An Adaptive Phase 3, Randomized, Double-blind, Placebo-controlled Study Assessing Efficacy and Safety of Sarilumab for Hospitalized Patients With COVID19
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- Sanofi
- 入组人数
- 420
- 试验地点
- 47
- 主要终点
- Time to Improvement in Clinical Status of Participants (Using 7-point Ordinal Scale Score) by at Least 2 Points
研究概览
简要总结
Primary Objective:
To evaluate the clinical efficacy of sarilumab relative to the control arm in adult participants hospitalized with severe or critical Coronavirus Disease 2019 (COVID-19).
Secondary Objectives:
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Evaluate the 28-day survival rate.
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Evaluate the clinical efficacy of sarilumab compared to the control arm by clinical severity.
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Evaluate changes in the National Early Warning Score 2.
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Evaluate the duration of predefined symptoms and signs (if applicable).
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Evaluate the duration of supplemental oxygen dependency (if applicable).
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Evaluate the incidence of new mechanical ventilation use during the study.
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Evaluate the duration of new mechanical ventilation use during the Study.
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Evaluate the proportion of participants requiring rescue medication during the 28-day period.
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Evaluate need for admission into intensive care unit.
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Evaluate duration of hospitalization (days).
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The secondary safety objectives of the study were to evaluate the safety of sarilumab through hospitalization (up to Day 29 if participant was still hospitalized) compared to the control arm as assessed by incidence of:
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Serious adverse events.
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Major or opportunistic bacterial or fungal infections in participants with grade 4 neutropenia.
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Grade greater than or equal to (>=) 2 infusion related reactions.
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Grade >=2 hypersensitivity reactions.
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Increase in alanine transaminase (ALT) >=3X upper limit of normal (ULN) (for participants with normal baseline) or greater than 3X ULN AND at least 2-fold increase from baseline value (for participants with abnormal baseline).
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Major or opportunistic bacterial or fungal infections.
详细描述
An individual participant would complete the study approximately 60 days from screening to follow-up on day 60 ±7 days.
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 —（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
Sarilumab 200 mg
Sarilumab 200 milligrams (mg), single dose of intravenous (IV) injection on Day 1. Participants could receive a second dose of sarilumab 200 mg 24 to 48 hours after the first dose if first and any one of last three criteria was met as compared to Day 1 (as per following protocol amendment 2 [dated 08-Apr-2020]):
- Benefit risk assessment by the investigator favored the administration of another dose of study drug without compromising safety and
- Increase/recurrence of fever or
- Increase/no change in fraction of inspired oxygen (FiO2) requirement or
- Required vasopressors, extracorporeal membrane oxygenation (ECMO) or development of multi-organ dysfunction.
干预措施: Sarilumab SAR153191 (Drug)
Sarilumab 400 mg
Sarilumab 400 mg, single dose of IV injection on Day 1. Participants could receive a second dose of sarilumab 400 mg 24 to 48 hours after the first dose if first and any one of last three criteria was met as compared to Day 1 (as per following protocol amendment 2 [dated 08-Apr-2020]):
- Benefit risk assessment by the investigator favored the administration of another dose of study drug without compromising safety and
- Increase/recurrence of fever or
- Increase/no change in FiO2 requirement or
- Required vasopressors, ECMO or development of multi-organ dysfunction.
干预措施: Sarilumab SAR153191 (Drug)
Placebo
Placebo (for sarilumab), single dose of IV injection on Day 1. Participants could receive a second dose of placebo (for sarilumab) 24 to 48 hours after the first dose if first and any one of last three criteria was met as compared to Day 1 (as per following protocol amendment 2 [dated 08-Apr-2020]):
- Benefit risk assessment by the investigator favored the administration of another dose of study drug without compromising safety and
- Increase/recurrence of fever or
- Increase/no change in FiO2 requirement or
- Required vasopressors, ECMO or development of multi-organ dysfunction.
