NCT04852978 - COVID-19 Study to Assess Immunogenicity, Safety, and Tolerability of Moderna mRNA-1273 Vaccine Administered With Casirivimab+Imdevimab in Healthy Adult Volunteers | Crick | Crick

NCT04852978 - COVID-19 Study to Assess Immunogenicity, Safety, and Tolerability of Moderna mRNA-1273 Vaccine Administered With Casirivimab+Imdevimab in Healthy Adult Volunteers | Crick | Crick

Eligibility

Sex: ALLMin age: 18 YearsMax age: 90 YearsHealthy volunteers:

Medical Language ↔ Plain English

Key Inclusion Criteria: 1. Healthy or has chronic medical condition(s) that are stable and well-controlled in the opinion of the investigator and that are not likely to require significant medical intervention through the end of study 2. Willing and able to comply with study visits and study-related procedures, including compliance with site precautionary requirements related to SARS-CoV-2 infection and transmission Key Exclusion Criteria: 1. Positive RT-PCR test result for SARS-CoV-2 infection at screening or baseline 2. Positive serology test result for anti-SARS-CoV-2 antibodies at screening or baseline 3. COVID-19 diagnosis, positive SARS-CoV-2 infection, or positive SARS-CoV-2 serology at any time prior to screening 4. Previously received an investigational, authorized, or approved coronavirus vaccine (eg, SARS-CoV-2 vaccine, MERS-CoV vaccine) 5. Currently enrolled in, or has plans to enroll in, any interventional study to prevent or treat COVID-19 6. Received investigational or approved passive antibodies for SARS-CoV-2 infection prophylaxis ad defined in the protocol 7. Received intravenous immunoglobulin (IVIG) or blood products in the last 3 months 8. Any physical examination findings and/or history of any illness that, in the opinion of the study investigator, might confound the results of the study or pose an additional risk to the subject by study participation 9. History of clinically significant cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine, hematological, psychiatric or neurological disease, as assessed by the investigator, that may confound the results of the study or pose an additional risk to the subject by study participation 10. Medically attended acute illness or hospitalization (ie, \>24 hours) for any reason within 30 days prior to screening 11. Clinical history of myocarditis and/or pericarditis Note: Other protocol-defined Inclusion/ Exclusion Criteria apply

Outcomes

Primary Outcomes

50% Inhibitory Dilution (ID50) Titers of Vaccine-induced Neutralizing Antibodies to the SARS-CoV-2 S Protein in Individuals Who Received High Dose REGN10933+REGN10987 (1200 mg)

High dose - (1200 mg arms)

Time frame: 56 days after first dose of vaccine

50% Inhibitory Dilution (ID50) Titers of Vaccine-induced Neutralizing Antibodies to the SARS-CoV-2 S Protein in Individual Who Received Submaximal Dose Levels of REGN10933+REGN10987 (Less Than 1200 mg)

Submaximal dose - (150 mg, 300 mg, 600 mg, 48 mg, and 12 mg)

Time frame: 56 days after first dose of vaccine

Secondary Outcomes

Absolute Values in Concentrations of Vaccine-induced Antibodies to SARS-CoV-2 Antigens Over Time (S1-RBD IgA)

Anti-S1-RBD protein

Time frame: Up to 365 Days from 1st dose of Vaccination

Median Fold Change of Concentrations of Vaccine-induced Antibodies to SARS-CoV-2 Antigens Over Time (S1-RBD IgA)

Anti-S1-RBD protein. Fold Change based on medians = (median value in vaccine only arm / median value in the active arm)

Time frame: Up to 365 Days from 1st dose of Vaccination

Relative Difference Expressed as a Percent in Vaccine-induced Antibodies to SARS-CoV-2 Antigens Over Time (S1-RBD IgA)

Anti-S1-RBD protein. Relative difference is calculated as: \[(LS Geometric Mean Active Arm - LS Geometric Mean Vaccine Alone Arm) / LS Geometric Mean Vaccine Alone Arm\] x 100%

Time frame: Up to 365 Days from 1st dose of Vaccination

Absolute Values in Concentrations of Vaccine-induced Antibodies to SARS-CoV-2 Antigens Over Time (S-IgA)

\- Anti-S protein (Spike protein)

Time frame: Up to 365 Days from 1st dose of Vaccination

Fold Change of Concentrations of Vaccine-induced Antibodies to SARS-CoV-2 Antigens Over Time (S-IgA)

Anti-S protein Fold Change based on medians = (median value in vaccine only arm / median value in the active arm)

Time frame: Up to 365 Days from 1st dose of vaccination

Relative Difference Expressed as a Percent in Vaccine-induced Antibodies to SARS-CoV-2 Antigens Over Time (S-IgA)

Anti-S protein Relative difference is calculated as: \[(LS Geometric Mean Active Arm - LS Geometric Mean Vaccine Alone Arm) / LS Geometric Mean Vaccine Alone Arm\] x 100%

Time frame: Up to 365 Days from 1st dose of Vaccination

Absolute Values in Concentrations of Vaccine-induced Antibodies to SARS-CoV-2 Antigens Over Time (S-IgG)

Anti-S protein

Time frame: Up to 365 Days from 1st dose of vaccination

Fold Change of Concentrations of Vaccine-induced Antibodies to SARS-CoV-2 Antigens Over Time (S-IgG)

Anti-S protein Fold Change based on medians = (median value in vaccine only arm / median value in the active arm)

