COVID-19
Conditions
Keywords
Coronavirus disease 2019 (COVID-19), Severe acute respiratory syndrome coronavirus 2 (SARS-COV-2), coronavirus
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
Interventions
DRUGcasirivimab+imdevimab combination therapy
Administered intravenously (IV) single dose
Sponsors
Regeneron Pharmaceuticals
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Phase 1/Phase 2/Phase 3
Eligibility
Sex/Gender
ALL
Healthy volunteers
No
Inclusion 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/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Treatment-emergent Serious Adverse Events (SAEs) - [Ph1, Ph2, Ph3 Cohort 1 - Cohort 3] | 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) | 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) | 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) | 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) | 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) | Through Day 29 | Primary: Phase 3 (Cohort 1) |
| Concentration of REGN10983 + REGN10987 in Serum Over Time (Ph3 Cohort 2) | Up to Nominal Sampling Day 28 | Phase 3 Cohort 2 \[Nominal Sampling Time\] = \[Clinical Study Time (Visit Day - 1)\] |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With ≥1 COVID-19 Related Hospitalization, Emergency Room, or Urgent Care Visit Through Day 29 (Ph1, Ph2) | Through Day 29 | Phase 1, Phase 2 |
| Time to First Onset of Symptoms Consistent With COVID-19 (Phase 2 Asymptomatic Cohort Only) | 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 | 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 | 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) | 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) | Through Day 29 | Phase 1 Only |
| Assessment of PK Parameter: Time to Cmax (Tmax) for REGN10933+REGN10987 (Phase 1) | 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) | Through Day 29 | Phase 1 Only |
| Immunogenicity as Measured by Anti-drug (ADA) to REGN10933 (Ph1 Cohort 1, Ph2 Cohort 1, Ph3 Cohort 1) | 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) | 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) | 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) | 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) | 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) | 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) | Through Day 29 | Phase 3 (Cohort 2) |
| Percentage of Participants With ≥1 COVID-19-related Medically-attended Visit (Phase 1, Phase 2) | 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 | 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 | Through Day 29 | Phase 3 Cohort 1 |
| Total Number of COVID-19-related Medically-attended Visits (Phase 1 and Phase 2) | 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) | Through Day 29 | Phase 1 Only |
| Assessment of PK Parameter: Cmax-to-dose Ratio (Cmax/Dose) of REGN10933 and REGN10987 (Phase 1 Only) | Though Day 29 | Phase 1 Only |
| Assessment of PK Parameter: Time to Cmax (Tmax) for REGN10933 and REGN10987 (Phase 1 Only) | 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) | 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) | 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) | 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) | 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) | 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) | 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) | 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) | 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) | 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) | 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) | 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) | 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) | 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) | 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) | 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) | 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) | Through Day 29 | Phase 3 Cohort 1 |
| Percentage of Participants With All-Cause Death (Ph3 Cohort 1) Placebo vs. 1.2g | 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 | 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) | 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) | 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) | 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) | 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) | 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) | 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) | Through Day 29 | Phase 2 Only |
| Duration of Symptoms Consistent With COVID-19 (Phase 2 Only) | Through Day 29 | Phase 2 Only |
| Number of Participants Admitted to a Hospital Due to COVID-19 (Phase 1, Phase 2) | 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) | Through Day 29 | Phase 1 Only |
| Proportion of Participants With All-cause Mortality (Phase 2 Asymptomatic) | Through Day 29 | Phase 2 Asymptomatic |
| Time to All-cause Death (Ph3 Cohort 1- 1.2g vs Placebo) | Through Day 169 | Phase 3 Cohort 1 (1.2g IV) |
| Time to All-cause Death (Ph3 Cohort 1- 2.4g vs Placebo) | Through Day 169 | Phase 3 Cohort 1 (2.4g IV) |
| Time to All-cause Death (Phase 3 Cohort 2) | Through Day 29 | Phase 3 (Cohort 2) |
| 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 | 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) | 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) | 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) | 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) | 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) | 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) | 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) | 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 | Through Day 29 | Phase 3 (Cohort 1) |
| Number of Days of Hospitalization Due to COVID-19 (Ph3 Cohort 1) Placebo vs. 2.4g IV | Through Day 29 | Phase 3 (Cohort 1) |
| Number of Days of Hospitalization Due to COVID-19 (Ph3 Cohort 2) | Through Day 29 | Phase 3 (Cohort 2) |
| Number of Days of Hospitalization Due to COVID-19 (Phase 2 Asymptomatic) | 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 | 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 | Through Day 29 | Phase 3 (Cohort 1) |
| Time to COVID-19 Symptoms Resolution (Ph3 Cohort 1 - 1.2g vs Placebo) | Up to Day 29 | Phase 3 Cohort 1 |
| Proportion of Participants Admitted to an Intensive Care Unit (ICU) Due to COVID-19 - (Next Phase 2) #87 | Through Day 29 | Next Phase 2 |
| Total Number of COVID-19-related Medically-attended Visits (Phase 3 Cohort 1) Placebo vs. 1.2g | Through Day 29 | Phase 3 Cohort 1 |
| Total Number of COVID-19-related Medically-attended Visits (Phase 3 Cohort 1) Placebo vs. 2.4g | Through Day 29 | Phase 3 Cohort 1 |
| Total Number of COVID-19-related Medically-attended Visits (Phase 3 Cohort 2) | Through Day 29 | Phase 3 Cohort 2 |
| Proportion of Participants Admitted to an Intensive Care Unit (ICU) Due to COVID-19 - (Ph 3 Cohort 2) | Through Day 29 | Phase 3 (Cohort 2) |
| Time to COVID-19 Symptoms Resolution (Ph3 Cohort 1 - 2.4g vs Placebo) | 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) | 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) | 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) | 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) | 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) | Through Day 29 | Phase 1, Phase 2 |
Countries
Mexico, Romania, United States
Participant flow
Pre-assignment details
10065 were randomized, 135 randomized but not treated
Participants by arm
| Arm | Count |
|---|---|
| Phase 1 Symptomatic: Placebo Placebo of R10933 + R10987 Adult Symptomatic Participants with COVID-19 | 24 |
| Phase 1 Symptomatic: 2.4 IV 2.4g of R10933 + R10987 Adult Symptomatic Participants with COVID-19 | 24 |
| Phase 1 Symptomatic: 8.0 IV 8.0g of R10933 + R10987 Adult Symptomatic Participants with COVID-19 | 24 |
| Phase 2 Symptomatic: Placebo Placebo of R10933 + R10987 Adult Symptomatic Participants with COVID-19 | 242 |
| Phase 2 Symptomatic: 2.4 IV 2.4g of R10933 + R10987 Adult Symptomatic Participants with COVID-19 | 242 |
| Phase 2 Symptomatic: 8.0 IV 8.0g of R10933 + R10987 Adult Symptomatic Participants with COVID-19 | 243 |
| Phase 2 Asymptomatic: Placebo Placebo of R10933 + R10987 Adult Participants with asymptomatic SARS-CoV-2 infection | 76 |
| Phase 2 Asymptomatic: 2.4 IV 2.4g of R10933 + R10987 Adult Participants with asymptomatic SARS-CoV-2 infection | 76 |
| Phase 2 Asymptomatic: 8.0 IV 8.0g of R10933 + R10987 Adult Participants with asymptomatic SARS-CoV-2 infection | 76 |
| Phase 3 Age>=18: Placebo Placebo of R10933 + R10987 Participants \>=18 with COVID-19, not pregnant at randomization | 2,378 |
| Phase 3 Age>=18: 1.2 IV 1.2g of R10933 + R10987 Participants \>=18 with COVID-19, not pregnant at randomization | 2,156 |
| Phase 3 Age>=18: 2.4 IV 2.4g of R10933 + R10987 Participants \>=18 with COVID-19, not pregnant at randomization | 3,189 |
| Phase 3 Age>=18: 8.0 IV 8.0g of R10933 + R10987 Participants \>=18 with COVID-19, not pregnant at randomization | 1,027 |
| Phase 3 Age <18: Placebo Placebo of R10933 + R10987 Participants \<18 with COVID-19, not pregnant at randomization | 2 |
| Phase 3 Age <18: 1.2 IV 1.2g of R10933 + R10987 Participants \<18 with COVID-19 | 129 |
| Phase 3 Age <18: 2.4 IV 2.4g of R10933 + R10987 Participants \<18 with COVID-19 | 75 |
| Phase 3 Pregnant Placebo Placebo of R10933 + R10987 Participants who are pregnant with COVID-19 | 3 |
| Phase 3 Pregnant 1.2 IV 1.2g of R10933 + R10987 Participants who are pregnant with COVID-19 | 43 |
| Phase 3 Pregnant: 2.4 IV 2.4g of R10933 + R10987 Participants who are pregnant with COVID-19 | 36 |
| Total | 10,065 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 | FG009 | FG010 | FG011 | FG012 | FG013 | FG014 | FG015 | FG016 | FG017 | FG018 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 3 | 2 | 1 | 1 | 0 | 0 | 0 | 0 | 0 | 0 |
| Overall Study | Death | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 11 | 2 | 4 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Overall Study | Lack of Efficacy | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Overall Study | Lost to Follow-up | 1 | 3 | 1 | 7 | 1 | 2 | 1 | 0 | 1 | 64 | 70 | 98 | 30 | 0 | 5 | 4 | 0 | 3 | 1 |
| Overall Study | Physician Decision | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 4 | 3 | 5 | 1 | 0 | 0 | 1 | 0 | 0 | 0 |
| Overall Study | Sponsor Request | 0 | 0 | 0 | 2 | 2 | 2 | 1 | 0 | 0 | 9 | 9 | 10 | 8 | 0 | 0 | 1 | 0 | 0 | 0 |
| Overall Study | Subject Decision | 0 | 2 | 1 | 3 | 6 | 6 | 3 | 3 | 1 | 70 | 95 | 124 | 25 | 0 | 1 | 4 | 1 | 0 | 2 |
Baseline characteristics
| Characteristic | Total | Phase 3 Pregnant: 2.4 IV | Phase 3 Pregnant 1.2 IV | Phase 3 Pregnant Placebo | Phase 3 Age <18: 2.4 IV | Phase 3 Age <18: 1.2 IV | Phase 3 Age <18: Placebo | Phase 3 Age>=18: 8.0 IV | Phase 3 Age>=18: 2.4 IV | Phase 3 Age>=18: 1.2 IV | Phase 3 Age>=18: Placebo | Phase 2 Asymptomatic: 8.0 IV | Phase 2 Asymptomatic: 2.4 IV | Phase 2 Asymptomatic: Placebo | Phase 2 Symptomatic: 8.0 IV | Phase 2 Symptomatic: 2.4 IV | Phase 2 Symptomatic: Placebo | Phase 1 Symptomatic: 8.0 IV | Phase 1 Symptomatic: 2.4 IV | Phase 1 Symptomatic: Placebo |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age Continous | 44.7 years STANDARD_DEVIATION 15.51 | 28.3 years STANDARD_DEVIATION 6.02 | 28.9 years STANDARD_DEVIATION 5.87 | 31.0 years STANDARD_DEVIATION 3.46 | 12.2 years STANDARD_DEVIATION 3.36 | 10.9 years STANDARD_DEVIATION 4.14 | 14.0 years STANDARD_DEVIATION 2.83 | 44.8 years STANDARD_DEVIATION 15.09 | 46.1 years STANDARD_DEVIATION 14.89 | 46.7 years STANDARD_DEVIATION 14.59 | 45.4 years STANDARD_DEVIATION 14.61 | 44.0 years STANDARD_DEVIATION 17.43 | 44.8 years STANDARD_DEVIATION 16.7 | 43.5 years STANDARD_DEVIATION 15.51 | 41.7 years STANDARD_DEVIATION 14.38 | 42.7 years STANDARD_DEVIATION 15.59 | 42.5 years STANDARD_DEVIATION 15.21 | 40.4 years STANDARD_DEVIATION 11.83 | 38.9 years STANDARD_DEVIATION 11.11 | 43.8 years STANDARD_DEVIATION 14.42 |
| Age, Continuous | 45.0 years | 28.0 years | 30.0 years | 33.0 years | 12.0 years | 11.0 years | 14.0 years | 44.0 years | 46.0 years | 48.0 years | 46.0 years | 44.5 years | 44.5 years | 43.5 years | 42.0 years | 43.0 years | 42.0 years | 39.0 years | 39.5 years | 40.5 years |
| Age, Customized <18 | 207 Participants | 1 Participants | 0 Participants | 0 Participants | 75 Participants | 129 Participants | 2 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Customized >=18, <65 | 8874 Participants | 35 Participants | 43 Participants | 3 Participants | 0 Participants | 0 Participants | 0 Participants | 911 Participants | 2843 Participants | 1937 Participants | 2159 Participants | 65 Participants | 62 Participants | 71 Participants | 228 Participants | 223 Participants | 226 Participants | 23 Participants | 23 Participants | 22 Participants |
| Age, Customized >=65 | 984 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 116 Participants | 346 Participants | 219 Participants | 219 Participants | 11 Participants | 14 Participants | 5 Participants | 15 Participants | 19 Participants | 16 Participants | 1 Participants | 1 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 4527 Participants | 8 Participants | 6 Participants | 0 Participants | 40 Participants | 87 Participants | 0 Participants | 316 Participants | 1413 Participants | 1140 Participants | 1002 Participants | 35 Participants | 43 Participants | 34 Participants | 117 Participants | 121 Participants | 129 Participants | 17 Participants | 11 Participants | 8 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 5439 Participants | 28 Participants | 37 Participants | 2 Participants | 33 Participants | 42 Participants | 2 Participants | 701 Participants | 1740 Participants | 992 Participants | 1357 Participants | 39 Participants | 33 Participants | 40 Participants | 126 Participants | 121 Participants | 112 Participants | 6 Participants | 12 Participants | 16 Participants |
| Ethnicity (NIH/OMB) Not Reported | 99 Participants | 0 Participants | 0 Participants | 1 Participants | 2 Participants | 0 Participants | 0 Participants | 10 Participants | 36 Participants | 24 Participants | 19 Participants | 2 Participants | 0 Participants | 2 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants | 1 Participants | 0 Participants |
| Race American Indian or Alaska Native | 197 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 5 Participants | 84 Participants | 72 Participants | 30 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants | 2 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race Asian | 325 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 45 Participants | 96 Participants | 71 Participants | 89 Participants | 3 Participants | 4 Participants | 1 Participants | 4 Participants | 6 Participants | 4 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race Black or African American | 551 Participants | 2 Participants | 4 Participants | 1 Participants | 7 Participants | 8 Participants | 1 Participants | 46 Participants | 172 Participants | 112 Participants | 110 Participants | 5 Participants | 3 Participants | 6 Participants | 23 Participants | 20 Participants | 21 Participants | 0 Participants | 7 Participants | 3 Participants |
| Race Native Hawaiian or Other Pacific Islander | 17 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 6 Participants | 7 Participants | 3 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race Not Reported | 229 Participants | 1 Participants | 1 Participants | 0 Participants | 2 Participants | 2 Participants | 0 Participants | 21 Participants | 76 Participants | 52 Participants | 54 Participants | 0 Participants | 0 Participants | 2 Participants | 5 Participants | 6 Participants | 5 Participants | 1 Participants | 1 Participants | 0 Participants |
