medical Center
city: Hifa
country: Israel
facility: Carmel Medical Center
city: Jerusalem
country: Israel
facility: Hadassah Medical Center
city: Ramat Gan
country: Israel
facility: Sheba Medical Center
city: Tel Aviv
country: Israel
facility: Tel Aviv Sourasky Medical Center
city: Napoli
country: Italy
facility: Azienda Ospedaliera Universitaria Federico II
city: Palermo
country: Italy
facility: Azienda Ospedaliero Universitaria Policlinico Paolo Giaccone
city: Roma
country: Italy
facility: Policlinico Tor Vergata
city: Rome
country: Italy
facility: Complesso Integrato Columbus
city: Rozzano (MI)
country: Italy
facility: Humanitas Hospital
city: Bydgoszcz
country: Poland
facility: Szpital Uniwersytecki Nr 2 w Bydgoszczy
city: Elblag
country: Poland
facility: Centrum Kliniczno Badawcze
city: Lodz
country: Poland
facility: Dermed Centrum Medyczne Sp z o o
city: Lodz
country: Poland
facility: Centrum Terapii Wspolczesnej J M Jasnorzewska Spolka Komandytowo Akcyjna
city: Nadarzyn
country: Poland
facility: NZOZ Lecznica MAK MED S C
city: Warsaw
country: Poland
facility: Medycyna Kliniczna
city: Warszawa
country: Poland
facility: Mazowieckie Centrum Reumatologii i Osteoporozy
city: Wroclaw
country: Poland
facility: WroMedica I Bielicka A Strzalkowska s c
city: Almada
country: Portugal
facility: Uls Almada Seixal - Hosp. Garcia de Orta
city: Aveiro
country: Portugal
facility: Uls Regiao Aveiro - Hosp. Infante D. Pedro
city: Braga
country: Portugal
facility: Uls Braga - Hosp. Braga
city: Lisboa
country: Portugal
facility: Ipr Inst Port de Reumatologia
city: Lisboa
country: Portugal
facility: Uls Lisboa Ocidental - Hosp. Egas Moniz
city: Lisboa
country: Portugal
facility: Uls Santa Maria - Hosp. Santa Maria
city: Ponte de Lima
country: Portugal
facility: Ulsam - Hosp. Conde de Bertiandos
city: Chelyabinsk
country: Russian Federation
facility: Chelyabinck Regional Clinical Hospital
city: Kemerovo
country: Russian Federation
facility: Kemerovo State Medical University
city: Kemerovo
country: Russian Federation
facility: Medical Centre Maximum Health
city: Korolev
country: Russian Federation
facility: Family polyclinic #4
city: Krasnodar
country: Russian Federation
facility: Krasnodar Clinical Dermatovenerologic Dispensary
city: Krasnoyarsk
country: Russian Federation
facility: Krasnoyarsk State Medical University
city: Orenburg
country: Russian Federation
facility: Orenburg State Medical Academy
city: Rostov
country: Russian Federation
facility: Rostov Regional Clinical Dermatovenerological Dispensary
city: Ryazan
country: Russian Federation
facility: Ryazan Regional Clinical Dermatovenerological Dispensary
city: Samara
country: Russian Federation
facility: Samara Regional Clinical Hospital Named After V.D.Seredavin
city: Saratov
country: Russian Federation
facility: Sararov Regional Clinical Hospital
city: Smolensk
country: Russian Federation
facility: Smolensk regional hospital on Smolensk railway station
city: St-Petersburg
country: Russian Federation
facility: Leningrad region clinical hospital
city: Tula
country: Russian Federation
facility: Tula Regional Clinical Dermatovenerological Dispensary
city: Ufa
country: Russian Federation
facility: Republican Clinical Hospital - G.G. Kuvatov
city: Ulyanovsk
country: Russian Federation
facility: Ulyanovsk Regional Clinical Hospital
city: Velikiy Novgorod
country: Russian Federation
facility: Regional Clinical Hospital
city: Yaroslavl
country: Russian Federation
facility: Clinical Emergency Hospital n.a. N.V. Solovyev
city: Yaroslavl
country: Russian Federation
facility: Clinical Hospital #3
city: A Coruna
country: Spain
facility: Hosp Univ A Coruna
city: Barakaldo
country: Spain
facility: Hosp. Univ. de Cruces
city: Barcelona
country: Spain
facility: Hosp. Univ. Germans Trias I Pujol
city: Bilbao
country: Spain
facility: Hosp. Univ. de Basurto
city: Cordoba
country: Spain
