A Study of SARS CoV-2 Infection and Potential Transmission in Individuals Immunized With Moderna COVID-19 Vaccine (CoVPN 3006)

A Randomized Controlled Study to Assess SARS CoV-2 Infection, Viral Shedding, and Subsequent Potential Transmission in Individuals Immunized With Moderna COVID-19 Vaccine

The purpose of this study is to assess SARS CoV-2 infection, viral shedding, and subsequent potential transmission in individuals immunized with the Moderna COVID-19 vaccine.

Study Overview

• Status: Completed
• Conditions: SARS-CoV-2 Infection
• Intervention / Treatment: Biological: Moderna COVID-19 Vaccine

Detailed Description

This study will evaluate the efficacy of the Moderna COVID-19 vaccine against SARS-CoV-2 infection, as well as its effect on peak nasal viral load as a measure of infection and a proxy of infectiousness, in adults aged 18-29.

In the Main study, up to 12,000 participants will be randomized 1:1 to Immediate Vaccination Group 1 (at Months 0 and 1) or Standard of Care Group 2, with vaccination given at Months 4 and 5 if not received off-study previously. Up to an additional 6,000 participants will be enrolled into the Vaccine Declined Group 3 and will also be offered vaccine at Months 4 and 5.

Additional study visits for Group 1 will occur at Months 2 and 4; for Groups 2 and 3, at Months 0 and 2. Study visits may include medical history, vaccine injections, blood collection, nasal swab, SARS-CoV-2 screening, COVID-19 symptom check, and questionnaires.

In addition to the main study participants, the study will also evaluate infectiousness following close contacts with main study participants. Study procedures for close contacts include questionnaires and blood samples; for those who become SARS-CoV-2 infected, study procedures will also include nasal swabs.

• Study Type: Interventional
• Enrollment (Actual): 1923
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35222
      • Alabama CRS
  • Arizona
    • Scottsdale, Arizona, United States, 85260
      • Headlands Research Scottsdale
    • Tempe, Arizona, United States, 85281
      • AMR Phoenix
    • Tucson, Arizona, United States, 85724
      • University of Arizona
  • California
    • Los Angeles, California, United States, 90059
      • Charles Drew University
    • Sacramento, California, United States, 95817
      • UC Davis
    • San Diego, California, United States, 92103
      • University of California, San Diego
  • Colorado
    • Boulder, Colorado, United States, 80301
      • University of Colorado- Boulder
  • Florida
    • Atlantis, Florida, United States, 33462
      • JEM Headlands LLC
    • Gainesville, Florida, United States, 32610
      • University of Florida
    • Jacksonville, Florida, United States, 32209
      • UF CARES
    • Orlando, Florida, United States, 32803
      • Orlando Immunology Center CRS
    • Sarasota, Florida, United States, 34243
      • Headlands Research Sarasota
    • Tampa, Florida, United States, 33612
      • University of South Florida
  • Georgia
    • Atlanta, Georgia, United States, 30310
      • Morehouse University
    • Decatur, Georgia, United States, 30030
      • The Hope Clinic of the Emory Vaccine Center CRS
  • Illinois
    • Champaign, Illinois, United States, 61820
      • Champaign-Urbana Public Health District
    • Chicago, Illinois, United States, 60612
      • Rush University CRS
    • Evanston, Illinois, United States, 60208
      • Northwestern University
  • Indiana
    • Bloomington, Indiana, United States, 47405-7000
      • Indiana University
  • Kansas
    • Wichita, Kansas, United States, 67214
      • Univ, of Kansas School of Medicine CRS
  • Kentucky
    • Lexington, Kentucky, United States, 40536
      • University Of Kentucky
  • Louisiana
    • Lake Charles, Louisiana, United States, 70601
      • Centex Studies, Inc. - Lake Charles
  • Maryland
    • College Park, Maryland, United States, 20742-2611
      • University of Maryland College Park
  • Massachusetts
    • Boston, Massachusetts, United States, 02215-4302
      • Fenway Health (FH) CRS
  • Michigan
    • Detroit, Michigan, United States, 48201
      • Wayne State - Harper Hospital
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455
      • University of Minnesota
  • Missouri
    • Columbia, Missouri, United States, 65201
      • Columbia - Missouri VTEU
    • Saint Louis, Missouri, United States, 63110
      • Washington University Therapeutics CRS
  • Nebraska
    • Omaha, Nebraska, United States, 68105
      • University of Nebraska
  • Nevada
    • Las Vegas, Nevada, United States, 89119
      • AMR Las Vegas
  • New Mexico
    • Albuquerque, New Mexico, United States, 87131
      • University of New Mexico
  • New York
    • Bronx, New York, United States, 10451
      • Bronx Prevention Research Center CRS
    • Mineola, New York, United States, 11501
      • NYU Long Island Vaccine Center
    • New York, New York, United States, 10016
      • NYU Bellevue Vaccine Center
    • New York, New York, United States, 10027
      • Harlem Prevention Center CRS
    • New York, New York, United States, 10065
      • New York Blood Center CRS
    • Stony Brook, New York, United States, 11794
      • Stony Brook University
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599
      • University of North Carolina
    • Winston-Salem, North Carolina, United States, 27157
      • Wake Forest University
  • Rhode Island
    • Providence, Rhode Island, United States, 02904
      • The Miriam Hopsital CRS
  • South Carolina
    • Clemson, South Carolina, United States, 29634
      • Clemson University
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt Vaccine CRS
  • Texas
    • Amarillo, Texas, United States, 79106
      • Texas Tech
    • Brownsville, Texas, United States, 78526
      • Centex Studies, Inc. - Brownsville
    • College Station, Texas, United States, 77843
      • Texas A&M University
    • Houston, Texas, United States, 77058
      • Centex Studies, Inc. - Houston
    • Houston, Texas, United States, 77090
      • Centex Studies, Inc. - Westfield
    • Kingsville, Texas, United States, 77843
      • Texas A&M - Kingsville
  • Virginia
    • Charlottesville, Virginia, United States, 22908
      • University of Virginia
  • Washington
    • Seattle, Washington, United States, 98109
      • University of Washington

