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

• ClinicalTrials.gov Identifier: NCT04425629
• Recruitment Status: Terminated
• First Posted: June 11, 2020
• Results First Posted: December 21, 2023
• Last Update Posted: December 21, 2023
• Sponsor: Regeneron Pharmaceuticals
• Information provided by (Responsible Party): Regeneron Pharmaceuticals

Tracking Information

• First Submitted Date: June 8, 2020
• First Posted Date: June 11, 2020
• Results First Submitted Date: January 20, 2023
• Results First Posted Date: December 21, 2023
• Last Update Posted Date: December 21, 2023
• Actual Study Start Date: June 16, 2020
• Actual Primary Completion Date: January 21, 2022 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: January 20, 2023)

• Number of Participants With Treatment-emergent Serious Adverse Events (SAEs) - [Ph1, Ph2, Ph3 Cohort 1 - Cohort 3] [ Time Frame: Through Day 29 ]
  Primary: Phase 1, Phase 3 (Cohort 2 and Cohort 3) Secondary: Phase 2, Phase 3 (Cohort 1)
• Number of Participants With Infusion-related Reactions (Ph1, Ph2, Ph3 Cohort 1 - Cohort 3) [ Time Frame: Through Day 4 ]
  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) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: Through Day 29 ]
  Primary: Phase 3 (Cohort 1)
• Concentration of REGN10983 + REGN10987 in Serum Over Time (Ph3 Cohort 2) [ Time Frame: Up to Nominal Sampling Day 28 ]
  Phase 3 Cohort 2 [Nominal Sampling Time] = [Clinical Study Time (Visit Day - 1)]

Original Primary Outcome Measures (submitted: June 8, 2020)

• Proportion of patients with treatment-emergent serious adverse events (SAEs) [ Time Frame: Through Day 29 ]
  Primary: Phase 1 Secondary: Phase 2, Phase 3
• Proportion of patients with infusion-related reactions [ Time Frame: Through Day 4 ]
  Primary: Phase 1 Secondary: Phase 2, Phase 3
• Proportion of patients with hypersensitivity reactions [ Time Frame: Through Day 29 ]
  Primary: Phase 1 Secondary: Phase 2, Phase 3
• Time-weighted average change from baseline in viral shedding as measured by quantitative reverse transcription quantitative polymerase chain reaction (RT-qPCR) in nasopharyngeal (NP) swab samples [ Time Frame: Baseline up to Day 22 ]
  Phase 1 only
• Time-weighted average change from baseline in viral shedding as measured by RT-qPCR in saliva samples [ Time Frame: Baseline up to Day 22 ]
  Primary: Phase 2 Secondary: Phase 1, Phase 3
• Proportion of patients with at least one COVID-19 related medically attended visit [ Time Frame: Through Day 29 ]
  Primary: Phase 3 Secondary: Phase 1, Phase 2

Current Secondary Outcome Measures (submitted: September 29, 2023)

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

Original Secondary Outcome Measures (submitted: June 8, 2020)

