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

Regeneron Pharmaceuticals2,252 enrolled

Overview

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

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

2,252

Conditions

COVID-19

Interventions

REGN10933+REGN10987 combination therapy

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Key Inclusion Criteria: * 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: 1. Cohort 1A: With COVID-19 symptoms but not requiring supplemental oxygen 2. Cohort 1: Maintains O2 saturation \>93% on low-flow oxygen as defined in the protocol 3. Cohort 2: High-intensity oxygen therapy without mechanical ventilation as defined in the protocol 4. Cohort 3: On mechanical ventilation Key Exclusion Criteria: * 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

Locations (123)

Regeneron Study Site

Birmingham, Alabama, United States

Regeneron Study Site

Chandler, Arizona, United States

Regeneron Study Site

Phoenix, Arizona, United States

Regeneron Study Site 1

Tucson, Arizona, United States

Regeneron Study Site

Long Beach, California, United States

Regeneron Study Site

Outcomes

Primary Outcomes

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

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.

Time frame: Day 1 to Day 7

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

Percentage of participants who died or went on mechanical ventilation from Day 6 through Day 29 based on high viral load mFAS were reported.

Time frame: Day 6 to Day 29

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

Percentage of participants who died or went on mechanical ventilation from Day 6 through Day 29 based on seronegative mFAS were reported.

Time frame: Day 6 to Day 29

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

Percentage of participants who died or went on mechanical ventilation from Day 6 through Day 29 based on overall FAS were reported.

Time frame: Day 6 to Day 29

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

Percentage of participants who died or went on mechanical ventilation from Day 1 through Day 29 based on high viral load mFAS were reported.

Time frame: Day 1 to Day 29

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

Percentage of participants who died or went on mechanical ventilation from Day 1 through Day 29 based on seronegative mFAS were reported.

Time frame: Day 1 to Day 29

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

Percentage of participants who died or went on mechanical ventilation from Day 1 through Day 29 based on overall mFAS were reported.

Time frame: Day 1 to Day 29

Pooled Analysis (Phase 1 [Cohort 1] and Phase 2 [Cohort 1]): Number of Participants With Treatment-Emergent Serious Adverse Events

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.

Time frame: Up to Day 169

Pooled Analysis (Phase 1 [Cohort 1] and Phase 2 [Cohort 1]): Number of Participants With Grade >=2 Infusion Related Reactions 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).

Time frame: Up to Day 4

Pooled Analysis (Phase 1 [Cohort 1] and Phase 2 [Cohort 1]): Number of Participants With Grade >=2 Hypersensitivity Reactions 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.

Time frame: Up to Day 29

Pooled Analysis (Phase 1 [Cohort 1] and Phase 2 [Cohort 1]): Cumulative Incidence of Death or Mechanical Ventilation Based on Seronegative mFAS

Cumulative incidence percentage was estimated using Kaplan-Meier method.

Time frame: Up to Day 29

Pooled Analysis (Phase 1 [Cohort 1] and Phase 2 [Cohort 1]): Cumulative Incidence of Death or Mechanical Ventilation Based on High Viral Load mFAS

Cumulative incidence percentage was estimated using Kaplan-Meier method.

Time frame: Up to Day 29

Secondary Outcomes

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

Percentage of participants who went on mechanical ventilation by Day 29 based on High Viral Load mFAS in pooled analysis phase 3 (Cohort 1) and phase 2 (Cohort 1A) was reported.

Time frame: 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

Percentage of participants who went on mechanical ventilation at Day 29 based on Seronegative mFAS in pooled analysis phase 3 (Cohort 1) and phase 2 (Cohort 1A) was reported.

Time frame: 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

Percentage of participants who died from Day 6 through Day 29 based on high viral load mFAS were reported.

Time frame: Day 6 to 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

Percentage of participants who died from Day 6 through Day 29 Based on seronegative mFAS in pooled analysis phase 3 (cohort 1) and phase 2 (cohort 1A) were reported.

Time frame: 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 High Viral Load mFAS

Percentage of participants who died from Day 1 through Day 29 based on High Viral Load mFAS in pooled analysis phase 3 (Cohort 1) and phase 2 (Cohort 1A) were reported.

Time frame: Day 1 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

Percentage of participants who died from Day 1 through Day 29 based on seronegative mFAS in pooled analysis phase 3 (Cohort 1) and phase 2 (Cohort 1A) were reported.

