Guselkumab in Active Psoriatic Arthritis Participants With Inadequate Response/Intolerance to One Prior Anti-TNF Alpha Agent

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to evaluate the efficacy of guselkumab treatment in participants with active psoriatic arthritis (PsA) and inadequate response (IR) and/or intolerance to a prior anti-tumor necrosis factor (TNF) by assessing the reduction in signs and symptoms of PsA.

Detailed Description
-----------------
PsA is a chronic, immune-mediated inflammatory disease characterized by peripheral joint inflammation, enthesitis, dactylitis, axial disease, and the skin lesions associated with psoriasis. Guselkumab is a fully human monoclonal antibody (mAb) that binds to p19 protein subunit of interleukin (IL)-23 and 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. The primary hypothesis of this study is that guselkumab is superior to placebo as assessed by the proportion of participants who had an inadequate response (IR) and/or intolerance to one prior anti-tumor necrosis factor (anti-TNF) achieving an American College of Rheumatology 20 (ACR 20) response at Week 24. This study will consist of a screening phase (up to 6 weeks), blinded treatment phase (approximately up to 2 years), which includes a placebo-controlled period from Week 0 to Week 24, and an active-controlled treatment phase from Week 24 to Week 100, and safety follow-up phase (Week 112). Safety assessments will include physical examinations, vital signs, height, weight, electrocardiograms, and clinical safety laboratory assessments. The total duration of the study will be up to 118 weeks.

Official Title
-----------------
A Phase 3B, Multicenter, Randomized, Double-blind, Placebo-controlled Study Evaluating the Efficacy and Safety of Guselkumab Administered Subcutaneously in Participants With Active Psoriatic Arthritis Who Had an Inadequate Response and/or Intolerance to One Prior Anti-Tumor Necrosis Factor Alpha Agent

Conditions
-----------------
Arthritis, Psoriatic

Intervention / Treatment
-----------------
* Drug: Guselkumab
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Have a diagnosis of active psoriatic arthritis (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 at least 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 at least one of the following PsA subsets: distal interphalangeal joint involvement, polyarticular arthritis with absence of rheumatoid nodules, asymmetric peripheral arthritis, or spondylitis with peripheral arthritis Have active plaque psoriasis, with at least one psoriatic plaque of >= 2 centimeters (cm) diameter and/or nail changes consistent with psoriasis, or documented history of plaque psoriasis Have an inadequate response and/or intolerance to anti-tumor necrosis factor alpha (TNF alpha) therapy, defined as presence of active PsA despite previous treatment with one prior anti-TNF alpha agent Exclusion Criteria: Has other inflammatory diseases that might confound the evaluations of benefit of guselkumab therapy in the treatment of PsA, including but not limited to rheumatoid arthritis, ankylosing spondylitis/nonradiographic axial spondyloarthritis, systemic lupus erythematosus, or Lyme disease Has received more than 1 prior anti-tumor necrosis factor (TNF) alpha agent (or biosimilars) Has ever received Janus kinase (JAK) inhibitor including but not limited to tofacitinib, baricitinib, filgotinib, peficitinib, decernotinib, upadacitinib or any other investigational 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 Has known allergies, hypersensitivity, or intolerance to guselkumab or its excipients Has a history of chronic or recurrent infectious disease, including but not limited to chronic renal infection, chronic chest infection (example, bronchiectasis), recurrent urinary tract infection (example, recurrent pyelonephritis or chronic non-remitting cystitis), fungal infection (example, mucocutaneous candidiasis), or open, draining, or infected skin wounds or ulcers

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

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. | Drug: Guselkumab<br>* Participants will receive guselkumab as SC injection.<br>* Other names: CNTO1959;Drug: Placebo<br>* Participants will receive matching placebo as SC injection.<br>|
| Experimental: Group 2: Guselkumab<br>Participants will receive guselkumab SC. | Drug: Guselkumab<br>* Participants will receive guselkumab as SC injection.<br>* Other names: CNTO1959;|
| Experimental: Group 3: Placebo Followed by Guselkumab<br>Participants will receive placebo SC and will cross over to receive guselkumab SC. | Drug: Guselkumab<br>* Participants will receive guselkumab as SC injection.<br>* Other names: CNTO1959;Drug: Placebo<br>* Participants will receive matching placebo as SC injection.<br>|