| Race Unknown | 402 Participants | 0 Participants | 1 Participants | 0 Participants | 2 Participants | 3 Participants | 0 Participants | 21 Participants | 143 Participants | 138 Participants | 82 Participants | 3 Participants | 0 Participants | 2 Participants | 3 Participants | 1 Participants | 3 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race White | 8344 Participants | 33 Participants | 35 Participants | 2 Participants | 63 Participants | 115 Participants | 1 Participants | 889 Participants | 2612 Participants | 1704 Participants | 2010 Participants | 65 Participants | 69 Participants | 65 Participants | 207 Participants | 208 Participants | 207 Participants | 23 Participants | 16 Participants | 20 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 197 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 5 Participants | 84 Participants | 72 Participants | 30 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants | 2 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 325 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 45 Participants | 96 Participants | 71 Participants | 89 Participants | 3 Participants | 4 Participants | 1 Participants | 4 Participants | 6 Participants | 4 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 551 Participants | 2 Participants | 4 Participants | 1 Participants | 7 Participants | 8 Participants | 1 Participants | 46 Participants | 172 Participants | 112 Participants | 110 Participants | 5 Participants | 3 Participants | 6 Participants | 23 Participants | 20 Participants | 21 Participants | 0 Participants | 7 Participants | 3 Participants |
| Race (NIH/OMB) More than one race | 402 Participants | 0 Participants | 1 Participants | 0 Participants | 2 Participants | 3 Participants | 0 Participants | 21 Participants | 143 Participants | 138 Participants | 82 Participants | 3 Participants | 0 Participants | 2 Participants | 3 Participants | 1 Participants | 3 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 17 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 6 Participants | 7 Participants | 3 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 229 Participants | 1 Participants | 1 Participants | 0 Participants | 2 Participants | 2 Participants | 0 Participants | 21 Participants | 76 Participants | 52 Participants | 54 Participants | 0 Participants | 0 Participants | 2 Participants | 5 Participants | 6 Participants | 5 Participants | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) White | 8344 Participants | 33 Participants | 35 Participants | 2 Participants | 63 Participants | 115 Participants | 1 Participants | 889 Participants | 2612 Participants | 1704 Participants | 2010 Participants | 65 Participants | 69 Participants | 65 Participants | 207 Participants | 208 Participants | 207 Participants | 23 Participants | 16 Participants | 20 Participants |
| Sex: Female, Male Female | 5203 Participants | 36 Participants | 43 Participants | 3 Participants | 22 Participants | 69 Participants | 2 Participants | 518 Participants | 1635 Participants | 1117 Participants | 1227 Participants | 32 Participants | 37 Participants | 40 Participants | 136 Participants | 130 Participants | 122 Participants | 10 Participants | 14 Participants | 10 Participants |
| Sex: Female, Male Male | 4862 Participants | 0 Participants | 0 Participants | 0 Participants | 53 Participants | 60 Participants | 0 Participants | 509 Participants | 1554 Participants | 1039 Participants | 1151 Participants | 44 Participants | 39 Participants | 36 Participants | 107 Participants | 112 Participants | 120 Participants | 14 Participants | 10 Participants | 14 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk | EG010 affected / at risk | EG011 affected / at risk | EG012 affected / at risk | EG013 affected / at risk | EG014 affected / at risk | EG015 affected / at risk | EG016 affected / at risk | EG017 affected / at risk | EG018 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 24 | 0 / 22 | 0 / 23 | 0 / 238 | 0 / 236 | 0 / 237 | 0 / 73 | 0 / 74 | 0 / 75 | 11 / 2,347 | 2 / 2,130 | 4 / 3,157 | 0 / 1,012 | 0 / 2 | 0 / 129 | 0 / 71 | 0 / 2 | 0 / 43 | 0 / 35 |
| other Total, other adverse events | 0 / 24 | 0 / 22 | 0 / 23 | 2 / 238 | 1 / 236 | 1 / 237 | 0 / 73 | 0 / 74 | 0 / 75 | 16 / 2,347 | 16 / 2,130 | 19 / 3,157 | 4 / 1,012 | 1 / 2 | 0 / 129 | 1 / 71 | 0 / 2 | 5 / 43 | 3 / 35 |
| serious Total, serious adverse events | 0 / 24 | 1 / 22 | 0 / 23 | 6 / 238 | 3 / 236 | 2 / 237 | 0 / 73 | 0 / 74 | 0 / 75 | 103 / 2,347 | 39 / 2,130 | 52 / 3,157 | 19 / 1,012 | 0 / 2 | 3 / 129 | 0 / 71 | 0 / 2 | 11 / 43 | 7 / 35 |
Outcome results
Primary
Concentration of REGN10983 + REGN10987 in Serum Over Time (Ph3 Cohort 2)
Phase 3 Cohort 2 \[Nominal Sampling Time\] = \[Clinical Study Time (Visit Day - 1)\]
Time frame: Up to Nominal Sampling Day 28
Population: The pharmacokinetics (PK) analysis population includes all patients who received any study drug (safety population) and who had at least 1 non-missing result following the first dose of study drug
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (Placebo) | Concentration of REGN10983 + REGN10987 in Serum Over Time (Ph3 Cohort 2) | Day 0: End of Infusion | 402 mg/L | Standard Deviation 196 |
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (Placebo) | Concentration of REGN10983 + REGN10987 in Serum Over Time (Ph3 Cohort 2) | Nominal Sampling Day 28 | 108 mg/L | Standard Deviation 60.1 |
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (2.4 IV) | Concentration of REGN10983 + REGN10987 in Serum Over Time (Ph3 Cohort 2) | Day 0: End of Infusion | 710 mg/L | Standard Deviation 275 |
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (2.4 IV) | Concentration of REGN10983 + REGN10987 in Serum Over Time (Ph3 Cohort 2) | Nominal Sampling Day 28 | 198 mg/L | Standard Deviation 78.7 |
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)
Time frame: Through Day 29
Population: Analysis populations were prespecified in the SAP. Pooled analyses were performed for symptomatic adult participants randomized in Phase 1, 2, or 3 (cohort 1) on or before 2/24/21 to placebo, R10933+R10987 1.2 g, 2.4 g, or 8.0 g IV. No phase 1 or 2 participants were randomized to R10933+R10987 1.2 g IV. Asymptomatic adult participants randomized to the asymptomatic cohort of phase 2, symptomatic pediatric / pregnant participants randomized in phase 3 to cohort 2 or 3 were analyzed separately.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (Placebo) | Number of Participants With Hypersensitivity Reactions (Ph1, Ph2, Ph3 Cohort 1 - Cohort 3) | 3 Participants |
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (2.4 IV) | Number of Participants With Hypersensitivity Reactions (Ph1, Ph2, Ph3 Cohort 1 - Cohort 3) | 1 Participants |
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (8.0 IV) | Number of Participants With Hypersensitivity Reactions (Ph1, Ph2, Ph3 Cohort 1 - Cohort 3) | 0 Participants |
| Phase 2 Asymptomatic (Placebo) | Number of Participants With Hypersensitivity Reactions (Ph1, Ph2, Ph3 Cohort 1 - Cohort 3) | 0 Participants |
| Phase 2 Asymptomatic (2.4g IV) | Number of Participants With Hypersensitivity Reactions (Ph1, Ph2, Ph3 Cohort 1 - Cohort 3) | 0 Participants |
| Phase 2 Asymptomatic (8.0g IV) | Number of Participants With Hypersensitivity Reactions (Ph1, Ph2, Ph3 Cohort 1 - Cohort 3) | 0 Participants |
| Phase 3 Cohort 1 (1.2g IV) Symptomatic | Number of Participants With Hypersensitivity Reactions (Ph1, Ph2, Ph3 Cohort 1 - Cohort 3) | 1 Participants |
| Phase 3 Cohort 2 Pediatric (Placebo) | Number of Participants With Hypersensitivity Reactions (Ph1, Ph2, Ph3 Cohort 1 - Cohort 3) | 0 Participants |
| Phase 3 Cohort 2 Pediatric (1.2g IV) | Number of Participants With Hypersensitivity Reactions (Ph1, Ph2, Ph3 Cohort 1 - Cohort 3) | 1 Participants |
| Phase 3 Cohort 2 Pediatric (2.4g IV) | Number of Participants With Hypersensitivity Reactions (Ph1, Ph2, Ph3 Cohort 1 - Cohort 3) | 0 Participants |
| Phase 3 Cohort 3 Pregnant (Placebo) | Number of Participants With Hypersensitivity Reactions (Ph1, Ph2, Ph3 Cohort 1 - Cohort 3) | 0 Participants |
| Phase 3 Cohort 3 Pregnant (1.2g IV) | Number of Participants With Hypersensitivity Reactions (Ph1, Ph2, Ph3 Cohort 1 - Cohort 3) | 0 Participants |
| Phase 3 Cohort 3 Pregnant (2.4g IV) | Number of Participants With Hypersensitivity Reactions (Ph1, Ph2, Ph3 Cohort 1 - Cohort 3) | 0 Participants |
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)
Time frame: Through Day 4
Population: Analysis populations were prespecified in the SAP. Pooled analyses were performed for symptomatic adult participants randomized in Phase 1, 2, or 3 (cohort 1) on or before 2/24/21 to placebo, R10933+R10987 1.2 g, 2.4 g, or 8.0 g IV. No phase 1 or 2 participants were randomized to R10933+R10987 1.2 g IV. Asymptomatic adult participants randomized to the asymptomatic cohort of phase 2, symptomatic pediatric / pregnant participants randomized in phase 3 to cohort 2 or 3 were analyzed separately.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (Placebo) | Number of Participants With Infusion-related Reactions (Ph1, Ph2, Ph3 Cohort 1 - Cohort 3) | 2 Participants |
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (2.4 IV) | Number of Participants With Infusion-related Reactions (Ph1, Ph2, Ph3 Cohort 1 - Cohort 3) | 4 Participants |
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (8.0 IV) | Number of Participants With Infusion-related Reactions (Ph1, Ph2, Ph3 Cohort 1 - Cohort 3) | 7 Participants |
| Phase 2 Asymptomatic (Placebo) | Number of Participants With Infusion-related Reactions (Ph1, Ph2, Ph3 Cohort 1 - Cohort 3) | 0 Participants |
| Phase 2 Asymptomatic (2.4g IV) | Number of Participants With Infusion-related Reactions (Ph1, Ph2, Ph3 Cohort 1 - Cohort 3) | 0 Participants |
| Phase 2 Asymptomatic (8.0g IV) | Number of Participants With Infusion-related Reactions (Ph1, Ph2, Ph3 Cohort 1 - Cohort 3) | 0 Participants |
| Phase 3 Cohort 1 (1.2g IV) Symptomatic | Number of Participants With Infusion-related Reactions (Ph1, Ph2, Ph3 Cohort 1 - Cohort 3) | 1 Participants |
| Phase 3 Cohort 2 Pediatric (Placebo) | Number of Participants With Infusion-related Reactions (Ph1, Ph2, Ph3 Cohort 1 - Cohort 3) | 0 Participants |
| Phase 3 Cohort 2 Pediatric (1.2g IV) | Number of Participants With Infusion-related Reactions (Ph1, Ph2, Ph3 Cohort 1 - Cohort 3) | 0 Participants |
| Phase 3 Cohort 2 Pediatric (2.4g IV) | Number of Participants With Infusion-related Reactions (Ph1, Ph2, Ph3 Cohort 1 - Cohort 3) | 1 Participants |
| Phase 3 Cohort 3 Pregnant (Placebo) | Number of Participants With Infusion-related Reactions (Ph1, Ph2, Ph3 Cohort 1 - Cohort 3) | 0 Participants |
| Phase 3 Cohort 3 Pregnant (1.2g IV) | Number of Participants With Infusion-related Reactions (Ph1, Ph2, Ph3 Cohort 1 - Cohort 3) | 0 Participants |
| Phase 3 Cohort 3 Pregnant (2.4g IV) | Number of Participants With Infusion-related Reactions (Ph1, Ph2, Ph3 Cohort 1 - Cohort 3) | 0 Participants |
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)
Time frame: Through Day 29
Population: Analysis populations were prespecified in the SAP. Pooled analyses were performed for symptomatic adult participants randomized in Phase 1, 2, or 3 (cohort 1) on or before 2/24/21 to placebo, R10933+R10987 1.2 g, 2.4 g, or 8.0 g IV. No phase 1 or 2 participants were randomized to R10933+R10987 1.2 g IV. Asymptomatic adult participants randomized to the asymptomatic cohort of phase 2, symptomatic pediatric / pregnant participants randomized in phase 3 to cohort 2 or 3 were analyzed separately
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (Placebo) | Number of Participants With Treatment-emergent Serious Adverse Events (SAEs) - [Ph1, Ph2, Ph3 Cohort 1 - Cohort 3] | 97 Participants |
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (2.4 IV) | Number of Participants With Treatment-emergent Serious Adverse Events (SAEs) - [Ph1, Ph2, Ph3 Cohort 1 - Cohort 3] | 31 Participants |
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (8.0 IV) | Number of Participants With Treatment-emergent Serious Adverse Events (SAEs) - [Ph1, Ph2, Ph3 Cohort 1 - Cohort 3] | 19 Participants |
| Phase 2 Asymptomatic (Placebo) | Number of Participants With Treatment-emergent Serious Adverse Events (SAEs) - [Ph1, Ph2, Ph3 Cohort 1 - Cohort 3] | 0 Participants |
| Phase 2 Asymptomatic (2.4g IV) | Number of Participants With Treatment-emergent Serious Adverse Events (SAEs) - [Ph1, Ph2, Ph3 Cohort 1 - Cohort 3] | 0 Participants |
| Phase 2 Asymptomatic (8.0g IV) | Number of Participants With Treatment-emergent Serious Adverse Events (SAEs) - [Ph1, Ph2, Ph3 Cohort 1 - Cohort 3] | 0 Participants |
| Phase 3 Cohort 1 (1.2g IV) Symptomatic | Number of Participants With Treatment-emergent Serious Adverse Events (SAEs) - [Ph1, Ph2, Ph3 Cohort 1 - Cohort 3] | 14 Participants |
| Phase 3 Cohort 2 Pediatric (Placebo) | Number of Participants With Treatment-emergent Serious Adverse Events (SAEs) - [Ph1, Ph2, Ph3 Cohort 1 - Cohort 3] | 0 Participants |
| Phase 3 Cohort 2 Pediatric (1.2g IV) | Number of Participants With Treatment-emergent Serious Adverse Events (SAEs) - [Ph1, Ph2, Ph3 Cohort 1 - Cohort 3] | 2 Participants |
| Phase 3 Cohort 2 Pediatric (2.4g IV) | Number of Participants With Treatment-emergent Serious Adverse Events (SAEs) - [Ph1, Ph2, Ph3 Cohort 1 - Cohort 3] | 0 Participants |
| Phase 3 Cohort 3 Pregnant (Placebo) | Number of Participants With Treatment-emergent Serious Adverse Events (SAEs) - [Ph1, Ph2, Ph3 Cohort 1 - Cohort 3] | 0 Participants |
| Phase 3 Cohort 3 Pregnant (1.2g IV) | Number of Participants With Treatment-emergent Serious Adverse Events (SAEs) - [Ph1, Ph2, Ph3 Cohort 1 - Cohort 3] | 2 Participants |
| Phase 3 Cohort 3 Pregnant (2.4g IV) | Number of Participants With Treatment-emergent Serious Adverse Events (SAEs) - [Ph1, Ph2, Ph3 Cohort 1 - Cohort 3] | 2 Participants |
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
Time frame: Through Day 29
Population: Participants that were ≥18 years old and not pregnant at randomization, and randomized on or before 17-Jan-2021 with detectable SARS-CoV-2 RNA by RT-qPCR in nasopharyngeal swabs at randomization and at least 1 risk factor for severe COVID-19 at baseline
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (Placebo) | Proportion of Participants With at Least One (≥1) COVID-19-related Hospitalization or All-cause Death (Ph3 Cohort 1- 1.2g vs Placebo) | 3.2 Percentage of Participants |
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (2.4 IV) | Proportion of Participants With at Least One (≥1) COVID-19-related Hospitalization or All-cause Death (Ph3 Cohort 1- 1.2g vs Placebo) | 1.0 Percentage of Participants |
p-value: =0.0024Cochran-Mantel-Haenszel
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)
Time frame: Through Day 29
Population: Participants that were ≥18 years old and not pregnant at randomization, and randomized on or before 17-Jan-2021 with detectable SARS-CoV-2 RNA by RT-qPCR in nasopharyngeal swabs at randomization and at least 1 risk factor for severe COVID-19 at baseline
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (Placebo) | Proportion of Participants With at Least One (≥1) COVID-19-related Hospitalization or All-cause Death (Ph3 Cohort 1 - 2.4g vs Placebo) | 4.6 Percentage of Participants |
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (2.4 IV) | Proportion of Participants With at Least One (≥1) COVID-19-related Hospitalization or All-cause Death (Ph3 Cohort 1 - 2.4g vs Placebo) | 1.3 Percentage of Participants |
