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

Phase 2

Completed

• Conditions: Healthy; Chronic Stable Illness
• Interventions: Drug: casirivimab+imdevimab; Biological: Moderna mRNA-1273 vaccine

• Registration Number: NCT04852978
• Lead Sponsor: Regeneron Pharmaceuticals

Brief Summary

The primary objectives of the study are:

* To evaluate the extent of effect, if any, of REGN10933+REGN10987 administration on vaccine-induced neutralizing antibody responses to SARS-CoV-2 by Moderna mRNA-1273

* To evaluate the time interval required between REGN10933+REGN10987 administration and Moderna mRNA-1273 vaccination, to ensure no meaningful impact on vaccine-induced neutralizing antibody responses to SARS-CoV-2

The secondary objectives of the study are:

* To quantify the alteration of antigen specificity of vaccine-induced SARS-CoV-2 antibody responses when administered with different dose regimens of REGN10933+REGN10987

* To evaluate the safety and tolerability of REGN10933+REGN10987 and Moderna mRNA-1273 vaccine when administered in close succession

* To assess the concentrations of REGN10933 and REGN10987 in serum over time in participants who receive REGN10933+REGN10987 and Moderna mRNA-1273 vaccine

* To evaluate the immunogenicity of REGN10933 and REGN10987 over time

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2021-04-19
• Study First Submitted QC: 2021-04-19
• Study First Posted: 2021-04-21
• Study Start: 2021-04-29
• Primary Completion: 2022-11-21
• Study Completion: 2022-11-21
• Results First Submitted: 2023-11-20
• Status Verified: 2024-07
• Results First Submitted QC: 2024-07-25
• Last Update Submitted: 2024-07-25
• Results First Posted: 2024-08-20
• Last Update Posted: 2024-08-20

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 295

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Wave 1 Dose 3	Moderna mRNA-1273 vaccine	-
Wave 2 Dose 1	casirivimab+imdevimab	-
Wave 2 Vaccine only	Moderna mRNA-1273 vaccine	-
Wave 3 Dose 1	Moderna mRNA-1273 vaccine	-
Wave 1 Dose 1	Moderna mRNA-1273 vaccine	-
Wave 1 Dose 2	Moderna mRNA-1273 vaccine	-
Wave 1 Dose 3	casirivimab+imdevimab	-
Wave 3 Dose 1	casirivimab+imdevimab	-
Wave 3 Dose 2	casirivimab+imdevimab	-
Wave 3 Vaccine only	Moderna mRNA-1273 vaccine	-
Wave 4 Vaccine only	Moderna mRNA-1273 vaccine	-
Wave 1 Dose 1	casirivimab+imdevimab	-
Wave 1 Dose 2	casirivimab+imdevimab	-
Wave 1 Vaccine only	Moderna mRNA-1273 vaccine	-
Wave 2 Dose 1	Moderna mRNA-1273 vaccine	-
Wave 2 Dose 2	Moderna mRNA-1273 vaccine	-
Wave 3 Dose 2	Moderna mRNA-1273 vaccine	-
Wave 4 Dose 1	Moderna mRNA-1273 vaccine	-
Wave 2 Dose 2	casirivimab+imdevimab	-
Wave 4 Dose 1	casirivimab+imdevimab	-

Primary Outcome Measures

Name	Time	Method
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)	56 days after first dose of vaccine	Submaximal dose - (150 mg, 300 mg, 600 mg, 48 mg, and 12 mg)
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)	56 days after first dose of vaccine	High dose - (1200 mg arms)

