Phase 3
N=3,298
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
Healthy Participants
Bottom Line
View on ClinicalTrials.gov: NCT04452318 ↗Enrolled (actual)
3,298
Serious AEs
1.6%
Results posted
May 2023
Primary outcome: Primary: Cohort A: Percentage of Participants Who Have a Symptomatic RT-qPCR Confirmed SARS-CoV-2 Infection (Broad-term) During the EAP — 7.8; 1.4 Percentage of Participants — p=< 0.0001
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 3
- Interventions
- REGN10933 + REGN10987 (Drug); Placebo (Drug)
- Age
- Pediatric, Adult, Older Adult · 0+ yrs
- Sex
- All
- Sponsor
- Regeneron Pharmaceuticals
- Primary completion
- Oct 2021
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Cohort A: Percentage of Participants Who Have a Symptomatic RT-qPCR Confirmed SARS-CoV-2 Infection (Broad-term) During the EAP |
7.8; 1.4 | < 0.0001 sig |
| PRIMARY 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 |
42.5; 28.4 | = 0.0380 sig |
| PRIMARY Cohort A and Cohort B: Number of Participants With at Least One Treatment-emergent Adverse Event (TEAEs) and Severity of TEAEs |
512; 405; 88; 60; 384; 284 | — |
| SECONDARY Cohort A and Cohort B: Percentage of Participants With High Viral Load in Nasopharyngeal (NP) Swab Samples During the EAP |
11.3; 1.6; 62.6; 40.5 | < 0.0001 sig |
| SECONDARY Cohort A: Number of Weeks of Symptomatic RT-qPCR Confirmed SARS-CoV-2 Infection (Broad Term) During the EAP |
0.25; 0.02 | < 0.0001 sig |
| SECONDARY Cohort A and Cohort B: Number of Weeks of High Viral Load in NP Swab Samples During the EAP |
0.18; 0.02; 0.81; 0.49 | < 0.0001 sig |
| SECONDARY Cohort A: Number of Weeks of RT-qPCR Confirmed SARS-CoV-2 Infection (Regardless of Symptoms) During the EAP |
0.31; 0.05 | < 0.0001 sig |
| SECONDARY Cohort A: Percentage of Participants Who Have a RT-qPCR Confirmed SARS-CoV-2 Infection (Regardless of Symptoms) During the EAP |
14.56; 5.00 | < 0.0001 sig |
| SECONDARY 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) |
19.8; 19.6; 10.5 | — |
| SECONDARY Cohort A: Percentage of Participants With a Symptomatic RT-qPCR Confirmed SARS-CoV-2 Infection (CDC Definition) During the EAP |
5.9; 0.8 | < 0.0001 sig |
| SECONDARY Cohort A: Number of Weeks of Symptomatic RT-qPCR-confirmed SARS-CoV-2 Infection (CDC Definition) During the EAP |
0.21; 0.01 | < 0.0001 sig |
| SECONDARY Cohort A: Percentage of Participants Who Have a Symptomatic RT-qPCR Confirmed SARS-CoV-2 Infection (Strict-term) During the EAP |
2.8; 0.2 | = 0.0010 sig |
| SECONDARY Cohort A: Number of Weeks of Symptomatic RT-qPCR Confirmed SARS-CoV-2 Infection (Strict-term) During the EAP |
0.12; 0.00 | < 0.0001 sig |
| SECONDARY Cohort A: Percentage of Participants Who Have a RT-qPCR Confirmed SARS-CoV-2 Infections at Each Week in the EAP |
8.9; 3.1; 8.5; 1.1; 7.7; 0.7 | — |
| SECONDARY Cohort A: Percentage of Participants Who Have a Symptomatic RT-qPCR Confirmed SARS-CoV-2 Infection (Broad-term) at Each Week in the EAP |
5.2; 1.2; 4.8; 0.4; 3.3; 0.0 | — |
| SECONDARY 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 |
3.065; 0.942 | < 0.0001 sig |
| SECONDARY 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 |
3.689; 1.205 | < 0.0001 sig |
| SECONDARY 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 |
6.133; 3.705 | < 0.0001 sig |
| SECONDARY 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 |
6.141; 3.700 | < 0.0001 sig |
| SECONDARY 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 |
65.982; 19.700 | — |
| SECONDARY 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 |
9; 0 | — |
| SECONDARY 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 |
0.5; 0.0 | = 0.0621 |
| SECONDARY 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 |
1.1; 0.0 | = 0.0038 sig |
| SECONDARY Cohort A: Proportion of Participants Hospitalized Related to a RT-qPCR Confirmed SARS-CoV-2 Infection That Has an Onset During the EAP |
0.001; 0.0 | — |