p-value: <0.0001Cochran-Mantel-Haenszel
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
Time frame: Baseline up to Day 7
Population: All randomized participants in Phase 1 or Phase 2 with qualitatively positive RT-qPCR in NP swab samples at randomization or collected within 2 hours after study drug infusion was initiated. This pooled modified full analysis set (mFAS) includes all randomized patients with positive RT-qPCR in NP swab samples at randomization and is based on the treatment allocated (as randomized).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (Placebo) | 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) | -1.32 log10 copies/mL | Standard Deviation 1.047 |
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (2.4 IV) | 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) | -1.65 log10 copies/mL | Standard Deviation 0.977 |
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (8.0 IV) | 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) | -1.67 log10 copies/mL | Standard Deviation 1.157 |
p-value: =0.000695% CI: [-0.52, -0.14]ANCOVA
p-value: <0.000195% CI: [-0.56, -0.19]ANCOVA
Secondary
Assessment of Pharmacokinetic (PK) Parameter: Maximum Serum Concentration Observed (Cmax) of REGN10933 and REGN10987 (Phase 1 Only)
Phase 1 Only
Time frame: Through Day 29
Population: The pharmacokinetics (PK) analysis pooled population includes all patients who received any study drug (safety population) and who had at least 1 non-missing result following the first dose of study drug
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (Placebo) | Assessment of Pharmacokinetic (PK) Parameter: Maximum Serum Concentration Observed (Cmax) of REGN10933 and REGN10987 (Phase 1 Only) | REGN10933 | 343 mg/L (milligram/Liters) | Standard Deviation 160 |
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (Placebo) | Assessment of Pharmacokinetic (PK) Parameter: Maximum Serum Concentration Observed (Cmax) of REGN10933 and REGN10987 (Phase 1 Only) | REGN10987 | 353 mg/L (milligram/Liters) | Standard Deviation 233 |
Secondary
Assessment of Pharmacokinetic (PK) Parameter: Maximum Serum Concentration Observed (Cmax) of REGN10933+REGN10987 (Phase 1)
Phase 1 Only
Time frame: Through Day 29
Population: The pharmacokinetics (PK) analysis population includes all patients who received any study drug (safety population) and who had at least 1 non-missing result following the first dose of study drug
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (Placebo) | Assessment of Pharmacokinetic (PK) Parameter: Maximum Serum Concentration Observed (Cmax) of REGN10933+REGN10987 (Phase 1) | 2.4g IV | 689 mg/L | Standard Deviation 391 |
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (Placebo) | Assessment of Pharmacokinetic (PK) Parameter: Maximum Serum Concentration Observed (Cmax) of REGN10933+REGN10987 (Phase 1) | 8.0g IV | 1805 mg/L | Standard Deviation 720 |
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
Time frame: Through Day 29
Population: The pharmacokinetics (PK) analysis population includes all patients who received any study drug (safety population) and who had at least 1 non-missing result following the first dose of study drug
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (Placebo) | 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) | 2.4g IV | 7158 day*milligram/Liter | Standard Deviation 4255 |
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (Placebo) | 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) | 8.0g IV | 19084 day*milligram/Liter | Standard Deviation 5172 |
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)
Time frame: Through Day 29
Population: The pharmacokinetics (PK) analysis population includes all patients who received any study drug (safety population) and who had at least 1 non-missing result following the first dose of study drug
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (Placebo) | 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) | REGN10933 | 27.7 ((day*mg/L)/mg) |
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (Placebo) | 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) | REGN10987 | 27.7 ((day*mg/L)/mg) |
Secondary
Assessment of PK Parameter: Cmax-to-dose Ratio (Cmax/Dose) of REGN10933 and REGN10987 (Phase 1 Only)
Phase 1 Only
Time frame: Though Day 29
Population: The pharmacokinetics (PK) analysis population includes all patients who received any study drug (safety population) and who had at least 1 non-missing result following the first dose of study drug
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (Placebo) | Assessment of PK Parameter: Cmax-to-dose Ratio (Cmax/Dose) of REGN10933 and REGN10987 (Phase 1 Only) | REGN10933 | 0.286 mg/L/mg (milligram/Liter/milligram) | Standard Deviation 0.134 |
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (Placebo) | Assessment of PK Parameter: Cmax-to-dose Ratio (Cmax/Dose) of REGN10933 and REGN10987 (Phase 1 Only) | REGN10987 | 0.294 mg/L/mg (milligram/Liter/milligram) | Standard Deviation 0.194 |
Secondary
Assessment of PK Parameter: Time to Cmax (Tmax) for REGN10933 and REGN10987 (Phase 1 Only)
Phase 1 Only
Time frame: Through Day 29
Population: The pharmacokinetics (PK) analysis population includes all patients who received any study drug (safety population) and who had at least 1 non-missing result following the first dose of study drug
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (Placebo) | Assessment of PK Parameter: Time to Cmax (Tmax) for REGN10933 and REGN10987 (Phase 1 Only) | REGN10933 | 0.0861 Day |
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (Placebo) | Assessment of PK Parameter: Time to Cmax (Tmax) for REGN10933 and REGN10987 (Phase 1 Only) | REGN10987 | 0.0861 Day |
Secondary
Assessment of PK Parameter: Time to Cmax (Tmax) for REGN10933+REGN10987 (Phase 1)
Phase 1 Only
Time frame: Through Day 29
Population: The pharmacokinetics (PK) analysis population includes all patients who received any study drug (safety population) and who had at least 1 non-missing result following the first dose of study drug
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (Placebo) | Assessment of PK Parameter: Time to Cmax (Tmax) for REGN10933+REGN10987 (Phase 1) | 2.4g IV | 27.7 Days |
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (Placebo) | Assessment of PK Parameter: Time to Cmax (Tmax) for REGN10933+REGN10987 (Phase 1) | 8.0g IV | 0.0854 Days |
Secondary
Change From Baseline in Viral Load at Each Visit, as Measured by RT-qPCR in Nasal Swabs - (Phase 1 Only)
Phase 1 Only
Time frame: Baseline Up To Day 29
Population: Nasal and saliva sample collection was discontinued early in the study because nasopharyngeal samples were determined to be more reliable for quantitative analysis. Therefore, data was not collected for this outcome measure. The Phase 1/2 SAP does not specify any analyses related to nasal and saliva samples collections
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
Time frame: Day 5, Day 7, Day 15, Day 29
Population: Participants analyzed are part of modified Full Analysis Set (mFAS) and have documented status at baseline. Next Phase 2 participants included the next 524 participants randomized to Phase 2 subsequent to the first 275 symptomatic participants randomized in Phase 1 / 2
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (Placebo) | Change From Baseline in Viral Load at Each Visit, as Measured by RT-qPCR in Nasopharyngeal Swabs (Next Phase 2 Cohort) | Day 5 | -1.79 log10 copies/mL | Standard Error 0.14 |
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (Placebo) | Change From Baseline in Viral Load at Each Visit, as Measured by RT-qPCR in Nasopharyngeal Swabs (Next Phase 2 Cohort) | Day 7 | -2.54 log10 copies/mL | Standard Error 0.13 |
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (Placebo) | Change From Baseline in Viral Load at Each Visit, as Measured by RT-qPCR in Nasopharyngeal Swabs (Next Phase 2 Cohort) | Day 15 | -4.56 log10 copies/mL | Standard Error 0.14 |
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (Placebo) | Change From Baseline in Viral Load at Each Visit, as Measured by RT-qPCR in Nasopharyngeal Swabs (Next Phase 2 Cohort) | Day 29 | -5.42 log10 copies/mL | Standard Error 0.1 |
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (2.4 IV) | Change From Baseline in Viral Load at Each Visit, as Measured by RT-qPCR in Nasopharyngeal Swabs (Next Phase 2 Cohort) | Day 29 | -5.60 log10 copies/mL | Standard Error 0.1 |
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (2.4 IV) | Change From Baseline in Viral Load at Each Visit, as Measured by RT-qPCR in Nasopharyngeal Swabs (Next Phase 2 Cohort) | Day 5 | -2.33 log10 copies/mL | Standard Error 0.14 |
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (2.4 IV) | Change From Baseline in Viral Load at Each Visit, as Measured by RT-qPCR in Nasopharyngeal Swabs (Next Phase 2 Cohort) | Day 15 | -4.67 log10 copies/mL | Standard Error 0.14 |
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (2.4 IV) | Change From Baseline in Viral Load at Each Visit, as Measured by RT-qPCR in Nasopharyngeal Swabs (Next Phase 2 Cohort) | Day 7 | -2.79 log10 copies/mL | Standard Error 0.13 |
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (8.0 IV) | Change From Baseline in Viral Load at Each Visit, as Measured by RT-qPCR in Nasopharyngeal Swabs (Next Phase 2 Cohort) | Day 29 | -5.45 log10 copies/mL | Standard Error 0.1 |
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (8.0 IV) | Change From Baseline in Viral Load at Each Visit, as Measured by RT-qPCR in Nasopharyngeal Swabs (Next Phase 2 Cohort) | Day 7 | -3.08 log10 copies/mL | Standard Error 0.13 |
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (8.0 IV) | Change From Baseline in Viral Load at Each Visit, as Measured by RT-qPCR in Nasopharyngeal Swabs (Next Phase 2 Cohort) | Day 15 | -4.58 log10 copies/mL | Standard Error 0.14 |
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (8.0 IV) | Change From Baseline in Viral Load at Each Visit, as Measured by RT-qPCR in Nasopharyngeal Swabs (Next Phase 2 Cohort) | Day 5 | -2.28 log10 copies/mL | Standard Error 0.14 |
p-value: =0.1903Mixed Models Analysis
p-value: =0.8431Mixed Models Analysis
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
Time frame: Baseline up to Day 29
Population: Participants that were ≥18 years old and not pregnant at randomization, and randomized on or before 17-Jan-2021 with detectable SARS-CoV-2 RNA by RT-qPCR in nasopharyngeal swabs at randomization and at least 1 risk factor for severe COVID-19 at baseline
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (Placebo) | 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) | Day 7 | -3.14 log10 copies/mL | Standard Deviation 1.964 |
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (Placebo) | 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) | Day 15 | -5.01 log10 copies/mL | Standard Deviation 2.068 |
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (Placebo) | 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) | Day 29 | -6.06 log10 copies/mL | Standard Deviation 1.976 |
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (2.4 IV) | 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) | Day 7 | -3.90 log10 copies/mL | Standard Deviation 2.027 |
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (2.4 IV) | 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) | Day 15 | -5.37 log10 copies/mL | Standard Deviation 2.098 |
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (2.4 IV) | 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) | Day 29 | -6.32 log10 copies/mL | Standard Deviation 2.107 |
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
Time frame: Baseline up to Day 29
Population: Participants that were ≥18 years old and not pregnant at randomization, and randomized on or before 17-Jan-2021 with detectable SARS-CoV-2 RNA by RT-qPCR in nasopharyngeal swabs at randomization and at least 1 risk factor for severe COVID-19 at baseline
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (Placebo) | 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) | Day 7 | -3.01 log10 copies/mL | Standard Deviation 1.951 |
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (Placebo) | 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) | Day 15 | -5.02 log10 copies/mL | Standard Deviation 2.034 |
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (Placebo) | 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) | Day 29 | -6.08 log10 copies/mL | Standard Deviation 1.943 |
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (2.4 IV) | 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) | Day 7 | -3.89 log10 copies/mL | Standard Deviation 1.94 |
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (2.4 IV) | 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) | Day 15 | -5.44 log10 copies/mL | Standard Deviation 2.104 |
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (2.4 IV) | 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) | Day 29 | -6.19 log10 copies/mL | Standard Deviation 1.968 |
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
Time frame: Baseline up to Day 29
Population: Participants \<18 years old who, at baseline, were not pregnant, had symptomatic COVID-19, and had at least 1 risk factor for developing severe disease
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (Placebo) | Change From Baseline in Viral Load at Each Visit, as Measured by RT-qPCR in Nasopharyngeal Swabs - (Phase 3 Cohort 2) | Day 15 | -4.50 log10 copies/mL | — |
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (Placebo) | Change From Baseline in Viral Load at Each Visit, as Measured by RT-qPCR in Nasopharyngeal Swabs - (Phase 3 Cohort 2) | Day 7 | -1.95 log10 copies/mL | — |
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (Placebo) | Change From Baseline in Viral Load at Each Visit, as Measured by RT-qPCR in Nasopharyngeal Swabs - (Phase 3 Cohort 2) | Day 29 | -4.50 log10 copies/mL | — |
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (2.4 IV) | Change From Baseline in Viral Load at Each Visit, as Measured by RT-qPCR in Nasopharyngeal Swabs - (Phase 3 Cohort 2) | Day 15 | -6.10 log10 copies/mL | Standard Deviation 2.058 |
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (2.4 IV) | Change From Baseline in Viral Load at Each Visit, as Measured by RT-qPCR in Nasopharyngeal Swabs - (Phase 3 Cohort 2) | Day 7 | -4.47 log10 copies/mL | Standard Deviation 2.522 |
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (2.4 IV) | Change From Baseline in Viral Load at Each Visit, as Measured by RT-qPCR in Nasopharyngeal Swabs - (Phase 3 Cohort 2) | Day 29 | -6.50 log10 copies/mL | Standard Deviation 1.93 |
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (8.0 IV) | Change From Baseline in Viral Load at Each Visit, as Measured by RT-qPCR in Nasopharyngeal Swabs - (Phase 3 Cohort 2) | Day 7 | -5.23 log10 copies/mL | Standard Deviation 1.985 |
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (8.0 IV) | Change From Baseline in Viral Load at Each Visit, as Measured by RT-qPCR in Nasopharyngeal Swabs - (Phase 3 Cohort 2) | Day 29 | -7.06 log10 copies/mL | Standard Deviation 1.724 |
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (8.0 IV) | Change From Baseline in Viral Load at Each Visit, as Measured by RT-qPCR in Nasopharyngeal Swabs - (Phase 3 Cohort 2) | Day 15 | -6.83 log10 copies/mL | Standard Deviation 1.94 |
Secondary
Change From Baseline in Viral Load at Each Visit, as Measured by RT-qPCR in Saliva Samples - (Phase 1 Only)
Phase 1 Only
