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

Study Overview
=================
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

Official Title
-----------------
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

Conditions
-----------------
Healthy, Chronic Stable Illness

Intervention / Treatment
-----------------
* Drug: casirivimab+imdevimab
* Biological: Moderna mRNA-1273 vaccine


Participation Criteria
=================
Eligibility Criteria
-----------------
Key Inclusion Criteria: 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 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: Positive RT-PCR test result for SARS-CoV-2 infection at screening or baseline Positive serology test result for anti-SARS-CoV-2 antibodies at screening or baseline COVID-19 diagnosis, positive SARS-CoV-2 infection, or positive SARS-CoV-2 serology at any time prior to screening Previously received an investigational, authorized, or approved coronavirus vaccine (eg, SARS-CoV-2 vaccine, MERS-CoV vaccine) Currently enrolled in, or has plans to enroll in, any interventional study to prevent or treat COVID-19 Received investigational or approved passive antibodies for SARS-CoV-2 infection prophylaxis ad defined in the protocol Received intravenous immunoglobulin (IVIG) or blood products in the last 3 months 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 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 Medically attended acute illness or hospitalization (ie, >24 hours) for any reason within 30 days prior to screening Clinical history of myocarditis and/or pericarditis Note: Other protocol-defined Inclusion/ Exclusion Criteria apply

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 90 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Wave 1 Dose 1<br> | Drug: casirivimab+imdevimab<br>* Wave 1 Intravenous (IV) administration Wave 2 Subcutaneous administration<br>* Other names: Ronapreve™;Biological: Moderna mRNA-1273 vaccine<br>* Single intramuscular (IM) injection<br>|
| Experimental: Wave 1 Dose 2<br> | Drug: casirivimab+imdevimab<br>* Wave 1 Intravenous (IV) administration Wave 2 Subcutaneous administration<br>* Other names: Ronapreve™;Biological: Moderna mRNA-1273 vaccine<br>* Single intramuscular (IM) injection<br>|
| Experimental: Wave 1 Dose 3<br> | Drug: casirivimab+imdevimab<br>* Wave 1 Intravenous (IV) administration Wave 2 Subcutaneous administration<br>* Other names: Ronapreve™;Biological: Moderna mRNA-1273 vaccine<br>* Single intramuscular (IM) injection<br>|
| Experimental: Wave 1 Vaccine only<br> | Biological: Moderna mRNA-1273 vaccine<br>* Single intramuscular (IM) injection<br>|
| Experimental: Wave 2 Dose 1<br> | Drug: casirivimab+imdevimab<br>* Wave 1 Intravenous (IV) administration Wave 2 Subcutaneous administration<br>* Other names: Ronapreve™;Biological: Moderna mRNA-1273 vaccine<br>* Single intramuscular (IM) injection<br>|
| Experimental: Wave 2 Dose 2<br> | Drug: casirivimab+imdevimab<br>* Wave 1 Intravenous (IV) administration Wave 2 Subcutaneous administration<br>* Other names: Ronapreve™;Biological: Moderna mRNA-1273 vaccine<br>* Single intramuscular (IM) injection<br>|
| Experimental: Wave 2 Vaccine only<br> | Biological: Moderna mRNA-1273 vaccine<br>* Single intramuscular (IM) injection<br>|
| Experimental: Wave 3 Dose 1<br> | Drug: casirivimab+imdevimab<br>* Wave 1 Intravenous (IV) administration Wave 2 Subcutaneous administration<br>* Other names: Ronapreve™;Biological: Moderna mRNA-1273 vaccine<br>* Single intramuscular (IM) injection<br>|
| Experimental: Wave 3 Dose 2<br> | Drug: casirivimab+imdevimab<br>* Wave 1 Intravenous (IV) administration Wave 2 Subcutaneous administration<br>* Other names: Ronapreve™;Biological: Moderna mRNA-1273 vaccine<br>* Single intramuscular (IM) injection<br>|
| Experimental: Wave 3 Vaccine only<br> | Biological: Moderna mRNA-1273 vaccine<br>* Single intramuscular (IM) injection<br>|
| Experimental: Wave 4 Dose 1<br> | Drug: casirivimab+imdevimab<br>* Wave 1 Intravenous (IV) administration Wave 2 Subcutaneous administration<br>* Other names: Ronapreve™;Biological: Moderna mRNA-1273 vaccine<br>* Single intramuscular (IM) injection<br>|
| Experimental: Wave 4 Vaccine only<br> | Biological: Moderna mRNA-1273 vaccine<br>* Single intramuscular (IM) injection<br>|

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 | High dose | 56 days after first dose of vaccine | 
| 50% inhibitory dilution (ID50) titers of vaccine-induced neutralizing antibodies to the SARS-CoV-2 S protein | Submaximal dose | 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 | Anti-S protein Anti-RBD Other S protein subdomains (including S1, S2, and NTD) | Up to 401 Days | 
| Change from baseline in concentrations of vaccine-induced antibodies to SARS-CoV-2 antigens over time | Anti-S protein Anti-RBD Other S protein subdomains (including S1, S2, and NTD) | Up to 401 Days | 
| Percentage change from baseline in concentrations of vaccine-induced antibodies to SARS-CoV-2 antigens over time | Anti-S protein Anti-RBD Other S protein subdomains (including S1, S2, and NTD) | Up to 401 Days | 
| 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 401 Days | 
| Proportion of participants with treatment-emergent adverse events (TEAEs) throughout the study |  | Up to 401 Days | 
| Proportion of participants with treatment-emergent serious adverse events (SAEs) throughout the study |  | Up to 401 Days | 
| Proportion of participants with infusion-related reactions (grade ≥2) to REGN10933+REGN10987 |  | Through Day 4 post-infusion | 
| Proportion of participants with injection site reactions (grade ≥3) to REGN10933+REGN10987 or each dose of Moderna mRNA-1273 vaccine |  | Through Day 4 post-injection | 
| Proportion 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 | 
| Concentrations of REGN10933 in serum over time |  | Up to Day 183 | 
| Concentrations of REGN10987 in serum over time |  | Up to Day 183 | 
| Immunogenicity, as measured by anti-drug antibodies (ADA) to REGN10933 |  | Up to Day 183 | 
| Immunogenicity, as measured by ADA to REGN10987 |  | Up to Day 183 | 
| Immunogenicity, as measured by neutralizing antibodies (NAb) to REGN10933 |  | Up to Day 183 | 
| Immunogenicity, as measured by NAb to REGN10987 |  | Up to Day 183 |