COVID-19 Study Assessing the Efficacy and Safety of Anti-Spike SARS CoV-2 Monoclonal Antibodies for Prevention of SARS CoV-2 Infection Asymptomatic in Healthy Adults and Adolescents Who Are Household Contacts to an Individual With a Positive SARS-CoV-2 RT-PCR Assay

• ClinicalTrials.gov Identifier: NCT04452318
• Recruitment Status: Completed
• First Posted: June 30, 2020
• Results First Posted: May 15, 2023
• Last Update Posted: May 15, 2023
• Sponsor: Regeneron Pharmaceuticals
• Information provided by (Responsible Party): Regeneron Pharmaceuticals

Tracking Information

• First Submitted Date: June 26, 2020
• First Posted Date: June 30, 2020
• Results First Submitted Date: September 29, 2022
• Results First Posted Date: May 15, 2023
• Last Update Posted Date: May 15, 2023
• Actual Study Start Date: July 13, 2020
• Actual Primary Completion Date: October 4, 2021 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: January 10, 2023)

• Cohort A: Percentage of Participants Who Have a Symptomatic RT-qPCR Confirmed SARS-CoV-2 Infection (Broad-term) During the EAP [ Time Frame: Up to 1 month ]
  Symptomatic SARS-CoV-2 infection (broad-term) is defined as a positive central lab SARS-CoV-2 RT-qPCR result (either NP, nasal or saliva) associated with signs and symptoms with the onset date occurring within 14 days of a positive RT-qPCR during the EAP. Percentage estimated by Logistic Regression.
• Cohort B: Percentage of Participants Who Subsequently Develop Signs and Symptoms (Broad-Term) Within 14 Days of a Positive RT-qPCR at Baseline or During the EAP [ Time Frame: Up to 14 Days ]
  The percentage of participants was estimated by using the logistic regression model with fixed categorical effects of treatment group, age group (age in years:>=12 to=50), and region (US vs ex-US).
• Cohort A and Cohort B: Number of Participants With at Least One Treatment-emergent Adverse Event (TEAEs) and Severity of TEAEs [ Time Frame: Up to 8 months ]

Original Primary Outcome Measures (submitted: June 26, 2020)

• Proportion of participants who have a positive SARS-CoV-2 RT-qPCR (based on central lab test) and signs and symptoms (strict-term) of SARS-CoV-2 infection during the Efficacy assessment period (EAP) [ Time Frame: Up to 1 month ]
  Cohort A: SARS-CoV-2 RT-qPCR Negative at Baseline
• Proportion of participants who have a RT-qPCR confirmed SARS-CoV-2 infection (either symptomatic or asymptomatic) during the EAP [ Time Frame: Up to 1 month ]
  Cohort A: SARS-CoV-2 RT-qPCR Negative at Baseline
• Incidence and severity of treatment-emergent adverse events (TEAEs) [ Time Frame: Up to 8 months ]
  Primary: Cohort A: SARS-CoV-2 RT-qPCR Negative at Baseline Secondary: Cohort B: SARS-CoV-2 RT-qPCR Positive at Baseline

Current Secondary Outcome Measures (submitted: March 3, 2023)