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 29 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion criteria for Main cohort, Vaccine Declined Group General and Demographic Criteria

• Age of 18 through 29 years.
• Ability and willingness to provide informed consent.
• Prefers not to receive COVID-19 vaccine.
• Willingness to be followed for the planned duration of the study.
• Assessment of understanding: volunteer demonstrates understanding of this study; completes a questionnaire with demonstration of understanding of all questionnaire items answered incorrectly.
• Access to device and internet for completion of study procedures.

Exclusion criteria for Main cohort, Vaccine Declined Group

• Prior administration of a coronavirus (SARS-CoV-2, SARS-CoV, MERS-CoV) vaccine or current/planned simultaneous participation in another interventional study to prevent or treat COVID-19 (participation in studies of other investigational research agents allowed).
• Any medical, psychiatric, occupational, or other condition that, in the judgment of the investigator, would interfere with, or serve as a contraindication to, protocol adherence, or a volunteer's ability to give informed consent.

Inclusion criteria for Prospective Close Contact (PCC) cohort

• Age of 18 years or older, at the time of signing the informed consent.
• Willing and able to provide informed consent.
• Expected to be in frequent close physical proximity with Main Cohort participant during the study.
• Willing to share results of SARS-CoV-2 testing.
• Access to device and internet for completion of study procedures

Inclusion criteria for Case-ascertained Close Contact (CACC) cohort

• Age of 18 years or older, at the time of signing the informed consent.
• Willing and able to provide informed consent.
• Access to device and internet for completion of study procedures.
• Willing to share results of SARS-CoV-2 testing.
• Had close contact with Main Cohort participant with known PCR-confirmed SARS-CoV-2 infection (eg, index case). Close contacts will have had exposure to the index participant, generally within 72 hours of an index diagnosis, and may include individuals that meet any of the following guidelines:

Prolonged close physical proximity with Main Cohort participant within a residence/vehicle/enclosed space without maintaining social distance,

Medical staff, first responders, or other care persons who cared for the index case without appropriate personal protective equipment.

