SARS-CoV-2
Conditions
Keywords
mRNA-1273, mRNA-1273 vaccine, SARS-CoV-2, SARS-CoV-2 Vaccine, Coronavirus, Virus Diseases, Messenger RNA, COVID-19, COVID-19 Vaccine, Moderna
Brief summary
The mRNA-1273 vaccine is being developed to prevent COVID-19, the disease resulting from Severe Acute Respiratory Syndrome coronavirus (SARS-CoV-2) infection. The study is designed to primarily evaluate the efficacy, safety, and immunogenicity of mRNA-1273 to prevent COVID-19 for up to 2 years after the second dose of mRNA-1273.
Detailed description
This is a 3-part Phase 3 study, with Part A (Blinded Phase), Part B (Open-label Observational Phase), and Part C (Booster Dose Phase). Participants in Part A are blinded to their treatment assignment, with participants receiving either mRNA-1273 vaccine or placebo. Part B of the study is designed to offer participants to be unblinded so that participants who received placebo in Part A can request 2 doses of open-label mRNA-1273 vaccine. Additionally, participants who choose to be unblinded and were only able to receive 1 dose of mRNA-1273 due to administrative reasons, can choose to receive the second dose of mRNA-1273 during Part B. In Part C, a booster dose will be provided for all eligible participants who choose to receive one. Please access www.modernatx.com/cove-study for additional information, such as Study Overview, Participation, and Site Locations along with contact numbers for each location for the study.
Interventions
BIOLOGICALmRNA-1273
Sterile liquid for injection
BIOLOGICALPlacebo
0.9% sodium chloride (normal saline) injection
Sponsors
Biomedical Advanced Research and Development Authority
National Institute of Allergy and Infectious Diseases (NIAID)
ModernaTX, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Part A is observer-blind. Part B is open-label; participants can request to be unblinded by scheduling a Participant Decision clinic visit. Part C offers participants the option to receive a booster dose for those participants who received at least one dose of mRNA-1273 in the study.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
* (Part A only) Participants who are at high risk of SARS-CoV-2 infection, defined as adults whose locations or circumstances put them at appreciable risk of exposure to SARS-CoV-2 and COVID-19. * Understands and agrees to comply with the study procedures and provides written informed consent. * Able to comply with study procedures based on the assessment of the Investigator. * Female participants of non-childbearing potential may be enrolled in the study. Non-childbearing potential is defined as surgically sterile (history of bilateral tubal ligation, bilateral oophorectomy, hysterectomy) or postmenopausal (defined as amenorrhea for ≥12 consecutive months prior to Screening without an alternative medical cause). A follicle-stimulating hormone (FSH) level may be measured at the discretion of the Investigator to confirm postmenopausal status. * Female participants of childbearing potential may be enrolled in the study if the participant fulfills all the following criteria: * Has a negative pregnancy test at Screening and on the day of the first dose (Day 1, open-label Day 1, and booster dose Day 1). * Has practiced adequate contraception or has abstained from all activities that could result in pregnancy for at least 28 days prior to the first dose (Day 1). * Has agreed to continue adequate contraception through 3 months following the last dose (Day 29, open-label Day 29, and booster dose Day 1). * Is not currently breastfeeding. * Healthy adults or adults with pre-existing medical conditions who are in stable condition. A stable medical condition is defined as disease not requiring significant change in therapy or hospitalization for worsening disease during the 3 months before enrollment. * (Part C Only) Is currently enrolled in Part B of the current study (mRNA-1273-P301). * (Part C Only) Has received at least 1 dose of mRNA-1273 in the current study (mRNA-1273-P301).
