Trial Outcomes & Findings for A Study of SARS CoV-2 Infection and Potential Transmission in Individuals Immunized With Moderna COVID-19 Vaccine (NCT NCT04811664)

Last Updated: 2023-08-02

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

1923 participants

Primary outcome timeframe

Measured through Month 4 study visit

Results posted on

2023-08-02

Participant Flow

Participant milestones

Participant milestones
Measure	Immediate Vaccination Immediate Vaccination Group: 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.	Standard of Care Standard of Care Group: 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.	Vaccine Declined 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
Overall Study STARTED	725	728	470
Overall Study Full Analysis Set (FAS)	725	728	470
Overall Study Full Analysis Set With Study PCR (FAS-P)	701	646	454
Overall Study FAS-P With Outside Vaccination Censored Incidence Rate Follow-up	563	622	452
Overall Study Baseline Negative	600	549	311
Overall Study Baseline Negative With Outside Vaccination Censored Incidence Rate Follow-up	489	531	311
Overall Study FAS-P Viral Load	22	23	44
Overall Study COMPLETED	571	450	255
Overall Study NOT COMPLETED	154	278	215

Reasons for withdrawal

Reasons for withdrawal
Measure	Immediate Vaccination Immediate Vaccination Group: 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.	Standard of Care Standard of Care Group: 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.	Vaccine Declined 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
Overall Study Lost to Follow-up	78	125	46
Overall Study Withdrawal by Subject	39	76	12
Overall Study Participant Unable to Adhere to Visit Schedule	6	13	17
Overall Study Participant is unwilling or unable to comply with required study	24	47	16
Overall Study Protocol Violation	0	5	11
Overall Study Study Terminated by Sponsor	4	3	34
Overall Study Early Study Closure	3	7	79
Overall Study Other (Unable to receive payment visa status)	0	2	0

Baseline Characteristics

Because some participants did not report the characteristic sum of Ns across categories is less than the Overall Number of Baseline Participants.

Baseline characteristics by cohort

PRIMARY outcome

Timeframe: Measured through Month 4 study visit

Population: Baseline negative with outside vaccination censored incidence rate follow-up

Outcome measures

Outcome measures
Measure	Immediate Vaccination n=90 person-years Immediate Vaccination Group: 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.	Standard of Care n=76 person-years Standard of Care Group: 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.	Vaccine Declined n=50 person-years 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
Efficacy of Moderna COVID-19 Vaccine Against SARS-CoV-2 Infection	12.2 events per 100 person years Interval 6.1 to 21.9	31.8 events per 100 person years Interval 20.3 to 47.2	89.6 events per 100 person years Interval 65.4 to 119.9

PRIMARY outcome

Timeframe: Measured through Month 4 study visit

Population: FAS-P 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.

Outcome measures

Outcome measures
Measure	Immediate Vaccination n=22 Participants Immediate Vaccination Group: 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.	Standard of Care n=23 Participants Standard of Care Group: 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.	Vaccine Declined n=44 Participants 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
Effect of Moderna COVID-19 Vaccine on Mean Peak Nasal Viral Load Lab:Corteva, Target:N2	26.3 Cycle Thresholds Interval 17.3 to 38.2	20.7 Cycle Thresholds Interval 15.0 to 37.0	22.8 Cycle Thresholds Interval 13.2 to 37.5
Effect of Moderna COVID-19 Vaccine on Mean Peak Nasal Viral Load Lab:Corteva, Target:N1	25.8 Cycle Thresholds Interval 17.0 to 37.2	20.2 Cycle Thresholds Interval 14.6 to 35.8	22.3 Cycle Thresholds Interval 12.8 to 37.2
Effect of Moderna COVID-19 Vaccine on Mean Peak Nasal Viral Load Lab:UW/Northwell, Target:N1	34.4 Cycle Thresholds Interval 31.3 to 37.5	28.8 Cycle Thresholds Interval 18.0 to 39.1	24.4 Cycle Thresholds Interval 16.0 to 38.3
Effect of Moderna COVID-19 Vaccine on Mean Peak Nasal Viral Load Lab:UW/Northwell, Target:N2	34.1 Cycle Thresholds Interval 34.1 to 34.1	30.5 Cycle Thresholds Interval 21.1 to 38.6	26.2 Cycle Thresholds Interval 18.8 to 34.9

PRIMARY outcome

Timeframe: Measured through Month 4 study visit

Population: FAS-P 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.

