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
Overview
- Phase
- Phase 3
- Intervention
- Placebo
- Conditions
- Arthritis, Psoriatic
- Sponsor
- Janssen Research & Development, LLC
- Enrollment
- 453
- Locations
- 288
- Primary Endpoint
- Percentage of Participants Who Achieved an American College of Rheumatology (ACR) 20 Response at Week 24
- Status
- Active, Not Recruiting
- Last Updated
- 19 days ago
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.
Investigators
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
Arms & Interventions
Group 1: Guselkumab and Placebo
Participants will receive guselkumab and placebo subcutaneously (SC) to maintain the blind.
Intervention: Placebo
Group 3: Placebo Followed by Guselkumab
Participants will receive placebo SC and will cross over to receive guselkumab SC.
Intervention: Placebo
Group 1: Guselkumab and Placebo
Participants will receive guselkumab and placebo subcutaneously (SC) to maintain the blind.
Intervention: Guselkumab
Group 2: Guselkumab
Participants will receive guselkumab SC.
Intervention: Guselkumab
Group 3: Placebo Followed by Guselkumab
Participants will receive placebo SC and will cross over to receive guselkumab SC.
Intervention: Guselkumab
Outcomes
Primary Outcomes
Percentage of Participants Who Achieved an American College of Rheumatology (ACR) 20 Response at Week 24
Time Frame: 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.
Secondary Outcomes
- Change From Baseline in 36-item Short Form Health Survey (SF-36) Physical Component Summary (PCS) Score at Week 24(Baseline (pre dose Week 0) and Week 24)
- 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)(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(At Week 24)
- Change From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) Score at Week 24(Baseline (pre dose Week 0) and Week 24)
- Percentage of Participants Who Achieved Minimal Disease Activity (MDA) at Week 24(At Week 24)
- Change From Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Score at Week 24(Baseline (pre dose Week 0) and Week 24)
- Percentage of Participants Who Achieved ACR 20 Response at Week 16(At Week 16)
- Percentage of Participants With Infections(From first administration of study drug (Week 0) up to Week 112)
- Percentage of Participants Who Achieved ACR 50 Response at Week 16(At Week 16)
- Percentage of Participants Who Achieved ACR 50 Response at Week 24(At Week 24)
- Percentage of Participants Who Achieved ACR 70 Response at Week 24(At Week 24)
- Percentage of Participants With Treatment Emergent Adverse Events (TEAEs)(From first administration of study drug (Week 0) up to Week 112)
- Percentage of Participants With Treatment Emergent Serious Adverse Events (TESAEs)(From first administration of study drug (Week 0) up to Week 112)
- Percentage of Participants With Treatment Emergent Related AEs (TERAEs)(From first administration of study drug (Week 0) up to Week 112)
- Treatment Emergent AEs Leading to Discontinuation of Study Intervention(From first administration of study drug (Week 0) up to Week 112)
- Percentage of Participants With Injection-site Reactions(From first administration of study drug (Week 0) up to Week 112)
- Percentage of Participants With Infusion Related Reactions(From first administration of study drug (Week 0) up to Week 112)
- Number of Participants With Post-baseline Laboratory Abnormalities With Maximum Toxicity Grade Greater Than or Equal to >=3 Based on Common Terminology Criteria for Adverse Events (CTCAE)(From first administration of study drug (Week 0) up to Week 112)
- Serum Guselkumab Concentration Over Time(At Weeks 0, 4, 8, 12, 16, 20,and 24)
- Number of Participants With Antibodies to Guselkumab(Baseline (pre dose Week 0) up to Week 24)