Exclusion criteria
* Is acutely ill or febrile 72 hours prior to or at Screening or dosing (Part B and Part C). Fever is defined as a body temperature ≥38.0°Celsius/100.4°Fahrenheit. Participants meeting this criterion may be rescheduled within the relevant window periods. Afebrile participants with minor illnesses can be enrolled/dosed at the discretion of the Investigator. * Is pregnant or breastfeeding. * (Part A Only) Known history of SARS-CoV-2 infection. * Prior (Part A) or concurrent (Part B and Part C) administration of non-study coronavirus (SARS-CoV, Middle East Respiratory Syndrome \[MERS\]-CoV) vaccine or current/planned simultaneous participation in another interventional study to prevent or treat COVID-19. * (Part A Only) Demonstrated inability to comply with the study procedures. * An immediate family member or household member of this study's personnel. * Known or suspected allergy or history of anaphylaxis, urticaria, or other significant adverse reaction to the vaccine or its excipients. * Bleeding disorder considered a contraindication to intramuscular injection or phlebotomy. * Has received or plans to receive a vaccine within 28 days prior to the first dose (Day 1) or plans to receive a non-study vaccine within 28 days prior to or after any dose of investigational product (IP) (except for seasonal influenza vaccine). * (Part A only) Has participated in an interventional clinical study within 28 days prior to the day of enrollment. * Immunosuppressive or immunodeficient state, including human immunodeficiency virus (HIV) infection, asplenia, and recurrent severe infections. * Has received systemic immunosuppressants or immune-modifying drugs for \>14 days in total within 6 months prior to IP dose administration (for corticosteroids ≥20 milligram (mg)/day of prednisone equivalent). * Has received systemic immunoglobulins or blood products within 3 months prior to the day of IP dose administration. * Has donated ≥450 milliliters (mL) of blood products within 28 days prior to IP dose administration.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Part A: Number of Participants With a First Occurrence of COVID-19 Starting 14 Days After Second Dose | From Day 43 (14 days after second dose) up to approximately 7 months after the second dose | COVID-19 cases were defined as participants meeting clinical criteria based both on symptoms for COVID-19 and on RT-PCR detection of SARS-CoV-2 from samples collected within 72 hours of the study participant reporting symptoms that met the definition of COVID-19. An adjudication committee was assembled for the purpose of reviewing potential cases to determine if the criteria for COVID-19 were met. |
| Part A: Number of Participants With Solicited Local and Systemic Adverse Reactions (ARs) After First Dose | up to Day 7 (7 days after first dose) | Solicited ARs (local and systemic) were collected in electronic diary (eDiary) within 7 days of dosing. Local ARs included: pain at injection site, erythema (redness) at injection site, swelling/induration (hardness) at injection site, and localized axillary swelling or tenderness ipsilateral to the injection arm. Systemic ARs included: headache, fatigue, myalgia (muscle aches all over the body), arthralgia (aching in several joints), nausea/vomiting, rash, body temperature (potentially fever), and chills. Severity grading for solicited ARs is based on modified Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventative Vaccine Clinical Trials. Severity was graded 0-4; a lower score indicated lower severity and a higher score indicated greater severity. The Investigator determined if solicited AR was also to be recorded as an AE. Summary of serious AEs (SAEs) and nonserious AEs (Other), regardless of causality, is in Reported Adverse Events section. |
| Part A: Number of Participants With Solicited Local and Systemic Adverse Reactions (ARs) After Second Dose | Day 29 to Day 35 (from second dose to 7 days after second dose) | Solicited ARs (local and systemic) were collected in eDiary within 7 days of dosing. Local ARs included: pain at injection site, erythema (redness) at injection site, swelling/induration (hardness) at injection site, and localized axillary swelling or tenderness ipsilateral to the injection arm. Systemic ARs included: headache, fatigue, myalgia (muscle aches all over the body), arthralgia (aching in several joints), nausea/vomiting, rash, body temperature (potentially fever), and chills. Severity grading for solicited ARs is based on modified Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventative Vaccine Clinical Trials. Severity was graded 0-4; lower score indicated lower severity and a higher score indicated greater severity. The Investigator determined if solicited AR was also to be recorded as an AE. Summary of serious AEs (SAEs) and nonserious AEs (Other), regardless of causality, is in Reported Adverse Events section |
| Parts A and B: Number of Participants With Medically Attended AEs (MAAEs) and AEs Leading to Discontinuation | Day 1 (after dosing) through end of study (up to Day 759) | An MAAE is an AE that leads to an unscheduled visit to a healthcare practitioner (HCP). A summary of SAEs and all nonserious AEs (Other), regardless of causality, is located in the Reported Adverse Events section. |
| Parts A and B: Number of Participants With Serious AEs (SAEs) | Day 1 (after dosing) through end of study (up to Day 759) | An SAE was defined as any AE that resulted in death, is life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in disability/permanent damage, was a congenital anomaly/birth defect, or was an important medical event. A summary of SAEs and all nonserious AEs (Other), regardless of causality, is located in the Reported Adverse Events section. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Part A: Number of Participants With a First Occurrence of COVID-19 Starting 14 Days After First Dose | From 14 days after first dose up to approximately 8 months | COVID-19 cases were defined as participants meeting clinical criteria based both on symptoms for COVID-19 and on RT-PCR detection of SARS-CoV-2 from samples collected within 72 hours of the study participant reporting symptoms that met the definition of COVID-19. An adjudication committee was assembled for the purpose of reviewing potential cases to determine if the criteria for COVID-19 were met. |
| Part A: Number of Participants With a First Occurrence of COVID-19 Starting 14 Days After Second Dose Regardless of Evidence of Prior SARS-CoV-2 Infection | From Day 43 (14 days after second dose) up to approximately 7 months after the second dose | COVID-19 cases were defined as participants meeting clinical criteria based both on symptoms for COVID-19 and on RT-PCR detection of SARS-CoV-2 from samples collected within 72 hours of the study participant reporting symptoms that met the definition of COVID-19. An adjudication committee was assembled for the purpose of reviewing potential cases to determine if the criteria for COVID-19 were met. |
| Part A: Number of Participants With a First Occurrence of SARS-CoV-2 Infection in the Absence of Symptoms Defining COVID-19 Starting 14 Days After Second Dose | From Day 43 (14 days after second dose) up to approximately 7 months after the second dose | SARS-CoV-2 infection was defined by seroconversion due to infection measured by binding antibody (bAb) levels against SARS-CoV-2 nucleocapsid or by positive RT-PCR at predefined timepoints. Seroconversion was defined by the participant's serostatus at baseline. |
| Part C: Geometric Mean Concentration (GMC) of SARS-CoV-2 Specific nAb After BD Compared to After Second Dose in Part A Measured by Pseudovirus (VAC62) | Part C BD Day 29 and Part A Day 57 | 95% CI is calculated based on the t-distribution of the log-transformed values for GMC, then back transformed to the original scale for presentation. |
| Part A: Geometric Mean Titer (GMT) of SARS-CoV-2 Specific Neutralizing Antibody (nAb) | Day 1, Day 29, Day 57 | GMT (50% inhibitory dose \[ID50\], 80% inhibitory dose \[ID80\]) of nAb against SARS-CoV-2 pseudotyped viruses as measured by pseudovirus nAb assay is reported. 95% CI was based on the t-distribution of log-transformed values for GM titer, then back transformed to original scale for presentation. Baseline SARS-CoV-2 Status: Positive if there is immunologic or virologic evidence of prior COVID-19, defined as positive RT-PCR test or positive Elecsys result at Day 1. Negative is defined as negative RT-PCR test and negative Elecsys result at Day 1. |
| Part A: Number of Participants With Unsolicited AEs up to 28 Days After Any Injection Dose | Up to 28 days after any dose | Unsolicited AE was any AE reported by the participant that was not specified as an AR or was specified as a solicited AR in the protocol but started outside the protocol-defined, post-injection period for reporting solicited ARs. Unsolicited AEs were collected for the 28 days after any injection. An AE was as any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. A summary of all SAEs and all nonserious AEs (Other) reported up to the end of the study, regardless of causality, is located in the Reported Adverse Events section. |