Outcome measures

Outcome measures
Measure	Immediate Vaccination n=22 Participants Immediate Vaccination Group: 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.	Standard of Care n=23 Participants Standard of Care Group: 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.	Vaccine Declined n=44 Participants 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
Effect of Moderna COVID-19 Vaccine on Median Peak Nasal Viral Load Lab:UW/Northwell, Target:N2	34.1 Cycle Thresholds Interval 34.1 to 34.1	31.2 Cycle Thresholds Interval 24.8 to 36.3	25.7 Cycle Thresholds Interval 22.1 to 31.1
Effect of Moderna COVID-19 Vaccine on Median Peak Nasal Viral Load Lab:Corteva, Target:N1	23.9 Cycle Thresholds Interval 21.3 to 29.1	19.6 Cycle Thresholds Interval 16.9 to 21.6	21.0 Cycle Thresholds Interval 17.3 to 25.9
Effect of Moderna COVID-19 Vaccine on Median Peak Nasal Viral Load Lab:Corteva, Target:N2	24.3 Cycle Thresholds Interval 21.9 to 29.5	20.0 Cycle Thresholds Interval 17.6 to 22.1	21.3 Cycle Thresholds Interval 18.2 to 26.2
Effect of Moderna COVID-19 Vaccine on Median Peak Nasal Viral Load Lab:UW/Northwell, Target:N1	34.4 Cycle Thresholds Interval 32.9 to 35.9	29.4 Cycle Thresholds Interval 22.8 to 34.6	22.5 Cycle Thresholds Interval 19.0 to 29.2

SECONDARY outcome

Timeframe: Measured through Month 4 study visit

Population: Baseline negative with outside vaccination censored incidence rate follow-up

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.

Outcome measures

Outcome measures
Measure	Immediate Vaccination n=90 person-years Immediate Vaccination Group: 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.	Standard of Care n=76 person-years Standard of Care Group: 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.	Vaccine Declined n=50 person-years 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
Efficacy of Moderna COVID-19 Vaccine Against COVID-19 Disease Confirmed by PCR Test and Symptoms	4.5 events per 100 person years Interval 1.2 to 11.4	18.5 events per 100 person years Interval 10.1 to 31.1	53.8 events per 100 person years Interval 35.5 to 78.3

SECONDARY outcome

Timeframe: Measured through Month 4 study visit

Population: FAS-P with outside vaccination censored incidence rate follow-up

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.

Outcome measures

Outcome measures
Measure	Immediate Vaccination n=103 person-years Immediate Vaccination Group: 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.	Standard of Care n=88 person-years Standard of Care Group: 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.	Vaccine Declined n=452 Participants 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
Efficacy of Moderna COVID-19 Vaccine Against SARS-CoV-2 Infection Regardless of Baseline Negativity	11.7 events per 100 person years Interval 6.0 to 20.4	28.3 events per 100 person years Interval 18.3 to 41.8	76.0 events per 100 person years Interval 57.4 to 98.7

SECONDARY outcome

Timeframe: Measured through Month 4 study visit

Population: Data have not been collected and outcome cannot be reported.

Evaluated by the number of secondary transmission events in close-contact cohorts from main study participants who were SARS-CoV-2 seronegative at enrollment

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Measured through Month 4 study visit

Population: Data have not been collected and outcome cannot be reported.

Evaluated by SARS-CoV-2 antibodies to the nucleocapsid protein post Month 1 visit among participants who were SARS-CoV-2 seronegative at enrollment

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Measured through Month 4 study visit

Population: Data have not been collected and outcome cannot be reported.

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

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Measured through Month 4 study visit

Population: Data have not been collected and outcome cannot be reported.

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

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Measured through Month 4 study visit

Population: Data have not been collected and outcome cannot be reported.

Evaluated by SARS-CoV-2 infection diagnosed by PCR

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Measured through Month 4 study visit

Population: Data have not been collected and outcome cannot be reported.

Evaluated by peak viral load in nasal samples from diagnosed participants

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Measured through Month 4 study visit

Population: Data have not been collected and outcome cannot be reported.

Evaluated by number of secondary transmission events in close-contact cohorts

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Measured through Month 2

Population: Data have not been collected and outcome cannot be reported.

Magnitude and response rate of immune responses to vaccination as measured by binding antibody and neutralization assays

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Measured through Month 2

Population: Data have not been collected and outcome cannot be reported.

Magnitude and response rate of immune responses to vaccination as measured by binding antibody and neutralization assays

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Measured through Month 4 study visit

Population: Data have not been collected and outcome cannot be reported.

SARS-CoV-2 infection by PCR or periodic serology

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Measured through Month 4 study visit

Population: Data have not been collected and outcome cannot be reported.

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

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Measured through Month 4 study visit

Population: Data have not been collected and outcome cannot be reported.

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

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Measured through Month 4 study visit

Population: Data have not been collected and outcome cannot be reported.

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

Outcome measures

Outcome data not reported

Adverse Events

Immediate Vaccination

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Standard of Care

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Vaccine Declined

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

Jessica Andriesen, PhD, Associate Director of HVTN SDMC Operations

Fred Hutchinson Cancer Center

Phone: 206-667-5812

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place