Clinical trial NCT04852978: COVID-19 Study to Assess Immunogenicity, Safety, and Tolerability of Moderna mRNA-1273 Vaccine Administered With Casirivimab+Imdevimab in Healthy Adult Volunteers
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Healthy
Chronic Stable Illness
Lead sponsor: Regeneron Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2021-04-21
Enrollment: 295
Sex: ALL
Minimum age (years): 18
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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


Eligibility criteria: 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

Primary outcomes:
measure: 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)
timeFrame: 56 days after first dose of vaccine
measure: 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)
timeFrame: 56 days after first dose of vaccine
Secondary outcomes:
measure: Absolute Values in Concentrations of Vaccine-induced Antibodies to SARS-CoV-2 Antigens Over Time (S1-RBD IgA)
timeFrame: Up to 365 Days from 1st dose of Vaccination
measure: Median Fold Change of Concentrations of Vaccine-induced Antibodies to SARS-CoV-2 Antigens Over Time (S1-RBD IgA)
timeFrame: Up to 365 Days from 1st dose of Vaccination
measure: Relative Difference Expressed as a Percent in Vaccine-induced Antibodies to SARS-CoV-2 Antigens Over Time (S1-RBD IgA)
timeFrame: Up to 365 Days from 1st dose of Vaccination
measure: Absolute Values in Concentrations of Vaccine-induced Antibodies to SARS-CoV-2 Antigens Over Time (S-IgA)
timeFrame: Up to 365 Days from 1st dose of Vaccination
measure: Fold Change of Concentrations of Vaccine-induced Antibodies to SARS-CoV-2 Antigens Over Time (S-IgA)
timeFrame: Up to 365 Days from 1st dose of vaccination
measure: Relative Difference Expressed as a Percent in Vaccine-induced Antibodies to SARS-CoV-2 Antigens Over Time (S-IgA)
timeFrame: Up to 365 Days from 1st dose of Vaccination
measure: Absolute Values in Concentrations of Vaccine-induced Antibodies to SARS-CoV-2 Antigens Over Time (S-IgG)
timeFrame: Up to 365 Days from 1st dose of vaccination
measure: Fold Change of Concentrations of Vaccine-induced Antibodies to SARS-CoV-2 Antigens Over Time (S-IgG)
timeFrame: Up to 365 Days from 1st dose of vaccination
measure: Relative Difference Expressed as a Percent in Vaccine-induced Antibodies to SARS-CoV-2 Antigens Over Time (S-IgG)
timeFrame: Up to 365 Days from 1st dose of vaccination
measure: Absolute Values in Concentrations of Vaccine-induced Antibodies to SARS-CoV-2 Antigens Over Time (S1-RBD IgG)
timeFrame: Up to 365 Days from 1st dose of vaccination
measure: Fold Change of Concentrations of Vaccine-induced Antibodies to SARS-CoV-2 Antigens Over Time (S1-RBD IgG)
timeFrame: Up to 365 Days from 1st dose of vaccination
measure: Relative Difference Expressed as a Percent in Vaccine-induced Antibodies to SARS-CoV-2 Antigens Over Time (S1-RBD IgG)
timeFrame: Up to 365 Days from 1st dose of vaccination
measure: Absolute Values in Concentrations of Vaccine-induced Antibodies to SARS-CoV-2 Antigens Over Time (S1-RBD IgM)
timeFrame: Up to 365 Days from 1st dose of vaccination
measure: Relative Difference Expressed as a Percent in Vaccine-induced Antibodies to SARS-CoV-2 Antigens Over Time (S1-RBD IgM)
timeFrame: Up to 365 Days from 1st dose of vaccination
measure: Fold Change of Concentrations of Vaccine-induced Antibodies to SARS-CoV-2 Antigens Over Time (S1-RBD IgM)
timeFrame: Up to 365 Days from 1st dose of vaccination
measure: Absolute Values in Concentrations of Vaccine-induced Antibodies to SARS-CoV-2 Antigens Over Time (S-IgM)
timeFrame: Up to 365 Days from 1st dose of vaccination
measure: Relative Difference Expressed as a Percent in Concentrations of Vaccine-induced Antibodies to SARS-CoV-2 Antigens Over Time (S-IgM)
timeFrame: Up to 365 Days from 1st dose of vaccination
measure: Fold Change of Concentrations of Vaccine-induced Antibodies to SARS-CoV-2 Antigens Over Time (S-IgM)
timeFrame: Up to 365 Days from 1st dose of vaccination
measure: 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
timeFrame: Up to 365 Days from 1st dose of vaccination
measure: Number of Participants With Treatment-emergent Adverse Events (TEAEs) Throughout the Study
timeFrame: Up to 401 Days
measure: Number of Participants With Treatment-emergent Serious Adverse Events (SAEs) Throughout the Study
timeFrame: Up to 401 Days
measure: Number of Participants With Infusion-related Reactions (Grade ≥2) to REGN10933+REGN10987
timeFrame: Through Day 4 post-infusion
measure: Number of Participants With Injection Site Reactions (Grade ≥3) to REGN10933+REGN10987
timeFrame: Through Day 4 post-infusion
measure: Number of Participants With Injection Site Reactions (Grade ≥3) to Moderna mRNA-1273 Vaccine
timeFrame: Through Day 4 post-infusion
measure: Number of Participants With Hypersensitivity Reactions (Grade ≥2) to REGN10933+REGN10987 or Each Dose of Moderna mRNA-1273 Vaccine
timeFrame: Through Day 29 post-infusion or post-injection
measure: Concentrations of REGN10933 in Serum Over Time
timeFrame: Up to 182 Days
measure: Concentrations of REGN10987 in Serum Over Time
timeFrame: Up to 182 Days
measure: Immunogenicity, as Measured by Anti-drug Antibodies (ADA) to REGN10987
timeFrame: Up to Day 183
measure: Immunogenicity, as Measured by Anti-drug Antibodies (ADA) to REGN10933
timeFrame: Up to Day 183
measure: Immunogenicity, as Measured by Neutralizing Antibodies (NAb) to REGN10987
timeFrame: Up to Day 183
measure: Immunogenicity, as Measured by Neutralizing Antibodies (NAb) to REGN10933
timeFrame: Up to Day 183
Other outcomes:
Locations:
city: Little Rock
country: United States
facility: Regeneron Research Site
state: Arkansas
city: Rogers
country: United States
facility: Regeneron Research Site
state: Arkansas
city: Hialeah
country: United States
facility: Regeneron Research Site
state: Florida
city: Miami
country: United States
facility: Regeneron Research Site
state: Florida
city: Orlando
country: United States
facility: Regeneron Research Site
state: Florida
city: Dayton
country: United States
facility: Regeneron Research Site
state: Ohio
Study officials:
affiliation: Regeneron Pharmaceuticals
name: Clinical Trial Management
role: STUDY_DIRECTOR
References: