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

A Phase 2 Randomized, Open-Label, Parallel Group Study to Assess the Immunogenicity, Safety, and Tolerability of Moderna mRNA-1273 Vaccine Administered With Casirivimab+Imdevimab in Healthy Adult Volunteers

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

Study Overview

• Status: Completed
• Conditions: Healthy; Chronic Stable Illness
• Intervention / Treatment: Drug: casirivimab+imdevimab; Biological: Moderna mRNA-1273 vaccine

• Study Type: Interventional
• Enrollment (Actual): 295
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Arkansas
    • Little Rock, Arkansas, United States, 72211
      • Regeneron Research Site
    • Rogers, Arkansas, United States, 72758
      • Regeneron Research Site
  • Florida
    • Hialeah, Florida, United States, 33012
      • Regeneron Research Site
    • Miami, Florida, United States, 33186
      • Regeneron Research Site
    • Orlando, Florida, United States, 32789
      • Regeneron Research Site
  • Ohio
    • Dayton, Ohio, United States, 45417
      • Regeneron Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 90 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

12

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Wave 1 Dose 1	Drug: casirivimab+imdevimab; Wave 1 Intravenous (IV) administration Wave 2 Subcutaneous administration; Other Names: REGN-COV2; REGEN-COV™; Ronapreve™; REGN10933; REGN10987; Biological: Moderna mRNA-1273 vaccine; Single intramuscular (IM) injection
Experimental: Wave 1 Dose 2	Drug: casirivimab+imdevimab; Wave 1 Intravenous (IV) administration Wave 2 Subcutaneous administration; Other Names: REGN-COV2; REGEN-COV™; Ronapreve™; REGN10933; REGN10987; Biological: Moderna mRNA-1273 vaccine; Single intramuscular (IM) injection
Experimental: Wave 1 Dose 3	Drug: casirivimab+imdevimab; Wave 1 Intravenous (IV) administration Wave 2 Subcutaneous administration; Other Names: REGN-COV2; REGEN-COV™; Ronapreve™; REGN10933; REGN10987; Biological: Moderna mRNA-1273 vaccine; Single intramuscular (IM) injection
Experimental: Wave 1 Vaccine only	Biological: Moderna mRNA-1273 vaccine; Single intramuscular (IM) injection
Experimental: Wave 2 Dose 1	Drug: casirivimab+imdevimab; Wave 1 Intravenous (IV) administration Wave 2 Subcutaneous administration; Other Names: REGN-COV2; REGEN-COV™; Ronapreve™; REGN10933; REGN10987; Biological: Moderna mRNA-1273 vaccine; Single intramuscular (IM) injection
Experimental: Wave 2 Dose 2	Drug: casirivimab+imdevimab; Wave 1 Intravenous (IV) administration Wave 2 Subcutaneous administration; Other Names: REGN-COV2; REGEN-COV™; Ronapreve™; REGN10933; REGN10987; Biological: Moderna mRNA-1273 vaccine; Single intramuscular (IM) injection
Experimental: Wave 2 Vaccine only	Biological: Moderna mRNA-1273 vaccine; Single intramuscular (IM) injection
Experimental: Wave 3 Dose 1	Drug: casirivimab+imdevimab; Wave 1 Intravenous (IV) administration Wave 2 Subcutaneous administration; Other Names: REGN-COV2; REGEN-COV™; Ronapreve™; REGN10933; REGN10987; Biological: Moderna mRNA-1273 vaccine; Single intramuscular (IM) injection
Experimental: Wave 3 Dose 2	Drug: casirivimab+imdevimab; Wave 1 Intravenous (IV) administration Wave 2 Subcutaneous administration; Other Names: REGN-COV2; REGEN-COV™; Ronapreve™; REGN10933; REGN10987; Biological: Moderna mRNA-1273 vaccine; Single intramuscular (IM) injection
Experimental: Wave 3 Vaccine only	Biological: Moderna mRNA-1273 vaccine; Single intramuscular (IM) injection
Experimental: Wave 4 Dose 1	Drug: casirivimab+imdevimab; Wave 1 Intravenous (IV) administration Wave 2 Subcutaneous administration; Other Names: REGN-COV2; REGEN-COV™; Ronapreve™; REGN10933; REGN10987; Biological: Moderna mRNA-1273 vaccine; Single intramuscular (IM) injection
Experimental: Wave 4 Vaccine only	Biological: Moderna mRNA-1273 vaccine; Single intramuscular (IM) injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)	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)	56 days after first dose of vaccine

