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

Study Overview
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Brief Summary
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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
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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

Official Title
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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

Conditions
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Healthy Participants

Intervention / Treatment
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* Drug: REGN10933 + REGN10987
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: 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) 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 Participant anticipates living in the same household with the index case until study day 29 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 Willing and able to comply with study visits and study-related procedures/assessments. Provide informed consent signed by study participant or legally acceptable representative. Key Exclusion Criteria: History of prior positive SARS-CoV-2 RT-PCR test or positive SARS-CoV-2 serology test at any time before the screening 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 Active respiratory or non-respiratory symptoms consistent with COVID-19 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 Nursing home resident 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

Ages Eligible for Study
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Minimum Age: 1 Day

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: REGN10933 + REGN10987<br> | Drug: REGN10933 + REGN10987<br>* Subcutaneous (SC) or Intramuscular (IM) injections<br>* Other names: REGEN-COV™;|
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* SC or IM injections<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cohort A: Percentage of Participants Who Have a Symptomatic RT-qPCR Confirmed SARS-CoV-2 Infection (Broad-term) During the EAP | 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. | Up to 1 month | 
| 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 | 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). | Up to 14 Days | 
| Cohort A and Cohort B: Number of Participants With at Least One Treatment-emergent Adverse Event (TEAEs) and Severity of TEAEs |  | Up to 8 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cohort A and Cohort B: Percentage of Participants With High Viral Load in Nasopharyngeal (NP) Swab Samples During the EAP | High viral load (> 4 log 10 copies/ml) | Up to 1 month | 
| Cohort A: Number of Weeks of Symptomatic RT-qPCR Confirmed SARS-CoV-2 Infection (Broad Term) During the EAP |  | Up to 1 month | 
| Cohort A and Cohort B: Number of Weeks of High Viral Load in NP Swab Samples During the EAP | High viral load (> 4 log 10 copies/ml) | Up to 1 month | 
| Cohort A: Number of Weeks of RT-qPCR Confirmed SARS-CoV-2 Infection (Regardless of Symptoms) During the EAP |  | 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 | 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) | Up to 1 month | 
| 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) |  | Up to 1 month | 
| Cohort A: Percentage of Participants With a Symptomatic RT-qPCR Confirmed SARS-CoV-2 Infection (CDC Definition) During the EAP | 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. | Up to 1 month | 
| Cohort A: Number of Weeks of Symptomatic RT-qPCR-confirmed SARS-CoV-2 Infection (CDC Definition) During the EAP |  | 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 | 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) | Up to 1 month | 
| Cohort A: Number of Weeks of Symptomatic RT-qPCR Confirmed SARS-CoV-2 Infection (Strict-term) During the EAP |  | 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 |  | 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 | 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) | Week 1, Week 2, Week 3, Week 4 | 
| 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 |  | 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 |  | 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 |  | 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 |  | 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 |  | 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 | Medically attended visits referred to hospitalizations, Emergency Room visits, or visits at an Urgent Care center. | Up to 1 month | 
| 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 |  | 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 |  | 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 | The proportion of participants hospitalized related to a RT-qPCR confirmed SARS-CoV-2 infection that has an onset during the EAP | Up to 14 Days | 
| 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 |  | 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 | Daily responsibilities including work (employed adults) or school (students), daycare or family obligations/responsibilities (childcare or eldercare) | Up to 1 month | 
| Cohort A: Proportion of Baseline Seropositive Participants (Based on Central Lab Test) With TEAEs and Severity of TEAEs |  | Up to 8 months | 
| Cohort A and Cohort B: Incidence and Severity of Symptomatic SARS-CoV-2 Infections During the EAP |  | Up to Day 29 | 
| Cohort A and Cohort B: Incidence and Severity of Symptomatic SARS-CoV-2 Infections During the Follow-Up Period |  | 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 |  | 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 |  | 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 |  | 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 |  | 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 |  | 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 | 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) | Up to 1 month | 
| 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 | 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) | Up to 14 Days | 
| 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 |  | 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 |  | Up to 14 Days | 
| Cohort B: Change in Viral Load From Baseline to Day 8 Visit in NP Swab Samples |  | Up to day 8 visit | 
| Cohort B: Change in Viral Load From Baseline to Day 15 Visit in NP Swab Samples |  | 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 |  | 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 |  | 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 |  | 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 |  | 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 |  | 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 |  | 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 |  | 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 |  | Up to 1 month | 
| Concentrations of REGN10987 in Serum Over Time (Cohort A) |  | 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) |  | 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) |  | 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) |  | 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 |  | Up to 8 months | 
| Immunogenicity as Measured by Anti-drug Antibodies (ADAs) to REGN10987 |  | Up to 8 months | 
| Immunogenicity as Measured by Neutralizing Anti-drug Antibody (NAb) to REGN10933 | (TE&TB+;NAb+) = TE = Treatment-Emergent; TB = Treatment-boosted; NAb+ = Positive in NAb assay | Up to 8 months | 
| Immunogenicity as Measured by Neutralizing Anti-drug Antibody (NAb) to REGN10987 | (TE&TB+;NAb+) = TE = Treatment-emergent; TB = Treatment-boosted; NAb+ = Positive in NAb assay | Up to 8 Months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Asymptomatic, Individuals at risk of exposure to SARS-CoV-2, Household Contacts of a Person Infected with SARS-CoV-2