| SECONDARY 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 |
11 | — |
| SECONDARY 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 |
0.98; 0.15 | < 0.0001 sig |
| SECONDARY Cohort A: Proportion of Baseline Seropositive Participants (Based on Central Lab Test) With TEAEs and Severity of TEAEs |
79; 83; 5; 6 | — |
| SECONDARY Cohort A and Cohort B: Incidence and Severity of Symptomatic SARS-CoV-2 Infections During the EAP |
81; 15; 57; 35; 68; 11 | — |
| SECONDARY Cohort A and Cohort B: Incidence and Severity of Symptomatic SARS-CoV-2 Infections During the Follow-Up Period |
68; 14; 1; 1; 50; 12 | — |
| SECONDARY Cohort A and Cohort B: Incidence and Severity of Symptomatic SARS-CoV-2 Infections in Seronegative Subjects During the EAP |
74; 12; 47; 32; 64; 9 | — |
| SECONDARY Cohort A and Cohort B: Incidence and Severity of Symptomatic SARS-CoV-2 Infections in Seronegative Subjects During the Follow-Up Period |
64; 10; 1; 1; 47; 8 | — |
| SECONDARY Cohort A and Cohort B: Incidence and Severity of Symptomatic SARS-CoV-2 Infections in Seropositive Subjects During the EAP |
6; 3; 6; 3; 3; 2 | — |
| SECONDARY Cohort A and Cohort B: Incidence and Severity of Symptomatic SARS-CoV-2 Infections in Seropositive Subjects During the Follow-Up Period |
3; 3; 0; 0; 3; 3 | — |
| SECONDARY 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 |
1.64; 0.90 | = 0.0273 sig |
| SECONDARY 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 |
39.7; 26.3 | = 0.0460 sig |
| SECONDARY 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 |
18.5; 9.7 | = 0.0721 |
| SECONDARY 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 |
1.71; 0.88 | = 0.0260 sig |
| SECONDARY 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 |
0.68; 0.40 | = 0.0614 |
| SECONDARY Cohort B: Change in Viral Load From Baseline to Day 8 Visit in NP Swab Samples |
-1.543; -3.004 | < 0.0001 sig |
| SECONDARY Cohort B: Change in Viral Load From Baseline to Day 15 Visit in NP Swab Samples |
-4.014; -4.864 | = 0.0026 sig |
| SECONDARY Cohort B: Time-weighted Average Change From Baseline in Viral Load (log10 Copies/mL) in NP Swab Samples Until the Day 22 Visit |
-2.639; -3.580 | < 0.0001 sig |
| SECONDARY 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 |
82.008; 55.964 | < 0.0001 sig |
| SECONDARY 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 |
4.731; 3.336 | < 0.0001 sig |
| SECONDARY 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 |
0.06; 0.00 | = 0.0138 sig |
| SECONDARY 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 |
5.8; 0.0 | = 0.0292 sig |
| SECONDARY 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 |
2.9; 0.0 | = 0.2466 |
| SECONDARY 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 |
5.69; 5.18 | = 0.7861 |
| SECONDARY 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 |
0.38; 0.00 | = 0.0842 |
| SECONDARY Concentrations of REGN10987 in Serum Over Time (Cohort A) |
0.0233; 24.6; 10.4; 2.10 | — |
| SECONDARY Concentrations of REGN10987 in Serum Over Time (Cohort B) |
0; 31.0; 14.0; 4.62 | — |
| SECONDARY Concentrations of REGN10933 in Serum Over Time (Cohort A) |
0.0190; 30.8; 14.8; 3.61 | — |
| SECONDARY Concentrations of REGN10933 in Serum Over Time (Cohort B) |
0; 37.6; 19.1; 4.58 | — |
| SECONDARY Immunogenicity as Measured by Anti-drug Antibodies (ADAs) to REGN10933 |
1544; 1319 | — |
| SECONDARY Immunogenicity as Measured by Anti-drug Antibodies (ADAs) to REGN10987 |
1500; 1251 | — |
| SECONDARY Immunogenicity as Measured by Neutralizing Anti-drug Antibody (NAb) to REGN10933 |
4; 33 | — |
| SECONDARY Immunogenicity as Measured by Neutralizing Anti-drug Antibody (NAb) to REGN10987 |
27; 160 | — |
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
Eligibility Criteria
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
Data sourced from ClinicalTrials.gov (NCT04452318). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.