A Study of Guselkumab in Participants With Active Psoriatic Arthritis

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the efficacy of guselkumab treatment in participants with active psoriatic arthritis (PsA) by assessing the reduction in signs and symptoms of PsA.

Official Title
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A Phase 3b, Multicenter, Randomized, Double-blind, Placebo-controlled Study Evaluating the Efficacy and Safety of Subcutaneously Administered Guselkumab in Improving the Signs and Symptoms and Inhibiting Radiographic Progression in Participants With Active Psoriatic Arthritis

Conditions
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Arthritis, Psoriatic

Intervention / Treatment
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* Drug: Guselkumab
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Have active psoriatic arthritis (PsA) despite previous non-biologic disease-modifying antirheumatic drug (DMARD), apremilast, and/or nonsteroidal anti-inflammatory drug (NSAID) therapy Have a diagnosis of PsA for at least 6 months before the first administration of study agent and meet Classification criteria for Psoriatic Arthritis (CASPAR) at screening Have active PsA as defined by: at least 3 swollen joints and 3 tender joints at screening and at baseline; and C-reactive protein (CRP) greater than or equal to (>=) 0.3 milligrams per deciliter (mg/dL) at screening from the central laboratory Have >= 2 joints with erosions on baseline radiographs of the hands and feet as determined by central read Have at least one 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 Exclusion Criteria: Has known allergies, hypersensitivity, or intolerance to study intervention or its excipients Has other inflammatory diseases that might confound the evaluations of benefit of guselkumab therapy, including but not limited to rheumatoid arthritis (RA), axial spondyloarthritis (AS)/non-radiographic axial spondyloarthritis (nr-axSpA), systemic lupus erythematosus, or Lyme disease Has previously received any biologic treatment Has ever received tofacitinib, baricitinib, filgotinib, peficitinib, decernotinib, upadacitinib or any other Janus kinase (JAK) inhibitor Has received any systemic immunosuppressants (example, azathioprine, cyclosporine, 6 thioguanine, mercaptopurine, mycophenolate mofetil, hydroxyurea, tacrolimus) within 4 weeks of the first administration of study intervention

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group 1: Guselkumab and Placebo<br>Participants will receive guselkumab and placebo subcutaneously (SC) to maintain the blind. Participants who have not discontinued will be eligible to enter a long-term extension (LTE) and will receive guselkumab and placebo SC. After the study is unblinded to the investigative sites, participants will receive guselkumab and no longer be required to dose with placebo to maintain the blind. | Drug: Guselkumab<br>* Participants will receive guselkumab as SC injection.<br>* Other names: CNTO 1959;Drug: Placebo<br>* Participants will receive matching placebo as SC injection.<br>|
| Experimental: Group 2: Guselkumab<br>Participants will receive guselkumab SC. Participants who have not discontinued will be eligible to enter an LTE and will receive guselkumab SC. | Drug: Guselkumab<br>* Participants will receive guselkumab as SC injection.<br>* Other names: CNTO 1959;|
| Experimental: Group 3: Placebo Followed by Guselkumab<br>Participants will receive placebo SC and will cross over to receive SC guselkumab. Participants who have not discontinued will be eligible to enter an LTE and will receive guselkumab SC. | Drug: Guselkumab<br>* Participants will receive guselkumab as SC injection.<br>* Other names: CNTO 1959;Drug: Placebo<br>* Participants will receive matching placebo as SC injection.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Who Achieved 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; 0-100 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 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 Psoriatic Arthritis (PsA) Modified Van Der Heijde-Sharp (vdH-S) Total Score at Week 24 | Modified vdH-S score is the sum of the erosion score (hand, feet) and joint space narrowing (JSN) score (hand, feet). Total score ranges from 0 (best) to 528 (worst = worst possible erosion score of 320 + worst possible JSN score of 208). Higher score indicates more joint damage. Positive changes from baseline in the modified vdH-S total, erosion and JSN scores indicate progression of joint damage. | Baseline and Week 24 | 
| Number of Participants with Adverse Events (AEs), Serious Adverse Events (SAEs), Reasonably Related AEs, as a Measure of Safety and Tolerability | Number of Participants with AEs, SAEs 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 168 weeks | 
| Number of Participants with AEs leading to Discontinuation of Study Intervention | Number of participants with AEs leading to discontinuation of study intervention will be reported. | Up to 168 weeks | 
| Number of Participants with Infections | Number of participants with infections will be reported. | Up to 168 weeks | 
| Number of Participants with AEs Temporally Associated With an Injection-site Reactions | Number of participants with AEs temporally associated with an injection-site reactions will be reported. An injection-site reaction is any adverse reaction at a subcutaneous (SC) study intervention injection-site. 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. | Up to 168 weeks | 
| Number of Participants With Change from Baseline in Clinical Laboratory Abnormalities | Number of participants with change from baseline in clinical laboratory abnormalities including hematology and chemistry will be reported. | Baseline, up to 168 weeks | 
| Number of Participants with Maximum Common Terminology Criteria for Adverse Events (CTCAE) toxicity grade Laboratory Values | Number of participants with maximum CTCAE toxicity grade laboratory values will be reported. Grade refers to the severity of the AE as follows: Grade 1- Mild, asymptomatic or mild symptoms, clinical or diagnostic observations only, intervention not indicated; Grade 2- Moderate, minimal, local or noninvasive intervention indicated, limiting age-appropriate instrumental Activities of Daily Living (ADL); Grade 3- Severe or medically significant but not immediately life-threatening, hospitalization or prolongation of hospitalization indicated, disabling, limiting self-care ADL; Grade 4- Life-threatening consequences, urgent intervention indicated; Grade 5- Death related to AE. | Up to 168 weeks | 
| Serum Guselkumab Concentration | Serum guselkumab concentration will be measured. | Up to 168 weeks | 
| Number of Participants with Anti-guselkumab Antibodies | Number of participants with anti-guselkumab antibodies to guselkumab will be reported. | Up to 168 weeks |