A Phase 3 Randomized, Multi-center, Open Label Study to Assess the Efficacy, Safety, and Tolerability of Monoclonal Antibody VIR-7831 (Sotrovimab) Given Intramuscularly Versus Intravenously for the Treatment of Mild/Moderate Coronavirus Disease 2019 (COVID-19) in High-risk Non-hospitalized Patients; Safety Substudy Assessing the Safety and Tolerability of Single Ascending Dose Monoclonal Antibody VIR-7831
试验速览
- 阶段
- 3 期
- 状态
- 终止
- 入组人数
- 1,065
- 试验地点
- 52
- 主要终点
- Main Study: Percentage of Participants Who Had Progression of Coronavirus Disease 2019 (COVID-19) Through Day 29 by Hospitalization >24 Hours or Death Due to Any Cause (Weekly and Daily Imputation)
研究概览
简要总结
The COMET-TAIL main study evaluated efficacy, safety, and tolerability of IM sotrovimab versus IV sotrovimab in high-risk patients for the treatment of mild/moderate COVID-19. In the safety substudy, the aim was to evaluate the safety and tolerability of sotrovimab across a single ascending dose level and over different infusion times when given for the treatment of mild/moderate COVID-19 to participants at high risk of disease progression
Main study was completed successfully. The safety sub-study was discontinued early in the context of evolving variants with increased fold changes in the in vitro half maximal inhibitory concentration (IC50) and uncertainty in the clinical relevance of these changes.
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
- None
入排标准
- 年龄范围
- 12 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Main Study participant must be aged 12 years or older AND at high risk of progression of COVID-19 or > 55 years old
- •Sub-Study participants must be aged 18 years or older at time of consent AND at high risk of progression of COVID-19 or ≥ 55 years old
- •Participants must have a positive SARS-CoV-2 test result and oxygen saturation ≥94% on room air and have COVID-19 symptoms and be less than or equal to 7 days from onset of symptoms
排除标准
- •Currently hospitalized or judged by the investigator as likely to require hospitalization in the next 24 hours
- •Symptoms consistent with severe COVID-19
- •Participants who, in the judgement of the investigator are likely to die in the next 7 days
- •Known hypersensitivity to any constituent present in the investigational product
研究组 & 干预措施
Main Study - Sotrovimab 500 mg IM
干预措施: sotrovimab (Biological)
Main Study - Sotrovimab 250 mg IM
干预措施: sotrovimab (Biological)
Substudy (Cohort A) - Sotrovimab 2000 mg IV
干预措施: sotrovimab (Biological)
Main Study - Sotrovimab 500 mg IV
干预措施: sotrovimab (Biological)
结局指标
主要结局
Main Study: Percentage of Participants Who Had Progression of Coronavirus Disease 2019 (COVID-19) Through Day 29 by Hospitalization >24 Hours or Death Due to Any Cause (Weekly and Daily Imputation)
时间窗: Up to Day 29
Progression of COVID-19 through Day 29 as defined by hospitalization \>24 hours for acute management of illness due to any cause or death. Percentage values are rounded off.
Safety Sub-study: Number of Participants With Any Disease Related Events Through Day 8
时间窗: Up to Day 8
AEs related to expected progression, signs, or symptoms of COVID-19, unless more severe than expected for the participant's current clinical status and medical history, were reported as a disease related events.
Safety Sub-study: Number of Participants With Infusion-related Reaction Including Hypersensitivity Through Day 8
时间窗: Up to Day 8
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. Adverse events of special interest (AESI) included infusion-related reaction including hypersensitivity. Data for number of participants with infusion-related reaction including hypersensitivity has been presented.
Safety Sub-study: Number of Participants With Non-Serious Adverse Events (Non-SAE) and Serious Adverse Events (SAEs) Through Day 8
时间窗: Up to Day 8
An adverse event (AE) is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. An SAE is defined as any serious adverse event that, at any dose: results in death; is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, or any other situation according to medical or scientific judgement. Adverse events which were not Serious were considered as Non-Serious adverse events.