Time frame: Up to 365 Days from 1st dose of vaccination

Relative Difference Expressed as a Percent in Vaccine-induced Antibodies to SARS-CoV-2 Antigens Over Time (S-IgG)

Anti-S protein (Spike) Relative difference is calculated as: \[(LS Geometric Mean Active Arm - LS Geometric Mean Vaccine Alone Arm) / LS Geometric Mean Vaccine Alone Arm\] x 100%

Time frame: Up to 365 Days from 1st dose of vaccination

Absolute Values in Concentrations of Vaccine-induced Antibodies to SARS-CoV-2 Antigens Over Time (S1-RBD IgG)

Anti-S1-RBD

Time frame: Up to 365 Days from 1st dose of vaccination

Fold Change of Concentrations of Vaccine-induced Antibodies to SARS-CoV-2 Antigens Over Time (S1-RBD IgG)

Anti-S1-RBD protein Fold Change based on medians = (median value in vaccine only arm / median value in the active arm)

Time frame: Up to 365 Days from 1st dose of vaccination

Relative Difference Expressed as a Percent in Vaccine-induced Antibodies to SARS-CoV-2 Antigens Over Time (S1-RBD IgG)

Anti-S1-RBD protein Relative difference is calculated as: \[(LS Geometric Mean Active Arm - LS Geometric Mean Vaccine Alone Arm) / LS Geometric Mean Vaccine Alone Arm\] x 100%

Time frame: Up to 365 Days from 1st dose of vaccination

Absolute Values in Concentrations of Vaccine-induced Antibodies to SARS-CoV-2 Antigens Over Time (S1-RBD IgM)

Anti-S1-RBD

Time frame: Up to 365 Days from 1st dose of vaccination

Relative Difference Expressed as a Percent in Vaccine-induced Antibodies to SARS-CoV-2 Antigens Over Time (S1-RBD IgM)

Anti-S1-RBD protein Relative difference is calculated as: \[(LS Geometric Mean Active Arm - LS Geometric Mean Vaccine Alone Arm) / LS Geometric Mean Vaccine Alone Arm\] x 100%

Time frame: Up to 365 Days from 1st dose of vaccination

Fold Change of Concentrations of Vaccine-induced Antibodies to SARS-CoV-2 Antigens Over Time (S1-RBD IgM)

Anti-S1-RBD protein Fold Change based on medians = (median value in vaccine only arm / median value in the active arm)

Time frame: Up to 365 Days from 1st dose of vaccination

Absolute Values in Concentrations of Vaccine-induced Antibodies to SARS-CoV-2 Antigens Over Time (S-IgM)

Anti-S protein (Spike protein)

Time frame: Up to 365 Days from 1st dose of vaccination

Relative Difference Expressed as a Percent in Concentrations of Vaccine-induced Antibodies to SARS-CoV-2 Antigens Over Time (S-IgM)

Anti-S protein (Spike protein) Relative difference is calculated as: \[(LS Geometric Mean Active Arm - LS Geometric Mean Vaccine Alone Arm) / LS Geometric Mean Vaccine Alone Arm\] x 100%

Time frame: Up to 365 Days from 1st dose of vaccination

Fold Change of Concentrations of Vaccine-induced Antibodies to SARS-CoV-2 Antigens Over Time (S-IgM)

Anti-S protein (Spike protein) Fold Change based on medians = (median value in vaccine only arm / median value in the active arm)

Time frame: Up to 365 Days from 1st dose of vaccination

50% Inhibitory Dilution (ID50) Titers of Vaccine-induced Neutralizing Antibodies to SARS-CoV-2 S Protein Assessed Over Time After the First Dose of Moderna mRNA-1273 Vaccine

Time frame: Up to 365 Days from 1st dose of vaccination

Number of Participants With Treatment-emergent Adverse Events (TEAEs) Throughout the Study

Time frame: Up to 401 Days

Number of Participants With Treatment-emergent Serious Adverse Events (SAEs) Throughout the Study

Time frame: Up to 401 Days

Number of Participants With Infusion-related Reactions (Grade ≥2) to REGN10933+REGN10987

Time frame: Through Day 4 post-infusion

Number of Participants With Injection Site Reactions (Grade ≥3) to REGN10933+REGN10987

Time frame: Through Day 4 post-infusion

Number of Participants With Injection Site Reactions (Grade ≥3) to Moderna mRNA-1273 Vaccine

Time frame: Through Day 4 post-infusion

Number of Participants With Hypersensitivity Reactions (Grade ≥2) to REGN10933+REGN10987 or Each Dose of Moderna mRNA-1273 Vaccine

Grade 2 - characterized by an adverse local or general response from exposure and oral intervention indicated Grade 3 - hospitalization indicated and intravenous response required Grade 4 - Life Threatening consequence and urgent intervention indicated Grade 5 - Death

Time frame: Through Day 29 post-infusion or post-injection

Concentrations of REGN10933 in Serum Over Time

Time frame: Up to 182 Days

Concentrations of REGN10987 in Serum Over Time

Time frame: Up to 182 Days

Immunogenicity, as Measured by Anti-drug Antibodies (ADA) to REGN10987

Time frame: Up to Day 183

Immunogenicity, as Measured by Anti-drug Antibodies (ADA) to REGN10933

Time frame: Up to Day 183

Immunogenicity, as Measured by Neutralizing Antibodies (NAb) to REGN10987

Time frame: Up to Day 183

Immunogenicity, as Measured by Neutralizing Antibodies (NAb) to REGN10933

Time frame: Up to Day 183