A Study of Guselkumab in Participants With Active Psoriatic Arthritis and an Inadequate Response to Anti-Tumor Necrosis Factor Alpha (Anti-TNF Alpha) Therapy (COSMOS)

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

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.

Study Overview

• Status: Completed
• Conditions: Arthritis, Psoriatic
• Intervention / Treatment: Drug: Guselkumab 100 mg; Drug: Placebo

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).

• Study Type: Interventional
• Enrollment (Actual): 285
• Phase: Phase 3

Contacts and Locations

Study Locations

• Belgium
  • Brussels, Belgium, 1000
    • CHU Saint Pierre BXL
  • Genk, Belgium, 3600
    • Reuma Clinic
  • Gent, Belgium, 9000
    • Universitair Ziekenhuis Gent
  • Leuven, Belgium, 3000
    • UZ Leuven
• Bulgaria
  • Pleven, Bulgaria, 5800
    • Diagnostic - Consulting Center II-Pleven
  • Pleven, Bulgaria, 5800
    • Medical Center Medconsult-Pleven
  • Plovdiv, Bulgaria, 4003
    • Multiprofile Hospital for Active Treatment - Plovdiv
  • Plovdiv, Bulgaria, 4004
    • Multiprofile Hosptal for Active Treatment Eurohospital Plovdiv
  • Ruse, Bulgaria, 7003
    • Medical Center 'Teodora'
  • Sofia, Bulgaria, 1606
    • Military Medical Academy
  • Sofia, Bulgaria, 1505
    • Diagnostic Consulting Center No 17
• France
  • Bordeaux, France, 33076
    • Hopital Pellegrin Tripode - CHU de Bordeaux
  • Montpellier, Herault, France, 34295
    • CHU Lapeyronie
  • Orleans, France, 45067
    • Centre Hospitalier Regional d'Orleans (CHRO) - Hopital La Source
  • Paris, France, 75010
    • Hopital Lariboisiere
  • Paris, France, 75014
    • Hopital Cochin
  • Paris, France, 75013
    • Hôpital Pitié-Salpêtrière
  • Toulouse, France, 30159
    • Centre Hospitalier Universitaire de Toulouse - Hôpital Purpan
  • Tours, France, 37044
    • CHU Trousseau - Service de Rhumatologie
• Germany
  • Dusseldorf, Germany, 40225
    • Universitätsklinikum Düsseldorf
  • Hamburg, Germany, 20095
    • Hamburger Rheuma Forschungszentrum II
  • Hannover, Germany, 30625
    • Medizinische Hochschule Hannover
  • Herne, Germany, 44649
    • Rheumazentrum Ruhrgebiet
  • Rendsburg, Germany, 24768
    • Rheumatologische Schwerpunktpraxis
  • Wuppertal, Germany, 42105
    • Krankenhaus St. Josef
• Greece
  • Thessaloniki, Greece, 56429
    • 424 Military Hospital of Thessaloniki
• Hungary
  • Budapest, Hungary, 1023
    • Betegapolo Irgalmas Rend - Budai Irgalmasrendi Korhaz
  • Gyula, Hungary, 5700
    • Bekes Megyei Kozponti Korhaz Pandy Kalman Tagkorhaz
  • Nyiregyhaza, Hungary, 4400
    • Szabolcs-Szatmar-Bereg Megyei Korhazak es Egyetemi Oktatokorhaz
  • Szolnok, Hungary, 5000
    • MAV Korhaz es Rendelointezet
  • Székesfehérvár, Hungary, 8000
    • Fejer Megyei Szent Gyorgy Egyetemi Oktatokorhaz
  • Veszprem, Hungary, 8200
    • Vital Medical Center Orvosi es Fogaszati Kozpont
• Israel
  • Ashkelon, Israel, 7830604
    • Barzilai Medical Center
  • Hifa, Israel, 31048
    • Bnai Zion Medical Center
  • Hifa, Israel, 34362
    • Carmel Medical Center
  • Jerusalem, Israel, 91120
    • Hadassah Medical Center
  • Ramat Gan, Israel, 5265601
    • Sheba Medical Center
  • Tel Aviv, Israel, 64239
    • Tel Aviv Sourasky Medical Center
• Italy
  • Napoli, Italy, 80131
    • Azienda Ospedaliera Universitaria Federico II
  • Palermo, Italy, 90127
    • Azienda Ospedaliero Universitaria Policlinico Paolo Giaccone
  • Roma, Italy, 00133
    • Policlinico Tor Vergata
  • Rome, Italy, 00168
    • Complesso Integrato Columbus
  • Rozzano (MI), Italy, 20089
    • Humanitas Hospital
• Poland
  • Bydgoszcz, Poland, 85-168
    • Szpital Uniwersytecki Nr 2 w Bydgoszczy
  • Elblag, Poland, 82-300
    • Centrum Kliniczno Badawcze
  • Lodz, Poland, 90-242
    • Centrum Terapii Wspolczesnej J. M. Jasnorzewska J. M. Jasnorzewska Spolka Komandytowo-Akcyjna
  • Lodz, Poland, 90-265
    • Dermed Centrum Medyczne Sp. z o.o
  • Nadarzyn, Poland, 05-830
    • NZOZ Lecznica MAK-MED. S.C.
  • Warsaw, Poland, 00-874
    • Medycyna Kliniczna
  • Warszawa, Poland, 04-030
    • Mazowieckie Centrum Reumatologii i Osteoporozy
  • Wrocław, Poland, 51-685
    • WroMedica I.Bielicka, A.Strzałkowska s.c.
• Portugal
  • Almada, Portugal, 2805-267
    • Hosp. Garcia de Orta
  • Aveiro, Portugal, 3814-501
    • Chbv - Hosp. Infante D. Pedro
  • Braga, Portugal, 4710-243
    • Ccab - Hosp. de Braga
  • Lisboa, Portugal, 1050-034
    • Ipr - Inst. Port. de Reumatologia
  • Lisboa, Portugal, 1349-019
    • Chlo - Hosp. Egas Moniz
  • Lisboa, Portugal, 1649-035
    • Chln - Hosp. Santa Maria
  • Ponte de Lima, Portugal, 4990-041
    • Ulsam - Hosp. Conde de Bertiandos
• Russian Federation
  • Chelyabinsk, Russian Federation, 454076
    • Chelyabinck Regional Clinical Hospital
  • Kemerovo, Russian Federation, 650000
    • Kemerovo State Medical University
