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

COVID-19 Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT04425629
• Other study ID #: R10933-10987-COV-2067
• Secondary ID: 2020-003690-21
• Status: Terminated
• Phase: Phase 3
• Start date: June 16, 2020
• Est. completion date: June 9, 2022

Study information

• Verified date: December 2023
• Source: Regeneron Pharmaceuticals
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 10078
• Est. completion date: June 9, 2022
• Est. primary completion date: January 21, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A and older

Eligibility

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

Related Conditions & MeSH terms

• COVID-19

Intervention

Drug:
• casirivimab+imdevimab combination therapy
Administered intravenously (IV) single dose

Locations

Country	Name	City	State
Mexico	Regeneron Study Site	Chihuahua
Mexico	Regeneron Study Site	Ciudad de Mexico
Mexico	Regeneron Study Site	Durango
Mexico	Regeneron Study Site	Guadalajara	Jalisco
Mexico	Regeneron Study Site	Guadalajara	Jalisco
Mexico	Regeneron Study Site	Merida	Yucatan
Mexico	Regeneron Study Site	Mérida
Mexico	Regeneron Study Site	Monterrey	Nuevo Leon
Mexico	Regeneron Study Site	Monterrey	Nuevo León
Mexico	Regeneron Study Site	Veracruz
Mexico	Regeneron Study Site	Zapopan	Jalisco
Romania	Regeneron Study Site	Bucuresti
United States	Regeneron Study Site	Amarillo	Texas
United States	Regeneron Study Site	Ames	Iowa
United States	Regeneron Study Site	Atlanta	Georgia
United States	Regeneron Study Site	Atlanta	Georgia
United States	Regeneron Study Site	Augusta	Georgia
United States	Regeneron Study Site	Aurora	Colorado
United States	Regeneron Study Site	Baltimore	Maryland
United States	Regeneron Study Site	Boca Raton	Florida
United States	Regeneron Study Site	Bronx	New York
United States	Regeneron Study Site	Bronx	New York
United States	Regeneron Study Site	Canoga Park	California
United States	Regeneron Study Site	Charleston	South Carolina
United States	Regeneron Study Site	Charlotte	North Carolina
United States	Regeneron Study Site	Chicago	Illinois
United States	Regeneron Study Site	Clinton	South Carolina
United States	Regeneron Study Site	Colorado Springs	Colorado
United States	Regeneron Study Site	Columbus	Georgia
United States	Regeneron Study Site	Columbus	Ohio
United States	Regeneron Study Site	Corpus Christi	Texas
United States	Regeneron Study Site	Dallas	Texas
United States	Regeneron Study Site	Dallas	Texas
United States	Regeneron Study Site	Dayton	Ohio
United States	Regeneron Study Site	Dayton	Ohio
United States	Regeneron Study Site	DeLand	Florida
United States	Regeneron Study Site	Downers Grove	Illinois
United States	Regeneron Study Site 1	Downers Grove	Illinois
United States	Regeneron Study Site 2	Downers Grove	Illinois
United States	Regeneron Study Site	Durham	North Carolina
United States	Regeneron Study Site	Everett	Washington
United States	Regeneron Study Site	Falls Church	Virginia
United States	Regeneron Study Site	Fort Pierce	Florida
United States	Regeneron Study Site	Hialeah	Florida
United States	Regeneron Study Site	Houston	Texas
United States	Regeneron Study Site	Houston	Texas
United States	Regeneron Study Site	Houston	Texas
United States	Regeneron Study Site	Houston	Texas
United States	Regeneron Study Site	Houston	Texas
United States	Regeneron Study Site	Houston	Texas
United States	Regeneron Study Site	Iowa City	Iowa
United States	Regeneron Study Site	Jackson	Mississippi
