A Double-blind, Randomized, Placebo-controlled, Multicenter Dose-ranging Study To Evaluate The Efficacy And Safety Of Pf-04236921 In Subjects With Systemic Lupus Erythematosus (Sle)
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- Pfizer
- 入组人数
- 183
- 试验地点
- 213
- 主要终点
- Percentage of Participants Achieving Systemic Lupus Erythematosus (SLE) Responder Index (SRI) at Week 24
研究概览
简要总结
The objective of this study is to evaluate and compare efficacy of 3 dose levels of PF-04236921 to placebo in subjects with generalized lupus using a measure called the Systemic Lupus Erythematosus (SLE) Responder Index. The study will evaluate secondary and exploratory measures as well.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
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
- •Male or female subjects between ages of 18 and 75 years old at time of signing consent.
- •Have a clinical diagnosis of SLE according to 1997 update on the revised 1982 American College of Rheumatology (ACR) criteria.
- •Have a unequivocally positive anti-nuclear antibody (ANA) test result.
- •Active disease at screening defined by both: SLEDAI-2K score greater than or equal to 6 and BILAG Level A disease in more than or equal to 1 organ system (except renal or central nervous system) or BILAG B disease in more than or equal to 2 organ systems if no level A disease in present.
排除标准
- •Any prior history of treatment with PF-04236921, or anti-IL-6 agent;
- •Have received any of the following within 364 days of day 1: a biologic investigational agent other than B cell targeted therapy; required 3 or more courses of systemic corticosteroids for concomitant conditions; history of previously untreated or current evidence of active or untreated latent infection with Tuberculosis (TB), evidence of prior untreated or currently active TB by chest radiography, residing with or frequent close contact with an individual with active TB.
研究组 & 干预措施
200 mg of PF-04236921
干预措施: PF-04236921 (Biological)
Placebo
干预措施: PF-04236921 (Biological)
10 mg of PF-04236921
干预措施: PF-04236921 (Biological)
50 mg of PF-04236921
干预措施: PF-04236921 (Biological)
结局指标
主要结局
Percentage of Participants Achieving Systemic Lupus Erythematosus (SLE) Responder Index (SRI) at Week 24
时间窗: Week 24
SRI components include:Systemic Lupus Erythematosus Disease Activity Index 2000(SLEDAI-2K),British Isles Lupus Assessment Group(BILAG) 2004,Physician's Global Assessment(PhGA).Participants classified as responder if they did not meet definition of treatment failure and met all the following criteria: greater than or equal to(\>=) 4 point reduction in SLEDAI-2K score; no new BILAG A organ domain score or 2 new BILAG B organ domain scores; no worsening (less than \[\<\] 0.3 point increase) in PhGA score. Treatment failure: any new/increased use of corticosteroids,immunosuppressants/antimalarial drug, any death, hospitalization/treatment discontinuation due to SLE, any flare of lupus interfering with participation in study. SLEDAI-2K:assesses improvement in disease activity (range: 0 to 105; higher score = higher severity). BILAG:assesses disease extent, severity (range: A\[severe\] to E\[no disease\]). PhGA: assesses worsening in participant's general health status(range: 0\[none\] to 3\[severe\]).
次要结局
- Percentage of Participants Achieving Pre-defined Criteria for Systemic Lupus Erythematosus (SLE) Responder Index (SRI) Components at Week 24(Week 24)
- Number of Participants Who Discontinued Due to Adverse Events(Baseline up to Week 52)
- Percentage of Participants With Normalized Serological Activity(Baseline up to Week 24)
- Change From Baseline in European Quality of Life 5 Dimensions Questionnaire (EQ-5D) at Week 4, 8, 12, 16, 20 and 24(Baseline, Week 4, 8, 12, 16, 20, 24)
- Percentage of Participants Achieving Systemic Lupus Erythematosus (SLE) Responder Index (SRI) at Week 4, 8, 12, 16, and 20(Week 4, 8, 12, 16, 20)
- Percentage of Participants Achieving Modified Systemic Lupus Erythematosus (SLE) Responder Index (SRI) at Week 4, 8, 12, 16, 20, and 24(Week 4, 8, 12, 16, 20, 24)
- Number of Participants With Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs)(Baseline up to Week 52)
- Percentage of Participants Achieving British Isles Lupus Assessment Group-based Composite Lupus Assessment (BICLA) Response at Week 4, 8, 12, 16, 20, and 24(Week 4, 8, 12, 16, 20, 24)
- Number of Participants With Clinically Significant Laboratory Tests Results(Baseline up to Week 52)
- Number of Participants With Treatment-Emergent Infectious Adverse Events (AEs) or Serious Adverse Events (SAEs)(Baseline up to Week 52)
- Number of Participants With Potentially Clinically Important (PCI) Electrocardiogram (ECG) Findings(Baseline up to Week 52)
- Number of Participants With Potentially Clinically Important Vital Signs Findings(Baseline up to Week 52)
- Number of Participants With Anti-drug Antibodies (ADAs) and Neutralizing Antibodies (Nabs)(Baseline up to Week 52)
- Serum Concentration of PF-04236921(Day 1, Week 2, 4, 6, 8, 12, 16, 20, 24)
- Percentage of Participants With Corticosteroid Dose Reduced by Both Greater Than or Equal to (>=) 25 Percent (%) From Baseline and Less Than or Equal to (<=) 7.5 Milligrams Per Day (mg/Day)(Week 12, 16, 20, 24)
- Change From Baseline in Patient Global Visual Analog Scale (VAS) at Week 2, 4, 6, 8, 12, 16, 20 and 24(Baseline, Week 2, 4, 6, 8, 12, 16, 20, 24)
- Thirty Six-Item Short-Form Health Survey (SF-36) Physical Component Score (PCS) and Mental Component Score (MCS) at Baseline(Baseline)
- Change From Baseline in 36-Item Short-Form Health Survey (SF-36) PCS and MCS at Week 4, 8, 12, 16, 20 and 24(Baseline, Week 4, 8, 12, 16, 20, 24)
- Change From Baseline in Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) Score at Week 4, 8, 12, 16, 20 and 24(Baseline, Week 4, 8, 12, 16, 20, 24)
- Patient Global Visual Analog Scale (VAS) Scores at Baseline(Baseline)
- Change From Baseline in Vitality Scores at Week 4, 8, 12, 16, 20 and 24(Baseline, Week 4, 8, 12, 16, 20, 24)
- Change From Baseline in Short Form-6 Dimension (SF-6D) at Week 4, 8, 12, 16, 20 and 24(Baseline, Week 4, 8, 12, 16, 20, 24)
- Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) Score at Baseline(Baseline)