facility: Hosp Reina Sofia
city: Madrid
country: Spain
facility: Hosp. Univ. Ramon Y Cajal
city: Madrid
country: Spain
facility: Hosp. Univ. 12 de Octubre
city: Madrid
country: Spain
facility: Hosp. Univ. de Getafe
city: Málaga
country: Spain
facility: Hosp Regional Univ de Malaga
city: Santiago de Compostela
country: Spain
facility: Hosp. Clinico Univ. de Santiago
city: Sevilla
country: Spain
facility: Hosp. Virgen Macarena
city: Sevilla
country: Spain
facility: Hosp. Infanta Luisa
city: Sevilla
country: Spain
facility: Hosp. Virgen Del Rocio
city: Sevilla
country: Spain
facility: Hosp. Ntra. Sra. de Valme
city: Vigo
country: Spain
facility: Hosp. Do Meixoeiro
city: Cherkasy
country: Ukraine
facility: Communal Noncommercial Enterprise Cherkasy Regional Hospital of Cherkasy Regional Council
city: Ivano-Frankivsk
country: Ukraine
facility: Ivano-Frankivsk National Medical University, Ivano-Frankivsk City Clinical Hospital
city: Kharkiv
country: Ukraine
facility: City Multifield Hospital #18, Mechnikov Institute of Microbiology and Immunology of NAMS
city: Kharkiv
country: Ukraine
facility: Municipal non-commercial enterprise of Kharkiv Regional Council Regional Clinical Hospital
city: Khmelnytsky
country: Ukraine
facility: Khmelnitckiy regional hospital
city: Kyiv
country: Ukraine
facility: Kyiv City Clinical Hospital #3, National Medical University
city: Kyiv
country: Ukraine
facility: Medical Center 'Consylium Medical'
city: Kyiv
country: Ukraine
facility: Kyiv Railway Station Clinical Hospital #2
city: Kyiv
country: Ukraine
facility: SI National Scientific Center Institute of Cardiology of M.D. Strazhesko of NAMS of Ukraine
city: Poltava
country: Ukraine
facility: ME Poltava Regional Clinical Hospital named after M.V. Sklifosovsky of Poltava Regional Consuil
city: Sumy
country: Ukraine
facility: Municipal Institution of Sumy Regional Council Sumy Regional Clinical Hospital
city: Ternopil
country: Ukraine
facility: Municipal Non-commercial Enterprise Ternopil University Hospital of Ternopil Regional Council
city: Vinnytsya
country: Ukraine
facility: Medical Center LTD Health Clinic Department of Cardiology and Rheumatology
city: Vinnytsya
country: Ukraine
facility: VNMUn.af.Pyrogova,CNE Vinnytsia Regional Clinical Hospital n.af.Pyrogova Vinnytsia Regional Council
city: Zhytomyr
country: Ukraine
facility: Municipal institution Central Clinical Hospital #1 Zhytomir
city: Bath
country: United Kingdom
facility: Royal National Hospital for Rheumatic Diseases
city: Cambridge
country: United Kingdom
facility: Cambridge University Hospitals NHS Foundation Trust
city: Cannock
country: United Kingdom
facility: Cannock Chase Hospital
city: Leeds
country: United Kingdom
facility: Chapel Allerton Hospital
city: London
country: United Kingdom
facility: Barts Health NHS Trust Whipps Cross University Hospital NHS Trust
city: London
country: United Kingdom
facility: Guy's and St Thomas' NHS Foundation Trust - Rheumatoid Arthritis (RA) Clinic
city: Newcastle
country: United Kingdom
facility: North Tyneside General Hospital
city: Peterborough
country: United Kingdom
facility: Peterborough City Hospital
city: Stoke on Trent
country: United Kingdom
facility: Haywood Hospital
city: Torquay
country: United Kingdom
facility: Torbay Hospital-Devon
Study officials:
affiliation: Janssen Pharmaceutica N.V., Belgium
name: Janssen Pharmaceutica N.V., Belgium Clinical Trial
role: STUDY_DIRECTOR
References:
citation: Coates LC, Gossec L, Theander E, Bergmans P, Neuhold M, Karyekar CS, Shawi M, Noel W, Schett G, McInnes IB. Efficacy and safety of guselkumab in patients with active psoriatic arthritis who are inadequate responders to tumour necrosis factor inhibitors: results through one year of a phase IIIb, randomised, controlled study (COSMOS). Ann Rheum Dis. 2022 Mar;81(3):359-369. doi: 10.1136/annrheumdis-2021-220991. Epub 2021 Nov 24.