• Cohort A and Cohort B: Percentage of Participants With High Viral Load in Nasopharyngeal (NP) Swab Samples During the EAP [ Time Frame: Up to 1 month ]
  High viral load (> 4 log 10 copies/ml)
• Cohort A: Number of Weeks of Symptomatic RT-qPCR Confirmed SARS-CoV-2 Infection (Broad Term) During the EAP [ Time Frame: Up to 1 month ]
• Cohort A and Cohort B: Number of Weeks of High Viral Load in NP Swab Samples During the EAP [ Time Frame: Up to 1 month ]
  High viral load (> 4 log 10 copies/ml)
• Cohort A: Number of Weeks of RT-qPCR Confirmed SARS-CoV-2 Infection (Regardless of Symptoms) During the EAP [ Time Frame: Up to 1 month ]
• Cohort A: Percentage of Participants Who Have a RT-qPCR Confirmed SARS-CoV-2 Infection (Regardless of Symptoms) During the EAP [ Time Frame: Up to 1 month ]
  The percentage of participants was estimated by using the logistic regression model with fixed categorical effects of treatment group, age group (age in years:>=12 to=50), and region (US vs ex-US)
• Cohort A: Percentage of Participants in Placebo Group With a RT-qPCR Confirmed SARS-CoV-2 Infection During the EAP With an Index Case Participating in Study R10933-10987-COV-2067 (NCT04425629) [ Time Frame: Up to 1 month ]
• Cohort A: Percentage of Participants With a Symptomatic RT-qPCR Confirmed SARS-CoV-2 Infection (CDC Definition) During the EAP [ Time Frame: Up to 1 month ]
  Symptomatic SARS-CoV-2 infection (CDC definition) is defined as a positive central lab SARS-CoV-2 RT-qPCR result (either NP, nasal or saliva) associated with signs and symptoms with the onset date occurring within 14 days of a positive RT-qPCR during the EAP. Percentage estimated by Logistic Regression.
• Cohort A: Number of Weeks of Symptomatic RT-qPCR-confirmed SARS-CoV-2 Infection (CDC Definition) During the EAP [ Time Frame: Up to 1 month ]
• Cohort A: Percentage of Participants Who Have a Symptomatic RT-qPCR Confirmed SARS-CoV-2 Infection (Strict-term) During the EAP [ Time Frame: Up to 1 month ]
  The percentage of participants was estimated by using the logistic regression model with fixed categorical effects of treatment group, age group (age in years:>=12 to=50), and region (US vs ex-US)
• Cohort A: Number of Weeks of Symptomatic RT-qPCR Confirmed SARS-CoV-2 Infection (Strict-term) During the EAP [ Time Frame: Up to 1 month ]
• Cohort A: Percentage of Participants Who Have a RT-qPCR Confirmed SARS-CoV-2 Infections at Each Week in the EAP [ Time Frame: Week 1, Week 2, Week 3, Week 4 ]
• Cohort A: Percentage of Participants Who Have a Symptomatic RT-qPCR Confirmed SARS-CoV-2 Infection (Broad-term) at Each Week in the EAP [ Time Frame: Week 1, Week 2, Week 3, Week 4 ]
  The percentage of participants was estimated by using the logistic regression model with fixed categorical effects of treatment group, age group (age in years:>=12 to=50), and region (US vs ex-US)
• Cohort A: Time-weighted Average of Viral Load From the First Positive SARS CoV-2 RT-qPCR in NP Swab Samples (That Has an Onset During the EAP) Until the Third Weekly Visit After the First Positive Test During the EAP [ Time Frame: Up to 1 month ]
• Cohort A: Time-weighted Average of Viral Load From the First Positive SARS-CoV-2 RT-qPCR in NP Swab Samples (That Has an Onset During the EAP) Until the Second Weekly Visit After the First Positive Test During the EAP [ Time Frame: Up to 1 month ]
• Cohort A: Maximum SARS-CoV-2 RT-qPCR Viral Load in NP Swab Samples Among Individuals With ≥1 RT-qPCR Positive That Has an Onset During the EAP [ Time Frame: Up to 1 month ]
• Cohort A: SARS-CoV-2 RT-qPCR Viral Load in NP Swab Samples Corresponding to the Onset of First Positive RT-qPCR During the EAP [ Time Frame: Up to 1 month ]
