A Phase 2, Multicenter, Randomized, Placebo-controlled, Double-blind, Proof-of-Concept Study to Evaluate Guselkumab for the Treatment of Participants With New-onset or Relapsing Giant Cell Arteritis
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 53
- 试验地点
- 30
- 主要终点
- Main Study: Percentage of Participants Achieving Glucocorticoid (GC)-Free Remission at Week 28
研究概览
简要总结
The primary purpose of this study is to evaluate the efficacy of guselkumab compared to placebo, in combination with a 26-week glucocorticoid (GC) taper regimen, in adult participants with new-onset or relapsing giant cell arteritis (GCA).
详细描述
Giant cell arteritis (GCA) is a non-necrotizing granulomatous systemic vasculitis of unknown etiology affecting medium-sized and large arteries usually accompanied or preceded by systemic inflammation. Guselkumab is a monoclonal antibody (mAb) that binds to the p19 sub-unit of human interleukin (IL)-23 with high affinity and blocks binding of extracellular IL-23 to cell surface IL-23 receptor, inhibiting IL 23 specific intracellular signaling and subsequent activation and cytokine production. It is used in treatment of psoriatic arthritis, generalized pustular psoriasis, erythrodermic psoriasis. The study consists of a screening period (less than or equal to [<=] 6 weeks), double-blind treatment period (48 weeks), and safety follow-up period (12 weeks). Participants who complete the Week 52 visit and are assessed to be in glucocorticoid (GC)-free remission, may have the option to participate in the long-term extension (LTE) period of the study for up to 12 months. This study will evaluate the efficacy, safety, Pharmacokinetics (PK), and immunogenicity of guselkumab in combination with a 26-week GC taper regimen for the treatment of active new-onset or relapsing GCA in adult participants. The total duration of the study is up to 66 weeks for the main study and for participants that continue in the LTE period, the total study duration will be up to 112 weeks.
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
- 50 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Guselkumab
Participants will receive guselkumab subcutaneously (SC) every 4 weeks from Week 0 through Wweek 48. This will be in combination with a protocol specified 26-week GC taper. Participants of the long-term extension (LTE) period will continue to receive subcutaneous (SC) injections every 4 weeks starting at Week 52 (LTE Week 0) through Week 100 (LTE Week 48) or until the participants have a Giant cell arteritis (GCA) flare, or the participants discontinues treatment due to unblinding after the Week 60 DBL for the Main study, or until a decision is made not to continue clinical development in this GCA population, whichever occurs first.
干预措施: Guselkumab (Drug)
Placebo
Participants will receive matching placebo SC every 4 weeks from Week 0 through Week 48. This will be in combination with a protocol-specified 26-week GC taper. Participants of the LTE period will continue to receive SC injections every 4 weeks starting at Week 52 (LTE Week 0) through Week 100 (LTE Week 48) or until the participants have a GCA flare, or the participants discontinues treatment due to unblinding after the Week 60 DBL for the Main study, or until a decision is made not to continue clinical development in this GCA population, whichever occurs first.
干预措施: Placebo (Drug)
结局指标
主要结局
Main Study: Percentage of Participants Achieving Glucocorticoid (GC)-Free Remission at Week 28
时间窗: Week 28
GC free remission at Week 28 was defined as (1) no signs or symptoms of active Giant cell arteritis (GCA) at Week 28; (2) absence of GCA flare from first dose of the study drug through Week 28; and (3) adherence to the protocol specified 26-week GC taper regimen. GCA flare was defined as the recurrence of signs and symptoms of active GCA, with or without elevation of inflammatory markers, and with the necessity for an increase in GC dose for GCA.
次要结局
- Main Study: Percentage of Participants Achieving GC-Free Remission at Weeks 28, 32, 36, 40, 44, 48 and 52(Weeks 28, 32, 36, 40, 44, 48 and 52)
- Main Study: Percentage of Participants Achieving Both GC-Free Remission and Normalization of Erythrocyte Sedimentation Rate (ESR) at Weeks 28, 32, 36, 40, 44, 48 and 52(Weeks 28, 32, 36, 40, 44, 48 and 52)
- Main Study: Percentage of Participants Achieving Both GC-Free Remission and Normalization of C-Reactive Protein (CRP) at Weeks 28, 32, 36, 40, 44, 48 and 52(Weeks 28, 32, 36, 40, 44, 48 and 52)
- Main Study: Percentage of Participants Achieving Both GC-Free Remission and Normalization of Both ESR and CRP at Weeks 28, 32, 36, 40, 44, 48 and 52(Weeks 28, 32, 36, 40, 44, 48 and 52)
- Main Study: Cumulative Glucocorticoid (GC) Dose(Baseline (Day 1) up to Weeks 28 and 52)
- Main Study: Time to First GCA Disease Flare or Discontinuation of Study Intervention Due to Adverse Event (AE) of Worsening of GCA(Baseline (Day 1) up to Week 30 and Week 52)
- Main Study: Number of Participants With GCA Disease Flares or Discontinuation of Study Intervention Due to AE of Worsening of GCA(Baseline (Day 1) up to Week 30 and Week 52)
- Main Study: Number of Participants With Treatment-emergent Adverse Events (TEAEs)(Baseline (Day 1) up to Week 60)
- Number of Participants With TEAEs by System Organ Class (SOC) With a Frequency Threshold of 5 Percent (%) or More(Baseline (Day 1) up to Week 60)
- Main Study: Number of Participants With Treatment-emergent Serious Adverse Event (SAEs)(Baseline (Day 1) up to Week 60)
- Main Study: Number of Participants With Clinically Significant Abnormalities in Vital Signs(Baseline (Day 1) up to Week 60)
- Main Study: Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters(Baseline (Day 1) up to Week 60)
- Main Study: Serum Concentrations of Guselkumab(Pre-dose and 1 hour post dose on Week 0 (Day 1), Week 4 (Day 28), and Week 8 (Day 56); Week 12 (Day 84), Week 16 (Day 112), Week 28 (Day 196), Week 52 (Day 364))
- Main Study: Number of Participants With Antibodies to Guselkumab(Baseline (Day 1) up to Week 28, Week 52)