A Study of Guselkumab and Golimumab Combination Therapy in Participants With Active Psoriatic Arthritis

Arthritis, Psoriatic Clinical Trial

— AFFINITY  

Official title:

A Phase 2a, Multicenter, Randomized, Double-blind Study Evaluating the Efficacy and Safety of Subcutaneously Administered Guselkumab and Golimumab Combination Therapy in Participants With Active Psoriatic Arthritis

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05071664
• Other study ID #: CR109054
• Secondary ID: 2021-002012-31CN
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: October 25, 2021
• Est. completion date: August 13, 2024

Study information

• Verified date: March 2024
• Source: Janssen Research & Development, LLC
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to evaluate the efficacy of guselkumab plus golimumab combination treatment in participants with active psoriatic arthritis (PsA) and inadequate response (IR) to prior anti-tumor necrosis factor-alpha (anti-TNF-alpha) therapies by assessing clinical response compared with guselkumab monotherapy.

Description:

PsA is a chronic inflammatory multi-faceted disease that impacts the peripheral and axial joints, soft tissues, and skin. Guselkumab is a fully human monoclonal antibody (mAb) directed against the p19 subunit of interleukin (IL)-23, blocks the binding of extracellular IL-23 to the cell surface IL-23 receptor, inhibiting IL-23 specific intracellular signaling, subsequent activation, and cytokine production. Golimumab is a fully human anti-TNF-alpha mAb that binds to TNF-alpha with high affinity, prevents binding to its receptors, thereby inhibiting the biological activity of TNF-alpha and resulting in limited production or activity of inflammatory cytokines, thereby providing therapeutic benefit in various chronic inflammatory disorders, including PsA. This study will consist of a Screening Phase (up to 6 weeks), Double-blind Phase from Weeks 0 to 24 which includes the active treatment phase and the primary efficacy visit (Week 24), and Safety Follow-up Phase from Week 24 to Week 36. Key safety assessments will include adverse events (AEs), clinical laboratory safety tests (hematology and chemistry), vital signs, monitoring for injection-site and hypersensitivity reactions, and early detection of active tuberculosis (TB). The total duration of the study is up to 42 weeks.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 91
• Est. completion date: August 13, 2024
• Est. primary completion date: May 22, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

• Have a diagnosis of psoriatic arthritis (PsA) for greater than or equal to (>=) 6 months prior to the first administration of study intervention and meet Classification criteria for PsA (CASPAR) criteria at screening
• Have active PsA as defined by having at least 3 swollen joints and at least 3 tender joints at screening and at baseline
• Have at least 1 of the following PsA subsets: distal interphalangeal joint involvement, polyarticular arthritis with absence of rheumatoid nodules, arthritis mutilans, asymmetric peripheral arthritis, or spondylitis with peripheral arthritis
• Have active plaque psoriasis, with at least one psoriatic plaque of >=2 centimeter (cm) diameter or nail changes consistent with psoriasis
• Have an inadequate response (IR) to anti-tumor necrosis factor-alpha (anti-TNF-alpha) therapy, defined as presence of active PsA despite treatment with either 1 or 2 prior anti-TNF-alpha agent(s) and the following: a. Lack of benefit to either 1 or 2 prior anti-TNF-alpha therapies, as documented in the participant history by the treating physician, after at least 12 weeks of etanercept, adalimumab, or certolizumab pegol therapy, or at least 14-weeks of infliximab, or any biosimilar of these 4 therapies. Documented lack of benefit may include inadequate improvement in joint counts, physical function, or disease activity; b. The last dose of anti-TNF-alpha therapy must have occurred greater than 5 half-lives of the drug prior to first study intervention administration (washout period)

Exclusion Criteria:

• Has other inflammatory diseases that might confound the evaluations of benefit of guselkumab and/or golimumab therapy, including but not limited to rheumatoid arthritis (RA), ankylosing spondylitis (AS), nonradiographic axial spondyloarthritis (nr AxSpA), systemic lupus erythematosus, or lyme disease
• Has known intolerance or hypersensitivity to any biologic medication, or known allergies or clinically significant reactions to murine, chimeric, or human proteins, monoclonal antibodies (mAb), or antibody fragments
• Has received prior treatment with golimumab or guselkumab or has documented intolerance to prior anti-TNF-alpha therapy in the participant history by the treating physician
• Has received more than 2 prior anti-TNF-alpha agents (or biosimilars)
• Positive human immunodeficiency virus (HIV) antibody test

Related Conditions & MeSH terms

• Arthritis
• Arthritis, Psoriatic

Intervention

Drug:
• Guselkumab
Guselkumab will be administered as a SC injection.
• Golimumab
Golimumab will be administered as a SC injection.
• Placebo
Placebo will be administered as a SC injection.