• Cohort A: Area Under the Curve (AUC) in Viral Load From the First Positive SARS-CoV-2 RT-qPCR NP Swab Samples Detected During the EAP Until the First Confirmed Negative Test [ Time Frame: Up to 1 month ]
• Cohort A: Total Number of Medically Attended Visits in Emergency Rooms or Urgent Care Centers Related to a RT-qPCR Confirmed SARS-CoV-2 Infection That Has an Onset During the EAP [ Time Frame: Up to 1 month ]
  Medically attended visits referred to hospitalizations, Emergency Room visits, or visits at an Urgent Care center.
• Cohort A: Percentage of Participants With at Least 1 COVID-19-related Hospitalization or Emergency Room Visit Associated With a Positive RT-qPCR During the EAP or All-cause Death [ Time Frame: Up to 1 month ]
• Cohort A: Percentage of Participants Requiring Medically Attended Visits in Emergency Rooms or Urgent Care Centers Related to a RT-qPCR Confirmed SARS CoV-2 Infection That Has an Onset During the EAP [ Time Frame: Up to 1 month ]
• Cohort A: Proportion of Participants Hospitalized Related to a RT-qPCR Confirmed SARS-CoV-2 Infection That Has an Onset During the EAP [ Time Frame: Up to 14 Days ]
  The proportion of participants hospitalized related to a RT-qPCR confirmed SARS-CoV-2 infection that has an onset during the EAP
• Cohort A: Number of Days of Hospital and Intensive Care Unit (ICU) Stay in Participants Hospitalized for a RT-qPCR Confirmed SARS-CoV-2 Infection That Has an Onset During the EAP [ Time Frame: Up to Day 29 ]
• Cohort A: Number of Days Missed for Daily Responsibilities Due to a RT-qPCR Confirmed SARS-CoV-2 Infection That Has an Onset During the EAP [ Time Frame: Up to 1 month ]
  Daily responsibilities including work (employed adults) or school (students), daycare or family obligations/responsibilities (childcare or eldercare)
• Cohort A: Proportion of Baseline Seropositive Participants (Based on Central Lab Test) With TEAEs and Severity of TEAEs [ Time Frame: Up to 8 months ]
• Cohort A and Cohort B: Incidence and Severity of Symptomatic SARS-CoV-2 Infections During the EAP [ Time Frame: Up to Day 29 ]
• Cohort A and Cohort B: Incidence and Severity of Symptomatic SARS-CoV-2 Infections During the Follow-Up Period [ Time Frame: Day 30 Up to Day 225 (Approximately 8 months) ]
• Cohort A and Cohort B: Incidence and Severity of Symptomatic SARS-CoV-2 Infections in Seronegative Subjects During the EAP [ Time Frame: Up to Day 29 ]
• Cohort A and Cohort B: Incidence and Severity of Symptomatic SARS-CoV-2 Infections in Seronegative Subjects During the Follow-Up Period [ Time Frame: Day 30 Up to Day 225 (Approximately 8 months) ]
• Cohort A and Cohort B: Incidence and Severity of Symptomatic SARS-CoV-2 Infections in Seropositive Subjects During the EAP [ Time Frame: Up to Day 29 ]
• Cohort A and Cohort B: Incidence and Severity of Symptomatic SARS-CoV-2 Infections in Seropositive Subjects During the Follow-Up Period [ Time Frame: Day 30 Up to Day 225 (Approximately 8 months) ]
• Cohort B: Number of Weeks of Symptomatic SARS-CoV-2 Infection (Broad-term) Within 14 Days of a Positive RT-qPCR at Baseline or During the EAP [ Time Frame: Up to 14 Days ]
• Cohort B: Percentage of Participants With Asymptomatic Infection Who Develop Signs and Symptoms (CDC Definition) Within 14 Days of a Positive RT-qPCR at Baseline or During the EAP [ Time Frame: Up to 1 month ]
  The percentage of participants was estimated by using the logistic regression model with fixed categorical effects of treatment group, age group (age in years:>=12 to=50), and region (US vs ex-US)
• Cohort B: Percentage of Participants Who Subsequently Develop Signs and Symptoms (Strict-term) Within 14 Days of a Positive RT-qPCR at Baseline or During the EAP [ Time Frame: Up to 14 Days ]