United States	Regeneron Study Site	Jamaica	New York
United States	Regeneron Study Site	La Mesa	California
United States	Regeneron Study Site	La Palma	California
United States	Regeneron Study Site	Lake Charles	Louisiana
United States	Regeneron Study Site	Las Vegas	Nevada
United States	Regeneron Study Site 1	Long Beach	California
United States	Regeneron Study Site 2	Long Beach	California
United States	Regeneron Study Site 3	Long Beach	California
United States	Regeneron Study Site	Los Angeles	California
United States	Regeneron Study Site	Loxahatchee Groves	Florida
United States	Regeneron Study Site	Madison	Wisconsin
United States	Regeneron Study Site	Maitland	Florida
United States	Regeneron Study Site	Marietta	Georgia
United States	Regeneron Study Site	Marrero	Louisiana
United States	Regeneron Study Site	Memphis	Tennessee
United States	Regeneron Study Site 2	Memphis	Tennessee
United States	Regeneron Study Site	Mesa	Arizona
United States	Regeneron Study Site	Miami	Florida
United States	Regeneron Study Site	Miami	Florida
United States	Regeneron Study Site	Miami	Florida
United States	Regeneron Study Site	Miami	Florida
United States	Regeneron Study Site 1	Miami	Florida
United States	Regeneron Study Site 2	Miami	Florida
United States	Regeneron Study Site	Montclair	California
United States	Regeneron Study Site	New Orleans	Louisiana
United States	Regeneron Study Site	New York	New York
United States	Regeneron Study Site	New York	New York
United States	Regeneron Study Site	New York	New York
United States	Regeneron Study Site	New York	New York
United States	Regeneron Study Site	New York	New York
United States	Regeneron Study Site	New York	New York
United States	Regeneron Study Site	Pearland	Texas
United States	Regeneron Study Site	Philadelphia	Pennsylvania
United States	Regeneron Study Site	Providence	Rhode Island
United States	Regeneron Study Site	Red Oak	Texas
United States	Regeneron Study Site	Ridgewood	New Jersey
United States	Regeneron Study Site	Rolling Hills Estates	California
United States	Regeneron Study Site	Royal Oak	Michigan
United States	Regeneron Study Site	Sacramento	California
United States	Regeneron Study Site	Saint Petersburg	Florida
United States	Regeneron Study Site	San Antonio	Texas
United States	Regeneron Study Site	San Antonio	Texas
United States	Regeneron Study Site	San Antonio	Texas
United States	Regeneron Study Site	San Francisco	California
United States	Regeneron Study Site	Santa Fe	New Mexico
United States	Regeneron Study Site	Santa Monica	California
United States	Regeneron Study Site	Sarasota	Florida
United States	Regeneron Study Site	Seattle	Washington
United States	Regeneron Study Site	Seattle	Washington
United States	Regeneron Study Site	Shreveport	Louisiana
United States	Regeneron Study Site	Sioux Falls	South Dakota
United States	Regeneron Study Site	Stanford	California
United States	Regeneron Study Site	Tampa	Florida
United States	Regeneron Study Site	Teaneck	New Jersey
United States	Regeneron Study Site	Tucson	Arizona
United States	Regeneron Study Site	Tucson	Arizona
United States	Regeneron Study Site	Tyler	Texas
United States	Regeneron Study Site	Washington	District of Columbia
United States	Regeneron Study Site	West Palm Beach	Florida
United States	Regeneron Study Site	Wilmington	North Carolina
United States	Regeneron Study Site	Winter Haven	Florida
United States	Regeneron Study Site	Winter Park	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Regeneron Pharmaceuticals

