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临床试验/NCT04425629
NCT04425629终止3 期

A Master Protocol Assessing the Safety, Tolerability, and Efficacy of Anti-Spike (S) SARS-CoV-2 Monoclonal Antibodies for the Treatment of Ambulatory Patients With COVID-19

Regeneron Pharmaceuticals4 个研究点 分布在 2 个国家目标入组 10,078 人开始时间: 2020年6月16日最近更新:
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适应症
干预措施
相关药物

试验速览

阶段
3 期
状态
终止
入组人数
10,078
试验地点
4
主要终点
Concentration of REGN10983 + REGN10987 in Serum Over Time (Ph3 Cohort 2)
研究概览研究设计入排标准研究组 & 干预措施结局指标研究者研究点记录与标识符相似试验

研究概览

简要总结

Phase 1

  • To evaluate the safety and tolerability of REGN10933+REGN10987 compared to placebo
  • To evaluate the virologic efficacy of REGN10933+REGN10987 compared to placebo in reducing viral load of SARS-CoV-2

Phase 2

• To evaluate the virologic efficacy of REGN10933+REGN10987 compared to placebo in reducing viral load of SARS-CoV-2

Phase 3

  • Cohort 1 (≥18 Years Old, Not Pregnant at Randomization)

• To evaluate the clinical efficacy of REGN10933+REGN10987 compared to placebo as measured by COVID-19-related hospitalizations or all-cause death

  • Cohort 2 (<18 Years Old, Not Pregnant at Randomization)

  • To evaluate the safety and tolerability of REGN10933+REGN10987 compared to placebo

  • To further characterize the concentrations of REGN10933 and REGN10987 in serum over time

  • Cohort 3 (Pregnant at Randomization) • To evaluate the safety and tolerability of REGN10933+REGN10987

研究设计

研究类型
Interventional
分配方式
Na
干预模型
Single Group
主要目的
Treatment
盲法
None

入排标准

性别
All
接受健康志愿者
否

入选标准

  • •Has SARS-CoV-2-positive diagnostic test (from a sample collected ≤72 hours prior to randomization, using a validated SARS-CoV-2 antigen, RT-PCR, or other molecular diagnostic assay, and an appropriate sample such as nasopharyngeal [NP], nasal, oropharyngeal [OP], or saliva)
  • •Has symptoms consistent with COVID-19, as determined by the investigator, with onset ≤7 days before randomization
  • •Maintains O2 saturation ≥93% on room air
  • •Is able to understand and complete study-related questionnaires (patients aged ≥12 years only)

排除标准

  • •Was admitted to a hospital for COVID-19 prior to randomization, or is hospitalized (inpatient) for any reason at randomization
  • •Has participated, or is participating, in a clinical research study evaluating COVID-19 convalescent plasma, mAbs against SARS-CoV-2 (eg, bamlanivimab), or intravenous immunoglobulin (IVIG) within 3 months or within 5 half-lives of the investigational product (whichever is longer) prior to the screening visit
  • •Prior, current, or planned future use of any of the following treatments: COVID-19 convalescent plasma, mAbs against SARS-CoV-2 (eg, bamlanivimab), IVIG (any indication), systemic corticosteroids (any indication), or COVID-19 treatments (authorized, approved, or investigational)
  • •Prior use (prior to randomization), current use (at randomization) or planned use (within 90 days of study drug administration or per current CDC recommendations, as applicable) of any authorized or approved vaccine for COVID-19
  • •Has participated, is participating or plans to participate in a clinical research study evaluation any authorized, approved or investigational vaccine for COVID-19
  • •NOTE: Other Protocol defined Inclusion/Exclusion criteria apply

研究组 & 干预措施

casirivimab+imdevimab low dose

Experimental

Low dose or body-weight equivalent for those under 18 years of age.

