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

Phase 3TerminatedNCT04425629

Regeneron Pharmaceuticals10,078 enrolled

Overview

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

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

10,078

Conditions

COVID-19

Interventions

Administered intravenously (IV) single dose

Eligibility

Sex: ALL

Medical Language ↔ Plain English

Key Inclusion Criteria: * Has SARS-CoV-2-positive diagnostic test (from a sample collected ≤72 hours prior to randomization, using a validated SARS-CoV-2 antigen, RT-PCR, or other molecular diagnostic assay, and an appropriate sample such as nasopharyngeal \[NP\], nasal, oropharyngeal \[OP\], or saliva) * Has symptoms consistent with COVID-19, as determined by the investigator, with onset ≤7 days before randomization * Maintains O2 saturation ≥93% on room air * Is able to understand and complete study-related questionnaires (patients aged ≥12 years only) Key Exclusion Criteria: * Was admitted to a hospital for COVID-19 prior to randomization, or is hospitalized (inpatient) for any reason at randomization * Has participated, or is participating, in a clinical research study evaluating COVID-19 convalescent plasma, mAbs against SARS-CoV-2 (eg, bamlanivimab), or intravenous immunoglobulin (IVIG) within 3 months or within 5 half-lives of the investigational product (whichever is longer) prior to the screening visit * Prior, current, or planned future use of any of the following treatments: COVID-19 convalescent plasma, mAbs against SARS-CoV-2 (eg, bamlanivimab), IVIG (any indication), systemic corticosteroids (any indication), or COVID-19 treatments (authorized, approved, or investigational) * Prior use (prior to randomization), current use (at randomization) or planned use (within 90 days of study drug administration or per current CDC recommendations, as applicable) of any authorized or approved vaccine for COVID-19 * Has participated, is participating or plans to participate in a clinical research study evaluation any authorized, approved or investigational vaccine for COVID-19 NOTE: Other Protocol defined Inclusion/Exclusion criteria apply

Locations (114)

Regeneron Study Site

Mesa, Arizona, United States

Regeneron Study Site

Tucson, Arizona, United States

Regeneron Study Site

Tucson, Arizona, United States

Regeneron Study Site

Canoga Park, California, United States

Regeneron Study Site

La Mesa, California, United States

Regeneron Study Site

Outcomes

Primary Outcomes

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

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

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

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

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

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

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

Secondary Outcomes

Time to COVID-19 Symptoms Resolution (Ph3 Cohort 1 - 1.2g vs Placebo)

Phase 3 Cohort 1

Time frame: Up to Day 29

Time to COVID-19 Symptoms Resolution (Ph3 Cohort 1 - 2.4g vs Placebo)

Phase 3 (Cohort 1)

Time frame: Through Day 29

Proportion of Participants With ≥1 COVID-19-related Hospitalization or All-cause Death From Day 4 Through Day 29 (Ph3 Cohort 1 - 1.2g vs. Placebo)

Phase 3 (Cohort 1)

Time frame: Day 4 thru Day 29

Proportion of Participants With ≥1 COVID-19-related Hospitalization or All-cause Death From Day 4 Through Day 29 (Ph3 Cohort 1 - 2.4g vs. Placebo)

Phase 3 (Cohort 1)

Time frame: From Day 4 Through Day 29

Change From Baseline in Viral Load at Each Visit, as Measured by RT-qPCR in Nasopharyngeal Swabs (Next Phase 2 Cohort)

Next Phase 2 Symptomatic

Time frame: Day 5, Day 7, Day 15, Day 29

Time-weighted Average Change From Baseline in Viral Load (log10 Copies/mL) From Day 1 to Post-baseline Study Days (Ph1, Ph2)

Phase 1, Phase 2

Time frame: Day 1 to Day 29

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

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

Time to First Onset of Symptoms Consistent With COVID-19 (Phase 2 Asymptomatic Cohort Only)

Data from ClinicalTrials.gov

This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.