Countries where clinical trial is conducted

United States,  Mexico,  Romania, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants With Treatment-emergent Serious Adverse Events (SAEs) - [Ph1, Ph2, Ph3 Cohort 1 - Cohort 3]	Primary: Phase 1, Phase 3 (Cohort 2 and Cohort 3); Secondary: Phase 2, Phase 3 (Cohort 1)	Through Day 29
Primary	Number of Participants With Infusion-related Reactions (Ph1, Ph2, Ph3 Cohort 1 - Cohort 3)	Primary: Phase 1, Phase 3 (Cohort 2 and Cohort 3); Secondary: Phase 2, Phase 3 (Cohort 1)	Through Day 4
Primary	Number of Participants With Hypersensitivity Reactions (Ph1, Ph2, Ph3 Cohort 1 - Cohort 3)	Primary: Phase 1, Phase 3 (Cohort 2 and Cohort 3); Secondary: Phase 2, Phase 3 (Cohort 1)	Through Day 29
Primary	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)	Primary: Phase 1, Phase 2	Baseline up to Day 7
Primary	Proportion of Participants With at Least One (=1) COVID-19-related Hospitalization or All-cause Death (Ph3 Cohort 1- 1.2g vs Placebo)	Phase 3 Cohort 1	Through Day 29
Primary	Proportion of Participants With at Least One (=1) COVID-19-related Hospitalization or All-cause Death (Ph3 Cohort 1 - 2.4g vs Placebo)	Primary: Phase 3 (Cohort 1)	Through Day 29
Primary	Concentration of REGN10983 + REGN10987 in Serum Over Time (Ph3 Cohort 2)	Phase 3 Cohort 2; [Nominal Sampling Time] = [Clinical Study Time (Visit Day - 1)]	Up to Nominal Sampling Day 28
Secondary	Time to COVID-19 Symptoms Resolution (Ph3 Cohort 1 - 1.2g vs Placebo)	Phase 3 Cohort 1	Up to Day 29
Secondary	Time to COVID-19 Symptoms Resolution (Ph3 Cohort 1 - 2.4g vs Placebo)	Phase 3 (Cohort 1)	Through Day 29
Secondary	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)	Phase 3 (Cohort 1)	Day 4 thru Day 29
Secondary	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)	Phase 3 (Cohort 1)	From Day 4 Through Day 29
Secondary	Change From Baseline in Viral Load at Each Visit, as Measured by RT-qPCR in Nasopharyngeal Swabs (Next Phase 2 Cohort)	Next Phase 2 Symptomatic	Day 5, Day 7, Day 15, Day 29
Secondary	Time-weighted Average Change From Baseline in Viral Load (log10 Copies/mL) From Day 1 to Post-baseline Study Days (Ph1, Ph2)	Phase 1, Phase 2	Day 1 to Day 29
Secondary	Percentage of Participants With =1 COVID-19-related Medically-attended Visit Through Day 29 (Ph1, Ph2)	Phase 1, Phase 2	Through Day 29
Secondary	Percentage of Participants With =1 COVID-19 Related Hospitalization, Emergency Room, or Urgent Care Visit Through Day 29 (Ph1, Ph2)	Phase 1, Phase 2	Through Day 29
Secondary	Time to First Onset of Symptoms Consistent With COVID-19 (Phase 2 Asymptomatic Cohort Only)	Phase 2 Only	Up to Day 29
Secondary	Proportion of Participants With =1 COVID-19-related Hospitalization, Emergency Room Visit, or All-cause Death (Ph3 Cohort 1) - Placebo vs. 1.2g IV	Phase 3 Cohort 1 - Placebo vs. 1.2 g IV	Through Day 29
Secondary	Proportion of Participants With =1 COVID-19-related Hospitalization, Emergency Room Visit, or All-cause Death (Ph3 Cohort 1) - Placebo vs. 2.4g IV	Phase 3 (Cohort 1)	Through day 29
Secondary	Concentration of REGN10933 + REGN10987 in Serum Over Time (Ph1 Cohort 1, Ph2 Cohort 1, Ph3 Cohort 1 and Cohort 3)	Secondary: Phase 1, Phase 2, Phase 3 (Cohort 1 and Cohort 3) - Symptomatic Participants; [Nominal Sampling Time] = [Clinical Study Time (Visit Day - 1)]	Up to Nominal Sampling Day 28
