A Phase 2a, Multicenter, Randomized, Double-blind Study Evaluating the Efficacy and Safety of Subcutaneously Administered Guselkumab and Golimumab Combination Therapy in Participants With Active Psoriatic Arthritis
Trial Snapshot
- Phase
- Phase 2
- Status
- Completed
- Enrollment
- 91
- Locations
- 82
- Primary Endpoint
- Percentage of Participants who Achieve Minimal Disease Activity (MDA) at Week 24
Study Overview
Brief Summary
The purpose of this study is to evaluate the efficacy of guselkumab plus golimumab combination treatment in participants with active psoriatic arthritis (PsA) and inadequate response (IR) to prior anti-tumor necrosis factor-alpha (anti-TNF-alpha) therapies by assessing clinical response compared with guselkumab monotherapy.
Detailed Description
PsA is a chronic inflammatory multi-faceted disease that impacts the peripheral and axial joints, soft tissues, and skin. Guselkumab is a fully human monoclonal antibody (mAb) directed against the p19 subunit of interleukin (IL)-23, 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. Golimumab is a fully human anti-TNF-alpha mAb that binds to TNF-alpha with high affinity, prevents binding to its receptors, thereby inhibiting the biological activity of TNF-alpha and resulting in limited production or activity of inflammatory cytokines, thereby providing therapeutic benefit in various chronic inflammatory disorders, including PsA. This study will consist of a Screening Phase (up to 6 weeks), Double-blind Phase from Weeks 0 to 24 which includes the active treatment phase and the primary efficacy visit (Week 24), and Safety Follow-up Phase from Week 24 to Week 36. Key safety assessments will include adverse events (AEs), clinical laboratory safety tests (hematology and chemistry), vital signs, monitoring for injection-site and hypersensitivity reactions, and early detection of active tuberculosis (TB). The total duration of the study is up to 42 weeks.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Double (Participant, Investigator)
Eligibility Criteria
- Ages
- 18 Years to 65 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Have a diagnosis of psoriatic arthritis (PsA) for greater than or equal to (>=) 6 months prior to the first administration of study intervention and meet Classification criteria for PsA (CASPAR) criteria at screening
- •Have active PsA as defined by having at least 3 swollen joints and at least 3 tender joints at screening and at baseline
- •Have at least 1 of the following PsA subsets: distal interphalangeal joint involvement, polyarticular arthritis with absence of rheumatoid nodules, arthritis mutilans, asymmetric peripheral arthritis, or spondylitis with peripheral arthritis
- •Have active plaque psoriasis, with at least one psoriatic plaque of >=2 centimeter (cm) diameter or nail changes consistent with psoriasis
- •Have an inadequate response (IR) to anti-tumor necrosis factor-alpha (anti-TNF-alpha) therapy, defined as presence of active PsA despite treatment with either 1 or 2 prior anti-TNF-alpha agent(s) and the following: a. Lack of benefit to either 1 or 2 prior anti-TNF-alpha therapies, as documented in the participant history by the treating physician, after at least 12 weeks of etanercept, adalimumab, or certolizumab pegol therapy, or at least 14-weeks of infliximab, or any biosimilar of these 4 therapies. Documented lack of benefit may include inadequate improvement in joint counts, physical function, or disease activity; b. The last dose of anti-TNF-alpha therapy must have occurred greater than 5 half-lives of the drug prior to first study intervention administration (washout period)
Exclusion Criteria
- •Has other inflammatory diseases that might confound the evaluations of benefit of guselkumab and/or golimumab therapy, including but not limited to rheumatoid arthritis (RA), ankylosing spondylitis (AS), nonradiographic axial spondyloarthritis (nr AxSpA), systemic lupus erythematosus, or lyme disease
- •Has known intolerance or hypersensitivity to any biologic medication, or known allergies or clinically significant reactions to murine, chimeric, or human proteins, monoclonal antibodies (mAb), or antibody fragments
- •Has received prior treatment with golimumab or guselkumab or has documented intolerance to prior anti-TNF-alpha therapy in the participant history by the treating physician
- •Has received more than 2 prior anti-TNF-alpha agents (or biosimilars)
- •Positive human immunodeficiency virus (HIV) antibody test
Arms & Interventions
Group 2: Guselkumab and Placebo
Participants will receive SC guselkumab and placebo.
Intervention: Guselkumab (Drug)
Group 2: Guselkumab and Placebo
Participants will receive SC guselkumab and placebo.
Intervention: Placebo (Drug)
Group 1: Guselkumab and Golimumab
Participants will receive subcutaneous (SC) guselkumab and golimumab.
Intervention: Guselkumab (Drug)
Group 1: Guselkumab and Golimumab
Participants will receive subcutaneous (SC) guselkumab and golimumab.
Intervention: Golimumab (Drug)
Outcomes
Primary Outcomes
Percentage of Participants who Achieve Minimal Disease Activity (MDA) at Week 24
Time Frame: Week 24
MDA defines a satisfactory state of disease activity that includes the 5 domains of psoriatic arthritis (PsA; joint symptoms, skin psoriasis, participant's assessment of pain and disease activity, physical function, and enthesitis). Participants are classified as achieving MDA if they fulfilled 5 of 7 outcome measures: tender joint count less than or equal to (\<=) 1; swollen joint count \<=1; psoriasis area and severity index (PASI) \<=1 or body surface area (BSA) \<=3 percent (%); participant's pain visual analog scale (VAS) score of \<=15; participant's global disease activity VAS (arthritis and psoriasis) score of \<=20; disability index of the health assessment questionnaire (HAQ-DI) score \<=0.5; and tender entheseal points \<=1.