Time frame: Baseline Up to Day 29
Population: Nasal and saliva sample collection was discontinued early in the study because nasopharyngeal samples were determined to be more reliable for quantitative analysis. Therefore, data was not collected for this outcome measure. The Phase 1/2 SAP does not specify any analyses related to nasal and saliva samples collections
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 \[Nominal Sampling Time\] = \[Clinical Study Time (Visit Day - 1)\]
Time frame: Up to Nominal Sampling Day 28
Population: The pharmacokinetics (PK) analysis population includes all patients who received any study drug (safety population) and who had at least 1 non-missing result following the first dose of study drug
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (Placebo) | Concentration of REGN10933 + REGN10987 in Serum Over Time (Ph1 Cohort 1, Ph2 Cohort 1, Ph3 Cohort 1 and Cohort 3) | Day 0: EOI | 594 mg/L | Standard Deviation 276 |
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (Placebo) | Concentration of REGN10933 + REGN10987 in Serum Over Time (Ph1 Cohort 1, Ph2 Cohort 1, Ph3 Cohort 1 and Cohort 3) | Day 28 | 141 mg/L | Standard Deviation 97.5 |
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (2.4 IV) | Concentration of REGN10933 + REGN10987 in Serum Over Time (Ph1 Cohort 1, Ph2 Cohort 1, Ph3 Cohort 1 and Cohort 3) | Day 0: EOI | 1652 mg/L | Standard Deviation 928 |
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (2.4 IV) | Concentration of REGN10933 + REGN10987 in Serum Over Time (Ph1 Cohort 1, Ph2 Cohort 1, Ph3 Cohort 1 and Cohort 3) | Day 28 | 384 mg/L | Standard Deviation 143 |
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (8.0 IV) | Concentration of REGN10933 + REGN10987 in Serum Over Time (Ph1 Cohort 1, Ph2 Cohort 1, Ph3 Cohort 1 and Cohort 3) | Day 0: EOI | 701 mg/L | Standard Deviation 287 |
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (8.0 IV) | Concentration of REGN10933 + REGN10987 in Serum Over Time (Ph1 Cohort 1, Ph2 Cohort 1, Ph3 Cohort 1 and Cohort 3) | Day 28 | 142 mg/L | Standard Deviation 62.5 |
| Phase 2 Asymptomatic (Placebo) | Concentration of REGN10933 + REGN10987 in Serum Over Time (Ph1 Cohort 1, Ph2 Cohort 1, Ph3 Cohort 1 and Cohort 3) | Day 0: EOI | 2142 mg/L | Standard Deviation 815 |
| Phase 2 Asymptomatic (Placebo) | Concentration of REGN10933 + REGN10987 in Serum Over Time (Ph1 Cohort 1, Ph2 Cohort 1, Ph3 Cohort 1 and Cohort 3) | Day 28 | 453 mg/L | Standard Deviation 179 |
| Phase 2 Asymptomatic (2.4g IV) | Concentration of REGN10933 + REGN10987 in Serum Over Time (Ph1 Cohort 1, Ph2 Cohort 1, Ph3 Cohort 1 and Cohort 3) | Day 0: EOI | 415 mg/L | Standard Deviation 178 |
| Phase 2 Asymptomatic (2.4g IV) | Concentration of REGN10933 + REGN10987 in Serum Over Time (Ph1 Cohort 1, Ph2 Cohort 1, Ph3 Cohort 1 and Cohort 3) | Day 28 | 85.1 mg/L | Standard Deviation 36.9 |
| Phase 2 Asymptomatic (8.0g IV) | Concentration of REGN10933 + REGN10987 in Serum Over Time (Ph1 Cohort 1, Ph2 Cohort 1, Ph3 Cohort 1 and Cohort 3) | Day 28 | 143 mg/L | Standard Deviation 55.1 |
| Phase 2 Asymptomatic (8.0g IV) | Concentration of REGN10933 + REGN10987 in Serum Over Time (Ph1 Cohort 1, Ph2 Cohort 1, Ph3 Cohort 1 and Cohort 3) | Day 0: EOI | 669 mg/L | Standard Deviation 236 |
| Phase 3 Cohort 1 (1.2g IV) Symptomatic | Concentration of REGN10933 + REGN10987 in Serum Over Time (Ph1 Cohort 1, Ph2 Cohort 1, Ph3 Cohort 1 and Cohort 3) | Day 28 | 463 mg/L | Standard Deviation 166 |
| Phase 3 Cohort 1 (1.2g IV) Symptomatic | Concentration of REGN10933 + REGN10987 in Serum Over Time (Ph1 Cohort 1, Ph2 Cohort 1, Ph3 Cohort 1 and Cohort 3) | Day 0: EOI | 2239 mg/L | Standard Deviation 740 |
| Phase 3 Cohort 2 Pediatric (Placebo) | Concentration of REGN10933 + REGN10987 in Serum Over Time (Ph1 Cohort 1, Ph2 Cohort 1, Ph3 Cohort 1 and Cohort 3) | Day 0: EOI | 305 mg/L | Standard Deviation 80.8 |
| Phase 3 Cohort 2 Pediatric (Placebo) | Concentration of REGN10933 + REGN10987 in Serum Over Time (Ph1 Cohort 1, Ph2 Cohort 1, Ph3 Cohort 1 and Cohort 3) | Day 28 | 63.7 mg/L | Standard Deviation 25.9 |
| Phase 3 Cohort 2 Pediatric (1.2g IV) | Concentration of REGN10933 + REGN10987 in Serum Over Time (Ph1 Cohort 1, Ph2 Cohort 1, Ph3 Cohort 1 and Cohort 3) | Day 0: EOI | 536 mg/L | Standard Deviation 165 |
| Phase 3 Cohort 2 Pediatric (1.2g IV) | Concentration of REGN10933 + REGN10987 in Serum Over Time (Ph1 Cohort 1, Ph2 Cohort 1, Ph3 Cohort 1 and Cohort 3) | Day 28 | 119 mg/L | Standard Deviation 31.1 |
Secondary
Concordance of RT-qPCR Results Over Time Between Different Sample Types (NP, Nasal, and Saliva) - (Phase 1 Only)
Phase 1 Only
Time frame: Up To Day 29
Population: Nasal and saliva sample collection was discontinued early in the study because nasopharyngeal samples were determined to be more reliable for quantitative analysis. Therefore, data was not collected for this outcome measure. The Phase 1/2 SAP does not specify any analyses related to nasal and saliva samples collections
Secondary
Correlation of RT-qPCR Results Over Time Between Different Sample Types (NP, Nasal, and Saliva) - (Phase 1 Only)
Phase 1 Only
Time frame: Up to Day 29
Population: Nasal and saliva sample collection was discontinued early in the study because nasopharyngeal samples were determined to be more reliable for quantitative analysis. Therefore, data was not collected for this outcome measure. The Phase 1/2 SAP does not specify any analyses related to nasal and saliva samples collections
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
Time frame: Through Day 29
Population: Participants that were ≥18 years old and not pregnant at randomization, and randomized on or before 17-Jan-2021 with detectable SARS-CoV-2 RNA by RT-qPCR in nasopharyngeal swabs at randomization and at least 1 risk factor for severe COVID-19 at baseline
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (Placebo) | 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) | 4.6 Cumulative Incidence Percentage |
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (2.4 IV) | 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) | 1.2 Cumulative Incidence Percentage |
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
Time frame: Through Day 29
Population: Participants that were ≥18 years old and not pregnant at randomization, and randomized on or before 17-Jan-2021 with detectable SARS-CoV-2 RNA by RT-qPCR in nasopharyngeal swabs at randomization and at least 1 risk factor for severe COVID-19 at baseline
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (Placebo) | 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) | 5.8 Cumulative Incidence Percentage |
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (2.4 IV) | 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) | 2.0 Cumulative Incidence Percentage |
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
Time frame: Through Day 29
Population: Participants that were ≥18 years old and not pregnant at randomization, and randomized on or before 17-Jan-2021 with detectable SARS-CoV-2 RNA by RT-qPCR in nasopharyngeal swabs at randomization and at least 1 risk factor for severe COVID-19 at baseline
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (Placebo) | Cumulative Incidence Percentage of Patients With COVID-19-related Hospitalization or All-cause Death Through Day 29 (Ph3 Cohort 1- 1.2g vs Placebo) | 3.2 Cumulative Incidence Percentage |
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (2.4 IV) | Cumulative Incidence Percentage of Patients With COVID-19-related Hospitalization or All-cause Death Through Day 29 (Ph3 Cohort 1- 1.2g vs Placebo) | 1.0 Cumulative Incidence Percentage |
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
Time frame: Through Day 29
Population: Participants that were ≥18 years old and not pregnant at randomization, and randomized on or before 17-Jan-2021 with detectable SARS-CoV-2 RNA by RT-qPCR in nasopharyngeal swabs at randomization and at least 1 risk factor for severe COVID-19 at baseline
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (Placebo) | Cumulative Incidence Percentage of Patients With COVID-19-related Hospitalization or All-cause Death Through Day 29 (Ph3 Cohort 1- 2.4g vs Placebo) | 4.6 Cumulative Incidence Percentage |
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (2.4 IV) | Cumulative Incidence Percentage of Patients With COVID-19-related Hospitalization or All-cause Death Through Day 29 (Ph3 Cohort 1- 2.4g vs Placebo) | 1.3 Cumulative Incidence Percentage |
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
Time frame: Through Day 29
Population: Participants that were ≥18 years old and not pregnant at randomization, and randomized on or before 17-Jan-2021 with detectable SARS-CoV-2 RNA by RT-qPCR in nasopharyngeal swabs at randomization and at least 1 risk factor for severe COVID-19 at baseline
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (Placebo) | 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) | 6.9 Cumulative Incidence Percentage |
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (2.4 IV) | 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) | 2.7 Cumulative Incidence Percentage |
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
Time frame: Through Day 29
Population: Participants that were ≥18 years old and not pregnant at randomization, and randomized on or before 17-Jan-2021 with detectable SARS-CoV-2 RNA by RT-qPCR in nasopharyngeal swabs at randomization and at least 1 risk factor for severe COVID-19 at baseline
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (Placebo) | 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) | 8.2 Cumulative Incidence Percentage |
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (2.4 IV) | 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) | 3.2 Cumulative Incidence Percentage |
Secondary
Duration of Symptoms Consistent With COVID-19 (Phase 2 Only)
Phase 2 Only
Time frame: Through Day 29
Population: Participants who were part of Phase 2 Asymptomatic modified Full Analysis Set (mFAS)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (Placebo) | Duration of Symptoms Consistent With COVID-19 (Phase 2 Only) | 12.6 Days | Standard Deviation 9.27 |
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (2.4 IV) | Duration of Symptoms Consistent With COVID-19 (Phase 2 Only) | 13.1 Days | Standard Deviation 9.34 |
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (8.0 IV) | Duration of Symptoms Consistent With COVID-19 (Phase 2 Only) | 14.4 Days | Standard Deviation 10.95 |
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
Time frame: Through Day 29
Population: The anti-drug antibody (ADA) analysis set (AAS) includes all subjects who received any study drug (safety population) and had at least one non-missing ADA result from the ADA assay after first dose of the study drug(s). Pooled participants will be analyzed according to the treatment actually received. This is an adaptive master protocol design, to allow for flexible adaptation for participants with symptomatic COVID-19, as well as with those with asymptomatic SARS-CoV-2.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (Placebo) | Immunogenicity as Measured by ADA to REGN10987 (Ph1 Cohort 1, Ph2 Cohort 1, Ph3 Cohort 1) | 59 Participants |
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (2.4 IV) | Immunogenicity as Measured by ADA to REGN10987 (Ph1 Cohort 1, Ph2 Cohort 1, Ph3 Cohort 1) | 56 Participants |
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (8.0 IV) | Immunogenicity as Measured by ADA to REGN10987 (Ph1 Cohort 1, Ph2 Cohort 1, Ph3 Cohort 1) | 54 Participants |
| Phase 2 Asymptomatic (Placebo) | Immunogenicity as Measured by ADA to REGN10987 (Ph1 Cohort 1, Ph2 Cohort 1, Ph3 Cohort 1) | 2 Participants |
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
Time frame: Through Day 29
Population: The anti-drug antibody (ADA) analysis set (AAS) includes all subjects who received any study drug (safety population) and had at least one non-missing ADA result from the ADA assay after first dose of the study drug(s). Participants will be analyzed according to the treatment actually received. This is an adaptive master protocol design, to allow for flexible adaptation for participants with symptomatic COVID-19, as well as with those with asymptomatic SARS-CoV-2.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (Placebo) | Immunogenicity as Measured by ADA to REGN10987 (Ph3 Cohort 2 and Cohort 3) | 0 Participants |
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (2.4 IV) | Immunogenicity as Measured by ADA to REGN10987 (Ph3 Cohort 2 and Cohort 3) | 1 Participants |
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (8.0 IV) | Immunogenicity as Measured by ADA to REGN10987 (Ph3 Cohort 2 and Cohort 3) | 0 Participants |
| Phase 2 Asymptomatic (Placebo) | Immunogenicity as Measured by ADA to REGN10987 (Ph3 Cohort 2 and Cohort 3) | 0 Participants |
| Phase 2 Asymptomatic (2.4g IV) | Immunogenicity as Measured by ADA to REGN10987 (Ph3 Cohort 2 and Cohort 3) | 2 Participants |
| Phase 2 Asymptomatic (8.0g IV) | Immunogenicity as Measured by ADA to REGN10987 (Ph3 Cohort 2 and Cohort 3) | 1 Participants |
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
Time frame: Through Day 29
Population: The anti-drug antibody (ADA) analysis set (AAS) includes all subjects who received any study drug (safety population) and had at least one non-missing ADA result from the ADA assay after first dose of the study drug(s). Pooled participants will be analyzed according to the treatment actually received. This is an adaptive master protocol design, to allow for flexible adaptation for participants with symptomatic COVID-19, as well as with those with asymptomatic SARS-CoV-2.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (Placebo) | Immunogenicity as Measured by Anti-drug (ADA) to REGN10933 (Ph1 Cohort 1, Ph2 Cohort 1, Ph3 Cohort 1) | 17 Participants |
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (2.4 IV) | Immunogenicity as Measured by Anti-drug (ADA) to REGN10933 (Ph1 Cohort 1, Ph2 Cohort 1, Ph3 Cohort 1) | 29 Participants |
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (8.0 IV) | Immunogenicity as Measured by Anti-drug (ADA) to REGN10933 (Ph1 Cohort 1, Ph2 Cohort 1, Ph3 Cohort 1) | 20 Participants |
| Phase 2 Asymptomatic (Placebo) | Immunogenicity as Measured by Anti-drug (ADA) to REGN10933 (Ph1 Cohort 1, Ph2 Cohort 1, Ph3 Cohort 1) | 1 Participants |
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
Time frame: Through Day 29
Population: The anti-drug antibody (ADA) analysis set (AAS) includes all subjects who received any study drug (safety population) and had at least one non-missing ADA result from the ADA assay after first dose of the study drug(s). Participants will be analyzed according to the treatment actually received. This is an adaptive master protocol design, to allow for flexible adaptation for participants with symptomatic COVID-19, as well as with those with asymptomatic SARS-CoV-2.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (Placebo) | Immunogenicity as Measured by Anti-drug (ADA) to REGN10933 (Ph3 Cohort 2 - Cohort 3) | 0 Participants |
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (2.4 IV) | Immunogenicity as Measured by Anti-drug (ADA) to REGN10933 (Ph3 Cohort 2 - Cohort 3) | 1 Participants |
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (8.0 IV) | Immunogenicity as Measured by Anti-drug (ADA) to REGN10933 (Ph3 Cohort 2 - Cohort 3) | 0 Participants |
| Phase 2 Asymptomatic (Placebo) | Immunogenicity as Measured by Anti-drug (ADA) to REGN10933 (Ph3 Cohort 2 - Cohort 3) | 0 Participants |
| Phase 2 Asymptomatic (2.4g IV) | Immunogenicity as Measured by Anti-drug (ADA) to REGN10933 (Ph3 Cohort 2 - Cohort 3) | 0 Participants |
| Phase 2 Asymptomatic (8.0g IV) | Immunogenicity as Measured by Anti-drug (ADA) to REGN10933 (Ph3 Cohort 2 - Cohort 3) | 1 Participants |
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
Time frame: Through Day 29
Population: The anti-drug antibody (ADA) analysis set (AAS) includes all subjects who received any study drug (safety population) and had at least one non-missing ADA result from the ADA assay after first dose of the study drug(s). Participants will be analyzed according to the treatment actually received.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (Placebo) | Immunogenicity as Measured by NAbs to REGN10987 (Ph3 Cohort 2 - Cohort 3) | 0 Participants |
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (2.4 IV) | Immunogenicity as Measured by NAbs to REGN10987 (Ph3 Cohort 2 - Cohort 3) | 1 Participants |
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (8.0 IV) | Immunogenicity as Measured by NAbs to REGN10987 (Ph3 Cohort 2 - Cohort 3) | 0 Participants |
| Phase 2 Asymptomatic (Placebo) | Immunogenicity as Measured by NAbs to REGN10987 (Ph3 Cohort 2 - Cohort 3) | 00 Participants |
| Phase 2 Asymptomatic (2.4g IV) | Immunogenicity as Measured by NAbs to REGN10987 (Ph3 Cohort 2 - Cohort 3) | 0 Participants |
| Phase 2 Asymptomatic (8.0g IV) | Immunogenicity as Measured by NAbs to REGN10987 (Ph3 Cohort 2 - Cohort 3) | 0 Participants |
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
Time frame: Through Day 29
Population: The anti-drug antibody (ADA) analysis set (AAS) includes all subjects who received any study drug (safety population) and had at least one non-missing ADA result from the ADA assay after first dose of the study drug(s). Participants will be analyzed according to the treatment actually received. This is an adaptive master protocol design, to allow for flexible adaptation for participants with symptomatic COVID-19, as well as with those with asymptomatic SARS-CoV-2.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (Placebo) | Immunogenicity as Measured by Neutralizing Antibodies (NAbs) to REGN10933 (Ph3 Cohort 2, Ph3 Cohort 3) | 0 Participants |
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (2.4 IV) | Immunogenicity as Measured by Neutralizing Antibodies (NAbs) to REGN10933 (Ph3 Cohort 2, Ph3 Cohort 3) | 0 Participants |
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (8.0 IV) | Immunogenicity as Measured by Neutralizing Antibodies (NAbs) to REGN10933 (Ph3 Cohort 2, Ph3 Cohort 3) | 0 Participants |
| Phase 2 Asymptomatic (Placebo) | Immunogenicity as Measured by Neutralizing Antibodies (NAbs) to REGN10933 (Ph3 Cohort 2, Ph3 Cohort 3) | 0 Participants |
| Phase 2 Asymptomatic (2.4g IV) | Immunogenicity as Measured by Neutralizing Antibodies (NAbs) to REGN10933 (Ph3 Cohort 2, Ph3 Cohort 3) | 0 Participants |
| Phase 2 Asymptomatic (8.0g IV) | Immunogenicity as Measured by Neutralizing Antibodies (NAbs) to REGN10933 (Ph3 Cohort 2, Ph3 Cohort 3) | 0 Participants |
Secondary
Number of Days of Hospitalization Due to COVID-19 (Ph3 Cohort 1) Placebo vs. 1.2g IV
Phase 3 (Cohort 1)
Time frame: Through Day 29
Population: Participants that were ≥18 years old and not pregnant at randomization, and randomized on or before 17-Jan-2021 with detectable SARS-CoV-2 RNA by RT-qPCR in nasopharyngeal swabs at randomization and at least 1 risk factor for severe COVID-19 at baseline
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (Placebo) | Number of Days of Hospitalization Due to COVID-19 (Ph3 Cohort 1) Placebo vs. 1.2g IV | 10.0 Days | Standard Deviation 7.16 |
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (2.4 IV) | Number of Days of Hospitalization Due to COVID-19 (Ph3 Cohort 1) Placebo vs. 1.2g IV | 7.0 Days | Standard Deviation 8.04 |
Secondary
Number of Days of Hospitalization Due to COVID-19 (Ph3 Cohort 1) Placebo vs. 2.4g IV
Phase 3 (Cohort 1)
Time frame: Through Day 29
Population: Participants that were ≥18 years old and not pregnant at randomization, and randomized on or before 17-Jan-2021 with detectable SARS-CoV-2 RNA by RT-qPCR in nasopharyngeal swabs at randomization and at least 1 risk factor for severe COVID-19 at baseline
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (Placebo) | Number of Days of Hospitalization Due to COVID-19 (Ph3 Cohort 1) Placebo vs. 2.4g IV | 8.4 Days | Standard Deviation 6.74 |
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (2.4 IV) | Number of Days of Hospitalization Due to COVID-19 (Ph3 Cohort 1) Placebo vs. 2.4g IV | 7.0 Days | Standard Deviation 8.04 |
Secondary
Number of Days of Hospitalization Due to COVID-19 (Ph3 Cohort 2)
Phase 3 (Cohort 2)
Time frame: Through Day 29
Population: Participants \<18 years old who, at baseline, were not pregnant, had symptomatic COVID-19, and had at least 1 risk factor for developing severe disease. No participants were hospitalized, therefore no hospitalizations days took place.
Secondary
Number of Days of Hospitalization Due to COVID-19 (Phase 2 Asymptomatic)
Phase 2 Only
Time frame: Up to Day 29
Population: Phase 2 asymptomatic cohort. No participants were hospitalized, therefore no hospitalizations days took place.
Secondary
Number of Participants Admitted to a Hospital Due to COVID-19 (Phase 1, Phase 2)
Phase 1, Phase 2
Time frame: Through Day 29
Population: All pooled randomized participants in Phase 1 or Phase 2 with qualitatively positive RT-qPCR in NP swab samples at randomization or collected within 2 hours after study drug infusion was initiated. This modified full analysis set (mFAS) includes all randomized patients with positive RT-qPCR in NP swab samples at randomization and is based on the treatment allocated (as randomized).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (Placebo) | Number of Participants Admitted to a Hospital Due to COVID-19 (Phase 1, Phase 2) | 1 Number Participants |
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (2.4 IV) | Number of Participants Admitted to a Hospital Due to COVID-19 (Phase 1, Phase 2) | 0 Number Participants |
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (8.0 IV) | Number of Participants Admitted to a Hospital Due to COVID-19 (Phase 1, Phase 2) | 0 Number Participants |
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)
Time frame: Through Day 29
Population: Participants \<18 years old who, at baseline, were not pregnant, had symptomatic COVID-19, and had at least 1 risk factor for developing severe disease
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (Placebo) | Number of Participants With at Least One (≥1) COVID-19-related Hospitalization or All-cause Death (Phase 3 Cohort 2) | 0 Participants |
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (2.4 IV) | Number of Participants With at Least One (≥1) COVID-19-related Hospitalization or All-cause Death (Phase 3 Cohort 2) | 0 Participants |
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (8.0 IV) | Number of Participants With at Least One (≥1) COVID-19-related Hospitalization or All-cause Death (Phase 3 Cohort 2) | 0 Participants |
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)
Time frame: Through Day 29
Population: Participants \<18 years old who, at baseline, were not pregnant, had symptomatic COVID-19, and had at least 1 risk factor for developing severe disease
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (Placebo) | 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) | 0 Participants |
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (2.4 IV) | 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) | 2 Participants |
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (8.0 IV) | 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) | 1 Participants |
Secondary
Number of Participants With Viral Loads Below the Limit of Detection at Each Visit - (Phase 2 Only)
Phase 2 Only
Time frame: Through Day 29
Population: In light of evolving information concerning SARS-CoV-2 infection, including the profile of viral load among patients and the adequacy of sampling methodologies, virologic efficacy endpoints and sampling methods were modified during the course of the study
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (Placebo) | Number of Participants With Viral Loads Below the Limit of Detection at Each Visit - (Phase 2 Only) | Day 15 | 36 Number of Participants |
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (Placebo) | Number of Participants With Viral Loads Below the Limit of Detection at Each Visit - (Phase 2 Only) | Day 7 | 18 Number of Participants |
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (Placebo) | Number of Participants With Viral Loads Below the Limit of Detection at Each Visit - (Phase 2 Only) | Day 0 (Baseline) | 0 Number of Participants |
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (Placebo) | Number of Participants With Viral Loads Below the Limit of Detection at Each Visit - (Phase 2 Only) | Day 5 | 14 Number of Participants |
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (Placebo) | Number of Participants With Viral Loads Below the Limit of Detection at Each Visit - (Phase 2 Only) | Day 29 | 48 Number of Participants |
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (2.4 IV) | Number of Participants With Viral Loads Below the Limit of Detection at Each Visit - (Phase 2 Only) | Day 7 | 22 Number of Participants |
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (2.4 IV) | Number of Participants With Viral Loads Below the Limit of Detection at Each Visit - (Phase 2 Only) | Day 0 (Baseline) | 0 Number of Participants |
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (2.4 IV) | Number of Participants With Viral Loads Below the Limit of Detection at Each Visit - (Phase 2 Only) | Day 5 | 15 Number of Participants |
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (2.4 IV) | Number of Participants With Viral Loads Below the Limit of Detection at Each Visit - (Phase 2 Only) | Day 15 | 39 Number of Participants |
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (2.4 IV) | Number of Participants With Viral Loads Below the Limit of Detection at Each Visit - (Phase 2 Only) | Day 29 | 44 Number of Participants |
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (8.0 IV) | Number of Participants With Viral Loads Below the Limit of Detection at Each Visit - (Phase 2 Only) | Day 29 | 36 Number of Participants |
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (8.0 IV) | Number of Participants With Viral Loads Below the Limit of Detection at Each Visit - (Phase 2 Only) | Day 15 | 32 Number of Participants |
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (8.0 IV) | Number of Participants With Viral Loads Below the Limit of Detection at Each Visit - (Phase 2 Only) | Day 0 (Baseline) | 0 Number of Participants |
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (8.0 IV) | Number of Participants With Viral Loads Below the Limit of Detection at Each Visit - (Phase 2 Only) | Day 7 | 14 Number of Participants |
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (8.0 IV) | Number of Participants With Viral Loads Below the Limit of Detection at Each Visit - (Phase 2 Only) | Day 5 | 10 Number of Participants |
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)
Time frame: Through Day 29
Population: Participants that were ≥18 years old and not pregnant at randomization, and randomized on or before 17-Jan-2021 with detectable SARS-CoV-2 RNA by RT-qPCR in nasopharyngeal swabs at randomization and at least 1 risk factor for severe COVID-19 at baseline
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (Placebo) | Percentage of Participants Admitted to an Intensive Care Unit (ICU) Due to COVID-19 - (Ph 3 Cohort 1) Placebo vs. 2.4g IV | 1.3 Percentage of Participants |
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (2.4 IV) | Percentage of Participants Admitted to an Intensive Care Unit (ICU) Due to COVID-19 - (Ph 3 Cohort 1) Placebo vs. 2.4g IV | 0.4 Percentage of Participants |
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
Time frame: Through Day 29
Population: All randomized participants pooled in Phase 1 or Phase 2 with qualitatively positive RT-qPCR in NP swab samples at randomization or collected within 2 hours after study drug infusion was initiated. This modified full analysis set (mFAS) includes all randomized patients with positive RT-qPCR in NP swab samples at randomization and is based on the treatment allocated (as randomized).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (Placebo) | Percentage of Participants With ≥1 COVID-19 Related Hospitalization, Emergency Room, or Urgent Care Visit Through Day 29 (Ph1, Ph2) | 4.7 Percentage of Participants |
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (2.4 IV) | Percentage of Participants With ≥1 COVID-19 Related Hospitalization, Emergency Room, or Urgent Care Visit Through Day 29 (Ph1, Ph2) | 2.7 Percentage of Participants |
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (8.0 IV) | Percentage of Participants With ≥1 COVID-19 Related Hospitalization, Emergency Room, or Urgent Care Visit Through Day 29 (Ph1, Ph2) | 2.3 Percentage of Participants |
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
Time frame: Through Day 29
Population: All randomized participants in Phase 1 or Phase 2 with qualitatively positive RT-qPCR in NP swab samples at randomization or collected within 2 hours after study drug infusion was initiated. This modified full analysis set (mFAS) includes all randomized patients with positive RT-qPCR in NP swab samples at randomization and is based on the treatment allocated (as randomized).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (Placebo) | Percentage of Participants With ≥1 COVID-19-related Medically-attended Visit (Phase 1, Phase 2) | 7.8 Percentage of Participants |
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (2.4 IV) | Percentage of Participants With ≥1 COVID-19-related Medically-attended Visit (Phase 1, Phase 2) | 3.2 Percentage of Participants |
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (8.0 IV) | Percentage of Participants With ≥1 COVID-19-related Medically-attended Visit (Phase 1, Phase 2) | 2.7 Percentage of Participants |
Secondary
Percentage of Participants With ≥1 COVID-19-related Medically-attended Visit Through Day 29 (Ph1, Ph2)
Phase 1, Phase 2
Time frame: Through Day 29
Population: All randomized participants pooled in Phase 1 or Phase 2 with qualitatively positive RT-qPCR in NP swab samples at randomization or collected within 2 hours after study drug infusion was initiated. This modified full analysis set (mFAS) includes all randomized patients with positive RT-qPCR in NP swab samples at randomization and is based on the treatment allocated (as randomized).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (Placebo) | Percentage of Participants With ≥1 COVID-19-related Medically-attended Visit Through Day 29 (Ph1, Ph2) | 7.8 Percentage of Participants |
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (2.4 IV) | Percentage of Participants With ≥1 COVID-19-related Medically-attended Visit Through Day 29 (Ph1, Ph2) | 3.2 Percentage of Participants |
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (8.0 IV) | Percentage of Participants With ≥1 COVID-19-related Medically-attended Visit Through Day 29 (Ph1, Ph2) | 2.7 Percentage of Participants |
Secondary
Percentage of Participants With ≥2 COVID-19-related Medically-attended Visit - (Ph3 Cohort 1) - Placebo vs. 1.2g IV
Phase 3 (Cohort 1)
Time frame: Through Day 29
Population: Participants that were ≥18 years old and not pregnant at randomization, and randomized on or before 17-Jan-2021 with detectable SARS-CoV-2 RNA by RT-qPCR in nasopharyngeal swabs at randomization and at least 1 risk factor for severe COVID-19 at baseline