Secondary	Assessment of Pharmacokinetic (PK) Parameter: Maximum Serum Concentration Observed (Cmax) of REGN10933+REGN10987 (Phase 1)	Phase 1 Only	Through Day 29
Secondary	Assessment of PK Parameter: Time to Cmax (Tmax) for REGN10933+REGN10987 (Phase 1)	Phase 1 Only	Through Day 29
Secondary	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)	Phase 1 Only	Through Day 29
Secondary	Immunogenicity as Measured by Anti-drug (ADA) to REGN10933 (Ph1 Cohort 1, Ph2 Cohort 1, Ph3 Cohort 1)	Phase 1, Phase 2, Phase 3 (Cohort 1) - Pooled Symptomatic Participants	Through Day 29
Secondary	Immunogenicity as Measured by Anti-drug (ADA) to REGN10933 (Ph3 Cohort 2 - Cohort 3)	Symptomatic Participants Phase 3 Cohort 2 Participants Phase 3 Cohort 3 Participants	Through Day 29
Secondary	Immunogenicity as Measured by ADA to REGN10987 (Ph1 Cohort 1, Ph2 Cohort 1, Ph3 Cohort 1)	Phase 1, Phase 2, Phase 3 (Cohort 1) - Pooled Symptomatic Participants	Through Day 29
Secondary	Immunogenicity as Measured by ADA to REGN10987 (Ph3 Cohort 2 and Cohort 3)	Symptomatic Participants Phase 3 Cohort 2 Participants Phase 3 Cohort 3 Participants	Through Day 29
Secondary	Immunogenicity as Measured by Neutralizing Antibodies (NAbs) to REGN10933 (Ph3 Cohort 2, Ph3 Cohort 3)	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	Through Day 29
Secondary	Immunogenicity as Measured by NAbs to REGN10987 (Ph3 Cohort 2 - Cohort 3)	Phase 3 Cohort 2 Participants Phase 3 Cohort 3 Participants; (TE&TB+;NAb+) = TE = Treatment-emergent; TB = Treatment-boosted; NAb+ = Positive in NAb assay	Through Day 29
Secondary	Number of Participants With at Least One (=1) COVID-19-related Hospitalization or All-cause Death (Phase 3 Cohort 2)	Phase 3 (Cohort 2)	Through Day 29
Secondary	Percentage of Participants With =1 COVID-19-related Medically-attended Visit (Phase 1, Phase 2)	Phase 1, Phase 2 Medically-attended Visits include Hospitalizations, ER visits, Urgent Care Clinic visits, Outpatient/physician office/telemedicine visits	Through Day 29
Secondary	Percentage of Participants With =2 COVID-19-related Medically-attended Visit - (Ph3 Cohort 1) - Placebo vs. 1.2g IV	Phase 3 (Cohort 1)	Through Day 29
Secondary	Percentage of Participants With =2 COVID-19-related Medically-attended Visit - (Ph3 Cohort 1) - Placebo vs. 2.4g IV	Phase 3 Cohort 1	Through Day 29
Secondary	Total Number of COVID-19-related Medically-attended Visits (Phase 1 and Phase 2)	Phase 1 and Phase 2	Through Day 29
Secondary	Assessment of Pharmacokinetic (PK) Parameter: Maximum Serum Concentration Observed (Cmax) of REGN10933 and REGN10987 (Phase 1 Only)	Phase 1 Only	Through Day 29
Secondary	Assessment of PK Parameter: Cmax-to-dose Ratio (Cmax/Dose) of REGN10933 and REGN10987 (Phase 1 Only)	Phase 1 Only	Though Day 29
Secondary	Assessment of PK Parameter: Time to Cmax (Tmax) for REGN10933 and REGN10987 (Phase 1 Only)	Phase 1 Only	Through Day 29
Secondary	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)	Phase 1 Only - Tlast (Time of last quantifiable concentration)	Through Day 29
Secondary	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)	Phase 3 Cohort 1	Day 4 Through Day 29
Secondary	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)	Phase 3 Cohort 1	Day 4 Through Day 29
Secondary	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)	Phase 3 Cohort 1	Through Day 29