Locations

Country	Name	City	State
Denmark	Frederiksberg Hospital	Frederiksberg
Denmark	Rigshospitalet Glostrup	Glostrup
Denmark	Køge Sygehus Region Sjaelland	Køge
Denmark	Silkeborg Hospital	Silkeborg
Denmark	Vejle Sygehus	Vejle
France	Centre Hospitalier Le Mans	Le Mans
France	Hopital Larrey CHU de Toulouse	Toulouse Cedex 9
France	CHU Trousseau - Service de Rhumatologie	Tours
Hungary	Obudai Egeszsegugyi Centrum Kft	Budapest
Hungary	Bekes Varmegyei Kozponti Korhaz Pandy Kalman Tagkorhaz	Gyula
Hungary	Complex Rendelo Med Zrt	Szekesfehervar
Hungary	Vital Medical Center	Veszprem
Italy	Azienda Ospedaliero-Universitaria di Cagliari	Cagliari
Italy	Centro Specialistico Ortopedico Traumatologico Gaetano Pini-CTO	Milano
Italy	Ospedale San Raffaele	Milano
Italy	IRCCS Policlinico San Matteo, Università degli studi di Pavi	Pavia
Italy	Arcispedale Santa Maria Nuova - IRCCS	Reggio Emilia
Italy	A.O.U.Policlinico Tor Vergata	Roma
Italy	Policlinico Universitario Agostino Gemelli	Roma
Italy	Università Campus Biomedico di Roma	Rome
Italy	AO Ordine Mauriziano	Torino
Poland	Centrum Kliniczno Badawcze	Elblag
Poland	Centrum Terapii Wspolczesnej J M Jasnorzewska Spolka Komandytowo Akcyjna	Lodz
Poland	NZOZ Lecznica MAK MED S C	Nadarzyn
Poland	Centrum Medyczne	Poznan
Poland	Medycyna Kliniczna	Warsaw
Poland	Centrum Medyczne AMED Targowek	Warszawa
Poland	WroMedica I.Bielicka, A.Strzalkowska s.c.	Wroclaw
Russian Federation	Kemerovo State Medical University	Kemerovo
Russian Federation	LLL Medical Center Revma-Med	Kemerovo
Russian Federation	LLC Family Outpatient Clinic # 4	Korolev
Russian Federation	GBUZ of Moscow Region 'Moscow Region SRI n.a. Vladimirskyi'	Moscow
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	Smolensk regional hospital on Smolensk railway station	Smolensk
Russian Federation	X7 Clinical Research Company Limited	St. Petersburg
Russian Federation	Republican Clinical Hospital - G.G. Kuvatov	Ufa
Russian Federation	Clinical Hospital #3	Yaroslavl
Spain	Hosp. Univ. A Coruna	A Coruna
Spain	Hosp. Univ. Germans Trias I Pujol	Barcelona
Spain	Hosp. Univ. de Basurto	Bilbao
Spain	Hosp. Reina Sofia	Cordoba
Spain	Hosp. Univ. 12 de Octubre	Madrid
Spain	Corporacio Sanitari Parc Tauli	Sabadell
Spain	Hosp. Clinico Univ. de Santiago	Santiago de Compostela
Spain	Hosp. Infanta Luisa	Sevilla
Spain	Hosp. Ntra. Sra. de Valme	Sevilla
Spain	Hosp. Virgen Macarena	Sevilla
Sweden	Skanes universitetssjukhus	Malmo
Sweden	Karolinska Universitetssjukhuset Solna	Solna
Ukraine	Municipal Institution Regional hospital-center of emergency care and disasters medicine	Kharkiv
Ukraine	State Institution Institute of therapy named after L.T.Malaya AMS Ukraine	Kharkiv
Ukraine	Kyiv Railway Clinical Hospital #2 Of Branch 'Health Center' Of The Company 'Ukrainian Railway'	Kyiv
Ukraine	Medical Research and Practice Center Medbud of the Public Joint Stock Holding Company Kyivmiskbud	Kyiv
Ukraine	Municipal Non-Profit Enterprise of Kyiv Regional Council 'Kyiv regional Clinical Hospital'	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 Tepnopil Regional Council 'Ternopil University Hospital'	Ternopil
Ukraine	MNCE Zakarpatska Regional Clinical Hospital named after A Novak of Zakarpatska Regional Council	Uzhgorod
Ukraine	Health Clinic Limited Liability Company	Vinnytsia
Ukraine	Medical Center LLC 'Modern Clinic'	Zaporizhzhya
United States	HARAC Research Corp	Avon Park	Florida
United States	Bay Pines VA Healthcare System	Bay Pines	Florida
United States	Jacobi Medical Center	Bronx	New York
United States	NYU Langone Ambulatory Care Brooklyn Heights	Brooklyn	New York
United States	Omega Research Consultants	DeBary	Florida
United States	Great Lakes Center of Rheumatology	Lansing	Michigan
United States	Atlanta Research Center for Rheumatology	Marietta	Georgia
United States	South Coast Research Center	Miami	Florida
United States	NYU School of Medicine	New York	New York
United States	Advanced Clinical Research of Orlando	Ocoee	Florida
United States	Millennium Research	Ormond Beach	Florida
United States	Arizona Arthritis and Rheumatology Research PLLC	Phoenix	Arizona
United States	Arizona Arthritis and Rheumatology Research PLLC	Phoenix	Arizona
United States	Trinity Universal Research Associates, LLC	Plano	Texas
United States	University of Rochester	Rochester	New York
United States	Unity Health-White County Medical Center	Searcy	Arkansas
United States	Swedish Medical Center	Seattle	Washington
United States	Clinvest	Springfield	Missouri
United States	DM Clinical Research	Tomball	Texas
United States	STAT Research, Inc.	Vandalia	Ohio