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (Placebo) | Percentage of Participants With ≥2 COVID-19-related Medically-attended Visit - (Ph3 Cohort 1) - Placebo vs. 1.2g IV | 0.5 Percentage of Participants |
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (2.4 IV) | Percentage of Participants With ≥2 COVID-19-related Medically-attended Visit - (Ph3 Cohort 1) - Placebo vs. 1.2g IV | 0.4 Percentage of Participants |
Secondary
Percentage of Participants With ≥2 COVID-19-related Medically-attended Visit - (Ph3 Cohort 1) - Placebo vs. 2.4g IV
Phase 3 Cohort 1
Time frame: Through Day 29
Population: Participants that were ≥18 years old and not pregnant at randomization, and randomized on or before 17-Jan-2021 with detectable SARS-CoV-2 RNA by RT-qPCR in nasopharyngeal swabs at randomization and at least 1 risk factor for severe COVID-19 at baseline
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (Placebo) | Percentage of Participants With ≥2 COVID-19-related Medically-attended Visit - (Ph3 Cohort 1) - Placebo vs. 2.4g IV | 1.1 Percentage of Participants |
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (2.4 IV) | Percentage of Participants With ≥2 COVID-19-related Medically-attended Visit - (Ph3 Cohort 1) - Placebo vs. 2.4g IV | 0.07 Percentage of Participants |
Secondary
Percentage of Participants With All-Cause Death (Ph3 Cohort 1) Placebo vs. 1.2g
Phase 3 Cohort 1
Time frame: by Day 29, Day 120, and Day 169
Population: Participants that were ≥18 years old and not pregnant at randomization, and randomized on or before 17-Jan-2021 with detectable SARS-CoV-2 RNA by RT-qPCR in nasopharyngeal swabs at randomization and at least 1 risk factor for severe COVID-19 at baseline
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (Placebo) | Percentage of Participants With All-Cause Death (Ph3 Cohort 1) Placebo vs. 1.2g | by Day 29 | 0.1 Percentage of Participants |
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (Placebo) | Percentage of Participants With All-Cause Death (Ph3 Cohort 1) Placebo vs. 1.2g | by Day 120 | 0.1 Percentage of Participants |
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (Placebo) | Percentage of Participants With All-Cause Death (Ph3 Cohort 1) Placebo vs. 1.2g | by Day 169 | 0.1 Percentage of Participants |
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (2.4 IV) | Percentage of Participants With All-Cause Death (Ph3 Cohort 1) Placebo vs. 1.2g | by Day 29 | 0.1 Percentage of Participants |
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (2.4 IV) | Percentage of Participants With All-Cause Death (Ph3 Cohort 1) Placebo vs. 1.2g | by Day 120 | 0.1 Percentage of Participants |
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (2.4 IV) | Percentage of Participants With All-Cause Death (Ph3 Cohort 1) Placebo vs. 1.2g | by Day 169 | 0.1 Percentage of Participants |
Secondary
Percentage of Participants With All-Cause Death (Ph3 Cohort 1) Placebo vs. 2.4g
Phase 3 Cohort 1 Placebo vs. 2.4g IV
Time frame: by Day 29, Day 120, and Day 169
Population: Participants that were ≥18 years old and not pregnant at randomization, and randomized on or before 17-Jan-2021 with detectable SARS-CoV-2 RNA by RT-qPCR in nasopharyngeal swabs at randomization and at least 1 risk factor for severe COVID-19 at baseline
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (Placebo) | Percentage of Participants With All-Cause Death (Ph3 Cohort 1) Placebo vs. 2.4g | by Day 29 | 0.2 Percentage of Participants |
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (Placebo) | Percentage of Participants With All-Cause Death (Ph3 Cohort 1) Placebo vs. 2.4g | by Day 120 | 0.4 Percentage of Participants |
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (Placebo) | Percentage of Participants With All-Cause Death (Ph3 Cohort 1) Placebo vs. 2.4g | by Day 169 | 0.1 Percentage of Participants |
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (2.4 IV) | Percentage of Participants With All-Cause Death (Ph3 Cohort 1) Placebo vs. 2.4g | by Day 29 | 0.07 Percentage of Participants |
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (2.4 IV) | Percentage of Participants With All-Cause Death (Ph3 Cohort 1) Placebo vs. 2.4g | by Day 120 | 0.07 Percentage of Participants |
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (2.4 IV) | Percentage of Participants With All-Cause Death (Ph3 Cohort 1) Placebo vs. 2.4g | by Day 169 | 0.07 Percentage of Participants |
Secondary
Proportion of Participants Admitted to an Intensive Care Unit (ICU) Due to COVID-19 - (Next Phase 2) #87
Next Phase 2
Time frame: Through Day 29
Population: Participants analyzed are part of modified Full Analysis Set (mFAS) and have documented status at baseline. Next Phase 2 participants included the next 524 participants randomized to Phase 2 subsequent to the first 275 symptomatic participants randomized in Phase 1 / 2
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (Placebo) | Proportion of Participants Admitted to an Intensive Care Unit (ICU) Due to COVID-19 - (Next Phase 2) #87 | 0 Participants |
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (2.4 IV) | Proportion of Participants Admitted to an Intensive Care Unit (ICU) Due to COVID-19 - (Next Phase 2) #87 | 0 Participants |
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (8.0 IV) | Proportion of Participants Admitted to an Intensive Care Unit (ICU) Due to COVID-19 - (Next Phase 2) #87 | 0 Participants |
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)
Time frame: Through Day 29
Population: Participants that were ≥18 years old and not pregnant at randomization, and randomized on or before 17-Jan-2021 with detectable SARS-CoV-2 RNA by RT-qPCR in nasopharyngeal swabs at randomization and at least 1 risk factor for severe COVID-19 at baseline
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (Placebo) | Proportion of Participants Admitted to an Intensive Care Unit (ICU) Due to COVID-19 - (Ph 3 Cohort 1) Placebo vs. 1.2g IV | 0.9 Proportion of Participants |
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (2.4 IV) | Proportion of Participants Admitted to an Intensive Care Unit (ICU) Due to COVID-19 - (Ph 3 Cohort 1) Placebo vs. 1.2g IV | 0.4 Proportion of Participants |
Secondary
Proportion of Participants Admitted to an Intensive Care Unit (ICU) Due to COVID-19 - (Ph 3 Cohort 2)
Phase 3 (Cohort 2)
Time frame: Through Day 29
Population: Participants \<18 years old who, at baseline, were not pregnant, had symptomatic COVID-19, and had at least 1 risk factor for developing severe disease
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (Placebo) | Proportion of Participants Admitted to an Intensive Care Unit (ICU) Due to COVID-19 - (Ph 3 Cohort 2) | 0 Participants |
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (2.4 IV) | Proportion of Participants Admitted to an Intensive Care Unit (ICU) Due to COVID-19 - (Ph 3 Cohort 2) | 0 Participants |
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (8.0 IV) | Proportion of Participants Admitted to an Intensive Care Unit (ICU) Due to COVID-19 - (Ph 3 Cohort 2) | 0 Participants |
Secondary
Proportion of Participants Requiring Mechanical Ventilation Due to COVID-19 (Ph3 Cohort 1- 1.2g vs Placebo)
Time frame: Through Day 29
Population: Participants that were ≥18 years old and not pregnant at randomization, and randomized on or before 17-Jan-2021 with detectable SARS-CoV-2 RNA by RT-qPCR in nasopharyngeal swabs at randomization and at least 1 risk factor for severe COVID-19 at baseline
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (Placebo) | Proportion of Participants Requiring Mechanical Ventilation Due to COVID-19 (Ph3 Cohort 1- 1.2g vs Placebo) | 0.3 Percentage of Participants |
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (2.4 IV) | Proportion of Participants Requiring Mechanical Ventilation Due to COVID-19 (Ph3 Cohort 1- 1.2g vs Placebo) | 0.1 Percentage of Participants |
Secondary
Proportion of Participants Requiring Mechanical Ventilation Due to COVID-19 (Ph3 Cohort 1- 2.4g vs Placebo)
Time frame: Through Day 29
Population: Participants that were ≥18 years old and not pregnant at randomization, and randomized on or before 17-Jan-2021 with detectable SARS-CoV-2 RNA by RT-qPCR in nasopharyngeal swabs at randomization and at least 1 risk factor for severe COVID-19 at baseline
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (Placebo) | Proportion of Participants Requiring Mechanical Ventilation Due to COVID-19 (Ph3 Cohort 1- 2.4g vs Placebo) | 0.4 Proportion of Participants |
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (2.4 IV) | Proportion of Participants Requiring Mechanical Ventilation Due to COVID-19 (Ph3 Cohort 1- 2.4g vs Placebo) | 0.0007 Proportion of Participants |
Secondary
Proportion of Participants Requiring Mechanical Ventilation Due to COVID-19 (Phase 3 Cohort 2)
Phase 3 (Cohort 2)
Time frame: Through Day 29
Population: There were 0 events in this endpoint. Phase 3 Cohort 2 data was not analyzed for this endpoint as there were 0 events in in this cohort
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (Placebo) | Proportion of Participants Requiring Mechanical Ventilation Due to COVID-19 (Phase 3 Cohort 2) | 0 Percent |
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (2.4 IV) | Proportion of Participants Requiring Mechanical Ventilation Due to COVID-19 (Phase 3 Cohort 2) | 0 Percent |
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (8.0 IV) | Proportion of Participants Requiring Mechanical Ventilation Due to COVID-19 (Phase 3 Cohort 2) | 0 Percent |
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
Time frame: Through Day 29
Population: Participants that were ≥18 years old and not pregnant at randomization, and randomized on or before 17-Jan-2021 with detectable SARS-CoV-2 RNA by RT-qPCR in nasopharyngeal swabs at randomization and at least 1 risk factor for severe COVID-19 at baseline
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (Placebo) | Proportion of Participants Requiring Supplemental Oxygen Due to COVID-19 by Day 29 (Ph3 Cohort 1- 1.2g vs Placebo) | 2.1 Percentage of Participants |
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (2.4 IV) | Proportion of Participants Requiring Supplemental Oxygen Due to COVID-19 by Day 29 (Ph3 Cohort 1- 1.2g vs Placebo) | 0.5 Percentage of Participants |
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
Time frame: Through Day 29
Population: Participants that were ≥18 years old and not pregnant at randomization, and randomized on or before 17-Jan-2021 with detectable SARS-CoV-2 RNA by RT-qPCR in nasopharyngeal swabs at randomization and at least 1 risk factor for severe COVID-19 at baseline
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (Placebo) | Proportion of Participants Requiring Supplemental Oxygen Due to COVID-19 by Day 29 (Ph3 Cohort 1- 2.4g vs Placebo) | 3.6 Percentage of Participants |
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (2.4 IV) | Proportion of Participants Requiring Supplemental Oxygen Due to COVID-19 by Day 29 (Ph3 Cohort 1- 2.4g vs Placebo) | 1.0 Percentage of Participants |
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
Time frame: Through Day 29
Population: Participants that were ≥18 years old and not pregnant at randomization, and randomized on or before 17-Jan-2021 with detectable SARS-CoV-2 RNA by RT-qPCR in nasopharyngeal swabs at randomization and at least 1 risk factor for severe COVID-19 at baseline
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (Placebo) | Proportion of Participants With ≥1 COVID-19-related Hospitalization, Emergency Room Visit, or All-cause Death (Ph3 Cohort 1) - Placebo vs. 1.2g IV | 51 Participants |
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (2.4 IV) | Proportion of Participants With ≥1 COVID-19-related Hospitalization, Emergency Room Visit, or All-cause Death (Ph3 Cohort 1) - Placebo vs. 1.2g IV | 20 Participants |
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)
Time frame: Through day 29
Population: Participants that were ≥18 years old and not pregnant at randomization, and randomized on or before 17-Jan-2021 with detectable SARS-CoV-2 RNA by RT-qPCR in nasopharyngeal swabs at randomization and at least 1 risk factor for severe COVID-19 at baseline
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (Placebo) | Proportion of Participants With ≥1 COVID-19-related Hospitalization, Emergency Room Visit, or All-cause Death (Ph3 Cohort 1) - Placebo vs. 2.4g IV | 62 Participants |
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (2.4 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 | 18 Participants |
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)
Time frame: Day 4 thru Day 29
Population: Participants that were ≥18 years old and not pregnant at randomization, and randomized on or before 17-Jan-2021 with detectable SARS-CoV-2 RNA by RT-qPCR in nasopharyngeal swabs at randomization and at least 1 risk factor for severe COVID-19 at baseline
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (Placebo) | 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) | 5 Participants |
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (2.4 IV) | 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) | 18 Participants |
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)
Time frame: From Day 4 Through Day 29
Population: Participants that were ≥18 years old and not pregnant at randomization, and randomized on or before 17-Jan-2021 with detectable SARS-CoV-2 RNA by RT-qPCR in nasopharyngeal swabs at randomization and at least 1 risk factor for severe COVID-19 at baseline
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (Placebo) | 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) | 46 Participants |
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (2.4 IV) | 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) | 5 Participants |
Secondary
Proportion of Participants With All-cause Mortality (Phase 2 Asymptomatic)
Phase 2 Asymptomatic
Time frame: Through Day 29
Population: Phase 2 asymptomatic cohort
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (Placebo) | Proportion of Participants With All-cause Mortality (Phase 2 Asymptomatic) | 0 Participants |
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (2.4 IV) | Proportion of Participants With All-cause Mortality (Phase 2 Asymptomatic) | 0 Participants |
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (8.0 IV) | Proportion of Participants With All-cause Mortality (Phase 2 Asymptomatic) | 0 Participants |
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
Time frame: Day 4 Through Day 29
Population: Participants that were ≥18 years old and not pregnant at randomization, and randomized on or before 17-Jan-2021 with detectable SARS-CoV-2 RNA by RT-qPCR in nasopharyngeal swabs at randomization and at least 1 risk factor for severe COVID-19 at baseline
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (Placebo) | 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) | 2.4 Percentage of Participants |
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (2.4 IV) | 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) | 0.7 Percentage of Participants |
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
Time frame: Day 4 Through Day 29
Population: Participants that were ≥18 years old and not pregnant at randomization, and randomized on or before 17-Jan-2021 with detectable SARS-CoV-2 RNA by RT-qPCR in nasopharyngeal swabs at randomization and at least 1 risk factor for severe COVID-19 at baseline