Secondary	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)	Phase 3 Cohort 1	Through Day 29
Secondary	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)	Phase 3 (Cohort 2)	Through Day 29
Secondary	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)	Phase 3 Cohort 1	Through Day 29
Secondary	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)	Phase 3 Cohort 1	Through Day 29
Secondary	Total Number of COVID-19-related Medically-attended Visits by Type of Visit Through Day 29 (Phase 3 Cohort 2)	Phase 3 (Cohort 2)	Through Day 29
Secondary	Cumulative Incidence Percentage of Patients With COVID-19-related Hospitalization or All-cause Death Through Day 29 (Ph3 Cohort 1- 1.2g vs Placebo)	Phase 3 Cohort 1	Through Day 29
Secondary	Cumulative Incidence Percentage of Patients With COVID-19-related Hospitalization or All-cause Death Through Day 29 (Ph3 Cohort 1- 2.4g vs Placebo)	Phase 3 Cohort 1	Through Day 29
Secondary	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)	Phase 3 Cohort 1	Through Day 29
Secondary	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)	Phase 3 Cohort 1	Through Day 29
Secondary	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)	Phase 3 Cohort 1	Through Day 29
Secondary	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)	Phase 3 Cohort 1	Through Day 29
Secondary	Proportion of Participants Requiring Supplemental Oxygen Due to COVID-19 by Day 29 (Ph3 Cohort 1- 1.2g vs Placebo)	Phase 3 Cohort 1	Through Day 29
Secondary	Proportion of Participants Requiring Supplemental Oxygen Due to COVID-19 by Day 29 (Ph3 Cohort 1- 2.4g vs Placebo)	Phase 3 Cohort 1	Through Day 29
Secondary	Percentage of Participants With All-Cause Death (Ph3 Cohort 1) Placebo vs. 1.2g	Phase 3 Cohort 1	by Day 29, Day 120, and Day 169
Secondary	Percentage of Participants With All-Cause Death (Ph3 Cohort 1) Placebo vs. 2.4g	Phase 3 Cohort 1 Placebo vs. 2.4g IV	by Day 29, Day 120, and Day 169
Secondary	Proportion of Participants With High Viral Load at Each Visit - (Phase 2 Only)	Next Phase 2 Only	Through Day 29
Secondary	Correlation of RT-qPCR Results Over Time Between Different Sample Types (NP, Nasal, and Saliva) - (Phase 1 Only)	Phase 1 Only	Up to Day 29
Secondary	Change From Baseline in Viral Load at Each Visit, as Measured by RT-qPCR in Nasal Swabs - (Phase 1 Only)	Phase 1 Only	Baseline Up To Day 29
Secondary	Change From Baseline in Viral Load at Each Visit, as Measured by RT-qPCR in Saliva Samples - (Phase 1 Only)	Phase 1 Only	Baseline Up to Day 29
Secondary	Concordance of RT-qPCR Results Over Time Between Different Sample Types (NP, Nasal, and Saliva) - (Phase 1 Only)	Phase 1 Only	Up To Day 29
Secondary	Time-weighted Average Change From Baseline in Viral Load (log10 Copies/mL), as Measured by RT-qPCR in Saliva Samples - (Phase 1)	Phase 1 Only	Baseline up to Day 22
Secondary	Number of Participants With Viral Loads Below the Limit of Detection at Each Visit - (Phase 2 Only)	Phase 2 Only	Through Day 29
Secondary	Duration of Symptoms Consistent With COVID-19 (Phase 2 Only)	Phase 2 Only	Through Day 29
Secondary	Time to First Onset of Symptoms Consistent With COVID-19 (Phase 2 Asymptomatic Cohort Only)	Phase 2 Only	Through Day 29
Secondary	Number of Participants Admitted to a Hospital Due to COVID-19 (Phase 1, Phase 2)	Phase 1, Phase 2	Through Day 29