Further information on the definition of close contact can be found in the CoVPN 3006 Study Specific Procedures (SSP).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Vaccine Declined; Participants who prefer not to be vaccinated, If requested, participant will be offered vaccine if they have not received vaccine outside of the study
Experimental: Immediate Vaccination; Participants will receive Moderna COVID-19 Vaccine in 100 mcg dose given as 0.5 ml Intramuscular into the deltoid muscle on Day 1 and Day 29.	Biological: Moderna COVID-19 Vaccine; A lipid nanoparticle (LNP) dispersion of a messenger ribonucleic acid (mRNA) encoding the prefusion stabilized S protein of SARS-CoV-2 formulated in LNPs composed of 4 lipids (1 proprietary and 3 commercially available). It is a suspension for intramuscular injection administered as a series of two doses (0.5 mL each) 1 month apart.; Other Names: mRNA-1273
Experimental: Standard of care; Participants will receive Moderna COVID-19 Vaccine in 100 mcg dose given as 0.5 ml Intramuscular into the deltoid muscle on Day 113 and Day 141.	Biological: Moderna COVID-19 Vaccine; A lipid nanoparticle (LNP) dispersion of a messenger ribonucleic acid (mRNA) encoding the prefusion stabilized S protein of SARS-CoV-2 formulated in LNPs composed of 4 lipids (1 proprietary and 3 commercially available). It is a suspension for intramuscular injection administered as a series of two doses (0.5 mL each) 1 month apart.; Other Names: mRNA-1273

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Efficacy of Moderna COVID-19 Vaccine Against SARS-CoV-2 Infection	Incidence of SARS-CoV-2 infection diagnosed by study PCR among baseline negative participants, with exposure starting from first study PCR and censored at last PCR/outside vaccination and exposure period for the Immediate arm additionally limited to period after the second vaccine dose (period unrestricted for Standard of Care and Vaccine Declined arms: by definition corresponds to unvaccinated exposure). Exact confidence interval.	Measured through Month 4 study visit
Effect of Moderna COVID-19 Vaccine on Mean Peak Nasal Viral Load	As a measure of infection and a proxy of infectiousness, mean observed peak viral load (minimum cycle threshold) in nasal samples from FAS-P participants diagnosed with SARS-CoV-2 infection, stratified by lab and target (nucleocapsid gene N1 or N2). Nasal swabs were to be collected daily, and viral load was measured on available specimens taken between the first and last days of PCR-confirmed SARS-CoV-2 infection. Due to early termination, the study was underpowered to look at the vaccine effect on viral load and limited descriptive analysis was performed. The number participants analyzed per row is less than the overall number analyzed as participants were only analyzed by one of the two labs and in few cases the N2 target values could not be measured.	Measured through Month 4 study visit
Effect of Moderna COVID-19 Vaccine on Median Peak Nasal Viral Load	As a measure of infection and a proxy of infectiousness, median observed peak viral load (minimum cycle threshold) in nasal samples from FAS-P participants diagnosed with SARS-CoV-2 infection, stratified by lab and target (nucleocapsid gene N1 or N2). Nasal swabs were to be collected daily, and viral load was measured on available specimens taken between the first and last days of PCR-confirmed SARS-CoV-2 infection. Due to early termination, the study was underpowered to look at the vaccine effect on viral load and limited descriptive analysis was performed. The number participants analyzed per row is less than the overall number analyzed as participants were only analyzed by one of the two labs and in few cases the N2 target values could not be measured.	Measured through Month 4 study visit