| Part A: Percentage of Participants With Seroresponse Against SARS-CoV-2 | Day 29, Day 57 | Seroresponse to pseudovirus neutralizing antibody ID50 titer at a participant level is defined as a change from below the LLOQ to equal or above the LLOQ, or at least a 3.3-fold rise if baseline is equal to or above the LLOQ. Seroresponse to pseudovirus neutralizing antibody ID80 titer at a participant level is defined as a change from below the LLOQ to equal or above the LLOQ, or at least a 2.3-fold rise if baseline is equal to or above the LLOQ. Baseline SARS-CoV-2 Status: Positive if there is immunologic or virologic evidence of prior COVID-19, defined as positive RT-PCR test or positive Elecsys result at Day 1. Negative is defined as negative RT-PCR test and negative Elecsys result at Day 1. |
| Part C: GMT of SARS-CoV-2 Specific nAb Measured by Pseudovirus (VAC62) | Pre-booster (Baseline), post-booster Day 29 and post-booster Day 181 | 95% CI is calculated based on the t-distribution of the log-transformed values for GM value, then back transformed to the original scale for presentation. |
| Part C: Percentage of Participants With Seroresponse Against SARS-CoV-2 Measured by Pseudovirus (VAC62) | Post-booster Day 29 and post-booster Day 181 | Pseudovirus neutralizing antibody (VAC62) from pre-booster is presented. Seroresponse at a participant level is defined as a change from below the LLOQ to \>= 4 x LLOQ, or at least a 4-fold rise if pre-booster is equal to or above the LLOQ. |
| Part C: Percentage of Participants With Seroresponse Against SARS-CoV-2 After BD Compared to After Second Dose in Part A | Part C BD Day 29 and Part A Day 57 | Pseudovirus neutralizing antibody (VAC62) are presented. Seroresponse at a participant level is defined as a change from below the LLOQ to equal or above 4 x LLOQ, or at least a4-fold rise if baseline (Pre- Dose 1) is equal to or above the LLOQ. |
| Part A: Geometric Mean Fold Rise (GMFR) of SARS-CoV-2 Specific nAb | Day 29, Day 57 | The GMFR measures the changes in immunogenicity titers or levels from Baseline within participants. 95% CI was calculated based on the difference in the log-transformed values for GMFR, then back transformed to the original scale for presentation. GMFR for ID50 and ID80 neutralizing antibodies against SARS-CoV-2 S-protein, as measured by pseudovirus neutralizing antibody is presented. Baseline SARS-CoV-2 Status: Positive if there is immunologic or virologic evidence of prior COVID-19, defined as positive RT-PCR test or positive Elecsys result at Day 1. Negative is defined as negative RT-PCR test and negative Elecsys result at Day 1 |
| Parts A and B: Number of Participants With a First Occurrence of Severe COVID-19 Starting 14 Days After Second Dose | From Day 43 (14 days after second dose) up to approximately 8 months for Part A and from PDV/unblinding (at 4 months) to up to 8 months for Part B | COVID-19 cases were defined as participants meeting clinical criteria based on symptoms for COVID-19 and reverse transcriptase polymerase chain reaction (RT-PCR) detection of SARS-CoV-2 from samples collected within 72 hours of the participant reporting symptoms meeting the definition of COVID-19. An adjudication committee reviewed potential cases to determine if the criteria for COVID-19 were met. Clinical signs indicative of severe COVID-19 systemic illness included any of the following: respiratory rate ≥30 per minute, heart rate ≥125 beats per minute, oxygen saturation (SpO2) ≤93% on room air at sea level, or partial pressure of oxygen (PaO2)/fraction of inspired oxygen (FIO2) \<300 millimeter of mercury (mm Hg), or respiratory failure or acute respiratory distress syndrome (ARDS), evidence of shock, or significant acute renal, hepatic, or neurologic dysfunction, or admission to an intensive care unit or death. |
| Part A: Number of Participants With a First Occurrence of Either COVID-19 or SARS-CoV-2 Infection Regardless of Symptomatology or Severity Starting 14 Days After Second Dose | From Day 43 (14 days after second dose) up to approximately 7 months after the second dose | COVID-19 cases were defined as participants meeting clinical criteria based both on symptoms for COVID-19 and on RT-PCR detection of SARS-CoV-2 from samples collected within 72 hours of the study participant reporting symptoms that met the definition of COVID-19. An adjudication committee was assembled for the purpose of reviewing potential cases to determine if the criteria for COVID-19 were met. SARS-CoV-2 infection was defined by seroconversion due to infection measured by binding antibody (bAb) levels against SARS-CoV-2 nucleocapsid or by positive RT-PCR at predefined timepoints. Seroconversion was defined by the participant's serostatus at baseline. |