干预措施: casirivimab+imdevimab combination therapy (Drug)

结局指标

主要结局

Concentration of REGN10983 + REGN10987 in Serum Over Time (Ph3 Cohort 2)

时间窗: Up to Nominal Sampling Day 28

Phase 3 Cohort 2 \[Nominal Sampling Time\] = \[Clinical Study Time (Visit Day - 1)\]

Number of Participants With Treatment-emergent Serious Adverse Events (SAEs) - [Ph1, Ph2, Ph3 Cohort 1 - Cohort 3]

时间窗: Through Day 29

Primary: Phase 1, Phase 3 (Cohort 2 and Cohort 3) Secondary: Phase 2, Phase 3 (Cohort 1)

Number of Participants With Hypersensitivity Reactions (Ph1, Ph2, Ph3 Cohort 1 - Cohort 3)

时间窗: Through Day 29

Primary: Phase 1, Phase 3 (Cohort 2 and Cohort 3) Secondary: Phase 2, Phase 3 (Cohort 1)

Time-weighted Average Change From Baseline in Viral Load (log10 Copies/mL) From Day 1 to Day 7, as Measured by Quantitative Reverse Transcription Quantitative Polymerase Chain Reaction (RT-qPCR) in Nasopharyngeal (NP) Swab Samples (Ph1, Ph2)

时间窗: Baseline up to Day 7

Primary: Phase 1, Phase 2

Proportion of Participants With at Least One (≥1) COVID-19-related Hospitalization or All-cause Death (Ph3 Cohort 1- 1.2g vs Placebo)

时间窗: Through Day 29

Phase 3 Cohort 1

Proportion of Participants With at Least One (≥1) COVID-19-related Hospitalization or All-cause Death (Ph3 Cohort 1 - 2.4g vs Placebo)

时间窗: Through Day 29

Primary: Phase 3 (Cohort 1)

Number of Participants With Infusion-related Reactions (Ph1, Ph2, Ph3 Cohort 1 - Cohort 3)

时间窗: Through Day 4

Primary: Phase 1, Phase 3 (Cohort 2 and Cohort 3) Secondary: Phase 2, Phase 3 (Cohort 1)