La Palma, California, United States

Regeneron Study Site 1

Long Beach, California, United States

Regeneron Study Site 2

Long Beach, California, United States

Regeneron Study Site 3

Long Beach, California, United States

Regeneron Study Site

Los Angeles, California, United States

...and 104 more locations

Time frame: Up to Day 29

Proportion of Participants With ≥1 COVID-19-related Hospitalization, Emergency Room Visit, or All-cause Death (Ph3 Cohort 1) - Placebo vs. 1.2g IV

Phase 3 Cohort 1 - Placebo vs. 1.2 g IV

Time frame: Through Day 29

Proportion of Participants With ≥1 COVID-19-related Hospitalization, Emergency Room Visit, or All-cause Death (Ph3 Cohort 1) - Placebo vs. 2.4g IV

Phase 3 (Cohort 1)

Time frame: Through day 29

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

Assessment of Pharmacokinetic (PK) Parameter: Maximum Serum Concentration Observed (Cmax) of REGN10933+REGN10987 (Phase 1)

Phase 1 Only

Time frame: Through Day 29

Assessment of PK Parameter: Time to Cmax (Tmax) for REGN10933+REGN10987 (Phase 1)

Phase 1 Only

Time frame: Through Day 29

Assessment of PK Parameter: Area Under the Curve (AUC) Computed From Time Zero to Day 28 Concentration (AUC 0-28) for REGN10933+REGN10987 (Phase 1)

Phase 1 Only

Time frame: Through Day 29

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

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

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

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

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

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

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

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

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

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

Total Number of COVID-19-related Medically-attended Visits (Phase 1 and Phase 2)

Phase 1 and Phase 2

Time frame: Through Day 29

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

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

Assessment of PK Parameter: Time to Cmax (Tmax) for REGN10933 and REGN10987 (Phase 1 Only)

Phase 1 Only

Time frame: Through Day 29

Assessment of PK Parameter: Area Under the Curve (AUC) Computed From Time Zero to the Time of the Last Positive Concentration (AUClast) for REGN10933 - (Phase 1 Only)

Phase 1 Only - Tlast (Time of last quantifiable concentration)

Time frame: Through Day 29

Proportion of Participants With at Least One (≥1) COVID-19-related Hospitalization or All-cause Death From Day 4 Through Day 29 (Ph3 Cohort 1- 1.2g vs Placebo)

Phase 3 Cohort 1

Time frame: Day 4 Through Day 29

Proportion of Participants With at Least One (≥1) COVID-19-related Hospitalization or All-cause Death From Day 4 Through Day 29 (Ph3 Cohort 1- 2.4g vs Placebo)

Phase 3 Cohort 1

Time frame: Day 4 Through Day 29

Proportion of Participants With at Least One (≥1) COVID-19-related Medically-attended Visit or All-cause Death Through Day 29 (Ph3 Cohort 1- 1.2g vs Placebo)

Phase 3 Cohort 1

Time frame: Through Day 29

Proportion of Participants With at Least One (≥1) COVID-19-related Medically-attended Visit or All-cause Death Through Day 29 (Ph3 Cohort 1- 2.4g vs Placebo)

Phase 3 Cohort 1

Time frame: Through Day 29

Number of Participants With at Least One (≥1) COVID-19-related Medically-attended Visit or All-cause Death Through Day 29 (Phase 3 Cohort 2)

Phase 3 (Cohort 2)

Time frame: Through Day 29

Proportion of Participants With at Least One (≥1) COVID-19-related Medically-attended Visit by Type of Visit Through Day 29 (Ph3 Cohort 1- 1.2g vs Placebo)

Phase 3 Cohort 1

Time frame: Through Day 29

Proportion of Participants With at Least One (≥1) COVID-19-related Medically-attended Visit by Type of Visit Through Day 29 (Ph3 Cohort 1- 2.4g vs Placebo)

Phase 3 Cohort 1

Time frame: Through Day 29

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

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

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

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

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

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

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

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

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

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

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

Proportion of Participants With High Viral Load at Each Visit - (Phase 2 Only)