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (Placebo) | 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) | 3.4 Percentage of Participants |
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (2.4 IV) | 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) | 0.4 Percentage of Participants |
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
Time frame: Through Day 29
Population: Participants that were ≥18 years old and not pregnant at randomization, and randomized on or before 17-Jan-2021 with detectable SARS-CoV-2 RNA by RT-qPCR in nasopharyngeal swabs at randomization and at least 1 risk factor for severe COVID-19 at baseline
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (Placebo) | 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) | Hospitalization | 3.1 Percentage of Participants |
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (Placebo) | 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) | Emergency Room | 1.3 Percentage of Participants |
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (Placebo) | 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) | Urgent Care | 0.7 Percentage of Participants |
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (Placebo) | 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) | Physician office visit/Telemedicine | 1.6 Percentage of Participants |
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (2.4 IV) | 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) | Physician office visit/Telemedicine | 1.4 Percentage of Participants |
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (2.4 IV) | 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) | Hospitalization | 0.8 Percentage of Participants |
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (2.4 IV) | 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) | Urgent Care | 0.1 Percentage of Participants |
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (2.4 IV) | 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) | Emergency Room | 0.3 Percentage of Participants |
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
Time frame: Through Day 29
Population: Participants that were ≥18 years old and not pregnant at randomization, and randomized on or before 17-Jan-2021 with detectable SARS-CoV-2 RNA by RT-qPCR in nasopharyngeal swabs at randomization and at least 1 risk factor for severe COVID-19 at baseline
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (Placebo) | 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) | Hospitalization | 4.4 Percentage of Participants |
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (Placebo) | 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) | Emergency Room | 1.2 Percentage of Participants |
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (Placebo) | 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) | Urgent Care | 0.5 Percentage of Participants |
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (Placebo) | 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) | Physician office visit/Telemedicine | 1.8 Percentage of Participants |
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (2.4 IV) | 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) | Physician office visit/Telemedicine | 1.0 Percentage of Participants |
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (2.4 IV) | 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) | Hospitalization | 1.3 Percentage of Participants |
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (2.4 IV) | 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) | Urgent Care | 0.2 Percentage of Participants |
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (2.4 IV) | 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) | Emergency Room | 0.7 Percentage of Participants |
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
Time frame: Through Day 29
Population: Participants that were ≥18 years old and not pregnant at randomization, and randomized on or before 17-Jan-2021 with detectable SARS-CoV-2 RNA by RT-qPCR in nasopharyngeal swabs at randomization and at least 1 risk factor for severe COVID-19 at baseline
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (Placebo) | 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) | 6.8 Percentage of Participants |
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (2.4 IV) | 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) | 2.7 Percentage of Participants |
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
Time frame: Through Day 29
Population: Participants that were ≥18 years old and not pregnant at randomization, and randomized on or before 17-Jan-2021 with detectable SARS-CoV-2 RNA by RT-qPCR in nasopharyngeal swabs at randomization and at least 1 risk factor for severe COVID-19 at baseline
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (Placebo) | 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) | 8.1 Percentage of Participants |
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (2.4 IV) | 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) | 3.2 Percentage of Participants |
Secondary
Proportion of Participants With High Viral Load at Each Visit - (Phase 2 Only)
Next Phase 2 Only
Time frame: Through Day 29
Population: In light of evolving information concerning SARS-CoV-2 infection, including the profile of viral load among patients and the adequacy of sampling methodologies, virologic efficacy endpoints and sampling methods were modified during the course of the study.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (Placebo) | Proportion of Participants With High Viral Load at Each Visit - (Phase 2 Only) | Day 15 | 10.0 Percentage of Participants |
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (Placebo) | Proportion of Participants With High Viral Load at Each Visit - (Phase 2 Only) | Day 7 | 48.9 Percentage of Participants |
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (Placebo) | Proportion of Participants With High Viral Load at Each Visit - (Phase 2 Only) | Day 3 | 77.2 Percentage of Participants |
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (Placebo) | Proportion of Participants With High Viral Load at Each Visit - (Phase 2 Only) | Day 5 | 61.4 Percentage of Participants |
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (Placebo) | Proportion of Participants With High Viral Load at Each Visit - (Phase 2 Only) | Day 29 | 0 Percentage of Participants |
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (2.4 IV) | Proportion of Participants With High Viral Load at Each Visit - (Phase 2 Only) | Day 3 | 67.4 Percentage of Participants |
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (2.4 IV) | Proportion of Participants With High Viral Load at Each Visit - (Phase 2 Only) | Day 5 | 47.0 Percentage of Participants |
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (2.4 IV) | Proportion of Participants With High Viral Load at Each Visit - (Phase 2 Only) | Day 7 | 31.3 Percentage of Participants |
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (2.4 IV) | Proportion of Participants With High Viral Load at Each Visit - (Phase 2 Only) | Day 15 | 5.1 Percentage of Participants |
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (2.4 IV) | Proportion of Participants With High Viral Load at Each Visit - (Phase 2 Only) | Day 29 | 2.0 Percentage of Participants |
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (8.0 IV) | Proportion of Participants With High Viral Load at Each Visit - (Phase 2 Only) | Day 29 | 1.8 Percentage of Participants |
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (8.0 IV) | Proportion of Participants With High Viral Load at Each Visit - (Phase 2 Only) | Day 15 | 4.2 Percentage of Participants |
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (8.0 IV) | Proportion of Participants With High Viral Load at Each Visit - (Phase 2 Only) | Day 3 | 62.2 Percentage of Participants |
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (8.0 IV) | Proportion of Participants With High Viral Load at Each Visit - (Phase 2 Only) | Day 7 | 28.8 Percentage of Participants |
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (8.0 IV) | Proportion of Participants With High Viral Load at Each Visit - (Phase 2 Only) | Day 5 | 44.1 Percentage of Participants |
Secondary
Proportion of Participants With Viral Loads Below the Lower Limit of Detection at Each Visit - (Phase 2 Only)
Next Phase 2 Symptomatic
Time frame: Day 0, Day 5, Day 7, Day 15, Day 29
Population: Participants analyzed are part of modified Full Analysis Set (mFAS) and have documented status at baseline. Next Phase 2 participants included the next 524 participants randomized to Phase 2 subsequent to the first 275 symptomatic participants randomized in Phase 1 / 2
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (Placebo) | Proportion of Participants With Viral Loads Below the Lower Limit of Detection at Each Visit - (Phase 2 Only) | Day 15 | 59 Participants |
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (Placebo) | Proportion of Participants With Viral Loads Below the Lower Limit of Detection at Each Visit - (Phase 2 Only) | Day 7 | 27 Participants |
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (Placebo) | Proportion of Participants With Viral Loads Below the Lower Limit of Detection at Each Visit - (Phase 2 Only) | Day 0 (Baseline) | 0 Participants |
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (Placebo) | Proportion of Participants With Viral Loads Below the Lower Limit of Detection at Each Visit - (Phase 2 Only) | Day 5 | 20 Participants |
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (Placebo) | Proportion of Participants With Viral Loads Below the Lower Limit of Detection at Each Visit - (Phase 2 Only) | Day 29 | 43 Participants |
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (2.4 IV) | Proportion of Participants With Viral Loads Below the Lower Limit of Detection at Each Visit - (Phase 2 Only) | Day 7 | 22 Participants |
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (2.4 IV) | Proportion of Participants With Viral Loads Below the Lower Limit of Detection at Each Visit - (Phase 2 Only) | Day 0 (Baseline) | 0 Participants |
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (2.4 IV) | Proportion of Participants With Viral Loads Below the Lower Limit of Detection at Each Visit - (Phase 2 Only) | Day 5 | 21 Participants |
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (2.4 IV) | Proportion of Participants With Viral Loads Below the Lower Limit of Detection at Each Visit - (Phase 2 Only) | Day 15 | 59 Participants |
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (2.4 IV) | Proportion of Participants With Viral Loads Below the Lower Limit of Detection at Each Visit - (Phase 2 Only) | Day 29 | 42 Participants |
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (8.0 IV) | Proportion of Participants With Viral Loads Below the Lower Limit of Detection at Each Visit - (Phase 2 Only) | Day 29 | 48 Participants |
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (8.0 IV) | Proportion of Participants With Viral Loads Below the Lower Limit of Detection at Each Visit - (Phase 2 Only) | Day 15 | 60 Participants |
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (8.0 IV) | Proportion of Participants With Viral Loads Below the Lower Limit of Detection at Each Visit - (Phase 2 Only) | Day 0 (Baseline) | 0 Participants |
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (8.0 IV) | Proportion of Participants With Viral Loads Below the Lower Limit of Detection at Each Visit - (Phase 2 Only) | Day 7 | 34 Participants |
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (8.0 IV) | Proportion of Participants With Viral Loads Below the Lower Limit of Detection at Each Visit - (Phase 2 Only) | Day 5 | 21 Participants |
Secondary
Proportion of Participants With Viral Loads Below the Lower Limit of Quantitation at Each Visit - (Phase 2 Only)
Next Phase 2 Symptomatic
Time frame: Day 0, Day 5, Day 7, Day 15, Day 29
Population: Participants analyzed are part of modified Full Analysis Set (mFAS) and have documented status at baseline. Next Phase 2 participants included the next 524 participants randomized to Phase 2 subsequent to the first 275 symptomatic participants randomized in Phase 1 / 2
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (Placebo) | Proportion of Participants With Viral Loads Below the Lower Limit of Quantitation at Each Visit - (Phase 2 Only) | Day 15 | 68 Participants |
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (Placebo) | Proportion of Participants With Viral Loads Below the Lower Limit of Quantitation at Each Visit - (Phase 2 Only) | Day 7 | 38 Participants |
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (Placebo) | Proportion of Participants With Viral Loads Below the Lower Limit of Quantitation at Each Visit - (Phase 2 Only) | Day 0 (Baseline) | 6 Participants |
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (Placebo) | Proportion of Participants With Viral Loads Below the Lower Limit of Quantitation at Each Visit - (Phase 2 Only) | Day 5 | 25 Participants |
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (Placebo) | Proportion of Participants With Viral Loads Below the Lower Limit of Quantitation at Each Visit - (Phase 2 Only) | Day 29 | 50 Participants |
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (2.4 IV) | Proportion of Participants With Viral Loads Below the Lower Limit of Quantitation at Each Visit - (Phase 2 Only) | Day 7 | 38 Participants |
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (2.4 IV) | Proportion of Participants With Viral Loads Below the Lower Limit of Quantitation at Each Visit - (Phase 2 Only) | Day 0 (Baseline) | 5 Participants |
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (2.4 IV) | Proportion of Participants With Viral Loads Below the Lower Limit of Quantitation at Each Visit - (Phase 2 Only) | Day 5 | 26 Participants |
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (2.4 IV) | Proportion of Participants With Viral Loads Below the Lower Limit of Quantitation at Each Visit - (Phase 2 Only) | Day 15 | 72 Participants |
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (2.4 IV) | Proportion of Participants With Viral Loads Below the Lower Limit of Quantitation at Each Visit - (Phase 2 Only) | Day 29 | 46 Participants |
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (8.0 IV) | Proportion of Participants With Viral Loads Below the Lower Limit of Quantitation at Each Visit - (Phase 2 Only) | Day 29 | 51 Participants |
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (8.0 IV) | Proportion of Participants With Viral Loads Below the Lower Limit of Quantitation at Each Visit - (Phase 2 Only) | Day 15 | 74 Participants |
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (8.0 IV) | Proportion of Participants With Viral Loads Below the Lower Limit of Quantitation at Each Visit - (Phase 2 Only) | Day 0 (Baseline) | 6 Participants |
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (8.0 IV) | Proportion of Participants With Viral Loads Below the Lower Limit of Quantitation at Each Visit - (Phase 2 Only) | Day 7 | 47 Participants |
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (8.0 IV) | Proportion of Participants With Viral Loads Below the Lower Limit of Quantitation at Each Visit - (Phase 2 Only) | Day 5 | 28 Participants |
Secondary
Time to All-cause Death (Ph3 Cohort 1- 1.2g vs Placebo)
Phase 3 Cohort 1 (1.2g IV)
Time frame: Through Day 169
Population: Participants that were ≥18 years old and not pregnant at randomization, and randomized on or before 17-Jan-2021 with detectable SARS-CoV-2 RNA by RT-qPCR in nasopharyngeal swabs at randomization and at least 1 risk factor for severe COVID-19 at baseline