• Time-weighted average change from baseline in viral shedding measured by RT-qPCR in nasal swab samples [ Time Frame: Baseline up to Day 22 ]
• Time to negative RT-qPCR in all tested samples with no subsequent positive RT-qPCR in any tested samples [ Time Frame: Through Day 29 ]
• Change from baseline in Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral shedding as measured by RT-qPCR in NP swabs [ Time Frame: Baseline up to Day 29 ]
  Phase 1 only
• Change from baseline in SARS-CoV-2 viral shedding as measured by RT-qPCR in saliva samples [ Time Frame: Baseline up to Day 29 ]
• Change from baseline in SARS-CoV-2 viral shedding as measured by RT-qPCR in nasal swabs [ Time Frame: Baseline up to Day 29 ]
• Proportion of patients with at least two COVID-19 related medically attended visits [ Time Frame: Through Day 29 ]
• Total number of COVID-19 related medically-attended visits [ Time Frame: Through Day 29 ]
• Proportion of patients admitted to a hospital due to COVID-19 [ Time Frame: Through Day 29 ]
• Proportion of patients admitted to an intensive care unit (ICU) due to COVID-19 [ Time Frame: Through Day 29 ]
• Proportion of patients at least 1 outpatient or telemedicine visit due to COVID-19 [ Time Frame: Through Day 29 ]
• Proportion of patients requiring mechanical ventilation due to COVID-19 [ Time Frame: Through Day 29 ]
• Serum concentration of REGN10933 over time [ Time Frame: Through Day 29 ]
• Serum concentration of REGN10987 over time [ Time Frame: Through Day 29 ]
• Assessment of pharmacokinetic (PK) parameter: maximum serum concentration observed (Cmax) of REGN10933 [ Time Frame: Through Day 29 ]
  Phase 1 only
• Assessment of PK parameter: maximum serum concentration observed (Cmax) of REGN10987 [ Time Frame: Through Day 29 ]
  Phase 1 only
• Assessment of PK parameter: Cmax-to-dose ratio (Cmax/dose) of REGN10933 [ Time Frame: Through Day 29 ]
  Phase 1 only
• Assessment of PK parameter: Cmax-to-dose ratio (Cmax/dose) of REGN10987 [ Time Frame: Through Day 29 ]
  Phase 1 only
• Assessment of PK parameter: Time to Cmax (tmax) for REGN10933 [ Time Frame: Through Day 29 ]
  Phase 1 only
• Assessment of PK parameter: Time to Cmax (tmax) for REGN10987 [ Time Frame: Through Day 29 ]
  Phase 1 only
• Assessment of PK parameter: Area Under the Curve (AUC) computed from time zero to the time of the last positive concentration (AUClast) for REGN10933 [ Time Frame: Through Day 29 ]
  Phase 1 only
• Assessment of PK parameter: AUC computed from time zero to the time of the last positive concentration (AUClast) for REGN10987 [ Time Frame: Through Day 29 ]
  Phase 1 only
• Incidence of anti-drug antibodies (ADA) to REGN10933 [ Time Frame: Through Day 29 ]
• Incidence of anti-drug antibodies (ADA) to REGN10987 [ Time Frame: Through Day 29 ]
• Number of days of hospitalization due to COVID-19 [ Time Frame: Through Day 29 ]
  Phase 2, Phase 3
• Number of deaths due to any cause (All-Cause Mortality) [ Time Frame: Through Day 29 ]
  Phase 2, Phase 3

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Safety, Tolerability, and Efficacy of Anti-Spike (S) SARS-CoV-2 Monoclonal Antibodies for the Treatment of Ambulatory Adult and Pediatric Patients With COVID-19
• Official Title: 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

Brief Summary

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

• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3

Study Design

Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description:

Phase 1/Phase 2/Phase 3

Masking: None (Open Label)
Primary Purpose: Treatment

• Condition: COVID-19

Intervention

Drug: casirivimab+imdevimab combination therapy

Administered intravenously (IV) single dose

Other Names:

