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

Study Overview
=================
Brief Summary
-----------------
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.

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.

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

Conditions
-----------------
SARS-CoV-2 Infection

Intervention / Treatment
-----------------
* Biological: Moderna COVID-19 Vaccine


Participation Criteria
=================
Eligibility Criteria
-----------------
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).

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 29 Years

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

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

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

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Immediate Vaccination<br>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<br>* 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.<br>* Other names: mRNA-1273;|
| Experimental: Standard of care<br>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<br>* 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.<br>* Other names: mRNA-1273;|
| No Intervention: Vaccine Declined<br>Participants who prefer not to be vaccinated, If requested, participant will be offered vaccine if they have not received vaccine outside of the study | |

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 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
SARS-CoV-2