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

Janssen Research & Development, LLC453 enrolled

Overview

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.

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Enrollment

453

Conditions

Arthritis, Psoriatic

Interventions

GuselkumabDRUG

Participants will receive guselkumab as SC injection.

PlaceboDRUG

Participants will receive matching placebo as SC injection.

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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

Locations (169)

Outcomes

Primary Outcomes

Percentage of Participants Who Achieved an American College of Rheumatology (ACR) 20 Response at Week 24

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= no difficulty, 3= inability to perform task in that area), and CRP.

Time frame: At Week 24

Secondary Outcomes

Percentage of Participants Who Achieved a Psoriasis Response of Investigator's Global Assessment (IGA) Psoriasis Score of 0 or 1 and >=2 Grade Reduction From Baseline at Week 24 Among the Participants With >=3 Percent(%) Body Surface Area (BSA)

A psoriasis IGA response was defined as an IGA score of 0 (cleared) or 1 (minimal) and greater than equal to (\>=2) grade reduction from baseline in the IGA psoriasis score. The IGA documents the investigator's assessment of the patient's 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 was based upon the average of induration, erythema and scaling scores. The participant's psoriasis was assessed as cleared (0), minimal (1), mild (2), moderate (3), or severe (4).

Time frame: At Week 24

Percentage of Participants Who Achieved Psoriasis Area and Severity Index (PASI) 90 Response at Week 24 Among the Participants With >=3% BSA Psoriatic Involvement and an IGA Score of >=2 (Mild) at Baseline

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 was 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 severtiy. 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.

Data from ClinicalTrials.gov

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Arthritis Associates

Mountain Brook, Alabama, United States

Arizona Arthritis and Rheumatology Research PLLC 2

Avondale, Arizona, United States

Arizona Arthritis and Rheumatology Research PLLC 3

Flagstaff, Arizona, United States

Arizona Arthritis and Rheumatology Research PLLC

Mesa, Arizona, United States

Arizona Arthritis and Rheumatology Research PLLC 1

Phoenix, Arizona, United States

Arizona Arthritis and Rheumatology Associates

Sun City, Arizona, United States

Southern Arizona VA Healthcare System

Tucson, Arizona, United States

Unity Health-White County Medical Center

Searcy, Arkansas, United States

Newport Huntington Medical Group

Huntington Beach, California, United States

Medvin Clinical Research 2

Thousand Oaks, California, United States

...and 159 more locations

Time frame: At 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 participant has in accomplishing tasks in 8 functional areas (dressing, arising, eating, walking, hygiene, reaching, gripping, and activities of daily living), each scored from 0 (no difficulty) to 3 (inability to perform a task in that area). Overall score was 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. Lower scores are indicative of better functioning. Negative change from baseline indicates improvement of physical function.

Time frame: Baseline (pre dose Week 0) 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 Physical Component Summary (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.

Time frame: Baseline (pre dose Week 0) and Week 24

Change From Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Score at Week 24

The FACIT-Fatigue 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 was 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 were reverse scored when appropriate to provide a scale in which higher scores represent better functioning or less fatigue.

Time frame: Baseline (pre dose Week 0) and Week 24

Percentage of Participants Who Achieved Minimal Disease Activity (MDA) at Week 24

MDA is a measure that defines a satisfactory state of disease activity that includes 5 domains of PsA (joint symptoms, skin psoriasis, patient's perspective of pain and disease activity on arthritis and psoriasis, physical function and enthesitis). Participants were classified as achieving MDA if they fulfilled 5 of the following 7 criteria at that visit: Tender joint count (68 joints)\<=1, Swollen joint count (66 joints) \<=1, Psoriasis activity and severity index \<=1, Patient's Assessment of Pain \<=15 on a 100-unit VAS, Patient's Global Assessment of Disease Activity (arthritis and psoriasis) \<=20 on a 100-unit VAS, HAQ-DI score \<=0.5, and Tender entheseal points \<= 1 (LEI index score \<= 1).

Time frame: At Week 24

Percentage of Participants Who Achieved ACR 20 Response at Week 16

Time frame: At Week 16

Percentage of Participants Who Achieved ACR 50 Response at Week 16

ACR 50 response: \>=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 Health Assessment Questionnaire (HAQ-DI; 20-question instrument assessing 8 functional areas; range: 0-3, 0= no difficulty, 3= inability to perform task in that area), and CRP.

Time frame: At Week 16

Percentage of Participants Who Achieved ACR 50 Response at Week 24

Time frame: At Week 24

Percentage of Participants Who Achieved ACR 70 Response at Week 24

ACR 70 response: \>=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 Health Assessment Questionnaire (HAQ-DI; 20-question instrument assessing 8 functional areas; range: 0-3, 0= no difficulty, 3= inability to perform task in that area), and CRP.

Time frame: At Week 24

Percentage of Participants With Treatment Emergent Adverse Events (TEAEs)