A Phase 4, Multicenter, Randomized, Double-blind, Placebo-controlled Study Evaluating the Efficacy and Safety of Guselkumab Administered Subcutaneously in Bio-naive Participants With Active Psoriatic Arthritis Axial Disease
试验速览
- 阶段
- 4 期
- 状态
- 进行中（未招募）
- 入组人数
- 411
- 试验地点
- 242
- 主要终点
- Change from Baseline in Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) Score at Week 24
研究概览
简要总结
The purpose of this study is to evaluate the efficacy of guselkumab treatment in participants with active psoriatic arthritis (PsA) axial disease by assessing reduction in axial symptoms and inflammation.
详细描述
PsA is a chronic inflammatory musculoskeletal disease that has 6 disease domains, and axial disease represents one of the domains. Guselkumab is a fully human immunoglobulin (Ig) G1 lambda monoclonal antibody (mAb) that by binding to the p19 protein subunit of interleukin (IL)-23, blocks the binding of extracellular IL-23 to the cell surface IL-23 receptor, inhibiting IL-23-mediated intracellular signaling, activation, and cytokine production. This study will consist of a screening phase (up to 6 weeks), a treatment phase (up to 48 weeks, including a placebo-controlled period from Week 0 to Week 24 and an active-controlled treatment phase from Week 24 to Week 48), and a safety follow-up phase (up to Week 60). The efficacy assessments will include assessment such as Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score and the safety assessments will include evaluations of physical examinations, vital signs, electrocardiograms, clinical laboratory tests, and adverse events. The overall duration of the study will be up to 14 months.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Have a diagnosis of psoriatic arthritis (PsA) for at least 6 months prior to the first administration of study intervention and meet classification criteria for psoriatic arthritis (CASPAR) criteria at screening
- •Have active PsA as defined by: a) at least 3 swollen joints and at least 3 tender joints at screening and at baseline and b) C-reactive protein (CRP) greater than or equal to (>=) 0.3 milligram/deciliter (mg/dL) at screening from the central laboratory, and despite previous non-biologic disease modifying antirheumatic drug (DMARD), apremilast, and/or nonsteroidal anti-inflammatory drug (NSAID) therapy
- •Have magnetic resonance imaging (MRI)-confirmed PsA axial disease (positive MRI spine and/or sacroiliac [SI] joints, shown by a Spondyloarthritis Research Consortium of Canada [SPARCC] score of >= 3 in either the spine or the sacroiliac joints)
- •Have a Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score of at least 4, and have a spinal pain score (on a visual analog scale [VAS]) of at least 4
- •Have active plaque psoriasis, with at least 1 psoriatic plaque of >= 2 centimeter (cm) diameter and/or nail changes consistent with psoriasis, or documented history of plaque psoriasis
排除标准
- •Has known allergies, hypersensitivity, or intolerance to guselkumab or its excipients
- •Has other inflammatory diseases that might confound the evaluations of benefit of guselkumab therapy, including but not limited to rheumatoid arthritis (RA), ankylosing spondylitis (AS)/non-radiographic-axial spondyloarthritis (this does not include a primary diagnosis of PsA with spondylitis), systemic lupus erythematosus, or Lyme disease
- •Has previously received any biologic treatment
- •Has ever received a 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
研究组 & 干预措施
Group 1: Guselkumab and Placebo
Participants will receive guselkumab and matching placebo subcutaneously (SC) to maintain the blind.
干预措施: Placebo (Drug)
Group 3: Placebo followed by Guselkumab
Participants will receive matching placebo and will cross over to receive guselkumab SC.
干预措施: Placebo (Drug)
Group 3: Placebo followed by Guselkumab
Participants will receive matching placebo and will cross over to receive guselkumab SC.
干预措施: Guselkumab (Drug)
Group 1: Guselkumab and Placebo
Participants will receive guselkumab and matching placebo subcutaneously (SC) to maintain the blind.
干预措施: Guselkumab (Drug)
Group 2: Guselkumab
Participants will receive guselkumab SC.
干预措施: Guselkumab (Drug)
结局指标
主要结局
Change from Baseline in Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) Score at Week 24
时间窗: Baseline and Week 24
BASDAI is a self-assessment tool that consists of 6 questions relating to 5 major symptoms of ankylosing spondylitis: fatigue, spinal pain, joint pain, enthesitis, qualitative morning stiffness and quantitative morning stiffness. First 5 items were scored on a 10 centimeter (cm) visual analog scale (VAS) ranging from 0 equals to (=) none to 10=very severe. Quantitative morning stiffness was scored on a 10 cm VAS ranging from 0=0 hours to 10=2 or more hours. 2 scores for qualitative and quantitative morning stiffness were averaged, and total BASDAI score was average of the 5 scores of each symptom, ranging from 0 (none) to 10 (very severe). Higher scores indicate greater disease severity.
次要结局
- Number of Participants with Reasonably Related AEs(Up to 60 weeks)
- Number of Participants with Infections(Up to 60 weeks)
- Number of Participants with Antibodies to Guselkumab(Up to 60 weeks)
- Change from Baseline in Spondyloarthritis Research Consortium of Canada (SPARCC) Score for Magnetic Resonance Imaging (MRI) Sacroiliac (SI) Joints at Week 24(Baseline and Week 24)
- Percentage of Participants who Achieve a >= 50 % Improvement from Baseline in BASDAI Score at Week 24(Baseline and Week 24)
- Serum Guselkumab Concentration Over Time(Up to 60 weeks)
- Number of participants with Injection-Site Reactions(Up to 60 weeks)
- Change from Baseline in Disease Activity Index for Psoriatic Arthritis (DAPSA) at Week 24(Baseline and Week 24)
- Percentage of Participants with Investigator's Global Assessment (IGA) 0/1 Response at Week 24 among Participants with >= 3% Body Surface Area (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) Score at Week 24(Baseline and Week 24)
- Percentage of Participants who Achieve ASDAS Major Improvement at Week 24(Week 24)
- Change from Baseline in SPARCC Score for MRI Spine at Week 24(Baseline and Week 24)
- Number of Participants with Serious Adverse Events (SAEs)(Up to 60 weeks)
- Change from Baseline in Ankylosing Spondylitis Disease Activity Score-C-Reactive Protein (ASDAS-CRP) at Week 24(Baseline and Week 24)
- Percentage of Participants who Achieve ASDAS Clinically Important Improvement at Week 24(Week 24)
- Percentage of Participants who Achieve Ankylosing Spondylitis Activity Score (ASAS) 40 Response at Week 24(Week 24)
- Number of Participants with Adverse Events (AEs)(Up to 60 weeks)
- Number of Participants with AEs Leading to Discontinuation of Study Intervention(Up to 60 weeks)
- Number of Participants with Laboratory Abnormalities (Chemistry, Hematology) by Maximum Toxicity (Common Terminology Criteria for Adverse Events [CTCAE 5.0]) Grades(Up to 60 weeks)