  The percentage of participants was estimated by using the logistic regression model with fixed categorical effects of treatment group, age group (age in years:>=12 to=50), and region (US vs ex-US)
• Cohort B: Number of Weeks of Symptomatic SARS-CoV-2 Infection (CDC Definition) Within 14 Days of a Positive RT-qPCR at Baseline or During the EAP [ Time Frame: Up to 14 Days ]
• Cohort B: Number of Weeks of Symptomatic SARS-CoV-2 Infection (Strict-term Definition) Within 14 Days of a Positive RT-qPCR at Baseline or During the EAP [ Time Frame: Up to 14 Days ]
• Cohort B: Change in Viral Load From Baseline to Day 8 Visit in NP Swab Samples [ Time Frame: Up to day 8 visit ]
• Cohort B: Change in Viral Load From Baseline to Day 15 Visit in NP Swab Samples [ Time Frame: Up to day 15 visit ]
• Cohort B: Time-weighted Average Change From Baseline in Viral Load (log10 Copies/mL) in NP Swab Samples Until the Day 22 Visit [ Time Frame: Day 22 ]
• Cohort B: AUC in Viral Load From the First Positive SARS-CoV-2 RT-qPCR NP Swab Samples Detected During the EAP to the First Confirmed Negative Test [ Time Frame: Up to 14 Days ]
• Cohort B: Maximum SARS-CoV-2 RT-qPCR Viral Load in NP Swab Samples in Participants With 1 or More Positive Test That Has an Onset During the EAP [ Time Frame: Up to 1 month ]
• Cohort B: Number of Medically Attended Visits in Emergency Rooms or Urgent Care Centers Related to RT-qPCR Confirmed SARS-CoV-2 Infection That Has an Onset at Baseline or During the EAP [ Time Frame: Up to 1 month ]
• Cohort B: Percentage of Participants Requiring Medically Attended Visits in Emergency Rooms or Urgent Care Centers Related to a RT-qPCR Confirmed SARS CoV-2 Infection That Has an Onset at Baseline or During the EAP [ Time Frame: Up to 1 month ]
• Cohort B: Percentage of Participants Hospitalized Related to a RT-qPCR Confirmed SARS-CoV-2 Infection That Has an Onset at Baseline or During the EAP [ Time Frame: Up to 14 Days ]
• Cohort B: Number of Days Missed for Daily Responsibilities (Where Applicable) Due to a RT-qPCR Confirmed SARS-CoV-2 Infection That Has an Onset at Baseline or During the EAP [ Time Frame: Up to 1 month ]
• Cohort B: Number of Days of Hospital and Intensive Care Unit (ICU) Stay in Participants Hospitalized for a RT-qPCR Confirmed SARS-CoV-2 Infection That Has an Onset at Baseline or During the EAP [ Time Frame: Up to 1 month ]
• Concentrations of REGN10987 in Serum Over Time (Cohort A) [ Time Frame: 0 Days Post-Dose, 28 Days Post-Dose, 56 Days Post-Dose, 112 Days Post-Dose ]
• Concentrations of REGN10987 in Serum Over Time (Cohort B) [ Time Frame: 0 Days Post-Dose, 28 Days Post-Dose, 56 Days Post-Dose, 112 Days Post-Dose ]
• Concentrations of REGN10933 in Serum Over Time (Cohort A) [ Time Frame: 0 Days Post-Dose, 28 Days Post-Dose, 56 Days Post-Dose, 112 Days Post-Dose ]
• Concentrations of REGN10933 in Serum Over Time (Cohort B) [ Time Frame: 0 Days Post-Dose, 28 Days Post-Dose, 56 Days Post-Dose, 112 Days Post-Dose ]
• Immunogenicity as Measured by Anti-drug Antibodies (ADAs) to REGN10933 [ Time Frame: Up to 8 months ]
• Immunogenicity as Measured by Anti-drug Antibodies (ADAs) to REGN10987 [ Time Frame: Up to 8 months ]
• Immunogenicity as Measured by Neutralizing Anti-drug Antibody (NAb) to REGN10933 [ Time Frame: Up to 8 months ]
  (TE&TB+;NAb+) = TE = Treatment-Emergent; TB = Treatment-boosted; NAb+ = Positive in NAb assay
• Immunogenicity as Measured by Neutralizing Anti-drug Antibody (NAb) to REGN10987 [ Time Frame: Up to 8 Months ]
  (TE&TB+;NAb+) = TE = Treatment-emergent; TB = Treatment-boosted; NAb+ = Positive in NAb assay