| Part A: Number of Participants With a Secondary Case Definition of COVID-19 Starting 14 Days After Second Dose | From Day 43 (14 days after second dose) up to approximately 7 months after the second dose | Secondary case definition of COVID-19 was defined as the presence of at least 1 of the following systemic symptoms: fever (temperature ≥38ºC), or chills, cough, shortness of breath or difficulty breathing, fatigue, muscle aches or body aches, headache, new loss of taste or smell, sore throat, nasal congestion or rhinorrhea, nausea or vomiting, or diarrhea and a positive nasopharyngeal swab, nasal swab, or saliva sample (or respiratory sample, if hospitalized) for SARS-CoV-2 by RT-PCR. |
| Parts A and B: Number of Participants Who Died Due to a Cause Directly Attributed to a Complication of COVID-19 Starting 14 Days After Second Dose | From Day 43 (14 days after second dose) up to approximately 8 months for Part A and from PDV/unblinding (at 4 months) to up to 8 months for Part B | — |
Countries
United States
Participant flow
Pre-assignment details
Part A participants received mRNA-1273, or placebo. After completion of Part A, participants could have chosen to be unblinded so that participants who received placebo in Part A could request to receive open-label mRNA-1273 in Part B. Eligible participants who received at least one dose of mRNA-1273 in the study had the option to receive a booster dose of mRNA-1273 in Part C.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Participants randomized to mRNA-1273-matching placebo and received any study injection in Part A. | 15,166 |
| mRNA-1273 Participants randomized to mRNA-1273 and received any study injection in Part A. | 15,180 |
| Total | 30,346 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Part A: Blinded | Discontinued from Study in Part A | 831 | 548 | 0 | 0 | 0 | 0 |
| Part B :Open-label | Discontinued from Study in Part B | 0 | 0 | 1,576 | 2,185 | 4,490 | 0 |
| Part B :Open-label | Other than specified | 0 | 0 | 788 | 0 | 523 | 0 |
| Part C: Booster | Discontinued from Study in Part C | 0 | 0 | 0 | 0 | 0 | 2,918 |
Baseline characteristics
| Characteristic | mRNA-1273 | Total | Placebo |
|---|---|---|---|
| Age, Continuous | 51.4 years STANDARD_DEVIATION 15.5 | 51.4 years STANDARD_DEVIATION 15.55 | 51.3 years STANDARD_DEVIATION 15.6 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3121 Participants | 6230 Participants | 3109 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 11917 Participants | 23838 Participants | 11921 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 142 Participants | 278 Participants | 136 Participants |
| Race/Ethnicity, Customized Race American Indian or Alaska Native | 113 Participants | 234 Participants | 121 Participants |
| Race/Ethnicity, Customized Race Asian | 656 Participants | 1395 Participants | 739 Participants |
| Race/Ethnicity, Customized Race Black or African American | 1567 Participants | 3098 Participants | 1531 Participants |
| Race/Ethnicity, Customized Race Multiracial | 319 Participants | 638 Participants | 319 Participants |
| Race/Ethnicity, Customized Race Native Hawaiian or other Pacific Islander | 36 Participants | 68 Participants | 32 Participants |
| Race/Ethnicity, Customized Race Not Reported | 97 Participants | 171 Participants | 74 Participants |
| Race/Ethnicity, Customized Race Other | 299 Participants | 593 Participants | 294 Participants |
| Race/Ethnicity, Customized Race Unknown | 62 Participants | 117 Participants | 55 Participants |
| Race/Ethnicity, Customized Race White | 12031 Participants | 24032 Participants | 12001 Participants |
| Sex: Female, Male Female | 7263 Participants | 14372 Participants | 7109 Participants |
| Sex: Female, Male Male | 7917 Participants | 15974 Participants | 8057 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 18 / 15,206 | 16 / 15,209 | 2 / 2,513 | 23 / 12,649 | 35 / 15,184 | 52 / 19,609 |
| other Total, other adverse events | 2,783 / 15,162 | 2,247 / 15,184 | 42 / 2,513 | 1,739 / 12,649 | 1,404 / 15,184 | 8,277 / 19,609 |
| serious Total, serious adverse events | 308 / 15,162 | 292 / 15,184 | 15 / 2,513 | 536 / 12,649 | 516 / 15,184 | 755 / 19,609 |
Outcome results
Primary
Part A: Number of Participants With a First Occurrence of COVID-19 Starting 14 Days After Second Dose
COVID-19 cases were defined as participants meeting clinical criteria based both on symptoms for COVID-19 and on RT-PCR detection of SARS-CoV-2 from samples collected within 72 hours of the study participant reporting symptoms that met the definition of COVID-19. An adjudication committee was assembled for the purpose of reviewing potential cases to determine if the criteria for COVID-19 were met.