Percentage of Participants Who Achieved Minimal Disease Activity (MDA) at Week 24
Time Frame: Week 24
MDA was a measure that defines a satisfactory state of disease activity that includes 5 domains of psoriatic arthritis (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 (PASI) \<=1, Patient's Assessment of Pain \<=15 on a 100-unit visual analog scale (VAS), Patient's Global Assessment of Disease Activity (arthritis and psoriasis) \<=20 on a 100-unit VAS, Disability Index of the Health Assessment Questionnaire (HAQ-DI) score \<=0.5, and Tender entheseal points \<= 1 (Leeds Enthesitis Index \[LEI\] score \<= 1).
Secondary Outcomes
- Percentage of Participants with an IGA-psoriasis Response of IGA Psoriasis Score of 0 or 1 AND >=2 Grade Reduction From Baseline at Week 24 Among Participants with >=3% BSA Psoriatic Involvement and an IGA Score of >=2 (Mild) at Baseline(Week 24)
- Percentage of Participants with Resolution of Dactylitis at Week 24 Among the Participants with Dactylitis at Baseline(Week 24)
- Percentage of Participants With AEs Leading to Discontinuation of Study Intervention(Up to 42 weeks)
- Percentage of Participants With Infections(Up to 42 weeks)
- Percentage of Participants with Antibodies to Guselkumab or Golimumab(Up to Week 36)
- Percentage of Participants who Achieve American College of Rheumatology (ACR) 50 at Week 24(Week 24)
- Percentage of Participants who Achieve PASI 100 at Week 24 Among the Participants with >=3% BSA Psoriatic involvement and an IGA Score of >=2 (Mild) at Baseline(Week 24)
- Change from Baseline in HAQ-DI at Week 24(Baseline and Week 24)
- Percentage of Participants who Achieve MDA at Week 16(Week 16)
- Percentage of Participants who Achieve PASI 90 at Week 24 Among the Participants with >=3% BSA Psoriatic involvement and an IGA Score of >=2 (Mild) at Baseline(Week 24)
- Percentage of Participants With Resolution of Enthesitis at Week 24 Among the Participants With Enthesitis at Baseline(Week 24)
- Serum Guselkumab and Golimumab Concentration(Up to Week 36)
- Change from Baseline in Short Form Health Survey (SF-36) Physical Component Score (PCS) at Week 24(Baseline and Week 24)
- Percentage of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), and Reasonably Related AEs(Up to 42 weeks)
- Percentage of Participants With Injection-site Reactions(Up to Week 20)
- Percentage of Participants Who Achieved American College of Rheumatology (ACR) 50 at Week 24(Week 24)
- Percentage of Participants Who Achieved Minimal Disease Activity (MDA) at Week 16(Week 16)
- Percentage of Participants Who Achieved Psoriasis Area and Severity Index (PASI) 90 Response at Week 24 Among Participants With >= 3% Body Surface Area (BSA) Psoriatic Involvement and an Investigator Global Assessment (IGA) Score of >=2 (Mild) at Baseline(Week 24)
- Percentage of Participants Who Achieved PASI 100 Response at Week 24 Among the Participants With >=3% BSA Psoriatic Involvement and an IGA Score of >=2 (Mild) at Baseline(Week 24)
- Percentage of Participants With an IGA-psoriasis Response at Week 24 Among Participants With >=3% BSA Psoriatic Involvement and an IGA Score of >=2 (Mild) at Baseline(Week 24)
- Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) at Week 24(Baseline (Week 0), Week 24)
- Percentage of Participants Who Had Resolution of Enthesitis at Week 24 Among the Participants With Enthesitis at Baseline(Week 24)
- Percentage of Participants Who Achieved Resolution of Dactylitis Response at Week 24 Among the Participants With Dactylitis at Baseline(Week 24)
- Change From Baseline in Short Form Health Survey (SF-36) Physical Component Score (PCS) at Week 24(Baseline (Week 0), Week 24)
- Percentage of Participants With Treatment-emergent Adverse Events (TEAEs)(From Week 0 up to Week 36)
- Percentage of Participants With Treatment-emergent Serious Adverse Events (TESAEs)(From Week 0 up to Week 36)
- Percentage of Participants With Reasonably Related Adverse Events (AEs)(From Week 0 up to Week 36)
- Percentage of Participants With AEs Leading to Discontinuation of Study Intervention(From Week 0 to Week 20)
- Percentage of Participants With Infections(From Week 0 up to Week 36)
- Percentage of Participants With Injection-site Reactions(From Week 0 up to Week 36)
- Group 1: Guselkumab Plus Golimumab - Serum Concentration of Golimumab(Weeks 0, 4, 8, 12, 16, 20, 24, and 36)
- Serum Concentration of Guselkumab(Weeks 0, 4, 8, 12, 16, 20, 24, and 36)
- Percentage of Participants With Anti-Guselkumab Antibodies(From Week 0 up to Week 36)
- Percentage of Participants With Anti-Golimumab Antibodies(From Week 0 up to Week 36)