• REGN-COV2
• REGN10933
• REGN10987
• REGEN-COV™
• Ronapreve™

Study Arms

Experimental: casirivimab+imdevimab low dose

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

Intervention: Drug: casirivimab+imdevimab combination therapy

Publications *

• Hirsch C, Park YS, Piechotta V, Chai KL, Estcourt LJ, Monsef I, Salomon S, Wood EM, So-Osman C, McQuilten Z, Spinner CD, Malin JJ, Stegemann M, Skoetz N, Kreuzberger N. SARS-CoV-2-neutralising monoclonal antibodies to prevent COVID-19. Cochrane Database Syst Rev. 2022 Jun 17;6(6):CD014945. doi: 10.1002/14651858.CD014945.pub2.
• Weinreich DM, Sivapalasingam S, Norton T, Ali S, Gao H, Bhore R, Xiao J, Hooper AT, Hamilton JD, Musser BJ, Rofail D, Hussein M, Im J, Atmodjo DY, Perry C, Pan C, Mahmood A, Hosain R, Davis JD, Turner KC, Baum A, Kyratsous CA, Kim Y, Cook A, Kampman W, Roque-Guerrero L, Acloque G, Aazami H, Cannon K, Simon-Campos JA, Bocchini JA, Kowal B, DiCioccio AT, Soo Y, Geba GP, Stahl N, Lipsich L, Braunstein N, Herman G, Yancopoulos GD; Trial Investigators. REGEN-COV Antibody Combination and Outcomes in Outpatients with Covid-19. N Engl J Med. 2021 Dec 2;385(23):e81. doi: 10.1056/NEJMoa2108163. Epub 2021 Sep 29.
• Kreuzberger N, Hirsch C, Chai KL, Tomlinson E, Khosravi Z, Popp M, Neidhardt M, Piechotta V, Salomon S, Valk SJ, Monsef I, Schmaderer C, Wood EM, So-Osman C, Roberts DJ, McQuilten Z, Estcourt LJ, Skoetz N. SARS-CoV-2-neutralising monoclonal antibodies for treatment of COVID-19. Cochrane Database Syst Rev. 2021 Sep 2;9(9):CD013825. doi: 10.1002/14651858.CD013825.pub2.
• Weinreich DM, Sivapalasingam S, Norton T, Ali S, Gao H, Bhore R, Musser BJ, Soo Y, Rofail D, Im J, Perry C, Pan C, Hosain R, Mahmood A, Davis JD, Turner KC, Hooper AT, Hamilton JD, Baum A, Kyratsous CA, Kim Y, Cook A, Kampman W, Kohli A, Sachdeva Y, Graber X, Kowal B, DiCioccio T, Stahl N, Lipsich L, Braunstein N, Herman G, Yancopoulos GD; Trial Investigators. REGN-COV2, a Neutralizing Antibody Cocktail, in Outpatients with Covid-19. N Engl J Med. 2021 Jan 21;384(3):238-251. doi: 10.1056/NEJMoa2035002. Epub 2020 Dec 17.

Recruitment Information

• Recruitment Status: Terminated
• Actual Enrollment (submitted: February 10, 2022): 10078
• Original Estimated Enrollment (submitted: June 8, 2020): 1054
• Actual Study Completion Date: June 9, 2022
• Actual Primary Completion Date: January 21, 2022 (Final data collection date for primary outcome measure)

Eligibility Criteria

Key Inclusion Criteria:

• 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)

Key Exclusion Criteria:

• 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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: Child, Adult, Older Adult
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Mexico, Romania, United States
• Removed Location Countries: Chile

Administrative Information

• NCT Number: NCT04425629
• Other Study ID Numbers: R10933-10987-COV-2067; 2020-003690-21 ( EudraCT Number )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Yes
• Plan Description: All Individual Patient Data (IPD) that underlie publicly available results will be considered for sharing
• Supporting Materials: Study Protocol
• Supporting Materials: Statistical Analysis Plan (SAP)
• Supporting Materials: Informed Consent Form (ICF)
• Supporting Materials: Clinical Study Report (CSR)
• Supporting Materials: Analytic Code
• Time Frame: Individual anonymized participant data will be considered for sharing once the indication has been approved by a regulatory body, if there is legal authority to share the data and there is not a reasonable likelihood of participant re-identification
• Access Criteria: Qualified researchers may request access to anonymized patient level data or aggregate study data when Regeneron has received marketing authorization from major health authorities (e.g., Food and Drug Administration (FDA), European Medicines Agency (EMA), Pharmaceuticals and Medical Devices Agency (PMDA), etc) for the product and indication, has the legal authority to share the data, and has made the study results publicly available (eg, scientific publication, scientific conference, clinical trial registry).
• URL: https://vivli.org/

• Current Responsible Party: Regeneron Pharmaceuticals
• Original Responsible Party: Same as current
• Current Study Sponsor: Regeneron Pharmaceuticals
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Clinical Trial Management; Regeneron Pharmaceuticals

• PRS Account: Regeneron Pharmaceuticals
• Verification Date: December 2023