Original Secondary Outcome Measures (submitted: June 26, 2020)

• Proportion of participants who have a symptomatic RT-qPCR confirmed SARS-CoV-2 infection (broad term) during the EAP [ Time Frame: Up to 1 month ]
  Cohort A: SARS-CoV-2 RT-qPCR Negative at Baseline
• Proportion of participants who have a positive SARS-CoV-2 RT-qPCR and absence of signs and symptoms (strict term) during the EAP [ Time Frame: Up to 1 month ]
  Cohort A: SARS-CoV-2 RT-qPCR Negative at Baseline
• Proportion of participants who have a positive SARS-CoV-2 RT-qPCR and absence of signs and symptoms (broad term) during the EAP [ Time Frame: Up to 1 month ]
  Cohort A: SARS-CoV-2 RT-qPCR Negative at Baseline
• Number of days of symptomatic SARS-CoV-2 infection (strict-term) [ Time Frame: Up to 8 months ]
  Cohort A: SARS-CoV-2 RT-qPCR Negative at Baseline Cohort B: SARS-CoV-2 RT-qPCR Positive at Baseline
• Number of days of symptomatic SARS CoV-2 infection (broad-term) [ Time Frame: Up to 8 months ]
  Cohort A: SARS-CoV-2 RT-qPCR Negative at Baseline Cohort B: SARS-CoV-2 RT-qPCR Positive at Baseline
• Time-weighted average of viral shedding from the first positive SARS CoV-2 RT-qPCR nasal swab sample (that has an onset during the EAP) until 22 days after the positive test during the EAP [ Time Frame: Up to 1 month or until 22 days after positive test ]
  Cohort A: SARS-CoV-2 RT-qPCR Negative at Baseline
• Time-weighted average of viral shedding from the first positive SARS CoV-2 RT-qPCR saliva sample (that has an onset during the EAP) until 22 days after the positive test during the EAP [ Time Frame: Up to 1 month or until 22 days after positive test ]
  Cohort A: SARS-CoV-2 RT-qPCR Negative at Baseline
• Maximum SARS-CoV-2 RT-qPCR in nasal swab samples [ Time Frame: Up to 8 months ]
  Cohort A: SARS-CoV-2 RT-qPCR Negative at Baseline Cohort B: SARS-CoV-2 RT-qPCR Positive at Baseline
• Maximum SARS-CoV-2 RT-qPCR in saliva samples [ Time Frame: Up to 8 months ]
  Cohort A: SARS-CoV-2 RT-qPCR Negative at Baseline Cohort B: SARS-CoV-2 RT-qPCR Positive at Baseline
• Area under the curve (AUC) in viral shedding from the first positive SARS-CoV-2 RT-qPCR nasal swab sample until the first confirmed negative test, that has an onset during the EAP [ Time Frame: Up to 8 months ]
  Cohort A: SARS-CoV-2 RT-qPCR Negative at Baseline Cohort B: SARS-CoV-2 RT-qPCR Positive at Baseline
• Area under the curve (AUC) in viral shedding from the first positive SARS-CoV-2 RT-qPCR saliva swab sample until the first confirmed negative test, that has an onset during the EAP [ Time Frame: Up to 8 months ]
  Cohort A: SARS-CoV-2 RT-qPCR Negative at Baseline Cohort B: SARS-CoV-2 RT-qPCR Positive at Baseline
• Number of medically attended visits in emergency rooms or urgent care centers related to a RT-qPCR confirmed SARS-CoV-2 infection [ Time Frame: Up to 8 months ]
  Cohort A: SARS-CoV-2 RT-qPCR Negative at Baseline Cohort B: SARS-CoV-2 RT-qPCR Positive at Baseline
• Proportion of participants requiring medically attended visits in emergency rooms or urgent care centers related to a RT-qPCR confirmed SARS CoV-2 infection [ Time Frame: Up to 8 months ]
  Cohort A: SARS-CoV-2 RT-qPCR Negative at Baseline Cohort B: SARS-CoV-2 RT-qPCR Positive at Baseline
• Proportion of participants hospitalized related to a RT-qPCR confirmed SARS-CoV-2 infection [ Time Frame: Up to 8 months ]
  Cohort A: SARS-CoV-2 RT-qPCR Negative at Baseline Cohort B: SARS-CoV-2 RT-qPCR Positive at Baseline
• Number of days of hospital and ICU stay in participants hospitalized for a RT-qPCR confirmed SARS-CoV-2 infection [ Time Frame: Up to 8 months ]
  Cohort A: SARS-CoV-2 RT-qPCR Negative at Baseline Cohort B: SARS-CoV-2 RT-qPCR Positive at Baseline
• Number of days missed for daily responsibilities due to a RT-qPCR confirmed SARS-CoV-2 infection [ Time Frame: Up to 8 months ]
  Daily responsibilities including work (employed adults) or school (matriculating students), or family obligations/responsibilities (childcare or eldercare) Cohort A: SARS-CoV-2 RT-qPCR Negative at Baseline Cohort B: SARS-CoV-2 RT-qPCR Positive at Baseline
• Concentrations of REGN10933 in serum over time and selected PK parameters [ Time Frame: Up to 8 months ]
  Pharmacokinetic (PK) parameters may include, but are not limited to: - Maximum observed plasma concentration (Cmax) - Cmax/Dose - Time of maximum observed plasma concentration (tmax) - Time of Clast (tlast) - Last measurable plasma concentration (Clast) - Area under plasma concentration-time curve from time 0 to infinity (AUCinf) - AUCinf/Dose - Elimination half-life (t1/2) - Concentration in serum 28 days (C28) after dosing) Cohort A: SARS-CoV-2 RT-qPCR Negative at Baseline Cohort B: SARS-CoV-2 RT-qPCR Positive at Baseline
• Concentrations of REGN10987 in serum over time and selected PK parameters [ Time Frame: Up to 8 months ]
  Cohort A: SARS-CoV-2 RT-qPCR Negative at Baseline Cohort B: SARS-CoV-2 RT-qPCR Positive at Baseline
• Immunogenicity as measured by anti-drug antibodies (ADA) to REGN10933 over time [ Time Frame: Up to 8 months ]
  Cohort A: SARS-CoV-2 RT-qPCR Negative at Baseline Cohort B: SARS-CoV-2 RT-qPCR Positive at Baseline
• Immunogenicity as measured by anti-drug antibodies (ADA) to REGN10987 over time [ Time Frame: Up to 8 months ]
  Cohort A: SARS-CoV-2 RT-qPCR Negative at Baseline Cohort B: SARS-CoV-2 RT-qPCR Positive at Baseline
• Incidence and severity of TEAEs in baseline seropositive participants (based on central lab test) [ Time Frame: Up to 8 months ]
  Cohort A: SARS-CoV-2 RT-qPCR Negative at Baseline
• Incidence and severity of symptomatic SARS-CoV-2 infection [ Time Frame: Up to 8 months ]
  Cohort A: SARS-CoV-2 RT-qPCR Negative at Baseline Cohort B: SARS-CoV-2 RT-qPCR Positive at Baseline
• Proportion of participants who subsequently develop signs and symptoms (strict-term) of symptomatic SARS-CoV-2 infection [ Time Frame: Within 14 and 28 days of positive RT-qPCR ]
  Cohort B: SARS-CoV-2 RT-qPCR Positive at Baseline
• Proportion of participants who subsequently develop signs and symptoms (broad-term) of symptomatic SARS-CoV-2 infection [ Time Frame: Within 14 and 28 days of a positive RT-qPCR ]
  Cohort B: SARS-CoV-2 RT-qPCR Positive at Baseline
• Number of days of symptomatic SARS CoV-2 infection (strict-term) [ Time Frame: Up to 8 months ]
  Cohort B: SARS-CoV-2 RT-qPCR Positive at Baseline
• Number of days of symptomatic SARS CoV-2 infection (broad-term) [ Time Frame: Up to 8 months ]
  Cohort B: SARS-CoV-2 RT-qPCR Positive at Baseline
• Time-weighted average change from baseline in viral shedding in nasal swab samples [ Time Frame: Until day 23 ]
  Cohort B: SARS-CoV-2 RT-qPCR Positive at Baseline
• Time-weighted average change from baseline in viral shedding in saliva samples [ Time Frame: Until day 23 ]
  Cohort B: SARS-CoV-2 RT-qPCR Positive at Baseline

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

Descriptive Information

• Brief Title: COVID-19 Study Assessing the Efficacy and Safety of Anti-Spike SARS CoV-2 Monoclonal Antibodies for Prevention of SARS CoV-2 Infection Asymptomatic in Healthy Adults and Adolescents Who Are Household Contacts to an Individual With a Positive SARS-CoV-2 RT-PCR Assay
• Official Title: A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study Assessing the Efficacy and Safety of Anti-Spike SARS-CoV-2 Monoclonal Antibodies in Preventing SARS-CoV-2 Infection in Household Contacts of Individuals Infected With SARS-CoV-2

Brief Summary

Primary Objectives:

Cohort A:

• To evaluate the efficacy of REGN10933+REGN10987 compared to placebo in preventing symptomatic SARS-CoV-2 infection (broad-term) confirmed by RT-qPCR

Cohort A and Cohort A1:

• To evaluate the safety and tolerability of REGN10933+REGN10987 following subcutaneous (SC) administration compared to placebo

Cohort B • To evaluate the efficacy of REGN10933+REGN10987 compared to placebo in preventing COVID-19 symptoms (broad-term)

Cohort B and Cohort B1

• To evaluate the safety and tolerability of REGN10933+REGN10987 following SC administration compared to placebo

Detailed Description

Cohort A: adult and adolescent subjects (≥12 years) who are SARS -CoV-2 RT-qPCR negative at baseline

Cohort A1: pediatric subjects (<12 years) who are SARS-CoV-2 RT--qPCR negative at baseline

Cohort B: adult and adolescent subjects (≥12 years) who are SARS -CoV-2 RT-qPCR positive at baseline

Cohort B1: pediatric subjects (<12 years) who are SARS-CoV-2 RT--qPCR positive at baseline

• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Healthy Participants

Intervention

• Drug: REGN10933 + REGN10987
  Subcutaneous (SC) or Intramuscular (IM) injections
  Other Names:

  • REGN-COV2
  • Casirivimab
  • Imdevimab
  • REGEN-COV™
• Drug: Placebo
  SC or IM injections

Study Arms

• Experimental: REGN10933 + REGN10987
  Intervention: Drug: REGN10933 + REGN10987
• Placebo Comparator: Placebo
  Intervention: Drug: Placebo

Publications *

• Herman GA, O'Brien MP, Forleo-Neto E, Sarkar N, Isa F, Hou P, Chan KC, Bar KJ, Barnabas RV, Barouch DH, Cohen MS, Hurt CB, Burwen DR, Marovich MA, Musser BJ, Davis JD, Turner KC, Mahmood A, Hooper AT, Hamilton JD, Parrino J, Subramaniam D, Baum A, Kyratsous CA, DiCioccio AT, Stahl N, Braunstein N, Yancopoulos GD, Weinreich DM; COVID-19 Phase 3 Prevention Trial Team. Efficacy and safety of a single dose of casirivimab and imdevimab for the prevention of COVID-19 over an 8-month period: a randomised, double-blind, placebo-controlled trial. Lancet Infect Dis. 2022 Oct;22(10):1444-1454. doi: 10.1016/S1473-3099(22)00416-9. Epub 2022 Jul 5. Erratum In: Lancet Infect Dis. 2022 Sep;22(9):e239.
• Hirsch C, Park YS, Piechotta V, Chai KL, Estcourt LJ, Monsef I, Salomon S, Wood EM, So-Osman C, McQuilten Z, Spinner CD, Malin JJ, Stegemann M, Skoetz N, Kreuzberger N. SARS-CoV-2-neutralising monoclonal antibodies to prevent COVID-19. Cochrane Database Syst Rev. 2022 Jun 17;6(6):CD014945. doi: 10.1002/14651858.CD014945.pub2.
• O'Brien MP, Forleo-Neto E, Sarkar N, Isa F, Hou P, Chan KC, Musser BJ, Bar KJ, Barnabas RV, Barouch DH, Cohen MS, Hurt CB, Burwen DR, Marovich MA, Brown ER, Heirman I, Davis JD, Turner KC, Ramesh D, Mahmood A, Hooper AT, Hamilton JD, Kim Y, Purcell LA, Baum A, Kyratsous CA, Krainson J, Perez-Perez R, Mohseni R, Kowal B, DiCioccio AT, Geba GP, Stahl N, Lipsich L, Braunstein N, Herman G, Yancopoulos GD, Weinreich DM; COVID-19 Phase 3 Prevention Trial Team. Effect of Subcutaneous Casirivimab and Imdevimab Antibody Combination vs Placebo on Development of Symptomatic COVID-19 in Early Asymptomatic SARS-CoV-2 Infection: A Randomized Clinical Trial. JAMA. 2022 Feb 1;327(5):432-441. doi: 10.1001/jama.2021.24939. Erratum In: JAMA. 2022 May 24;327(20):2024.
• Kreuzberger N, Hirsch C, Chai KL, Tomlinson E, Khosravi Z, Popp M, Neidhardt M, Piechotta V, Salomon S, Valk SJ, Monsef I, Schmaderer C, Wood EM, So-Osman C, Roberts DJ, McQuilten Z, Estcourt LJ, Skoetz N. SARS-CoV-2-neutralising monoclonal antibodies for treatment of COVID-19. Cochrane Database Syst Rev. 2021 Sep 2;9(9):CD013825. doi: 10.1002/14651858.CD013825.pub2.
• O'Brien MP, Forleo-Neto E, Musser BJ, Isa F, Chan KC, Sarkar N, Bar KJ, Barnabas RV, Barouch DH, Cohen MS, Hurt CB, Burwen DR, Marovich MA, Hou P, Heirman I, Davis JD, Turner KC, Ramesh D, Mahmood A, Hooper AT, Hamilton JD, Kim Y, Purcell LA, Baum A, Kyratsous CA, Krainson J, Perez-Perez R, Mohseni R, Kowal B, DiCioccio AT, Stahl N, Lipsich L, Braunstein N, Herman G, Yancopoulos GD, Weinreich DM; Covid-19 Phase 3 Prevention Trial Team. Subcutaneous REGEN-COV Antibody Combination to Prevent Covid-19. N Engl J Med. 2021 Sep 23;385(13):1184-1195. doi: 10.1056/NEJMoa2109682. Epub 2021 Aug 4.
• O'Brien MP, Forleo-Neto E, Musser BJ, Isa F, Chan KC, Sarkar N, Bar KJ, Barnabas RV, Barouch DH, Cohen MS, Hurt CB, Burwen DR, Marovich MA, Hou P, Heirman I, Davis JD, Turner KC, Ramesh D, Mahmood A, Hooper AT, Hamilton JD, Kim Y, Purcell LA, Baum A, Kyratsous CA, Krainson J, Perez-Perez R, Mohseni R, Kowal B, DiCioccio AT, Stahl N, Lipsich L, Braunstein N, Herman G, Yancopoulos GD, Weinreich DM. Subcutaneous REGEN-COV Antibody Combination for Covid-19 Prevention. medRxiv. 2021 Jun 17:2021.06.14.21258567. doi: 10.1101/2021.06.14.21258567. Preprint.
• O'Brien MP, Forleo-Neto E, Sarkar N, Isa F, Hou P, Chan KC, Musser BJ, Bar KJ, Barnabas RV, Barouch DH, Cohen MS, Hurt CB, Burwen DR, Marovich MA, Brown ER, Heirman I, Davis JD, Turner KC, Ramesh D, Mahmood A, Hooper AT, Hamilton JD, Kim Y, Purcell LA, Baum A, Kyratsous CA, Krainson J, Perez-Perez R, Mohseni R, Kowal B, DiCioccio AT, Stahl N, Lipsich L, Braunstein N, Herman G, Yancopoulos GD, Weinreich DM; COVID-19 Phase 3 Prevention Trial Team. Subcutaneous REGEN-COV Antibody Combination in Early Asymptomatic SARS-CoV-2 Infection: A Randomized Clinical Trial. medRxiv. 2021 Sep 18:2021.06.14.21258569. doi: 10.1101/2021.06.14.21258569. Preprint.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: November 21, 2022): 3303
• Original Estimated Enrollment (submitted: June 26, 2020): 2000
• Actual Study Completion Date: October 4, 2021
• Actual Primary Completion Date: October 4, 2021 (Final data collection date for primary outcome measure)