What is the study measuring?
-----------------
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 from baseline in both swollen joint count (66 joints) and tender joint count (68 joints) and >=20 percent (%) improvement from baseline 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 CRP. | Week 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants who Achieve a Psoriasis Response of IGA Psoriasis Score of 0 or 1 and >=2 Grade Reduction From Baseline at Week 24 Among Participants With >=3% Body Surface Area (BSA) Psoriatic Involvement and IGA Score of >=2 at Baseline | Psoriasis response is defined as an Investigator's Global Assessment (IGA) psoriasis score of 0 (cleared) or 1 (minimal) and >=2- grade reduction from baseline. The IGA documents the investigator's assessment of the participants psoriasis and lesions are graded for induration, erythema and scaling, each using a 5-point scale: 0 (no evidence), 1 (minimal), 2 (mild), 3 (moderate), and 4 (severe). 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 | 
| Percentage of Participants who Achieve PASI 90 Response at Week 24 Among the Participants With >=3% BSA Psoriatic Involvement and an IGA Score of >=2 (Mild) at Baseline | Psoriasis Area and Severity Index (PASI) is a tool to assess and grade severity of psoriasis and response to therapy. In PASI, body is divided into 4 areas: head, trunk, upper extremities, lower extremities. Each area is assessed separately for percentage of area involved and translated to numeric score ranging from 0 (no involvement) to 6 (90 to 100% involvement), and for erythema, induration, and scaling, each rated on scale of 0 to 4 that is none to maximum severity. PASI numeric score range from 0 (no psoriasis) to 72. Higher scores indicate more severe disease. A PASI 90 response: >=90% improvement in PASI score from baseline. | Week 24 | 
| Change From Baseline in HAQ-DI Score 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 | 
| Change From Baseline in 36-item Short Form Health Survey (SF-36) Physical Component Summary (PCS) Score 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 | 
| Change From Baseline in Functional Assessment of Chronic Illness Therapy-fatigue (FACIT-F) Score at Week 24 | The FACIT-F is a questionnaire that assesses self-reported tiredness, weakness, and difficulty conducting usual activities due to fatigue. The subscale consists 13-item instrument to measure fatigue. Each of the 13 items has a set of five response categories: Not at all (=0), A little bit (=1), Somewhat (=2), Quite a bit (=3) and Very much (=4). A total FACIT-Fatigue subscale score is calculated as the sum of the 13 item scores (reserved scores [4 - score]) and ranges from 0 to 52, with a higher score indicating less fatigue. Positive changes from baseline indicate improvement of fatigue. Items are reverse scored when appropriate to provide a scale in which higher scores represent better functioning or less fatigue. | Baseline and Week 24 | 
| Percentage of Participants Achieving Minimal Disease Activity (MDA) at Week 24 | MDA is considered achieved if at least 5 of the following 7 criteria were met at the analysis visit: tender joint count <=1; swollen joint count <=1; psoriasis activity and severity index <=1; patient's pain VAS score of <=15; patient's global disease activity VAS (arthritis and psoriasis) score of <=20; HAQ-DI <=0.5; and tender entheseal points <=1. | Week 24 | 
| Percentage of Participants who Achieve ACR 20 Response at Week 16 | ACR 20 response: >=20% improvement from baseline in both swollen joint count (66 joints) and tender joint count (68 joints), and >=20% improvement from baseline in 3 of 5 assessments: patient's assessment of pain using visual analog scale (VAS; 0-100 mm, 0=no pain and 100=worst possible pain), patient's global assessment of disease activity (arthritis, VAS; 0-100 mm, 0=excellent and 100= poor), physician's global assessment of disease activity (VAS; 0-100 mm, 0=no arthritis activity and 100=extremely active arthritis), patient's assessment of physical function measured by Disability Index of Health Assessment Questionnaire (HAQ-DI; 20-question instrument assessing 8 functional areas; range: 0-3, 0=indicating no difficulty, 3=indicating inability to perform task in that area), and CRP. | Week 16 | 