Time frame: From Day 43 (14 days after second dose) up to approximately 7 months after the second dose
Population: Part A PP Set. Number analyzed=participants evaluable at specified timepoint.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part A (Blinded): Placebo | Part A: Number of Participants With a First Occurrence of COVID-19 Starting 14 Days After Second Dose | 744 Participants |
| Part A (Blinded): mRNA-1273 | Part A: Number of Participants With a First Occurrence of COVID-19 Starting 14 Days After Second Dose | 55 Participants |
Comparison: Vaccine efficacy was defined as the percent reduction in the hazard of the primary endpoint (mRNA-1273 vs. placebo).~Null hypothesis of Vaccine Efficacy ≤30%, 95% CI.p-value: <0.000195% CI: [91, 94.8]Vaccine Efficacy (VE)
Primary
Part A: Number of Participants With Solicited Local and Systemic Adverse Reactions (ARs) After First Dose
Solicited ARs (local and systemic) were collected in electronic diary (eDiary) within 7 days of dosing. Local ARs included: pain at injection site, erythema (redness) at injection site, swelling/induration (hardness) at injection site, and localized axillary swelling or tenderness ipsilateral to the injection arm. Systemic ARs included: headache, fatigue, myalgia (muscle aches all over the body), arthralgia (aching in several joints), nausea/vomiting, rash, body temperature (potentially fever), and chills. Severity grading for solicited ARs is based on modified Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventative Vaccine Clinical Trials. Severity was graded 0-4; a lower score indicated lower severity and a higher score indicated greater severity. The Investigator determined if solicited AR was also to be recorded as an AE. Summary of serious AEs (SAEs) and nonserious AEs (Other), regardless of causality, is in Reported Adverse Events section.
Time frame: up to Day 7 (7 days after first dose)
Population: Solicited Safety Set: All randomized participants who received at least 1 dose and contributed any solicited AR data; (had at least 1 post-baseline solicited safety assessment. Participants were included in the treatment group corresponding to the study vaccination they actually received. Number analyzed=participants evaluable at specified timepoint.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part A (Blinded): Placebo | Part A: Number of Participants With Solicited Local and Systemic Adverse Reactions (ARs) After First Dose | Grade 1 | 5134 Participants |
| Part A (Blinded): Placebo | Part A: Number of Participants With Solicited Local and Systemic Adverse Reactions (ARs) After First Dose | Grade 2 | 1782 Participants |
| Part A (Blinded): Placebo | Part A: Number of Participants With Solicited Local and Systemic Adverse Reactions (ARs) After First Dose | Grade 3 | 363 Participants |
| Part A (Blinded): Placebo | Part A: Number of Participants With Solicited Local and Systemic Adverse Reactions (ARs) After First Dose | Grade 4 | 6 Participants |
| Part A (Blinded): mRNA-1273 | Part A: Number of Participants With Solicited Local and Systemic Adverse Reactions (ARs) After First Dose | Grade 4 | 5 Participants |
| Part A (Blinded): mRNA-1273 | Part A: Number of Participants With Solicited Local and Systemic Adverse Reactions (ARs) After First Dose | Grade 1 | 9329 Participants |
| Part A (Blinded): mRNA-1273 | Part A: Number of Participants With Solicited Local and Systemic Adverse Reactions (ARs) After First Dose | Grade 3 | 849 Participants |
| Part A (Blinded): mRNA-1273 | Part A: Number of Participants With Solicited Local and Systemic Adverse Reactions (ARs) After First Dose | Grade 2 | 3134 Participants |
Primary
Part A: Number of Participants With Solicited Local and Systemic Adverse Reactions (ARs) After Second Dose
Solicited ARs (local and systemic) were collected in eDiary within 7 days of dosing. Local ARs included: pain at injection site, erythema (redness) at injection site, swelling/induration (hardness) at injection site, and localized axillary swelling or tenderness ipsilateral to the injection arm. Systemic ARs included: headache, fatigue, myalgia (muscle aches all over the body), arthralgia (aching in several joints), nausea/vomiting, rash, body temperature (potentially fever), and chills. Severity grading for solicited ARs is based on modified Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventative Vaccine Clinical Trials. Severity was graded 0-4; lower score indicated lower severity and a higher score indicated greater severity. The Investigator determined if solicited AR was also to be recorded as an AE. Summary of serious AEs (SAEs) and nonserious AEs (Other), regardless of causality, is in Reported Adverse Events section
Time frame: Day 29 to Day 35 (from second dose to 7 days after second dose)