Eligibility Criteria

Key Inclusion Criteria:

1. Adult subjects 18 years of age (irrespective of weight) and above at the signing of informed consent or adolescent participants ≥12 to <18 years of age, or pediatric participants <12 years of age at the signing of the assent (parent/guardian sign the informed consent)
2. Asymptomatic household contact with exposure to an individual with a diagnosis of SARS-CoV-2 infection (index case). To be included in the study, participants must be randomized within 96 hours of collection of the index cases' positive SARS-COV-2 diagnostic test sample
3. Participant anticipates living in the same household with the index case until study day 29
4. Is judged by the investigator to be in good health based on medical history and physical examination at screening/baseline, including participants who are healthy or have a chronic, stable medical condition
5. Willing and able to comply with study visits and study-related procedures/assessments.
6. Provide informed consent signed by study participant or legally acceptable representative.

Key Exclusion Criteria:

1. History of prior positive SARS-CoV-2 RT-PCR test or positive SARS-CoV-2 serology test at any time before the screening
2. Participant has lived with individuals who have had previous SARS-CoV-2 infection or currently lives with individuals who have SARS-CoV-2 infection, with the exception of the index case(s), the first individual(s) known to be infected in the household
3. Active respiratory or non-respiratory symptoms consistent with COVID-19
4. History of respiratory illness with sign/symptoms of SARS-CoV-2 infection, in the opinion of the investigator, within the prior 6 months to screening
5. Nursing home resident
6. Any physical examination findings, and/or history of any illness, concomitant medications or recent live vaccines that, in the opinion of the study investigator, might confound the results of the study or pose an additional risk to the participant by their participation in the study

Note: Other protocol-defined Inclusion/ Exclusion criteria apply

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 1 Day and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Moldova, Republic of, Romania, United States

Administrative Information

• NCT Number: NCT04452318
• Other Study ID Numbers: R10933-10987-COV-2069; 2020-003654-71 ( EudraCT Number )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

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

IPD Sharing Statement

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

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

Investigators

• Study Director: Clinical Trial Management; Regeneron Pharmaceuticals

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