干预措施: Placebo (Drug)
结局指标
主要结局
Time to Improvement in Clinical Status of Participants (Using 7-point Ordinal Scale Score) by at Least 2 Points
时间窗: Baseline to Day 29
Time to improvement of greater than or equal (\>=) 2 points in clinical status assessment was defined as time (in days) from first dose of study drug to the time of first occurrence of improvement of \>=2 points in clinical status of participants assessed using 7-point ordinal scale (calculated as: Date of first occurrence/episode of the event - date of first dose + 1). Seven-point ordinal scale for clinical assessment ranges from 1= death; 2= hospitalized, on invasive mechanical ventilation/ECMO; 3= hospitalized, on non-invasive ventilation/high flow oxygen devices; 4= hospitalized, requiring supplemental oxygen; 5= hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related/otherwise); 6= hospitalized, not requiring supplemental oxygen - no longer required ongoing medical care; 7= not hospitalized, higher score = less severity. Kaplan-Meier method was used for analysis.
次要结局
- Number of Participants With Treatment-emergent Serious Adverse Events (SAEs)(Baseline up to 60 days)
- Number of Participants With Major or Opportunistic Bacterial or Fungal Infections(Baseline up to 60 days)
- Number of Participants With Grade 4 Neutropenia and Grade 4 Neutropenia With Concurrent Invasive Infection(Baseline up to 60 days)
- Percentage of Participants Who Were Alive at Day 29(Day 29)
- Percentage of Participants With Improvement in Clinical Status (According to 7-point Ordinal Scale Score) by at Least 1 Point From Baseline at Days 4, 7, 15, 21, and 29(Baseline, Days 4, 7, 15, 21, and 29)
- Change From Baseline at Days 4, 7, 15, 21, 29 in 7-point Ordinal Scale Score(Baseline, Days 4, 7, 15, 21, and 29)
- Time to Resolution of Fever(Baseline to Day 29)
- Time to Resolution of Fever and Improvement in Oxygenation(Baseline to Day 29)
- Number of Days With Fever(Baseline to Day 29)
- Percentage of Participants in Each National Early Warning Score 2 (NEWS2) Clinical Risk Category at Baseline and at Days 4, 7, 15, 21, and 29(Baseline, Days 4, 7, 15, 21, and 29)
- Time to National Early Warning Score of Less Than (<) 2 and Maintained for 24 Hours(Baseline to Day 29)
- Change From Baseline at Days 4, 7, 15, 21, and 29 in National Early Warning Score 2(Baseline, Days 4, 7, 15, 21, and 29)
- Time-to-improvement in Oxygenation(Baseline to Day 29)
- Percentage of Participants Alive Off Supplemental Oxygen at Day 29(Day 29)
- Percentage of Days With Hypoxemia(Baseline to Day 29)
- Percentage of Days With Supplemental Oxygen Use(Baseline to Day 29)
- Percentage of Days With Resting Respiratory Rate > 24 Breaths Per Minute(Baseline to Day 29)
- Time to Oxygen Saturation >= 94% on Room Air(Baseline to Day 29)
- Mean Number of Ventilator Free Days(Baseline to Day 29)
- Percentage of Participants With Initiation of Mechanical Ventilation, Non-invasive Ventilation, or Use of High Flow Nasal Cannula(Baseline to Day 29)
- Percentage of Participants Who Required Rescue Medication(Baseline to Day 28)
- Percentage of Participants Who Needed Intensive Care Unit (ICU) Care During Study(Baseline to Day 29)
- Number of Days of Hospitalization Among Survivors (Alive Participants)(At Day 60)
- Number of Participants With Grade >=2 Infusion Reactions, Grade >=2 Hypersensitivity Reactions and Gastrointestinal Perforation(Baseline up to 60 days)
- Number of Participants With Potentially Clinically Significant Laboratory Abnormalities (PCSA): Hematological Parameter - Hemoglobin, Leukocytes and Platelets(Baseline up to 60 days)
- Number of Participants With Potentially Clinically Significant Laboratory Abnormalities: Renal Function Parameters(Baseline up to 60 days)
- Number of Participants With Potentially Clinically Significant Laboratory Abnormalities: Liver Function Parameters(Baseline up to 60 days)