次要结局

  • Concentration of REGN10933 + REGN10987 in Serum Over Time (Ph1 Cohort 1, Ph2 Cohort 1, Ph3 Cohort 1 and Cohort 3)(Up to Nominal Sampling Day 28)
  • Assessment of Pharmacokinetic (PK) Parameter: Maximum Serum Concentration Observed (Cmax) of REGN10933+REGN10987 (Phase 1)(Through Day 29)
  • Assessment of PK Parameter: Time to Cmax (Tmax) for REGN10933+REGN10987 (Phase 1)(Through Day 29)
  • Assessment of PK Parameter: Area Under the Curve (AUC) Computed From Time Zero to Day 28 Concentration (AUC 0-28) for REGN10933+REGN10987 (Phase 1)(Through Day 29)
  • Immunogenicity as Measured by Anti-drug (ADA) to REGN10933 (Ph1 Cohort 1, Ph2 Cohort 1, Ph3 Cohort 1)(Through Day 29)
  • Immunogenicity as Measured by Anti-drug (ADA) to REGN10933 (Ph3 Cohort 2 - Cohort 3)(Through Day 29)
  • Immunogenicity as Measured by ADA to REGN10987 (Ph1 Cohort 1, Ph2 Cohort 1, Ph3 Cohort 1)(Through Day 29)
  • Immunogenicity as Measured by ADA to REGN10987 (Ph3 Cohort 2 and Cohort 3)(Through Day 29)
  • Percentage of Participants With ≥1 COVID-19-related Medically-attended Visit Through Day 29 (Ph1, Ph2)(Through Day 29)
  • Percentage of Participants With ≥1 COVID-19 Related Hospitalization, Emergency Room, or Urgent Care Visit Through Day 29 (Ph1, Ph2)(Through Day 29)
  • Time to COVID-19 Symptoms Resolution (Ph3 Cohort 1 - 1.2g vs Placebo)(Up to Day 29)
  • Time to COVID-19 Symptoms Resolution (Ph3 Cohort 1 - 2.4g vs Placebo)(Through Day 29)
  • Time to First Onset of Symptoms Consistent With COVID-19 (Phase 2 Asymptomatic Cohort Only)(Through Day 29)
  • Proportion of Participants With ≥1 COVID-19-related Hospitalization or All-cause Death From Day 4 Through Day 29 (Ph3 Cohort 1 - 1.2g vs. Placebo)(Day 4 thru Day 29)
  • Proportion of Participants With ≥1 COVID-19-related Hospitalization or All-cause Death From Day 4 Through Day 29 (Ph3 Cohort 1 - 2.4g vs. Placebo)(From Day 4 Through Day 29)
  • Change From Baseline in Viral Load at Each Visit, as Measured by RT-qPCR in Nasopharyngeal Swabs (Next Phase 2 Cohort)(Day 5, Day 7, Day 15, Day 29)
  • Time-weighted Average Change From Baseline in Viral Load (log10 Copies/mL) From Day 1 to Post-baseline Study Days (Ph1, Ph2)(Day 1 to Day 29)
  • Proportion of Participants With ≥1 COVID-19-related Hospitalization, Emergency Room Visit, or All-cause Death (Ph3 Cohort 1) - Placebo vs. 1.2g IV(Through Day 29)
  • Proportion of Participants With ≥1 COVID-19-related Hospitalization, Emergency Room Visit, or All-cause Death (Ph3 Cohort 1) - Placebo vs. 2.4g IV(Through day 29)
  • Proportion of Participants With at Least One (≥1) COVID-19-related Hospitalization or All-cause Death From Day 4 Through Day 29 (Ph3 Cohort 1- 1.2g vs Placebo)(Day 4 Through Day 29)
  • Immunogenicity as Measured by Neutralizing Antibodies (NAbs) to REGN10933 (Ph3 Cohort 2, Ph3 Cohort 3)(Through Day 29)
  • Immunogenicity as Measured by NAbs to REGN10987 (Ph3 Cohort 2 - Cohort 3)(Through Day 29)
  • Number of Participants With at Least One (≥1) COVID-19-related Hospitalization or All-cause Death (Phase 3 Cohort 2)(Through Day 29)
  • Percentage of Participants With ≥1 COVID-19-related Medically-attended Visit (Phase 1, Phase 2)(Through Day 29)
  • Percentage of Participants With ≥2 COVID-19-related Medically-attended Visit - (Ph3 Cohort 1) - Placebo vs. 1.2g IV(Through Day 29)
  • Percentage of Participants With ≥2 COVID-19-related Medically-attended Visit - (Ph3 Cohort 1) - Placebo vs. 2.4g IV(Through Day 29)
  • Total Number of COVID-19-related Medically-attended Visits (Phase 1 and Phase 2)(Through Day 29)
  • Assessment of Pharmacokinetic (PK) Parameter: Maximum Serum Concentration Observed (Cmax) of REGN10933 and REGN10987 (Phase 1 Only)(Through Day 29)
  • Assessment of PK Parameter: Cmax-to-dose Ratio (Cmax/Dose) of REGN10933 and REGN10987 (Phase 1 Only)(Though Day 29)