Sponsors (1)

Lead Sponsor	Collaborator
Janssen Research & Development, LLC

Countries where clinical trial is conducted

United States,  Denmark,  France,  Hungary,  Italy,  Poland,  Russian Federation,  Spain,  Sweden,  Ukraine, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants who Achieve Minimal Disease Activity (MDA) at Week 24	MDA defines a satisfactory state of disease activity that includes the 5 domains of psoriatic arthritis (PsA; joint symptoms, skin psoriasis, participant's assessment of pain and disease activity, physical function, and enthesitis). Participants are classified as achieving MDA if they fulfilled 5 of 7 outcome measures: tender joint count less than or equal to (<=) 1; swollen joint count <=1; psoriasis area and severity index (PASI) <=1 or body surface area (BSA) <=3 percent (%); participant's pain visual analog scale (VAS) score of <=15; participant's global disease activity VAS (arthritis and psoriasis) score of <=20; disability index of the health assessment questionnaire (HAQ-DI) score <=0.5; and tender entheseal points <=1.	Week 24
Secondary	Percentage of Participants who Achieve American College of Rheumatology (ACR) 50 at Week 24	ACR 50 response is defined as greater than or equal to (>=) 50% improvement from baseline in both swollen joint count (66 joints) and tender joint count (68 joints) and >=50% improvement from baseline in 3 of the following 5 assessments: participant's assessment of pain using VAS (0-100 millimeter [mm], 0 mm=no pain and 100 mm=worst possible pain), participant's global assessment of disease activity by using VAS (scale ranges from 0 mm to 100 mm, [0 mm= very well to 100 mm= very poor]), physician's global assessment of disease activity using VAS (scale ranges from 0 to 100, [0 = no arthritis to 100 = extremely active arthritis]), participant's assessment of physical function measured by 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	Percentage of Participants who Achieve MDA at Week 16	MDA defines a satisfactory state of disease activity that includes the 5 domains of PsA (joint symptoms, skin psoriasis, participant's assessment of pain and disease activity, physical function, and enthesitis). Participants are classified as achieving MDA if they fulfilled 5 of 7 outcome measures: tender joint count <=1; swollen joint count <=1; PASI <=1 or BSA <=3%; participant's pain VAS score of <=15; participant's global disease activity VAS (arthritis and psoriasis) score of <=20; HAQ-DI score <=0.5; and tender entheseal points <=1.	Week 16
Secondary	Percentage of Participants who Achieve PASI 90 at Week 24 Among the Participants with >=3% BSA Psoriatic involvement and an IGA Score of >=2 (Mild) at Baseline	The PASI is a system used for assessing and grading the severity of psoriatic lesions and their response to therapy. The PASI produces a numeric score that can range from 0 (no psoriasis) to 72. Higher scores indicate more severe disease. A PASI 90 response is defined as >=90% improvement in PASI score from baseline.	Week 24
Secondary	Percentage of Participants who Achieve PASI 100 at Week 24 Among the Participants with >=3% BSA Psoriatic involvement and an IGA Score of >=2 (Mild) at Baseline	The PASI is a system used for assessing and grading the severity of psoriatic lesions and their response to therapy. The PASI produces a numeric score that can range from 0 (no psoriasis) to 72. Higher scores indicate more severe disease. A PASI 100 response is defined as 100% improvement in PASI score from baseline.	Week 24
Secondary	Percentage of Participants with an IGA-psoriasis Response of IGA Psoriasis Score of 0 or 1 AND >=2 Grade Reduction From Baseline at Week 24 Among Participants with >=3% BSA Psoriatic Involvement and an IGA Score of >=2 (Mild) at Baseline	IGA psoriasis response is defined as an IGA psoriasis score of 0 (cleared) or 1 (minimal) and >=2 grade reduction from baseline. The IGA documents the investigator's assessment of the participant's psoriasis at a given time point. Overall lesions are graded for induration, erythema, and scaling, each using a 5-point scale: using 0 (no evidence), 1 (minimal), 2 (mild), 3 (moderate), and 4 (severe) scale. The IGA score of psoriasis is based upon the average of induration, erythema, and scaling scores. The participant's psoriasis is assessed as cleared (0), minimal (1), mild (2), moderate (3), or severe (4).	Week 24