次要结局
- Main Study: Number of Participants With Any Disease Related Events(Up to Week 36)
- Safety Sub-study: Number of Participants With Any Infusion-related Reaction Including Hypersensitivity Through Week 12(Up to Week 12)
- Safety Sub-study: Number of Participants With Any Disease Related Events Through Week 12(Up to Week 12)
- Main Study: Number of Participants With Any Local Site Reaction by Maximum Severity After IM Administration(Up to Week 36)
- Main Study: Titers of Anti-drug Antibodies Against Sotrovimab(Up to Week 24)
- Safety Sub-study: Number of Participants With Positive Neutralizing Antibodies(Up to Week 24)
- Main Study: Mean AUC of SARS-CoV-2 Viral Load From Day 1 to Day 8 After Administration of Sotrovimab 500 mg IV and IM(Day 1 to Day 8)
- Main Study: Percentage of Participants With Persistently High SARS-CoV-2 Viral Load at Day 8(At Day 8)
- Main Study: Number of Participants With Common Non-Serious Adverse Events (Non-SAEs)(Up to Week 12)
- Main Study: Serum Concentration of Sotrovimab After Intramuscular Administration(Day 1: Pre-dose, Day 8, Day 15, Day 29, Week 12, Week 20 and Week 24)
- Safety Sub-study: Terminal Elimination Half-life of Sotrovimab After Intravenous Administration (t1/2)(Day 1: Pre-dose and end of infusion; Days 3, 5, 8, 15, 29 post-dose, Weeks 12, 20 and 24 post-dose)
- Main Study: Number of Participants With Serious Adverse Events (SAEs)(Up to Week 36)
- Main Study: Number of Participants With Any Infusion- or Injection-related Reaction Including Hypersensitivity(Up to Week 36)
- Safety Sub-study: Number of Participants With Non-SAEs Through Week 12(Up to Week 12)
- Main Study: Number of Participants With Treatment-emergent Positive Anti-drug Antibody(Up to Week 24)
- Safety Sub-study: Titers of Anti-drug Antibodies Against Sotrovimab Through Week 24(Up to Week 24)
- Main Study: Percentage of Participants Who Progress to Develop Severe and/or Critical Respiratory COVID-19 by Visit(Day 8, Day 15, Day 22, and Day 29)
- Main Study: Change From Baseline in Viral Load as Measured by qRT-PCR at Day 8(Baseline (Day 1) and at Day 8)
- Safety Sub-study: Area Under the Serum Concentration-time Curve From Days 1 to 29 of After Intravenous Administration (AUCD1-29) of Sotrovimab(Day 1: Pre-dose and end of infusion; Days 3, 5, 8, 15, 29 post-dose)
- Safety Sub-study: Number of Participants With SAEs Through Week 36(Up to Week 36)
- Main Study: Mean Area Under the Curve (AUC) of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) Viral Load From Day 1 to Day 8(Day 1 to Day 8)
- Main Study: Serum Concentration of Sotrovimab After Intravenous Administration(Day 1: Pre-dose, Day 8, Day 15, Day 29, Week 12, Week 20 and Week 24)
- Safety Sub-study: Serum Concentration of Sotrovimab After Intravenous Administration(Day 1: Pre-dose and end of infusion; Days 3, 5, 8, 15, 29 post-dose, Weeks 12, 20 and 24 post-dose)
- Safety Sub-study: Maximum Serum Concentration of Sotrovimab After Intravenous Administration (Cmax)(Day 1: Pre-dose and end of infusion; Days 3, 5, 8, 15, 29 post-dose, Weeks 12, 20 and 24 post-dose)
- Safety Sub-study: Number of Participants With Treatment-emergent Positive Anti-drug Antibody Through Week 24(Up to Week 24)
- Main Study: Percentage of Participants Who Had Progression of COVID-19 Through Day 29 by Emergency Room Visit or Hospitalization or Death (Weekly Imputation)(Up to Day 29)
- Safety Sub-study: Apparent Volume of Distribution at Steady State of Sotrovimab After Intravenous Administration (Vss)(Day 1: Pre-dose and end of infusion; Days 3, 5, 8, 15, 29 post-dose, Weeks 12, 20 and 24 post-dose)
- Safety Sub-study: Clearance of Sotrovimab After Intravenous Administration (CL)(Day 1: Pre-dose and end of infusion; Days 3, 5, 8, 15, 29 post-dose, Weeks 12, 20 and 24 post-dose)
- Safety Sub-study: Area Under the Serum Concentration-Time Curve Extrapolated From Zero to Infinity of Sotrovimab After Intravenous Administration (AUC[0-inf])(Day 1: Pre-dose and end of infusion; Days 3, 5, 8, 15, 29 post-dose, Weeks 12, 20 and 24 post-dose)
- Safety Sub-study: Apparent Volume of Distribution During the Elimination Phase of Sotrovimab After Intravenous Administration (Vz)(Day 1: Pre-dose and end of infusion; Days 3, 5, 8, 15, 29 post-dose, Weeks 12, 20 and 24 post-dose)
- Safety Sub-study: Time to Reach Maximum Serum Concentration of Sotrovimab After Intravenous Administration (Tmax)(Day 1: Pre-dose and end of infusion; Days 3, 5, 8, 15, 29 post-dose, Weeks 12, 20 and 24 post-dose)