  • Assessment of PK Parameter: Time to Cmax (Tmax) for REGN10933 and REGN10987 (Phase 1 Only)(Through Day 29)
  • Assessment of PK Parameter: Area Under the Curve (AUC) Computed From Time Zero to the Time of the Last Positive Concentration (AUClast) for REGN10933 - (Phase 1 Only)(Through Day 29)
  • Number of Days of Hospitalization Due to COVID-19 (Phase 2 Asymptomatic)(Up to Day 29)
  • Proportion of Participants With at Least One (≥1) COVID-19-related Hospitalization or All-cause Death From Day 4 Through Day 29 (Ph3 Cohort 1- 2.4g vs Placebo)(Day 4 Through Day 29)
  • Number of Days of Hospitalization Due to COVID-19 (Ph3 Cohort 1) Placebo vs. 1.2g IV(Through Day 29)
  • Proportion of Participants With at Least One (≥1) COVID-19-related Medically-attended Visit or All-cause Death Through Day 29 (Ph3 Cohort 1- 1.2g vs Placebo)(Through Day 29)
  • Proportion of Participants With at Least One (≥1) COVID-19-related Medically-attended Visit or All-cause Death Through Day 29 (Ph3 Cohort 1- 2.4g vs Placebo)(Through Day 29)
  • Number of Participants With at Least One (≥1) COVID-19-related Medically-attended Visit or All-cause Death Through Day 29 (Phase 3 Cohort 2)(Through Day 29)
  • Proportion of Participants With at Least One (≥1) COVID-19-related Medically-attended Visit by Type of Visit Through Day 29 (Ph3 Cohort 1- 1.2g vs Placebo)(Through Day 29)
  • Proportion of Participants With at Least One (≥1) COVID-19-related Medically-attended Visit by Type of Visit Through Day 29 (Ph3 Cohort 1- 2.4g vs Placebo)(Through Day 29)
  • Total Number of COVID-19-related Medically-attended Visits by Type of Visit Through Day 29 (Phase 3 Cohort 2)(Through Day 29)
  • Cumulative Incidence Percentage of Patients With COVID-19-related Hospitalization or All-cause Death Through Day 29 (Ph3 Cohort 1- 1.2g vs Placebo)(Through Day 29)
  • Cumulative Incidence Percentage of Patients With COVID-19-related Hospitalization or All-cause Death Through Day 29 (Ph3 Cohort 1- 2.4g vs Placebo)(Through Day 29)
  • Cumulative Incidence Percentage of Patients With COVID-19-related Hospitalization, Emergency Room (ER) or All-cause Death Through Day 29 (Ph3 Cohort 1- 1.2g vs Placebo)(Through Day 29)
  • Cumulative Incidence Percentage of Patients With COVID-19-related Hospitalization, Emergency Room (ER) or All-cause Death Through Day 29 (Ph3 Cohort 1- 2.4g vs Placebo)(Through Day 29)
  • Cumulative Incidence Percentage of Patients With COVID-19-related Medically-attended Visit or All-cause Death Through Day 29 (Ph3 Cohort 1- 1.2g vs Placebo)(Through Day 29)
  • Cumulative Incidence Percentage of Patients With COVID-19-related Medically-attended Visit or All-cause Death Through Day 29 (Ph3 Cohort 1- 2.4g vs Placebo)(Through Day 29)
  • Proportion of Participants Requiring Supplemental Oxygen Due to COVID-19 by Day 29 (Ph3 Cohort 1- 1.2g vs Placebo)(Through Day 29)
  • Proportion of Participants Requiring Supplemental Oxygen Due to COVID-19 by Day 29 (Ph3 Cohort 1- 2.4g vs Placebo)(Through Day 29)
  • Percentage of Participants With All-Cause Death (Ph3 Cohort 1) Placebo vs. 1.2g(by Day 29, Day 120, and Day 169)
  • Percentage of Participants With All-Cause Death (Ph3 Cohort 1) Placebo vs. 2.4g(by Day 29, Day 120, and Day 169)
  • Correlation of RT-qPCR Results Over Time Between Different Sample Types (NP, Nasal, and Saliva) - (Phase 1 Only)(Up to Day 29)
  • Change From Baseline in Viral Load at Each Visit, as Measured by RT-qPCR in Nasal Swabs - (Phase 1 Only)(Baseline Up To Day 29)
  • Change From Baseline in Viral Load at Each Visit, as Measured by RT-qPCR in Saliva Samples - (Phase 1 Only)(Baseline Up to Day 29)
  • Concordance of RT-qPCR Results Over Time Between Different Sample Types (NP, Nasal, and Saliva) - (Phase 1 Only)(Up To Day 29)