| Percentage of Participants who Achieve ACR 50 Response at Week 16 | ACR 50 response is defined as >=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 5 assessments: patient's assessment of pain using visual analog scale (VAS; 0-100 mm, 0=no pain and 100=worst possible pain), patient's global assessment of disease activity (arthritis, VAS; 0-100 mm, 0=excellent and 100= poor), physician's global assessment of disease activity (VAS; 0-100 mm, 0=no arthritis activity and 100=extremely active arthritis), patient's assessment of physical function measured by Disability Index of the Health Assessment Questionnaire (HAQ-DI; a 20-question instrument assessing 8 functional areas; range: 0-3, 0=no difficulty, 3=inability to perform a task in that area), and CRP. | Week 16 | 
| Percentage of Participants who Achieve ACR 50 Response at Week 24 | ACR 50 response is defined as >=50 percent (%) improvement from baseline in both swollen joint count (66 joints) and tender joint count (68 joints), and >=50% improvement from baseline in 3 of 5 assessments: patient's assessment of pain using visual analog scale (VAS; 0-100 mm, 0=no pain and 100=worst possible pain), patient's global assessment of disease activity (arthritis, VAS; 0-100 mm, 0=excellent and 100= poor), physician's global assessment of disease activity (VAS; 0-100 mm, 0=no arthritis activity and 100=extremely active arthritis), patient's assessment of physical function measured by Disability Index of the Health Assessment Questionnaire (HAQ-DI; a 20-question instrument assessing 8 functional areas; range: 0-3, 0=no difficulty, 3=inability to perform a task in that area), and CRP. | Week 24 | 
| Percentage of Participants who Achieve ACR 70 Response at Week 24 | ACR 70 response is defined as >= 70% improvement from baseline in both swollen joint count (66 joints) and tender joint count (68 joints), and >=70% improvement from baseline in 3 of 5 assessments: patient's assessment of pain using visual analog scale (VAS; 0-100 mm, 0=no pain and 100=worst possible pain), patient's global assessment of disease activity (arthritis, VAS; 0-100 mm, 0=excellent and 100= poor), physician's global assessment of disease activity (VAS; 0-100 mm, 0=no arthritis activity and 100=extremely active arthritis), patient's assessment of physical function measured by Disability Index of the Health Assessment Questionnaire (HAQ-DI; a 20-question instrument assessing 8 functional areas; range: 0-3, 0=no difficulty, 3=inability to perform a task in that area), and CRP. | Week 24 | 
| Percentage of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), Reasonably Related AEs, as a Measure of Safety and Tolerability | Percentage 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 112 weeks | 
| 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 112 weeks | 
| Percentage of Participants With Infections | Percentage of participants with infections will be reported. | Up to 112 weeks | 
| 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 100 weeks | 
| Percentage of Participants With Change from Baseline in Clinical Laboratory Abnormalities | Percentage of participants with change from baseline in clinical laboratory abnormalities including chemistry and hematology will be reported. | Up to 112 weeks | 
| Percentage of participants With Laboratory Abnormalities With Maximum Toxicity Grades as per Common Terminology Criteria for Adverse Events (CTCAE) Toxicity | Percentage of participants with laboratory abnormalities (hematology, chemistry) with maximum toxicity grades as per CTCAE 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 112 weeks | 
| Serum Guselkumab Concentration | Serum guselkumab concentration will be measured. | Up to 112 weeks | 
| Percentage of Participants With Anti-guselkumab Antibodies | Percentage of participants with anti-guselkumab antibodies to guselkumab will be reported. | Up to 112 weeks |