Secondary	Time to Negative RT-qPCR in All Tested Samples With no Subsequent Positive RT-qPCR in Any Tested Samples - (Phase 1 Only)	Phase 1 Only	Through Day 29
Secondary	Proportion of Participants With All-cause Mortality (Phase 2 Asymptomatic)	Phase 2 Asymptomatic	Through Day 29
Secondary	Time to All-cause Death (Ph3 Cohort 1- 1.2g vs Placebo)	Phase 3 Cohort 1 (1.2g IV)	Through Day 169
Secondary	Time to All-cause Death (Ph3 Cohort 1- 2.4g vs Placebo)	Phase 3 Cohort 1 (2.4g IV)	Through Day 169
Secondary	Time to All-cause Death (Phase 3 Cohort 2)	Phase 3 (Cohort 2)	Through Day 29
Secondary	Proportion of Participants Requiring Mechanical Ventilation Due to COVID-19 (Ph3 Cohort 1- 1.2g vs Placebo)		Through Day 29
Secondary	Proportion of Participants Requiring Mechanical Ventilation Due to COVID-19 (Ph3 Cohort 1- 2.4g vs Placebo)		Through Day 29
Secondary	Proportion of Participants Requiring Mechanical Ventilation Due to COVID-19 (Phase 3 Cohort 2)	Phase 3 (Cohort 2)	Through Day 29
Secondary	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)	Phase 3 Cohort 1	Baseline up to Day 29
Secondary	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)	Phase 3 Cohort 1	Baseline up to Day 29
Secondary	Change From Baseline in Viral Load at Each Visit, as Measured by RT-qPCR in Nasopharyngeal Swabs - (Phase 3 Cohort 2)	Phase 3 Cohort 2	Baseline up to Day 29
Secondary	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)	Phase 3 (Cohort 1)	Baseline to Day 7
Secondary	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)	Phase 3 (Cohort 2)	Baseline to Day 7
Secondary	Proportion of Participants With Viral Loads Below the Lower Limit of Detection at Each Visit - (Phase 2 Only)	Next Phase 2 Symptomatic	Day 0, Day 5, Day 7, Day 15, Day 29
Secondary	Proportion of Participants With Viral Loads Below the Lower Limit of Quantitation at Each Visit - (Phase 2 Only)	Next Phase 2 Symptomatic	Day 0, Day 5, Day 7, Day 15, Day 29
Secondary	Number of Days of Hospitalization Due to COVID-19 (Ph3 Cohort 1) Placebo vs. 1.2g IV	Phase 3 (Cohort 1)	Through Day 29
Secondary	Number of Days of Hospitalization Due to COVID-19 (Ph3 Cohort 1) Placebo vs. 2.4g IV	Phase 3 (Cohort 1)	Through Day 29
Secondary	Number of Days of Hospitalization Due to COVID-19 (Ph3 Cohort 2)	Phase 3 (Cohort 2)	Through Day 29
Secondary	Number of Days of Hospitalization Due to COVID-19 (Phase 2 Asymptomatic)	Phase 2 Only	Up to Day 29
Secondary	Proportion of Participants Admitted to an Intensive Care Unit (ICU) Due to COVID-19 - (Ph 3 Cohort 1) Placebo vs. 1.2g IV	Phase 3 (Cohort 1)	Through Day 29
Secondary	Percentage of Participants Admitted to an Intensive Care Unit (ICU) Due to COVID-19 - (Ph 3 Cohort 1) Placebo vs. 2.4g IV	Phase 3 (Cohort 1)	Through Day 29
Secondary	Proportion of Participants Admitted to an Intensive Care Unit (ICU) Due to COVID-19 - (Ph 3 Cohort 2)	Phase 3 (Cohort 2)	Through Day 29
Secondary	Proportion of Participants Admitted to an Intensive Care Unit (ICU) Due to COVID-19 - (Next Phase 2) #87	Next Phase 2	Through Day 29
Secondary	Total Number of COVID-19-related Medically-attended Visits (Phase 3 Cohort 1) Placebo vs. 1.2g	Phase 3 Cohort 1	Through Day 29
Secondary	Total Number of COVID-19-related Medically-attended Visits (Phase 3 Cohort 1) Placebo vs. 2.4g	Phase 3 Cohort 1	Through Day 29
Secondary	Total Number of COVID-19-related Medically-attended Visits (Phase 3 Cohort 2)	Phase 3 Cohort 2	Through Day 29