Population: Solicited Safety Set: Randomized participants who received at least 1 dose and contributed any solicited AR data. Participants were included in the treatment group corresponding to the study vaccination they actually received. Number analyzed=participants evaluable at specified timepoint. No solicited ARs were collected in Part B because sufficient data had already been captured and analyzed in Part A.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part A (Blinded): Placebo | Part A: Number of Participants With Solicited Local and Systemic Adverse Reactions (ARs) After Second Dose | Grade 1 | 4346 Participants |
| Part A (Blinded): Placebo | Part A: Number of Participants With Solicited Local and Systemic Adverse Reactions (ARs) After Second Dose | Grade 2 | 1558 Participants |
| Part A (Blinded): Placebo | Part A: Number of Participants With Solicited Local and Systemic Adverse Reactions (ARs) After Second Dose | Grade 3 | 348 Participants |
| Part A (Blinded): Placebo | Part A: Number of Participants With Solicited Local and Systemic Adverse Reactions (ARs) After Second Dose | Grade 4 | 3 Participants |
| Part A (Blinded): mRNA-1273 | Part A: Number of Participants With Solicited Local and Systemic Adverse Reactions (ARs) After Second Dose | Grade 4 | 14 Participants |
| Part A (Blinded): mRNA-1273 | Part A: Number of Participants With Solicited Local and Systemic Adverse Reactions (ARs) After Second Dose | Grade 1 | 4847 Participants |
| Part A (Blinded): mRNA-1273 | Part A: Number of Participants With Solicited Local and Systemic Adverse Reactions (ARs) After Second Dose | Grade 3 | 2895 Participants |
| Part A (Blinded): mRNA-1273 | Part A: Number of Participants With Solicited Local and Systemic Adverse Reactions (ARs) After Second Dose | Grade 2 | 5800 Participants |
Primary
Parts A and B: Number of Participants With Medically Attended AEs (MAAEs) and AEs Leading to Discontinuation
An MAAE is an AE that leads to an unscheduled visit to a healthcare practitioner (HCP). A summary of SAEs and all nonserious AEs (Other), regardless of causality, is located in the Reported Adverse Events section.
Time frame: Day 1 (after dosing) through end of study (up to Day 759)
Population: Safety Set: All randomized participants who received at least 1 dose. Participants were included in the treatment group corresponding to dose they actually received. For a participant who was randomized to placebo but received any dose of mRNA-1273 at any injection, the participant was included in the mRNA-1273 group in the Safety Set.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part A (Blinded): Placebo | Parts A and B: Number of Participants With Medically Attended AEs (MAAEs) and AEs Leading to Discontinuation | AEs Leading to Discontinuation | 25 Participants |
| Part A (Blinded): Placebo | Parts A and B: Number of Participants With Medically Attended AEs (MAAEs) and AEs Leading to Discontinuation | MAAEs | 4561 Participants |
| Part A (Blinded): mRNA-1273 | Parts A and B: Number of Participants With Medically Attended AEs (MAAEs) and AEs Leading to Discontinuation | MAAEs | 3921 Participants |
| Part A (Blinded): mRNA-1273 | Parts A and B: Number of Participants With Medically Attended AEs (MAAEs) and AEs Leading to Discontinuation | AEs Leading to Discontinuation | 27 Participants |
| Part B (Open-label): Placebo | Parts A and B: Number of Participants With Medically Attended AEs (MAAEs) and AEs Leading to Discontinuation | MAAEs | 109 Participants |
| Part B (Open-label): Placebo | Parts A and B: Number of Participants With Medically Attended AEs (MAAEs) and AEs Leading to Discontinuation | AEs Leading to Discontinuation | 3 Participants |
| Part B (Open-label): Placebo/mRNA-1273 | Parts A and B: Number of Participants With Medically Attended AEs (MAAEs) and AEs Leading to Discontinuation | MAAEs | 5513 Participants |
| Part B (Open-label): Placebo/mRNA-1273 | Parts A and B: Number of Participants With Medically Attended AEs (MAAEs) and AEs Leading to Discontinuation | AEs Leading to Discontinuation | 30 Participants |
| Part B (Open-label): mRNA-1273 | Parts A and B: Number of Participants With Medically Attended AEs (MAAEs) and AEs Leading to Discontinuation | AEs Leading to Discontinuation | 35 Participants |
| Part B (Open-label): mRNA-1273 | Parts A and B: Number of Participants With Medically Attended AEs (MAAEs) and AEs Leading to Discontinuation | MAAEs | 5809 Participants |
Primary
Parts A and B: Number of Participants With Serious AEs (SAEs)
An SAE was defined as any AE that resulted in death, is life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in disability/permanent damage, was a congenital anomaly/birth defect, or was an important medical event. A summary of SAEs and all nonserious AEs (Other), regardless of causality, is located in the Reported Adverse Events section.