Secondary Outcome Measures

Name	Time	Method
Median Fold Change of Concentrations of Vaccine-induced Antibodies to SARS-CoV-2 Antigens Over Time (S1-RBD IgA)	Up to 365 Days from 1st dose of Vaccination	Anti-S1-RBD protein. Fold Change based on medians = (median value in vaccine only arm / median value in the active arm)
Number of Participants With Treatment-emergent Adverse Events (TEAEs) Throughout the Study	Up to 401 Days
Absolute Values in Concentrations of Vaccine-induced Antibodies to SARS-CoV-2 Antigens Over Time (S1-RBD IgM)	Up to 365 Days from 1st dose of vaccination	Anti-S1-RBD
Absolute Values in Concentrations of Vaccine-induced Antibodies to SARS-CoV-2 Antigens Over Time (S-IgA)	Up to 365 Days from 1st dose of Vaccination	- Anti-S protein (Spike protein)
Relative Difference Expressed as a Percent in Vaccine-induced Antibodies to SARS-CoV-2 Antigens Over Time (S-IgG)	Up to 365 Days from 1st dose of vaccination	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%
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	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 IgA)	Up to 365 Days from 1st dose of Vaccination	Anti-S1-RBD protein
Relative Difference Expressed as a Percent in Vaccine-induced Antibodies to SARS-CoV-2 Antigens Over Time (S-IgA)	Up to 365 Days from 1st dose of Vaccination	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%
Absolute Values in Concentrations of Vaccine-induced Antibodies to SARS-CoV-2 Antigens Over Time (S1-RBD IgG)	Up to 365 Days from 1st dose of vaccination	Anti-S1-RBD
Number of Participants With Infusion-related Reactions (Grade ≥2) to REGN10933+REGN10987	Through Day 4 post-infusion
Number of Participants With Injection Site Reactions (Grade ≥3) to REGN10933+REGN10987	Through Day 4 post-infusion
Concentrations of REGN10987 in Serum Over Time	Up to 182 Days
Immunogenicity, as Measured by Anti-drug Antibodies (ADA) to REGN10987	Up to Day 183
Fold Change of Concentrations of Vaccine-induced Antibodies to SARS-CoV-2 Antigens Over Time (S-IgA)	Up to 365 Days from 1st dose of vaccination	Anti-S protein Fold Change based on medians = (median value in vaccine only arm / median value in the active arm)
Absolute Values in Concentrations of Vaccine-induced Antibodies to SARS-CoV-2 Antigens Over Time (S-IgG)	Up to 365 Days from 1st dose of vaccination	Anti-S protein
Fold Change of Concentrations of Vaccine-induced Antibodies to SARS-CoV-2 Antigens Over Time (S1-RBD IgM)	Up to 365 Days from 1st dose of vaccination	Anti-S1-RBD protein Fold Change based on medians = (median value in vaccine only arm / median value in the active arm)
Fold Change of Concentrations of Vaccine-induced Antibodies to SARS-CoV-2 Antigens Over Time (S-IgM)	Up to 365 Days from 1st dose of vaccination	Anti-S protein (Spike protein) Fold Change based on medians = (median value in vaccine only arm / median value in the active arm)
Number of Participants With Injection Site Reactions (Grade ≥3) to Moderna mRNA-1273 Vaccine	Through Day 4 post-infusion
Concentrations of REGN10933 in Serum Over Time	Up to 182 Days
Immunogenicity, as Measured by Neutralizing Antibodies (NAb) to REGN10987	Up to Day 183
Fold Change of Concentrations of Vaccine-induced Antibodies to SARS-CoV-2 Antigens Over Time (S-IgG)	Up to 365 Days from 1st dose of vaccination	Anti-S protein Fold Change based on medians = (median value in vaccine only arm / median value in the active arm)
Fold Change of Concentrations of Vaccine-induced Antibodies to SARS-CoV-2 Antigens Over Time (S1-RBD IgG)	Up to 365 Days from 1st dose of vaccination	Anti-S1-RBD protein Fold Change based on medians = (median value in vaccine only arm / median value in the active arm)
Relative Difference Expressed as a Percent in Vaccine-induced Antibodies to SARS-CoV-2 Antigens Over Time (S1-RBD IgG)	Up to 365 Days from 1st dose of vaccination	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%
Relative Difference Expressed as a Percent in Concentrations of Vaccine-induced Antibodies to SARS-CoV-2 Antigens Over Time (S-IgM)	Up to 365 Days from 1st dose of vaccination	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%
Relative Difference Expressed as a Percent in Vaccine-induced Antibodies to SARS-CoV-2 Antigens Over Time (S1-RBD IgA)	Up to 365 Days from 1st dose of Vaccination	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%
Relative Difference Expressed as a Percent in Vaccine-induced Antibodies to SARS-CoV-2 Antigens Over Time (S1-RBD IgM)	Up to 365 Days from 1st dose of vaccination	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%
Absolute Values in Concentrations of Vaccine-induced Antibodies to SARS-CoV-2 Antigens Over Time (S-IgM)	Up to 365 Days from 1st dose of vaccination	Anti-S protein (Spike protein)
Number of Participants With Treatment-emergent Serious Adverse Events (SAEs) Throughout the Study	Up to 401 Days
Number of Participants With Hypersensitivity Reactions (Grade ≥2) to REGN10933+REGN10987 or Each Dose of Moderna mRNA-1273 Vaccine	Through Day 29 post-infusion or post-injection	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
Immunogenicity, as Measured by Neutralizing Antibodies (NAb) to REGN10933	Up to Day 183
Immunogenicity, as Measured by Anti-drug Antibodies (ADA) to REGN10933	Up to Day 183

Trial Locations

Locations (1)

Regeneron Research Site; 🇺🇸 Dayton, Ohio, United States