  • Proportion of Participants With High Viral Load at Each Visit - (Phase 2 Only)(Through Day 29)
  • Number of Days of Hospitalization Due to COVID-19 (Ph3 Cohort 1) Placebo vs. 2.4g IV(Through Day 29)
  • Time-weighted Average Change From Baseline in Viral Load (log10 Copies/mL), as Measured by RT-qPCR in Saliva Samples - (Phase 1)(Baseline up to Day 22)
  • Number of Days of Hospitalization Due to COVID-19 (Ph3 Cohort 2)(Through Day 29)
  • Number of Participants With Viral Loads Below the Limit of Detection at Each Visit - (Phase 2 Only)(Through Day 29)
  • Duration of Symptoms Consistent With COVID-19 (Phase 2 Only)(Through Day 29)
  • Number of Participants Admitted to a Hospital Due to COVID-19 (Phase 1, Phase 2)(Through Day 29)
  • Time to Negative RT-qPCR in All Tested Samples With no Subsequent Positive RT-qPCR in Any Tested Samples - (Phase 1 Only)(Through Day 29)
  • Proportion of Participants With All-cause Mortality (Phase 2 Asymptomatic)(Through Day 29)
  • Time to All-cause Death (Ph3 Cohort 1- 1.2g vs Placebo)(Through Day 169)
  • Time to All-cause Death (Ph3 Cohort 1- 2.4g vs Placebo)(Through Day 169)
  • Time to All-cause Death (Phase 3 Cohort 2)(Through Day 29)
  • Proportion of Participants Requiring Mechanical Ventilation Due to COVID-19 (Ph3 Cohort 1- 1.2g vs Placebo)(Through Day 29)
  • Proportion of Participants Requiring Mechanical Ventilation Due to COVID-19 (Ph3 Cohort 1- 2.4g vs Placebo)(Through Day 29)
  • Proportion of Participants Requiring Mechanical Ventilation Due to COVID-19 (Phase 3 Cohort 2)(Through Day 29)
  • Change From Baseline in Viral Load at Each Visit, as Measured by RT-qPCR in Nasopharyngeal Swabs - (Phase 3 Cohort 1 - 1.2g vs. Placebo)(Baseline up to Day 29)
  • Change From Baseline in Viral Load at Each Visit, as Measured by RT-qPCR in Nasopharyngeal Swabs - (Phase 3 Cohort 1 - 2.4g vs. Placebo)(Baseline up to Day 29)
  • Change From Baseline in Viral Load at Each Visit, as Measured by RT-qPCR in Nasopharyngeal Swabs - (Phase 3 Cohort 2)(Baseline up to Day 29)
  • Time-weighted Average Change From Baseline in Viral Load (log10 Copies/mL), as Measured by Quantitative Reverse Transcription Quantitative Polymerase Chain Reaction (RT-qPCR) in Nasopharyngeal (NP) Swab Samples (Ph3 Cohort 1)(Baseline to Day 7)
  • Time-weighted Average Change From Baseline in Viral Load (log10 Copies/mL), as Measured by Quantitative Reverse Transcription Quantitative Polymerase Chain Reaction (RT-qPCR) in Nasopharyngeal (NP) Swab Samples (Ph3 Cohort 2)(Baseline to Day 7)
  • Proportion of Participants With Viral Loads Below the Lower Limit of Detection at Each Visit - (Phase 2 Only)(Day 0, Day 5, Day 7, Day 15, Day 29)
  • Proportion of Participants With Viral Loads Below the Lower Limit of Quantitation at Each Visit - (Phase 2 Only)(Day 0, Day 5, Day 7, Day 15, Day 29)
  • Proportion of Participants Admitted to an Intensive Care Unit (ICU) Due to COVID-19 - (Ph 3 Cohort 1) Placebo vs. 1.2g IV(Through Day 29)
  • Percentage of Participants Admitted to an Intensive Care Unit (ICU) Due to COVID-19 - (Ph 3 Cohort 1) Placebo vs. 2.4g IV(Through Day 29)
  • Proportion of Participants Admitted to an Intensive Care Unit (ICU) Due to COVID-19 - (Ph 3 Cohort 2)(Through Day 29)
  • Proportion of Participants Admitted to an Intensive Care Unit (ICU) Due to COVID-19 - (Next Phase 2) #87(Through Day 29)
  • Total Number of COVID-19-related Medically-attended Visits (Phase 3 Cohort 1) Placebo vs. 1.2g(Through Day 29)
  • Total Number of COVID-19-related Medically-attended Visits (Phase 3 Cohort 1) Placebo vs. 2.4g(Through Day 29)
  • Total Number of COVID-19-related Medically-attended Visits (Phase 3 Cohort 2)(Through Day 29)

研究者

申办方类型
Industry
责任方
Sponsor

研究点 (4)

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