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

Percentage of participants who were discharged by Day 29 based on High Viral Load mFAS in Phase 3 (Cohort 1) and Phase 2 (Cohort 1A) were reported.

Time frame: by Day 29

Pooled Analysis Phase 3 (Cohort 1) and Phase 2 (Cohort 1A): Percentage of Participants Who Were Discharged by Day 29 Based on Seronegative mFAS

Percentage of participants who were discharged by Day 29 based on seronegative mFAS in Phase 3 (Cohort 1) and Phase 2 (Cohort 1A) were reported.

Time frame: 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

Percentage of participants who died or were readmitted to hospital over time based on High Viral Load mFAS in Phase 3 (Cohort 1) and Phase 2 (Cohort 1A)were reported. Readmission to hospital was based on investigator report.

Time frame: Up to 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

Percentage of participants who died or were readmitted to hospital at Day 29 based on seronegative mFAS in phase 3 (Cohort 1) and phase 2 (Cohort 1A) were reported. Readmission to hospital was based on investigator report.

Time frame: 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 High Viral Load mFAS

Overall Survival was defined as time interval from randomization to death. Percentage of participants with cumulative incidence of death (ie, overall survival) at Day 29 from randomization based on High Viral Load mFAS in Phase 3 (Cohort 1) and Phase 2 (Cohort 1A) were reported. Cumulative incidence percentage was estimated using Kaplan-Meier method.

Time frame: 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

Overall Survival was defined as time interval from randomization to death. Percentage of participants with cumulative incidence of death (ie, overall survival) at Day 29 from randomization based on seronegative mFAS in phase 3 (Cohort 1) and phase 2 (Cohort 1A)were reported. Cumulative incidence percentage was estimated using Kaplan-Meier method.

Time frame: 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

Number of participants with cumulative incidence of mechanical ventilation by Day 29 based on High Viral Load mFAS in Phase 3 (Cohort 1) and Phase 2 (Cohort 1A) were reported. Cumulative incidence percentage was estimated using Kaplan-Meier method.

Time frame: by 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

Percentage of participants with cumulative incidence of mechanical ventilation by Day 29 based on seronegative mFAS in phase 3 (Cohort 1) and phase 2 (Cohort 1A) were reported. Cumulative incidence percentage was estimated using Kaplan-Meier method.

Time frame: 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

Percentage of participants with cumulative incidence of death or mechanical ventilation by Day 29 based on High Viral Load mFAS in Phase 3 (Cohort 1) and Phase 2 (Cohort 1A) were reported. Cumulative incidence percentage was estimated using Kaplan-Meier method.

Time frame: 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 Seronegative mFAS

Percentage of participants with cumulative incidence of death or mechanical ventilation by Day 29 based on seronegative mFAS in phase 3 (Cohort 1) and phase 2 (Cohort 1A) were reported. Cumulative incidence percentage was estimated using Kaplan-Meier method.

Time frame: 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

Time to discharge from hospital based on High Viral Load mFAS in Phase 3 (Cohort 1) and Phase 2 (Cohort 1A) was reported.

Time frame: Up to Day 56

Pooled Analysis Phase 3 (Cohort 1) and Phase 2 (Cohort 1A): Time to Discharge From Hospital Based on Seronegative mFAS

Time to discharge from hospital based on Seronegative mFAS in Phase 3 (Cohort 1) and Phase 2 (Cohort 1A) was reported.

Time frame: Up to Day 56

Phase 3 (Cohort 1) and Phase 2 (Cohort 1A): Percentage of Participants Who Went on Mechanical Ventilation by Day 29 Based on Seronegative mFAS

Percentage of participants who went on mechanical ventilation in phase 3 (Cohort 1) and phase 2 (Cohort 1A) was reported.

Time frame: 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

Percentage of participants who died from Day 6 through Day 29 in phase 3 (cohort 1) and phase 2 (cohort 1A) were reported.

Time frame: 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

Percentage of participants who died from Day 1 through Day 29 in phase 3 (Cohort 1) and phase 2 (Cohort 1A) were reported.

Time frame: 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

Percentage of participants who were discharged in Phase 3 (Cohort 1) and Phase 2 (Cohort 1A) by Day 29 were reported.

Time frame: 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

Percentage of participants who died or were readmitted to hospital in phase 3 (Cohort 1) and phase 2 (Cohort 1A) by Day 29 were reported. Readmission to hospital was based on investigator report.