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (Placebo) | Time to All-cause Death (Ph3 Cohort 1- 1.2g vs Placebo) | NA Days |
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (2.4 IV) | Time to All-cause Death (Ph3 Cohort 1- 1.2g vs Placebo) | NA Days |
95% CI: [0.06, 16.12]
Secondary
Time to All-cause Death (Ph3 Cohort 1- 2.4g vs Placebo)
Phase 3 Cohort 1 (2.4g IV)
Time frame: Through Day 169
Population: Participants that were ≥18 years old and not pregnant at randomization, and randomized on or before 17-Jan-2021 with detectable SARS-CoV-2 RNA by RT-qPCR in nasopharyngeal swabs at randomization and at least 1 risk factor for severe COVID-19 at baseline
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (Placebo) | Time to All-cause Death (Ph3 Cohort 1- 2.4g vs Placebo) | NA Days |
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (2.4 IV) | Time to All-cause Death (Ph3 Cohort 1- 2.4g vs Placebo) | NA Days |
95% CI: [0.03, 3.13]
Secondary
Time to All-cause Death (Phase 3 Cohort 2)
Phase 3 (Cohort 2)
Time frame: Through Day 29
Population: There were no deaths in this cohort. Phase 3 Cohort 2 data was not analyzed for this endpoint as there were no deaths.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (Placebo) | Time to All-cause Death (Phase 3 Cohort 2) | 0 Days |
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (2.4 IV) | Time to All-cause Death (Phase 3 Cohort 2) | 0 Days |
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (8.0 IV) | Time to All-cause Death (Phase 3 Cohort 2) | 0 Days |
Secondary
Time to COVID-19 Symptoms Resolution (Ph3 Cohort 1 - 1.2g vs Placebo)
Phase 3 Cohort 1
Time frame: Up to Day 29
Population: Participants that were ≥18 years old and not pregnant at randomization, and randomized on or before 17-Jan-2021 with detectable SARS-CoV-2 RNA by RT-qPCR in nasopharyngeal swabs at randomization and at least 1 risk factor for severe COVID-19 at baseline
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (Placebo) | Time to COVID-19 Symptoms Resolution (Ph3 Cohort 1 - 1.2g vs Placebo) | 14.0 Days |
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (2.4 IV) | Time to COVID-19 Symptoms Resolution (Ph3 Cohort 1 - 1.2g vs Placebo) | 10.0 Days |
Secondary
Time to COVID-19 Symptoms Resolution (Ph3 Cohort 1 - 2.4g vs Placebo)
Phase 3 (Cohort 1)
Time frame: Through Day 29
Population: Participants that were ≥18 years old and not pregnant at randomization, and randomized on or before 17-Jan-2021 with detectable SARS-CoV-2 RNA by RT-qPCR in nasopharyngeal swabs at randomization and at least 1 risk factor for severe COVID-19 at baseline
| Arm | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (Placebo) | Time to COVID-19 Symptoms Resolution (Ph3 Cohort 1 - 2.4g vs Placebo) | 14.0 Days | 95% Confidence Interval 13 |
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (2.4 IV) | Time to COVID-19 Symptoms Resolution (Ph3 Cohort 1 - 2.4g vs Placebo) | 10.0 Days | 95% Confidence Interval 10 |
Secondary
Time to First Onset of Symptoms Consistent With COVID-19 (Phase 2 Asymptomatic Cohort Only)
Phase 2 Only
Time frame: Through Day 29
Population: Phase 2 asymptomatic cohort
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (Placebo) | Time to First Onset of Symptoms Consistent With COVID-19 (Phase 2 Asymptomatic Cohort Only) | 3.0 Days |
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (2.4 IV) | Time to First Onset of Symptoms Consistent With COVID-19 (Phase 2 Asymptomatic Cohort Only) | 2.5 Days |
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (8.0 IV) | Time to First Onset of Symptoms Consistent With COVID-19 (Phase 2 Asymptomatic Cohort Only) | 4.0 Days |
Secondary
Time to First Onset of Symptoms Consistent With COVID-19 (Phase 2 Asymptomatic Cohort Only)
Phase 2 Only
Time frame: Up to Day 29
Population: Phase 2 asymptomatic cohort
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (Placebo) | Time to First Onset of Symptoms Consistent With COVID-19 (Phase 2 Asymptomatic Cohort Only) | 4.0 Days |
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (2.4 IV) | Time to First Onset of Symptoms Consistent With COVID-19 (Phase 2 Asymptomatic Cohort Only) | NA Days |
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (8.0 IV) | Time to First Onset of Symptoms Consistent With COVID-19 (Phase 2 Asymptomatic Cohort Only) | 4.0 Days |
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
Time frame: Through Day 29
Population: In light of evolving information concerning SARS-CoV-2 infection, including the profile of viral load among patients and the adequacy of sampling methodologies, virologic efficacy endpoints and sampling methods were modified during the course of the study
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)
Time frame: Baseline to Day 7
Population: Participants that were ≥18 years old and not pregnant at randomization, and randomized on or before 17-Jan-2021 with detectable SARS-CoV-2 RNA by RT-qPCR in nasopharyngeal swabs at randomization and at least 1 risk factor for severe COVID-19 at baseline
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (Placebo) | 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) | -1.46 log10 copies/mL | Standard Deviation 1.22 |
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (2.4 IV) | 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) | -2.02 log10 copies/mL | Standard Deviation 1.021 |
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (8.0 IV) | 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) | -2.05 log10 copies/mL | Standard Deviation 1.079 |
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)
Time frame: Baseline to Day 7
Population: Participants \<18 years old who, at baseline, were not pregnant, had symptomatic COVID-19, and had at least 1 risk factor for developing severe disease
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (Placebo) | 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) | -0.97 log10 copies/mL | — |
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (2.4 IV) | 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) | -2.49 log10 copies/mL | Standard Deviation 1.413 |
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (8.0 IV) | 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) | -2.94 log10 copies/mL | Standard Deviation 1.435 |
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
Time frame: Baseline up to Day 22
Population: In light of evolving information concerning SARS-CoV-2 infection, including the profile of viral load among patients and the adequacy of sampling methodologies, virologic efficacy endpoints and sampling methods were modified during the course of the study
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
Time frame: Day 1 to Day 29
Population: All randomized participants pooled in Phase 1 or Phase 2 with qualitatively positive RT-qPCR in NP swab samples at randomization or collected within 2 hours after study drug infusion was initiated. This modified full analysis set (mFAS) includes all randomized patients with positive RT-qPCR in NP swab samples at randomization and is based on the treatment allocated (as randomized).
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (Placebo) | Time-weighted Average Change From Baseline in Viral Load (log10 Copies/mL) From Day 1 to Post-baseline Study Days (Ph1, Ph2) | TWA Change from BL: Day 1 to Day 5 | -0.93 log10 copies/mL | Standard Error 0.07 |
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (Placebo) | Time-weighted Average Change From Baseline in Viral Load (log10 Copies/mL) From Day 1 to Post-baseline Study Days (Ph1, Ph2) | TWA Change from BL: Day 1 to Day 7 | -1.35 log10 copies/mL | Standard Error 0.07 |
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (Placebo) | Time-weighted Average Change From Baseline in Viral Load (log10 Copies/mL) From Day 1 to Post-baseline Study Days (Ph1, Ph2) | TWA Change from BL: Day 1 to Day 15 | -2.57 log10 copies/mL | Standard Error 0.07 |
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (Placebo) | Time-weighted Average Change From Baseline in Viral Load (log10 Copies/mL) From Day 1 to Post-baseline Study Days (Ph1, Ph2) | TWA Change from BL: Day 1 to Day 29 | -3.74 log10 copies/mL | Standard Error 0.06 |
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (2.4 IV) | Time-weighted Average Change From Baseline in Viral Load (log10 Copies/mL) From Day 1 to Post-baseline Study Days (Ph1, Ph2) | TWA Change from BL: Day 1 to Day 29 | -3.97 log10 copies/mL | Standard Error 0.07 |
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (2.4 IV) | Time-weighted Average Change From Baseline in Viral Load (log10 Copies/mL) From Day 1 to Post-baseline Study Days (Ph1, Ph2) | TWA Change from BL: Day 1 to Day 5 | -1.23 log10 copies/mL | Standard Error 0.07 |
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (2.4 IV) | Time-weighted Average Change From Baseline in Viral Load (log10 Copies/mL) From Day 1 to Post-baseline Study Days (Ph1, Ph2) | TWA Change from BL: Day 1 to Day 15 | -2.93 log10 copies/mL | Standard Error 0.08 |
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (2.4 IV) | Time-weighted Average Change From Baseline in Viral Load (log10 Copies/mL) From Day 1 to Post-baseline Study Days (Ph1, Ph2) | TWA Change from BL: Day 1 to Day 7 | -1.68 log10 copies/mL | Standard Error 0.08 |
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (8.0 IV) | Time-weighted Average Change From Baseline in Viral Load (log10 Copies/mL) From Day 1 to Post-baseline Study Days (Ph1, Ph2) | TWA Change from BL: Day 1 to Day 29 | -4.03 log10 copies/mL | Standard Error 0.07 |
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (8.0 IV) | Time-weighted Average Change From Baseline in Viral Load (log10 Copies/mL) From Day 1 to Post-baseline Study Days (Ph1, Ph2) | TWA Change from BL: Day 1 to Day 7 | -1.72 log10 copies/mL | Standard Error 0.08 |
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (8.0 IV) | Time-weighted Average Change From Baseline in Viral Load (log10 Copies/mL) From Day 1 to Post-baseline Study Days (Ph1, Ph2) | TWA Change from BL: Day 1 to Day 15 | -2.96 log10 copies/mL | Standard Error 0.08 |
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (8.0 IV) | Time-weighted Average Change From Baseline in Viral Load (log10 Copies/mL) From Day 1 to Post-baseline Study Days (Ph1, Ph2) | TWA Change from BL: Day 1 to Day 5 | -1.25 log10 copies/mL | Standard Error 0.07 |
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)
Time frame: Through Day 29
Population: Participants \<18 years old who, at baseline, were not pregnant, had symptomatic COVID-19, and had at least 1 risk factor for developing severe disease
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (Placebo) | Total Number of COVID-19-related Medically-attended Visits by Type of Visit Through Day 29 (Phase 3 Cohort 2) | Emergency Room | 0 Medically-Attended Visit |
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (Placebo) | Total Number of COVID-19-related Medically-attended Visits by Type of Visit Through Day 29 (Phase 3 Cohort 2) | Outpatient/Telemedicine | 0 Medically-Attended Visit |
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (2.4 IV) | Total Number of COVID-19-related Medically-attended Visits by Type of Visit Through Day 29 (Phase 3 Cohort 2) | Emergency Room | 1 Medically-Attended Visit |
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (2.4 IV) | Total Number of COVID-19-related Medically-attended Visits by Type of Visit Through Day 29 (Phase 3 Cohort 2) | Outpatient/Telemedicine | 1 Medically-Attended Visit |
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (8.0 IV) | Total Number of COVID-19-related Medically-attended Visits by Type of Visit Through Day 29 (Phase 3 Cohort 2) | Emergency Room | 0 Medically-Attended Visit |
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (8.0 IV) | Total Number of COVID-19-related Medically-attended Visits by Type of Visit Through Day 29 (Phase 3 Cohort 2) | Outpatient/Telemedicine | 1 Medically-Attended Visit |
Secondary
Total Number of COVID-19-related Medically-attended Visits (Phase 1 and Phase 2)
Phase 1 and Phase 2
Time frame: Through Day 29
Population: Analysis populations were prespecified in the SAP. Pooled analyses were performed for symptomatic adult participants randomized in Phase 1, 2, or 3 (cohort 1) on or before 2/24/21 to placebo, R10933+R10987 1.2 g, 2.4 g, or 8.0 g IV. No phase 1 or 2 participants were randomized to R10933+R10987 1.2 g IV. Asymptomatic adult participants randomized to the asymptomatic cohort of phase 2, symptomatic pediatric / pregnant participants randomized in phase 3 to cohort 2 or 3 were analyzed separately.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (Placebo) | Total Number of COVID-19-related Medically-attended Visits (Phase 1 and Phase 2) | 18 Number of Participants |
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (2.4 IV) | Total Number of COVID-19-related Medically-attended Visits (Phase 1 and Phase 2) | 7 Number of Participants |
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (8.0 IV) | Total Number of COVID-19-related Medically-attended Visits (Phase 1 and Phase 2) | 6 Number of Participants |
Secondary
Total Number of COVID-19-related Medically-attended Visits (Phase 3 Cohort 1) Placebo vs. 1.2g
Phase 3 Cohort 1
Time frame: Through Day 29
Population: Participants that were ≥18 years old and not pregnant at randomization, and randomized on or before 17-Jan-2021 with detectable SARS-CoV-2 RNA by RT-qPCR in nasopharyngeal swabs at randomization and at least 1 risk factor for severe COVID-19 at baseline
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (Placebo) | Total Number of COVID-19-related Medically-attended Visits (Phase 3 Cohort 1) Placebo vs. 1.2g | 1.1 Number of Visits | Standard Deviation 0.27 |
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (2.4 IV) | Total Number of COVID-19-related Medically-attended Visits (Phase 3 Cohort 1) Placebo vs. 1.2g | 1.2 Number of Visits | Standard Deviation 0.52 |
Secondary
Total Number of COVID-19-related Medically-attended Visits (Phase 3 Cohort 1) Placebo vs. 2.4g
Phase 3 Cohort 1
Time frame: Through Day 29
Population: Participants that were ≥18 years old and not pregnant at randomization, and randomized on or before 17-Jan-2021 with detectable SARS-CoV-2 RNA by RT-qPCR in nasopharyngeal swabs at randomization and at least 1 risk factor for severe COVID-19 at baseline
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (Placebo) | Total Number of COVID-19-related Medically-attended Visits (Phase 3 Cohort 1) Placebo vs. 2.4g | 1.2 Number of Visits | Standard Deviation 0.41 |
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (2.4 IV) | Total Number of COVID-19-related Medically-attended Visits (Phase 3 Cohort 1) Placebo vs. 2.4g | 1.0 Number of Visits | Standard Deviation 0.15 |
Secondary
Total Number of COVID-19-related Medically-attended Visits (Phase 3 Cohort 2)
Phase 3 Cohort 2
Time frame: Through Day 29
Population: Participants \<18 years old who, at baseline, were not pregnant, had symptomatic COVID-19, and had at least 1 risk factor for developing severe disease
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (Placebo) | Total Number of COVID-19-related Medically-attended Visits (Phase 3 Cohort 2) | 1.0 Number of Visits | Standard Deviation 0 |
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (2.4 IV) | Total Number of COVID-19-related Medically-attended Visits (Phase 3 Cohort 2) | 1.0 Number of Visits | — |
| Combined Phases 1, 2, & 3 Cohort 1 Symptomatic (8.0 IV) | Total Number of COVID-19-related Medically-attended Visits (Phase 3 Cohort 2) | 1.0 Number of Visits | Standard Deviation 0 |