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Absolute Values in Concentrations of Vaccine-induced Antibodies to SARS-CoV-2 Antigens Over Time (S1-RBD IgA)	Anti-S1-RBD protein	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)	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%	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)	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)	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%	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	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)	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%	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	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)	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%	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	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%	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)	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)	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%	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)	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		Up to 365 Days from 1st dose of vaccination
Number of Participants With Treatment-emergent Adverse Events (TEAEs) Throughout the Study		Up to 401 Days
Number of Participants With Treatment-emergent Serious Adverse Events (SAEs) Throughout the Study		Up to 401 Days
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
Number of Participants With Injection Site Reactions (Grade ≥3) to Moderna mRNA-1273 Vaccine		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	Through Day 29 post-infusion or post-injection
Concentrations of REGN10933 in Serum Over Time		Up to 182 Days
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
Immunogenicity, as Measured by Anti-drug Antibodies (ADA) to REGN10933		Up to Day 183
Immunogenicity, as Measured by Neutralizing Antibodies (NAb) to REGN10987		Up to Day 183
Immunogenicity, as Measured by Neutralizing Antibodies (NAb) to REGN10933		Up to Day 183

Collaborators and Investigators

• Sponsor: Regeneron Pharmaceuticals
• Investigators: Study Director: Clinical Trial Management, Regeneron Pharmaceuticals

Publications and helpful links

General Publications

• Isa F, Gonzalez Ortiz AM, Meyer J, Hamilton JD, Olenchock BA, Brackin T, Ganguly S, Forleo-Neto E, Faria L, Heirman I, Marovich M, Hutter J, Polakowski L, Irvin SC, Thakur M, Hooper AT, Baum A, Petro CD, Fakih FA, McElrath MJ, De Rosa SC, Cohen KW, Williams LD, Hellman CA, Odeh AJ, Patel AH, Tomaras GD, Geba GP, Kyratsous CA, Musser B, Yancopoulos GD, Herman GA; Trial Working Group. Effect of timing of casirivimab and imdevimab administration relative to mRNA-1273 COVID-19 vaccination on vaccine-induced SARS-CoV-2 neutralising antibody responses: a prospective, open-label, phase 2, randomised controlled trial. Lancet Infect Dis. 2025 Jan;25(1):52-67. doi: 10.1016/S1473-3099(24)00421-3. Epub 2024 Sep 2.

Study record dates

Study Major Dates

• Study Start (Actual): April 29, 2021
• Primary Completion (Actual): November 21, 2022
• Study Completion (Actual): November 21, 2022

Study Registration Dates

• First Submitted: April 19, 2021
• First Submitted That Met QC Criteria: April 19, 2021
• First Posted (Actual): April 21, 2021

Study Record Updates

• Last Update Posted (Actual): October 20, 2025
• Last Update Submitted That Met QC Criteria: October 9, 2025
• Last Verified: October 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Amino Acids, Peptides, and Proteins; Proteins; Biological Factors; Biological Products; Complex Mixtures; Vaccines; Viral Vaccines; mRNA Vaccines; Nucleic Acid-Based Vaccines; Vaccines, Synthetic; Recombinant Proteins; COVID-19 Vaccines; Antigens; 2019-nCoV Vaccine mRNA-1273; casirivimab and imdevimab drug combination; casirivimab; imdevimab
• Other Study ID Numbers: R10933-10987-COV-2118

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: All Individual Patient Data (IPD) that underlie publicly available results will be considered for sharing
• IPD Sharing Time Frame: 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 made the study results publicly available (e.g., scientific publication, scientific conference, clinical trial registry), has the legal authority to share the data, and has ensured the ability to protect participant privacy.
• IPD Sharing Access Criteria: Qualified researchers can submit a proposal for access to individual patient or aggregate level data from a Regeneron-sponsored clinical trial through Vivli. Regeneron's Independent Research Request Evaluation Criteria can be found at: https://www.regeneron.com/sites/default/files/Regeneron-External-Data-Sharing-Policy-and-Independent-Research-Request-Evaluation-Criteria.pdf
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No