Time frame: 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

Percentage of participants with cumulative incidence of death in Phase 3 (Cohort 1) and Phase 2 (Cohort 1A) up to Day 29 from randomization were reported. Cumulative incidence percentage was estimated using Kaplan-Meier method.

Time frame: 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

Percentage of participants with cumulative incidence of mechanical ventilation in Phase 3 (Cohort 1) and Phase 2 (Cohort 1A) by Day 29 were reported. Cumulative incidence percentage was estimated using Kaplan-Meier method.

Time frame: 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

Percentage of participants with cumulative incidence of death or mechanical ventilation in Phase 3 (Cohort 1) and Phase 2 (Cohort 1A) by Day 29 were reported. Cumulative incidence percentage was estimated using Kaplan-Meier method.

Time frame: by Day 29

Phase 3 (Cohort 1) and Phase 2 (Cohort 1A): Time to Discharge From Hospital Based on Seronegative mFAS

Time to discharge from hospital up to Day 56 was reported.

Time frame: 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

TWA change from baseline in viral load up to Day 11 was calculated for each participant using the trapezoidal rule as the area under the curve for change from baseline at each time point divided by the time interval for the observation period. TWA change from baseline viral load in NP samples through Day 11, was measured by RT-qPCR in NP swab samples was reported. Baseline was defined as the last non-missing value measured prior to dosing. Negative changes indicate improvement in viral load.

Time frame: 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

TWA change from baseline in viral load up to Day 29 was calculated for each participant using the trapezoidal rule as the area under the curve for change from baseline at each time point divided by the time interval for the observation period. TWA change from baseline viral load in NP samples through Day 29, was measured by quantitative RT-qPCR in NP swab samples was reported. Baseline was defined as the last non-missing value measured prior to dosing. Negative changes indicate improvement in viral load.

Time frame: 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

Change from baseline in viral load as measured by RT-qPCR in NP swabs over time was reported. Baseline was defined as the last non-missing value measured prior to dosing. Negative changes indicates improvement in viral load.

Time frame: 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

Percent change from baseline in viral load as measured by RT-qPCR in NP swabs over time was reported. Baseline was defined as the last non-missing value measured prior to dosing. Negative changes indicates improvement in viral load.

Time frame: 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

Percentage of participants who went on mechanical ventilation in phase 3 (Cohort 1) and phase 2 (Cohort 1A) was reported.

Time frame: 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

Percentage of participants who died in phase 3 (Cohort 1) and phase 2 (Cohort 1A) was reported.

Time frame: 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

Percentage of participants who died in phase 3 (Cohort 1) and phase 2 (Cohort 1A) was reported.

Time frame: 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

Percentage of participants who were discharged in phase 3 (Cohort 1) and phase 2 (Cohort 1A) was reported.

Time frame: 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

Percentage of participants who died or were readmitted to hospital in phase 3 (Cohort 1) and phase 2 (Cohort 1A) over time were reported. Readmission to hospital was based on investigator report.

Time frame: 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

Cumulative Incidence of Death Over Time in phase 3 (Cohort 1) and phase 2 (Cohort 1A) were reported. Cumulative incidence percentage was estimated using Kaplan-Meier method.

Time frame: 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

Cumulative Incidence of Mechanical Ventilation Over Time in phase 3 (Cohort 1) and phase 2 (Cohort 1A) were reported. Cumulative incidence percentage was estimated using Kaplan-Meier method.

Time frame: 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

Cumulative Incidence of Death or Mechanical Ventilation Over Time in phase 3 (Cohort 1) and phase 2 (Cohort 1A) were reported. Cumulative incidence percentage was estimated using Kaplan-Meier method.

Time frame: Up to Day 29

Phase 3 (Cohort 1) and Phase 2 (Cohort 1A): Time to Discharge Based on High Viral Load mFAS

Time to Discharge in phase 3 (Cohort 1) and phase 2 (Cohort 1A) were reported.

Time frame: Up to Day 56

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

Time-weighted average daily change over time up to Day 29 in viral load (log10 copies/mL), as measured by reverse transcription quantitative polymerase chain reaction (RT-qPCR) in nasopharyngeal (NP) swab samples.

Time frame: Up to Day 29

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

Time frame: Days 3, 5, 7, 9, 11, 13, 15, 22 and 29