  • Kemerovo, Russian Federation, 650066
    • Medical Centre Maximum Health
  • Korolev, Russian Federation, 141060
    • Family polyclinic #4
  • Krasnodar, Russian Federation, 350020
    • Krasnodar Clinical Dermatovenerologic Dispensary
  • Krasnoyarsk, Russian Federation, 660022
    • Krasnoyarsk State Medical University
  • Orenburg, Russian Federation, 460000
    • Orenburg State Medical Academy
  • Rostov, Russian Federation, 344007
    • Rostov Regional Clinical Dermatovenerological Dispensary
  • Ryazan, Russian Federation, 390046
    • Ryazan Regional Clinical Dermatovenerological Dispensary
  • Samara, Russian Federation, 443095
    • Samara Regional Clinical Hospital Named After V.D.Seredavin
  • Saratov, Russian Federation, 410053
    • Sararov Regional Clinical Hospital
  • Smolensk, Russian Federation, 214025
    • Smolensk regional hospital on Smolensk railway station
  • St-Petersburg, Russian Federation, 194291
    • Leningrad region clinical hospital
  • Tula, Russian Federation, 300053
    • Tula Regional Clinical Dermatovenerological Dispensary
  • Ufa, Russian Federation, 450005
    • Republican Clinical Hospital - G.G. Kuvatov
  • Ulyanovsk, Russian Federation, 432063
    • Ulyanovsk Regional Clinical Hospital
  • Velikiy Novgorod, Russian Federation, 173008
    • Regional Clinical Hospital
  • Yaroslavl, Russian Federation, 150003
    • Clinical Emergency Hospital n.a. N.V. Solovyev
  • Yaroslavl, Russian Federation, 150007
    • Clinical Hospital #3
• Spain
  • A Coruña, Spain, 15006
    • Hosp. Univ. A Coruna
  • Barakaldo, Spain, 48902
    • Hosp. Univ. de Cruces
  • Barcelona, Spain, 08916
    • Hosp. Univ. Germans Trias I Pujol
  • Bilbao, Spain, 48013
    • Hosp. Univ. de Basurto
  • Córdoba, Spain, 14004
    • Hosp. Reina Sofia
  • Madrid, Spain, 28041
    • Hosp. Univ. 12 de Octubre
  • Madrid, Spain, 28034
    • Hosp. Univ. Ramon Y Cajal
  • Madrid, Spain, 28905
    • Hosp. Univ. de Getafe
  • Málaga, Spain, 29009
    • Hosp. Regional Univ. de Malaga
  • Santiago de Compostela, Spain, 15706
    • Hosp. Clinico Univ. de Santiago
  • Sevilla, Spain, 41013
    • Hosp. Virgen Del Rocio
  • Sevilla, Spain, 41009
    • Hosp. Virgen Macarena
  • Sevilla, Spain, 41014
    • Hosp. Ntra. Sra. de Valme
  • Sevilla, Spain, 41010
    • Hosp. Infanta Luisa
  • Vigo, Spain, 36312
    • Hosp. Do Meixoeiro
• Ukraine
  • Cherkasy, Ukraine, 18009
    • Communal Noncommercial Enterprise 'Cherkasy Regional Hospital of Cherkasy Regional Council'
  • Ivano-Frankivsk, Ukraine, 76018
    • Ivano-Frankivsk National Medical University, Ivano-Frankivsk City Clinical Hospital
  • Kharkiv, Ukraine, 61058
    • Municipal non-commercial enterprise of Kharkiv Regional Council Regional Clinical Hospital
  • Kharkiv, Ukraine, 61029
    • City Multifield Hospital #18, Mechnikov Institute of Microbiology and Immunology of NAMS
  • Khmelnytsky, Ukraine, 29000
    • Khmelnitckiy regional hospital
  • Kyiv, Ukraine, 04050
    • Medical Center 'Consylium Medical'
  • Kyiv, Ukraine, 02125
    • Kyiv City Clinical Hospital #3, National Medical University
  • Kyiv, Ukraine
    • Kyiv Railway Station Clinical Hospital #2
  • Kyiv, Ukraine
    • SI 'National Scientific Center Institute of Cardiology of M.D. Strazhesko' of NAMS of Ukraine
  • Poltava, Ukraine, 36011
    • ME 'Poltava Regional Clinical Hospital named after M.V. Sklifosovsky of Poltava Regional Consuil'
  • Sumy, Ukraine, 40031
    • Municipal Institution of Sumy Regional Council Sumy Regional Clinical Hospital
  • Ternopil, Ukraine, 46002
    • Municipal Non-commercial Enterprise 'Ternopil University Hospital' of Ternopil Regional Council
  • Vinnytsya, Ukraine, 21009
    • Medical Center LTD Health Clinic Department of Cardiology and Rheumatology
  • Vinnytsya, Ukraine, 21018
    • VNMUn.af.Pyrogova,CNE Vinnytsia Regional Clinical Hospital n.af.Pyrogova Vinnytsia Regional Council
  • Zhytomir, Ukraine, 10002
    • Municipal institution Central Clinical Hospital #1 Zhytomir
• United Kingdom
  • Bath, United Kingdom, BA1 1RL
    • Royal National Hospital for Rheumatic Diseases
  • Cambridge, United Kingdom, CB2 0QQ
    • Cambridge University Hospitals NHS Foundation Trust
  • Cannock, United Kingdom, WS11 5XY
    • Cannock Chase Hospital
  • Leeds, United Kingdom, LS7 4SA
    • Chapel Allerton Hospital
  • London, United Kingdom, E11 1NR
    • Barts Health NHS Trust Whipps Cross University Hospital NHS Trust
  • London, United Kingdom, SE1 9RS
    • Guy's and St Thomas' NHS Foundation Trust - Rheumatoid Arthritis (RA) Clinic
  • Newcastle, United Kingdom, NE29 8NH
    • North Tyneside General Hospital
  • Peterborough, United Kingdom, PE3 9GZ
    • Peterborough City Hospital
  • Stoke on Trent, United Kingdom, ST6 7AG
    • Haywood Hospital
  • Torquay, United Kingdom, TQ2 7AA
    • Torbay Hospital-Devon

