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.
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
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
TRIPLE
Enrollment
285
Participants will receive guselkumab 100mg as SC injection.
Participants will receive placebo as SC injection.
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).
Time frame: Week 24
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.
Time frame: 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).
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Time frame: 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.
Time frame: 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.
Time frame: Week 24