A Multicenter, Randomized, Placebo-controlled, Double-blind, Proof-of-concept Study of Guselkumab in Participants With Systemic Sclerosis
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 56
- 试验地点
- 4
- 主要终点
- Main Study: Change From Baseline in Modified Rodnan Skin Score (mRSS) at Week 24
研究概览
简要总结
The purpose of the study is to evaluate the efficacy of guselkumab in participants with systemic sclerosis (SSc).
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 75 Years（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
- •History of liver or renal insufficiency (estimated creatinine clearance below 60 milliliter per minute [mL/min]); significant cardiac, vascular, pulmonary, gastrointestinal, endocrine, neurologic, hematologic, rheumatologic, psychiatric, or metabolic disturbances
- •Has any known severe or uncontrolled SSc complications including hemoptysis, pulmonary hemorrhage, renal crisis
- •Has an interstitial lung disease requiring oxygen therapy
- •Has any rheumatic disease other than SSc such as rheumatoid arthritis (RA), polymyalgia rheumatica (PMR), systemic lupus erythematosus, polymyositis/dermatomyositis that could interfere with assessment of SSc
- •Has a current diagnosis or signs or symptoms of severe, progressive, or uncontrolled renal, cardiac, vascular, pulmonary, gastrointestinal, endocrine, neurologic, hematologic, rheumatologic, psychiatric, or metabolic disturbances. (or, in the investigator's opinion, any other concomitant medical condition that places the participant at risk by participating in this study)
研究组 & 干预措施
Group A: Guselkumab
Participants will receive intravenous (IV) injection of Guselkumab Dose 1 at Week 0, 4, and 8 followed by subcutaneous (SC) injection of Dose 2 Guselkumab every 4 weeks (Q4W) from Week 12 to Week 48 (end of maintenance phase). Participants will receive SC injection of Guselkumab Dose 2 and IV injection of placebo at long-term extension (LTE) Weeks 52, 56, and 60 followed by SC injection of Guselkumab Dose 2 Q4W from LTE Week 64 until Week 100.
干预措施: Guselkumab Dose 1 (Drug)
Group A: Guselkumab
Participants will receive intravenous (IV) injection of Guselkumab Dose 1 at Week 0, 4, and 8 followed by subcutaneous (SC) injection of Dose 2 Guselkumab every 4 weeks (Q4W) from Week 12 to Week 48 (end of maintenance phase). Participants will receive SC injection of Guselkumab Dose 2 and IV injection of placebo at long-term extension (LTE) Weeks 52, 56, and 60 followed by SC injection of Guselkumab Dose 2 Q4W from LTE Week 64 until Week 100.
干预措施: Guselkumab Dose 2 (Drug)
Group B: Placebo
Participants will receive IV injection of matching placebo at Week 0, 4, and 8 followed by SC injection of matching placebo Q4W from Week 12 to Week 48 (end of maintenance phase). Participants will receive SC injection of Placebo and IV injection of Guselkumab Dose 1 at LTE Weeks 52, 56, and 60 followed by SC injection of Guselkumab Dose 2 Q4W from LTE Week 64 until Week 100.
干预措施: Placebo (Drug)
结局指标
主要结局
Main Study: Change From Baseline in Modified Rodnan Skin Score (mRSS) at Week 24
时间窗: Baseline and Week 24
Change from baseline in mRSS at Week 24 was reported. The mRSS is an accepted clinical measure of skin thickness. The investigator assessed the thickening of the skin using the mRSS through simple palpation on 17 different skin sites in the fingers, hands, forearms, arms, feet, legs, and thighs (bilaterally) and face, chest, and abdomen (singly). Each skin site was rated on a 0 to 3 scale; where 0 = normal skin, 1 = mild thickness, 2 = moderate thickness, and 3 = severe thickness and unable to pinch. Individual skin scores in the 17 body areas were summed and defined as the total mRSS which ranged from 0 (no thickening) to 51 (severe thickening), where higher score indicated more severity of skin thickening/worst outcome.
次要结局
- Main Study: Change From Baseline in Modified Rodnan Skin Score at Week 52(Baseline and Week 52)
- Main Study: Percentage of Participants Who Experienced Worsening of Modified Rodnan Skin Score at Week 24 and Week 52(Week 24 and Week 52)
- Main Study: Percentage of Participants Who Achieved a Score of 0.6 in American College of Rheumatology Combined Response Index in Diffuse Cutaneous Systemic Sclerosis (ACR CRISS) at Week 24 and Week 52(Week 24 and Week 52)
- Main Study: Change From Baseline in Forced Vital Capacity (FVC) at Week 24 and Week 52(Baseline, Week 24 and Week 52)
- Main Study: Change From Baseline in Percent Predicted Forced Vital Capacity (FVC) at Week 24 and Week 52(Baseline, Week 24 and Week 52)
- Main Study: Change From Baseline in the Measured Absolute Diffusing Capacity of the Lung for Carbon Monoxide (DLCO) at Week 24 and Week 52(Baseline, Week 24 and Week 52)
- Main Study: Change From Baseline in the Percent Predicted Diffusing Capacity of the Lung for Carbon Monoxide (DLCO) at Week 24 and Week 52(Baseline, Week 24 and Week 52)
- Main Study: Change From Baseline in Digital Ulcer Counts at Week 24 and Week 52(Baseline, Week 24 and Week 52)
- Main Study: Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) Score at Week 24 and Week 52(Baseline, Week 24 and Week 52)
- Main Study: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Through Week 24 and Week 52(From Baseline (Week 0) up to Week 24 and Week 52)
- Long-term Extension (LTE) Period: Number of Participants With Treatment-emergent Adverse Events (TEAEs)(From Week 52 up to Week 112)
- Main Study: Number of Participants With Treatment-Emergent Serious Adverse Events (TESAEs) Through Week 24 and Week 52(From Baseline (Week 0) up to Week 24 and Week 52)
- Long-term Extension (LTE) Period: Number of Participants With Treatment-emergent Serious Adverse Events (TESAEs)(From Week 52 up to Week 112)
- Main Study: Number of Participants With Adverse Events of Special Interest (AESI) Through Week 24 and Week 52(From Baseline (Week 0) up to Week 24 and Week 52)
- Long-term Extension (LTE) Period: Number of Participants With Adverse Events of Special Interest (AESI)(From Week 52 up to Week 112)
- Main Study: Serum Concentration of Guselkumab(Pre-dose at Weeks 0, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 and Post- dose at Weeks 0, 4, 8)
- Long-term Extension (LTE) Study: Serum Concentrations of Guselkumab(Pre-dose (at Weeks 56, 60, 64, 76, 88, 96) and Week 104)
- Main Study: Number of Participants With Anti-Guselkumab Antibody(From Baseline (Week 0) up to Week 52)
- Long-term Extension (LTE) Study: Number of Participants With Anti-guselkumab Antibody(From Week 52 up to Week 104)