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

Arthritis, Psoriatic Clinical Trial

— COSMOS  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03796858
• Other study ID #: CR108573
• Secondary ID: 2018-003214-41CN
• Status: Completed
• Phase: Phase 3
• Start date: March 22, 2019
• Est. completion date: November 11, 2020

Study information

• Verified date: November 2021
• Source: Janssen Pharmaceutica N.V., Belgium
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 285
• Est. completion date: November 11, 2020
• Est. primary completion date: November 11, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Arthritis
• Arthritis, Psoriatic
• Necrosis

Intervention

Drug:
• Guselkumab 100 mg
Participants will receive guselkumab 100mg as SC injection.
• Placebo
Participants will receive placebo as SC injection.

Locations

Country	Name	City	State
Belgium	CHU Saint Pierre BXL	Brussels
Belgium	Reuma Clinic	Genk
Belgium	Universitair Ziekenhuis Gent	Gent
Belgium	UZ Leuven	Leuven
Bulgaria	Diagnostic - Consulting Center II-Pleven	Pleven
Bulgaria	Medical Center Medconsult-Pleven	Pleven
Bulgaria	Multiprofile Hospital for Active Treatment - Plovdiv	Plovdiv
Bulgaria	Multiprofile Hosptal for Active Treatment Eurohospital Plovdiv	Plovdiv
Bulgaria	Medical Center 'Teodora'	Ruse
Bulgaria	Diagnostic Consulting Center No 17	Sofia
Bulgaria	Military Medical Academy	Sofia
France	Hopital Pellegrin Tripode - CHU de Bordeaux	Bordeaux
France	CHU Lapeyronie	Montpellier, Herault
France	Centre Hospitalier Regional d'Orleans (CHRO) - Hopital La Source	Orleans
France	Hopital Cochin	Paris
France	Hopital Lariboisiere	Paris
France	Hôpital Pitié-Salpétrière	Paris
France	Centre Hospitalier Universitaire de Toulouse - Hopital Purpan	Toulouse
France	CHU Trousseau - Service de Rhumatologie	Tours
Germany	Universitätsklinikum Düsseldorf	Dusseldorf
Germany	Hamburger Rheuma Forschungszentrum II	Hamburg
Germany	Medizinische Hochschule Hannover	Hannover
Germany	Rheumazentrum Ruhrgebiet	Herne
Germany	Rheumatologische Schwerpunktpraxis	Rendsburg
Germany	Krankenhaus St. Josef	Wuppertal
Greece	424 Military Hospital of Thessaloniki	Thessaloniki
Hungary	Betegapolo Irgalmas Rend - Budai Irgalmasrendi Korhaz	Budapest
Hungary	Bekes Megyei Kozponti Korhaz Pandy Kalman Tagkorhaz	Gyula
Hungary	Szabolcs-Szatmar-Bereg Megyei Korhazak es Egyetemi Oktatokorhaz	Nyiregyhaza
Hungary	Fejer Megyei Szent Gyorgy Egyetemi Oktatokorhaz	Székesfehérvár
Hungary	MAV Korhaz es Rendelointezet	Szolnok
Hungary	Vital Medical Center Orvosi es Fogaszati Kozpont	Veszprem
Israel	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
Italy	Azienda Ospedaliera Universitaria Federico II	Napoli
Italy	Azienda Ospedaliero Universitaria Policlinico Paolo Giaccone	Palermo
Italy	Policlinico Tor Vergata	Roma
Italy	Complesso Integrato Columbus	Rome
Italy	Humanitas Hospital	Rozzano (MI)
Poland	Szpital Uniwersytecki Nr 2 w Bydgoszczy	Bydgoszcz
Poland	Centrum Kliniczno Badawcze	Elblag
Poland	Centrum Terapii Wspolczesnej J. M. Jasnorzewska J. M. Jasnorzewska Spolka Komandytowo-Akcyjna	Lodz
Poland	Dermed Centrum Medyczne Sp. z o.o	Lodz
Poland	NZOZ Lecznica MAK-MED. S.C.	Nadarzyn
Poland	Medycyna Kliniczna	Warsaw
Poland	Mazowieckie Centrum Reumatologii i Osteoporozy	Warszawa
Poland	WroMedica I.Bielicka, A.Strzalkowska s.c.	Wroclaw
Portugal	Hosp. Garcia de Orta	Almada
Portugal	Chbv - Hosp. Infante D. Pedro	Aveiro
Portugal	Ccab - Hosp. de Braga	Braga
Portugal	Chln - Hosp. Santa Maria	Lisboa
Portugal	Chlo - Hosp. Egas Moniz	Lisboa
Portugal	Ipr - Inst. Port. de Reumatologia	Lisboa
Portugal	Ulsam - Hosp. Conde de Bertiandos	Ponte de Lima
Russian Federation	Chelyabinck Regional Clinical Hospital	Chelyabinsk
Russian Federation	Kemerovo State Medical University	Kemerovo
Russian Federation	Medical Centre Maximum Health	Kemerovo
Russian Federation	Family polyclinic #4	Korolev
Russian Federation	Krasnodar Clinical Dermatovenerologic Dispensary	Krasnodar
Russian Federation	Krasnoyarsk State Medical University	Krasnoyarsk
Russian Federation	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
Spain	Hosp. Univ. A Coruña	A Coruña
Spain	Hosp. Univ. de Cruces	Barakaldo
Spain	Hosp. Univ. Germans Trias I Pujol	Barcelona
Spain	Hosp. Univ. de Basurto	Bilbao
Spain	Hosp. Reina Sofia	Córdoba
Spain	Hosp. Univ. 12 de Octubre	Madrid
Spain	Hosp. Univ. de Getafe	Madrid
Spain	Hosp. Univ. Ramon Y Cajal	Madrid
Spain	Hosp. Regional Univ. de Malaga	Málaga
Spain	Hosp. Clinico Univ. de Santiago	Santiago de Compostela
Spain	Hosp. Infanta Luisa	Sevilla
Spain	Hosp. Ntra. Sra. de Valme	Sevilla
Spain	Hosp. Virgen Del Rocio	Sevilla
Spain	Hosp. Virgen Macarena	Sevilla
Spain	Hosp. Do Meixoeiro	Vigo
Ukraine	Communal Noncommercial Enterprise 'Cherkasy Regional Hospital of Cherkasy Regional Council'	Cherkasy
Ukraine	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	Kyiv City Clinical Hospital #3, National Medical University	Kyiv
Ukraine	Kyiv Railway Station Clinical Hospital #2	Kyiv
Ukraine	Medical Center 'Consylium Medical'	Kyiv
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	Municipal Institution of Sumy Regional Council Sumy Regional Clinical Hospital	Sumy
Ukraine	Municipal Non-commercial Enterprise 'Ternopil University Hospital' of Ternopil Regional Council	Ternopil
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	Zhytomir
United Kingdom	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	North Tyneside General Hospital	Newcastle
United Kingdom	Peterborough City Hospital	Peterborough
United Kingdom	Haywood Hospital	Stoke on Trent
United Kingdom	Torbay Hospital-Devon	Torquay

Sponsors (1)

Lead Sponsor	Collaborator
Janssen Pharmaceutica N.V., Belgium

Countries where clinical trial is conducted

Belgium,  Bulgaria,  France,  Germany,  Greece,  Hungary,  Israel,  Italy,  Poland,  Portugal,  Russian Federation,  Spain,  Ukraine,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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

External Links

•   Link to results on EudraCT registry.