Secondary	Change from Baseline in HAQ-DI at Week 24	HAQ-DI score assess functional status of participant. It is 20 question instrument that assess 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=indicating no difficulty, to 3=indicating inability to perform a task in that area. Total HAQ score is average of the computed categories scores ranging from 0-3 where 0=least difficulty and 3=extreme difficulty. Lower scores are indicative of better functioning. Negative change from baseline indicates improvement of physical function.	Baseline and Week 24
Secondary	Percentage of Participants With Resolution of Enthesitis at Week 24 Among the Participants With Enthesitis at Baseline	Enthesitis will be assessed using the Leeds Enthesitis Index (LEI), a tool developed to assess enthesitis in participants with PsA and evaluates the presence (score of 1) or absence (score of 0) of pain by applying local pressure to the following entheses: left and right lateral epicondyle humerus, left and right medial femoral condyle, and left and right achilles tendon insertion. The enthesitis index score is a total score of the 6 evaluated sites from 0 (0 sites with tenderness) to 6 (worst possible score; 6 sites with tenderness). A LEI score of 0 at a post baseline visit indicates resolution of enthesitis when baseline LEI >0.	Week 24
Secondary	Percentage of Participants with Resolution of Dactylitis at Week 24 Among the Participants with Dactylitis at Baseline	The presence and severity of dactylitis is assessed in both hands and feet using a scoring system from 0 to 3 (0-no dactylitis, 1-mild dactylitis, 2-moderate dactylitis, and 3-severe dactylitis) for each digit. The results are summed to produce a final score ranging from 0 to 60. Higher score indicates more severe dactylitis. Resolution of dactylitis is defined as a dactylitis score of 0 with the baseline dactylitis score >0.	Week 24
Secondary	Change from Baseline in Short Form Health Survey (SF-36) Physical Component Score (PCS) at Week 24	SF-36 is a multi-domain instrument with 36 items to evaluate the health status and quality of life. It included 8 subscales (physical functioning, physical role functioning, bodily pain, general health perception, vitality, social functioning, emotional role functioning, and mental health), which yielded a PCS with score range 0-100 (higher score-better quality of life) and a Mental Component Summary (MCS) with score range 0-100 (higher score-better quality of life) in addition to subscale scores. The PCS scores are normalized to a mean of 50 and standard deviations of 10, based upon general US population norms. A positive change indicates improvement while a negative change indicates worsening of health status and quality of life.	Baseline and Week 24
Secondary	Percentage of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), and Reasonably Related AEs	Percentage of participants with AEs, SAEs, and reasonably related AEs will be assessed. An AE is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/biological agent under study. SAE is any AE that results in: death, persistent or significant disability/incapacity, requires inpatient hospitalization or prolongation of existing hospitalization, is life-threatening experience, is a congenital anomaly/birth defect, and suspects transmission of any infectious agent via a medicinal product. Reasonably related AEs are those AEs which are judged related to study treatment by the investigator.	Up to 42 weeks
Secondary	Percentage of Participants With AEs Leading to Discontinuation of Study Intervention	Percentage of participants with AEs leading to discontinuation of study intervention will be reported.	Up to 42 weeks
Secondary	Percentage of Participants With Infections	Percentage of participants with infections will be reported.	Up to 42 weeks
Secondary	Percentage of Participants With Injection-site Reactions	Percentage of participants with injection-site reactions will be reported. An injection-site reaction is any adverse reaction at a subcutaneous (SC) study intervention injection-site.	Up to Week 20
Secondary	Serum Guselkumab and Golimumab Concentration	Serum guselkumab and golimumab concentration will be measured.	Up to Week 36
Secondary	Percentage of Participants with Antibodies to Guselkumab or Golimumab	Percentage of participants with antibodies to guselkumab or golimumab will be reported.	Up to Week 36