Next Phase 2 Only

Time frame: Through Day 29

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

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

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

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

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

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

Duration of Symptoms Consistent With COVID-19 (Phase 2 Only)

Phase 2 Only

Time frame: Through Day 29

Time to First Onset of Symptoms Consistent With COVID-19 (Phase 2 Asymptomatic Cohort Only)

Phase 2 Only

Time frame: Through Day 29

Number of Participants Admitted to a Hospital Due to COVID-19 (Phase 1, Phase 2)

Phase 1, Phase 2

Time frame: Through Day 29

Time to Negative RT-qPCR in All Tested Samples With no Subsequent Positive RT-qPCR in Any Tested Samples - (Phase 1 Only)

Phase 1 Only

Time frame: Through Day 29

Proportion of Participants With All-cause Mortality (Phase 2 Asymptomatic)

Phase 2 Asymptomatic

Time frame: Through Day 29

Time to All-cause Death (Ph3 Cohort 1- 1.2g vs Placebo)

Phase 3 Cohort 1 (1.2g IV)

Time frame: Through Day 169

Time to All-cause Death (Ph3 Cohort 1- 2.4g vs Placebo)

Phase 3 Cohort 1 (2.4g IV)

Time frame: Through Day 169

Time to All-cause Death (Phase 3 Cohort 2)

Phase 3 (Cohort 2)

Time frame: Through Day 29

Proportion of Participants Requiring Mechanical Ventilation Due to COVID-19 (Ph3 Cohort 1- 1.2g vs Placebo)

Time frame: Through Day 29

Proportion of Participants Requiring Mechanical Ventilation Due to COVID-19 (Ph3 Cohort 1- 2.4g vs Placebo)

Time frame: Through Day 29

Proportion of Participants Requiring Mechanical Ventilation Due to COVID-19 (Phase 3 Cohort 2)

Phase 3 (Cohort 2)

Time frame: Through Day 29

Change From Baseline in Viral Load at Each Visit, as Measured by RT-qPCR in Nasopharyngeal Swabs - (Phase 3 Cohort 1 - 1.2g vs. Placebo)

Phase 3 Cohort 1

Time frame: Baseline up to Day 29

Change From Baseline in Viral Load at Each Visit, as Measured by RT-qPCR in Nasopharyngeal Swabs - (Phase 3 Cohort 1 - 2.4g vs. Placebo)

Phase 3 Cohort 1

Time frame: Baseline up to Day 29

Change From Baseline in Viral Load at Each Visit, as Measured by RT-qPCR in Nasopharyngeal Swabs - (Phase 3 Cohort 2)

Phase 3 Cohort 2

Time frame: Baseline up to Day 29

Time-weighted Average Change From Baseline in Viral Load (log10 Copies/mL), as Measured by Quantitative Reverse Transcription Quantitative Polymerase Chain Reaction (RT-qPCR) in Nasopharyngeal (NP) Swab Samples (Ph3 Cohort 1)

Phase 3 (Cohort 1)

Time frame: Baseline to Day 7

Phase 3 (Cohort 2)

Time frame: Baseline to Day 7

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

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

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

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

Number of Days of Hospitalization Due to COVID-19 (Ph3 Cohort 2)

Phase 3 (Cohort 2)

Time frame: Through Day 29

Number of Days of Hospitalization Due to COVID-19 (Phase 2 Asymptomatic)

Phase 2 Only

Time frame: Up to Day 29

Proportion of Participants Admitted to an Intensive Care Unit (ICU) Due to COVID-19 - (Ph 3 Cohort 1) Placebo vs. 1.2g IV

Phase 3 (Cohort 1)

Time frame: Through Day 29

Percentage of Participants Admitted to an Intensive Care Unit (ICU) Due to COVID-19 - (Ph 3 Cohort 1) Placebo vs. 2.4g IV

Phase 3 (Cohort 1)

Time frame: Through Day 29

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

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

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

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

Total Number of COVID-19-related Medically-attended Visits (Phase 3 Cohort 2)

Phase 3 Cohort 2

Time frame: Through Day 29