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

Study Overview
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Brief Summary
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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
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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).

Official Title
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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

Conditions
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Arthritis, Psoriatic

Intervention / Treatment
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* Drug: Guselkumab 100 mg
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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

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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group 1: Guselkumab<br>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<br>* Participants will receive guselkumab 100mg as SC injection.<br>* Other names: CNTO 1959;Drug: Placebo<br>* Participants will receive placebo as SC injection.<br>|
| Experimental: Group 2: Placebo followed by Guselkumab<br>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<br>* Participants will receive guselkumab 100mg as SC injection.<br>* Other names: CNTO 1959;Drug: Placebo<br>* Participants will receive 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 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 |