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group 1: Guselkumab; 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).	Drug: Guselkumab 100 mg; Participants will receive guselkumab 100mg as SC injection.; Other Names: CNTO 1959; Drug: Placebo; Participants will receive placebo as SC injection.
Experimental: Group 2: Placebo followed by Guselkumab; 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.	Drug: Guselkumab 100 mg; Participants will receive guselkumab 100mg as SC injection.; Other Names: CNTO 1959; Drug: Placebo; Participants will receive placebo as SC injection.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants who Achieve an American College of Rheumatology (ACR) 20 Response at 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).	Week 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) Score at 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.	Baseline, Week 24
Percentage of Participants who Achieve an ACR 50 Response at 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).	Week 24
Change from Baseline in 36-Item Short form Health Survey (SF-36) Physical Component Summary (PCS) Score at 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.	Baseline, Week 24
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	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.	Week 24

Collaborators and Investigators

• Sponsor: Janssen Pharmaceutica N.V., Belgium

Publications and helpful links

General Publications

• 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.

Helpful Links

• Link to results on EudraCT registry.

Study record dates

Study Major Dates

• Study Start (Actual): March 22, 2019
• Primary Completion (Actual): November 11, 2020
• Study Completion (Actual): November 11, 2020

Study Registration Dates

• First Submitted: January 7, 2019
• First Submitted That Met QC Criteria: January 7, 2019
• First Posted (Actual): January 8, 2019

Study Record Updates

• Last Update Posted (Actual): December 10, 2021
• Last Update Submitted That Met QC Criteria: November 29, 2021
• Last Verified: November 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Skin Diseases; Joint Diseases; Musculoskeletal Diseases; Skin Diseases, Papulosquamous; Spinal Diseases; Bone Diseases; Spondylarthropathies; Spondylarthritis; Spondylitis; Psoriasis; Arthritis; Necrosis; Arthritis, Psoriatic
• Other Study ID Numbers: CR108573; 2018-003214-41 (EudraCT Number); CNTO1959PSA3003 (Other Identifier: Janssen Pharmaceutica N.V., Belgium)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes

IPD Plan Description

The data sharing policy of the Janssen Pharmaceutical Companies of Johnson & Johnson is available at www.janssen.com/clinical-trials\transparency.

As noted on this site, requests for access to the study data can be submitted through Yale open Access (YODA) Project site at yoda.yale.edu

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No