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Efficacy of Moderna COVID-19 Vaccine Against COVID-19 Disease Confirmed by PCR Test and Symptoms	Incidence of study PCR-confirmed SARS-CoV-2 infection and concurrent symptoms captured by daily or weekly symptom reporting (at least one of the following: hospitalization, fever, chills, cough, shortness of breath, difficulty breathing, tiredness/fatigue, muscle aches, joint aches, body aches, headache, change in sense of taste, change in sense of smell, sore throat, nasal congestion, runny nose, nausea, vomiting, diarrhea, oral ulcers and clinical or radiographical evidence of pneumonia) among baseline negative participants. Exposure starting from first study PCR and censored at last PCR/outside vaccination. Participants without concurrent symptom data were assumed not symptomatic and were additionally censored at SARS-CoV-2 infection. Exposure period for the Immediate arm additionally limited to period after the second vaccine dose (period unrestricted for Standard of Care and Vaccine Declined arms: by definition corresponds to unvaccinated exposure). Exact confidence interval.	Measured through Month 4 study visit
Efficacy of Moderna COVID-19 Vaccine Against SARS-CoV-2 Infection Regardless of Baseline Negativity	Incidence of SARS-CoV-2 infection diagnosed by study PCR among FAS-P participants, with exposure starting from first study PCR and censored at last PCR/outside vaccination and exposure period for the Immediate arm additionally limited to period after the second vaccine dose (period unrestricted for Standard of Care and Vaccine Declined arms: by definition corresponds to unvaccinated exposure). Exact confidence interval.	Measured through Month 4 study visit
Impact of Moderna COVID-19 Vaccine on Secondary Transmission of SARS-CoV-2 Infection	Evaluated by the number of secondary transmission events in close-contact cohorts from main study participants who were SARS-CoV-2 seronegative at enrollment	Measured through Month 4 study visit
Efficacy of Moderna COVID-19 Vaccine to Prevent Serologically Confirmed SARS-CoV-2 Infection	Evaluated by SARS-CoV-2 antibodies to the nucleocapsid protein post Month 1 visit among participants who were SARS-CoV-2 seronegative at enrollment	Measured through Month 4 study visit
Efficacy of Moderna COVID-19 Vaccine Against COVID-19 Disease Confirmed by PCR Test and Symptoms	Evaluated by SARS-CoV-2 infection confirmed by PCR among participants who were SARS-CoV-2 seronegative at enrollment; reporting at least 2 of the following systemic symptoms: Fever (≥ 38ºC), chills, myalgia, headache, sore throat; or reporting at least one of the following signs/symptoms: cough, shortness of breath or difficulty breathing, new olfactory or taste disorder, clinical or radiographical evidence of pneumonia, thromboembolic event, myocardial infarction, myocarditis, chilblains, or multi-inflammatory syndrome	Measured through Month 4 study visit
Effect of Moderna COVID-19 Vaccine on Magnitude of Viral Load Over Time	Summary measures of the viral load curve, all evaluated among participants diagnosed with SARS-CoV-2 infection who were SARS-CoV-2 seronegative at enrollment	Measured through Month 4 study visit
Efficacy of Moderna Vaccine Regardless of Baseline Serostatus (SARS-CoV-2 Infection by PCR)	Evaluated by SARS-CoV-2 infection diagnosed by PCR	Measured through Month 4 study visit
Effect of Moderna Vaccine on Viral Load Regardless of Baseline Serostatus (Viral Load)	Evaluated by peak viral load in nasal samples from diagnosed participants	Measured through Month 4 study visit
Effect of Moderna Vaccine on Secondary Status Regardless of Baseline Serostatus (Secondary Transmission Events)	Evaluated by number of secondary transmission events in close-contact cohorts	Measured through Month 4 study visit
Immunogenicity of Moderna COVID-19 Vaccine	Magnitude and response rate of immune responses to vaccination as measured by binding antibody and neutralization assays	Measured through Month 2
Immune Responses as Correlates of Risk of SARS-CoV-2 Acquisition, Viral Load, Secondary Infection, and COVID-19 Disease	Magnitude and response rate of immune responses to vaccination as measured by binding antibody and neutralization assays	Measured through Month 2
Efficacy of Moderna COVID-19 Vaccine Against Asymptomatic SARS-CoV-2 Infection	SARS-CoV-2 infection by PCR or periodic serology	Measured through Month 4 study visit
Efficacy of Moderna COVID-19 Vaccine Against SARS-CoV-2 Infection and COVID-19 Disease	SARS-CoV-2 infection diagnosed by PCR among participants who were SARS-CoV-2 seronegative at enrollment and who received all planned immunizations at designated immunization visits	Measured through Month 4 study visit
Effect of Moderna COVID-19 Vaccine on Viral Load	Measure of peak viral load among participants who were SARS-CoV-2 seronegative at enrollment and who received all planned immunizations at designated immunization visits	Measured through Month 4 study visit
Effect of Moderna COVID-19 Vaccine on Secondary Transmission	Measure of secondary transmission events among participants who were SARS-CoV-2 seronegative at enrollment and who received all planned immunizations at designated immunization visits	Measured through Month 4 study visit

Collaborators and Investigators

• Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
• Investigators: Study Chair: Kathryn Stephenson, Harvard University School of Medicine; Study Chair: Audrey Pettifor, Gillings School of Global Public Health, University of North Carolina; Study Chair: Jasmine Marcelin, University of Nebraska

Study record dates

Study Major Dates

• Study Start (Actual): March 24, 2021
• Primary Completion (Actual): December 30, 2021
• Study Completion (Actual): December 30, 2021

Study Registration Dates

• First Submitted: March 19, 2021
• First Submitted That Met QC Criteria: March 19, 2021
• First Posted (Actual): March 23, 2021

Study Record Updates

• Last Update Posted (Actual): August 2, 2023
• Last Update Submitted That Met QC Criteria: July 25, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Keywords: SARS-CoV-2
• Additional Relevant MeSH Terms: Pathologic Processes; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; Disease Attributes; COVID-19; Infections; Communicable Diseases
• Other Study ID Numbers: CoVPN 3006

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes