A Master Protocol Assessing the Safety, Tolerability, and Efficacy of Anti-Spike (S) SARS-CoV-2 Monoclonal Antibodies for the Treatment of Hospitalized Patients With COVID-19
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 2,252
- 试验地点
- 3
- 主要终点
- Pooled Analysis (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): Percentage of Participants Who Died or Went on Mechanical Ventilation From Day 1 Through Day 29 Based on Seronegative mFAS
研究概览
简要总结
The primary objectives are:
Pooled Phase 3 (Cohort 1) and Phase 2 (Cohort 1A)
- To evaluate the virologic efficacy of REGN10933+REGN10987 compared to placebo in reducing viral load of SARS-CoV-2
- To evaluate the clinical efficacy of REGN10933+REGN10987 compared to placebo, as measured by death or mechanical ventilation
Phase 1/2 (Cohort 1)
- To exclude futility of REGN10933+REGN10987 compared to placebo, as measured by death or mechanical ventilation
- To evaluate the safety and tolerability of REGN10933+REGN10987 compared to placebo
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
- •Has SARS-CoV-2-positive antigen or molecular diagnostic test (by validated SARS-CoV-2 antigen, RT-PCR, or other molecular diagnostic assay, using an appropriate sample such as NP, nasal, oropharyngeal [OP], or saliva) ≤72 hours prior to randomization and no alternative explanation for current clinical condition. A historical record of positive result from test conducted ≤72 hours prior to randomization is acceptable.
- •Has symptoms consistent with COVID-19, as determined by investigator, with onset ≤10 days before randomization
- •Hospitalized for ≤72 hours with at least 1 of the following at randomization; patients meeting more than one criterion will be categorized in the most severely affected category:
- •Cohort 1A: With COVID-19 symptoms but not requiring supplemental oxygen
- •Cohort 1: Maintains O2 saturation >93% on low-flow oxygen as defined in the protocol
- •Cohort 2: High-intensity oxygen therapy without mechanical ventilation as defined in the protocol
- •Cohort 3: On mechanical ventilation
排除标准
- •Phase 1 Only: Patients maintaining O2 saturation >94% on room air
- •In the opinion of the investigator, unlikely to survive for >48 hours from screening
- •Receiving extracorporeal membrane oxygenation (ECMO)
- •Has new-onset stroke or seizure disorder during hospitalization
- •Initiated on renal replacement therapy due to COVID-19
- •NOTE: Other protocol defined inclusion / exclusion criteria apply
研究组 & 干预措施
On Low-Flow Oxygen
Cohort 1 (C1): O2 saturation >93% on low-flow oxygen via nasal cannula, simple face mask, or other similar device
干预措施: REGN10933+REGN10987 combination therapy (Drug)
On Low-Flow Oxygen
Cohort 1 (C1): O2 saturation >93% on low-flow oxygen via nasal cannula, simple face mask, or other similar device
干预措施: Placebo (Drug)
With COVID-19 symptoms but not requiring supplemental O2
Cohort 1A (C1A): With COVID-19 symptoms but not requiring supplemental oxygen
干预措施: REGN10933+REGN10987 combination therapy (Drug)
With COVID-19 symptoms but not requiring supplemental O2
Cohort 1A (C1A): With COVID-19 symptoms but not requiring supplemental oxygen
干预措施: Placebo (Drug)
High O2 No Mechanical Ventilation
Cohort 2 (C2): On high-intensity oxygen (O2) therapy but not on mechanical ventilation
干预措施: REGN10933+REGN10987 combination therapy (Drug)
High O2 No Mechanical Ventilation
Cohort 2 (C2): On high-intensity oxygen (O2) therapy but not on mechanical ventilation
干预措施: Placebo (Drug)
On Mechanical Ventilation
Cohort 3 (C3): On mechanical ventilation
干预措施: REGN10933+REGN10987 combination therapy (Drug)
On Mechanical Ventilation
Cohort 3 (C3): On mechanical ventilation
干预措施: Placebo (Drug)
结局指标
主要结局
Pooled Analysis (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): Percentage of Participants Who Died or Went on Mechanical Ventilation From Day 1 Through Day 29 Based on Seronegative mFAS
时间窗: Day 1 to Day 29
Percentage of participants who died or went on mechanical ventilation from Day 1 through Day 29 based on seronegative mFAS were reported.
Pooled Analysis (Phase 1 [Cohort 1] and Phase 2 [Cohort 1]): Number of Participants With Grade >=2 Hypersensitivity Reactions Up to Day 29
时间窗: Up to Day 29
Hypersensitivity reactions are defined as any relevant adverse event that occurs during the infusion or up to study day 29. The severity of adverse events (including test findings classified as adverse events) were graded according to NCI-CTCAE.
Pooled Analysis (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): Percentage of Participants Who Died or Went on Mechanical Ventilation From Day 6 Through Day 29 Based on Seronegative mFAS
时间窗: Day 6 to Day 29
Percentage of participants who died or went on mechanical ventilation from Day 6 through Day 29 based on seronegative mFAS were reported.
Pooled Analysis (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): Percentage of Participants Who Died or Went on Mechanical Ventilation From Day 1 Through Day 29 Based on High Viral Load mFAS
时间窗: Day 1 to Day 29
Percentage of participants who died or went on mechanical ventilation from Day 1 through Day 29 based on high viral load mFAS were reported.
Pooled Analysis (Phase 1 [Cohort 1] and Phase 2 [Cohort 1]): Number of Participants With Grade >=2 Infusion Related Reactions up to Day 4
时间窗: Up to Day 4
Infusion-related reactions are defined as any relevant adverse event that occurs during the infusion or up to day 4. The severity of adverse events (including test findings classified as adverse events) were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE).
Pooled Analysis (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): Percentage of Participants Who Died or Went on Mechanical Ventilation From Day 1 Through Day 29 Based on Overall mFAS
时间窗: Day 1 to Day 29
Percentage of participants who died or went on mechanical ventilation from Day 1 through Day 29 based on overall mFAS were reported.
Pooled Analysis (Phase 1 [Cohort 1] and Phase 2 [Cohort 1]): Cumulative Incidence of Death or Mechanical Ventilation Based on Seronegative mFAS
时间窗: Up to Day 29
Cumulative incidence percentage was estimated using Kaplan-Meier method.
Pooled Analysis (Phase 1 [Cohort 1] and Phase 2 [Cohort 1]): Cumulative Incidence of Death or Mechanical Ventilation Based on High Viral Load mFAS
时间窗: Up to Day 29
Cumulative incidence percentage was estimated using Kaplan-Meier method.
Pooled Analysis (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): Time-weighted Average (TWA) Change in Viral Load in Nasopharyngeal (NP) Samples Based on Seronegative mFAS
时间窗: Day 1 to Day 7
Time-weighted average daily change from Day 1 to Day 7 in viral load (log10 copies/mL), as measured by reverse transcription quantitative polymerase chain reaction (RT-qPCR) in nasopharyngeal (NP) swab samples.
Pooled Analysis (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): Percentage of Participants Who Died or Went on Mechanical Ventilation From Day 6 Through Day 29 Based on Overall mFAS
时间窗: Day 6 to Day 29
Percentage of participants who died or went on mechanical ventilation from Day 6 through Day 29 based on overall FAS were reported.
Pooled Analysis (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): Percentage of Participants Who Died or Went on Mechanical Ventilation From Day 6 Through Day 29 Based on High Viral Load mFAS
时间窗: Day 6 to Day 29
Percentage of participants who died or went on mechanical ventilation from Day 6 through Day 29 based on high viral load mFAS were reported.
Pooled Analysis (Phase 1 [Cohort 1] and Phase 2 [Cohort 1]): Number of Participants With Treatment-Emergent Serious Adverse Events
时间窗: Up to Day 169
Treatment-emergent adverse events are defined as those that are not present at baseline or represent the exacerbation of a pre-existing condition during the observation period.
次要结局
- Pooled Analysis Phase 3 (Cohort 1) and Phase 2 (Cohort 1A): Percentage of Participants Who Were Discharged by Day 29 Based on Seronegative mFAS(by Day 29)
- Pooled Analysis Phase 3 (Cohort 1) and Phase 2 (Cohort 1A): Percentage of Participants Who Died or Were Readmitted to Hospital by Day 29 Based on Seronegative mFAS(by Day 29)
- Pooled Analysis Phase 3 (Cohort 1) and Phase 2 (Cohort 1A): Cumulative Incidence of Mechanical Ventilation by Day 29 Based on High Viral Load mFAS(by Day 29)
- Pooled Analysis Phase 3 (Cohort 1) and Phase 2 (Cohort 1A): Percentage of Participants Who Died From Day 1 Through Day 29 Based on High Viral Load mFAS(Day 1 to Day 29)
- Pooled Analysis Phase 3 (Cohort 1) and Phase 2 (Cohort 1A): Percentage of Participants Who Went on Mechanical Ventilation by Day 29 Based on High Viral Load mFAS(by Day 29)
- Pooled Analysis Phase 3 (Cohort 1) and Phase 2 (Cohort 1A): Percentage of Participants Who Went on Mechanical Ventilation by Day 29 Based on Seronegative mFAS(by Day 29)
- Pooled Analysis Phase 3 (Cohort 1) and Phase 2 (Cohort 1A): Percentage of Participants Who Died From Day 6 Through Day 29 Based on High Viral Load mFAS(Day 6 to Day 29)
- Pooled Analysis Phase 3 (Cohort 1) and Phase 2 (Cohort 1A): Cumulative Incidence of Mechanical Ventilation by Day 29 Based on Seronegative mFAS(by Day 29)
- Pooled Analysis Phase 3 (Cohort 1) and Phase 2 (Cohort 1A): Percentage of Participants Who Died From Day 6 Through Day 29 Based on Seronegative mFAS(Day 6 to Day 29)
- Pooled Analysis Phase 3 (Cohort 1) and Phase 2 (Cohort 1A): Percentage of Participants Who Died From Day 1 Through Day 29 Based on Seronegative mFAS(Day 1 to Day 29)
- Pooled Analysis Phase 3 (Cohort 1) and Phase 2 (Cohort 1A): Percentage of Participants Who Were Discharged by Day 29 Based on High Viral Load mFAS(by Day 29)
- Phase 3 (Cohort 1) and Phase 2 (Cohort 1A): Percentage of Participants Who Died From Day 6 Through Day 29 Based on Seronegative mFAS(Day 6 to Day 29)
- Phase 3 (Cohort 1) and Phase 2 (Cohort 1A): Percentage of Participants Who Died From Day 1 Through Day 29 Based on Seronegative mFAS(Day 1 to Day 29)
- Phase 3 (Cohort 1) and Phase 2 (Cohort 1A): Percentage of Participants Who Were Discharged by Day 29 Based on Seronegative mFAS(by Day 29)
- Phase 3 (Cohort 1) and Phase 2 (Cohort 1A): Percentage of Participants Who Died or Were Readmitted to Hospital by Day 29 Based on Seronegative mFAS(Up to Day 29)
- Phase 3 (Cohort 1) and Phase 2 (Cohort 1A): Cumulative Incidence of Death up to Day 29 Based on Seronegative mFAS(Up to Day 29)
- Phase 3 (Cohort 1) and Phase 2 (Cohort 1A): Cumulative Incidence of Mechanical Ventilation by Day 29 Based on Seronegative mFAS(by Day 29)
- Phase 3 (Cohort 1) and Phase 2 (Cohort 1A): Cumulative Incidence of Death or Mechanical Ventilation by Day 29 Based on Seronegative mFAS(by Day 29)
- Pooled Analysis Phase 3 (Cohort 1) and Phase 2 (Cohort 1A): Percentage of Participants Who Died or Were Readmitted to Hospital Over Time Based on High Viral Load mFAS(Up to Day 29)
- Pooled Analysis Phase 3 (Cohort 1) and Phase 2 (Cohort 1A): Cumulative Incidence of Death (ie, Overall Survival) by Day 29 Based on High Viral Load mFAS(by Day 29)
- Pooled Analysis Phase 3 (Cohort 1) and Phase 2 (Cohort 1A): Cumulative Incidence of Death (ie, Overall Survival) by Day 29 Based on Seronegative mFAS(by Day 29)
- Pooled Analysis (Phases 1/2/3 [Cohort 1] and Phase 2 [Cohorts 1A/2/3]): Number of Participants With Grade >=2 Infusion Related Reactions up to Day 4(Up to Day 4)
- Pooled Analysis (Phases 1/2/3 [Cohort 1] and Phase 2 [Cohorts 1A/2/3]): Number of Participants With Grade >=2 Hypersensitivity Reactions Up to Day 29(Up to Day 29)
- Phase 3 (Cohort 1) and Phase 2 (Cohort 1A): Percentage of Participants Who Went on Mechanical Ventilation by Day 29 Based on Seronegative mFAS(by Day 29)
- Pooled Analysis Phase 3 (Cohort 1) and Phase 2 (Cohort 1A): Cumulative Incidence of Death or Mechanical Ventilation by Day 29 Based on High Viral Load mFAS(by Day 29)
- Pooled Analysis (Phases 1/2/3 [Cohort 1] and Phase 2 [Cohorts 1A/2/3]): Number of Participants With Treatment-Emergent Serious Adverse Events(Up to Day 169)
- Pooled Analysis Phase 3 (Cohort 1) and Phase 2 (Cohort 1A): Cumulative Incidence of Death or Mechanical Ventilation by Day 29 Based on Seronegative mFAS(by Day 29)
- Pooled Analysis Phase 3 (Cohort 1) and Phase 2 (Cohort 1A): Time to Discharge From Hospital Based on High Viral Load mFAS(Up to Day 56)
- Pooled Analysis Phase 3 (Cohort 1) and Phase 2 (Cohort 1A): Time to Discharge From Hospital Based on Seronegative mFAS(Up to Day 56)
- Phase 3 (Cohort 1) and Phase 2 (Cohort 1A): Time to Discharge From Hospital Based on Seronegative mFAS(Up to Day 56)
- Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]: TWA Change From Baseline Viral Load (Seronegative mFAS) in NP Samples up to Day 11 Based on Seronegative mFAS(Day 1 to Day 11)
- Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]: TWA Change From Baseline Viral Load (Seronegative mFAS) in NP Samples up to Day 29(Day 1 to Day 29)
- Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]: Change From Baseline in Viral Load (Seronegative mFAS) as Measured by RT-qPCR in NP Swabs Over Time(Days 3, 5, 7, 9, 11, 13, 15, 22 and 29)
- Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]: Percent Change From Baseline in Viral Load (Seronegative mFAS) as Measured by RT-qPCR in NP Swabs Over Time(Days 3, 5, 7, 9, 11, 13, 15, 22 and 29)
- Phase 3 (Cohort 1) and Phase 2 (Cohort 1A): Percentage of Participants Who Went on Mechanical Ventilation by Day 29 Based on High Viral Load mFAS(by Day 29)
- Phase 3 (Cohort 1) and Phase 2 (Cohort 1A): Percentage of Participants Who Died From Day 6 to Day 29 Based on High Viral Load mFAS(Day 6 to Day 29)
- Phase 3 (Cohort 1) and Phase 2 (Cohort 1A): Percentage of Participants Who Died From Day 1 to Day 29 Based on High Viral Load mFAS(Day 1 to Day 29)
- Phase 3 (Cohort 1) and Phase 2 (Cohort 1A): Percentage of Participants Who Were Discharged by Day 29 Based on High Viral Load mFAS(by Day 29)
- Phase 3 (Cohort 1) and Phase 2 (Cohort 1A): Percentage of Participants Who Died or Were Readmitted to Hospital Over Time Based on High Viral Load mFAS(Up to Day 29)
- Phase 3 (Cohort 1) and Phase 2 (Cohort 1A): Cumulative Incidence of Death Over Time Based on High Viral Load mFAS(Up to Day 29)
- Phase 3 (Cohort 1) and Phase 2 (Cohort 1A): Cumulative Incidence of Mechanical Ventilation Over Time Based on High Viral Load mFAS(Up to Day 29)
- Phase 3 (Cohort 1) and Phase 2 (Cohort 1A): Cumulative Incidence of Death or Mechanical Ventilation Over Time Based on High Viral Load mFAS(Up to Day 29)
- Phase 3 (Cohort 1) and Phase 2 (Cohort 1A): Time to Discharge Based on High Viral Load mFAS(Up to Day 56)
- Phase 1 [Cohort 1] and Phase 2 [Cohort 1]): Change From Baseline as Measured by RT-qPCR in NP Swabs Over Time Based on Seronegative mFAS(Days 3, 5, 7, 9, 11, 13, 15, 22 and 29)
- Phase 1 [Cohort 1] and Phase 2 [Cohort 1]: Percentage of Participants Who Died or Went On Mechanical Ventilation by Day 29 Based on High Viral Load mFAS(Through Day 29)
- Immunogenicity as Measured by Neutralizing Antibody Status (NAb) to REGN10933(Through Day 57)
- Immunogenicity as Measured by Neutralizing Antibody Status (NAb) to REGN10987(Through Day 57)
- Phase 1 [Cohort 1] and Phase 2 [Cohort 1]): Time-weighted Average (TWA) Change in Viral Load in Nasopharyngeal (NP) Samples Over Time Based on Seronegative mFAS(Up to Day 29)
- Phase 1 [Cohort 1] and Phase 2 [Cohort 1]: Percentage of Participants Who Died or Went On Mechanical Ventilation by Day 29 Based on Seronegative mFAS(Through Day 29)
- Phase 1 [Cohort 1]: Area Under the Concentration-Time Curve From Time 0 to 28 Days Post-dose (AUC0-28)(Up to Day 28)
- Concentration at Day 28 (C28)(Day 28)
- Immunogenicity as Measured by Anti-drug Antibodies (ADAs) to REGN10933(Through Day 169)
- Concentration at the End of Infusion (Ceoi)(Day 1)
- Immunogenicity as Measured by Anti-drug Antibodies (ADAs) to REGN10987(Through Day 169)