Time frame: Day 1 (after dosing) through end of study (up to Day 759)
Population: Safety Set: All randomized participants who received at least 1 dose. Participants were included in the treatment group corresponding to dose they actually received. For a participant who was randomized to placebo but received any dose of mRNA-1273 at any injection, the participant was included in the mRNA-1273 group in the Safety Set.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part A (Blinded): Placebo | Parts A and B: Number of Participants With Serious AEs (SAEs) | 308 Participants |
| Part A (Blinded): mRNA-1273 | Parts A and B: Number of Participants With Serious AEs (SAEs) | 292 Participants |
| Part B (Open-label): Placebo | Parts A and B: Number of Participants With Serious AEs (SAEs) | 15 Participants |
| Part B (Open-label): Placebo/mRNA-1273 | Parts A and B: Number of Participants With Serious AEs (SAEs) | 536 Participants |
| Part B (Open-label): mRNA-1273 | Parts A and B: Number of Participants With Serious AEs (SAEs) | 516 Participants |
Secondary
Part A: Geometric Mean Fold Rise (GMFR) of SARS-CoV-2 Specific nAb
The GMFR measures the changes in immunogenicity titers or levels from Baseline within participants. 95% CI was calculated based on the difference in the log-transformed values for GMFR, then back transformed to the original scale for presentation. GMFR for ID50 and ID80 neutralizing antibodies against SARS-CoV-2 S-protein, as measured by pseudovirus neutralizing antibody is presented. Baseline SARS-CoV-2 Status: Positive if there is immunologic or virologic evidence of prior COVID-19, defined as positive RT-PCR test or positive Elecsys result at Day 1. Negative is defined as negative RT-PCR test and negative Elecsys result at Day 1
Time frame: Day 29, Day 57
Population: Part A PPRSI Set. Number analyzed=participants evaluable at specified timepoint. Immunogenicity samples from the Part B were not tested and no data were generated as results were not thought to provide additional information.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Part A (Blinded): Placebo | Part A: Geometric Mean Fold Rise (GMFR) of SARS-CoV-2 Specific nAb | Baseline SARS-CoV-2 Negative, ID50 Day 29 | 1.03 Ratio |
| Part A (Blinded): Placebo | Part A: Geometric Mean Fold Rise (GMFR) of SARS-CoV-2 Specific nAb | Baseline SARS-CoV-2 Negative, ID50 Day 57 | 1.07 Ratio |
| Part A (Blinded): Placebo | Part A: Geometric Mean Fold Rise (GMFR) of SARS-CoV-2 Specific nAb | Baseline SARS-CoV-2, Negative, ID80 Day 29 | 1.02 Ratio |
| Part A (Blinded): Placebo | Part A: Geometric Mean Fold Rise (GMFR) of SARS-CoV-2 Specific nAb | Baseline SARS-CoV-2 Negative, ID80 Day 57 | 1.05 Ratio |
| Part A (Blinded): Placebo | Part A: Geometric Mean Fold Rise (GMFR) of SARS-CoV-2 Specific nAb | Baseline SARS-CoV-2, Positive, ID50 Day 29 | 0.64 Ratio |
| Part A (Blinded): Placebo | Part A: Geometric Mean Fold Rise (GMFR) of SARS-CoV-2 Specific nAb | Baseline SARS-CoV-2 Positive, ID50 Day 57 | 0.59 Ratio |
| Part A (Blinded): Placebo | Part A: Geometric Mean Fold Rise (GMFR) of SARS-CoV-2 Specific nAb | Baseline SARS-CoV-2 Positive, ID80 Day 29 | 0.71 Ratio |
| Part A (Blinded): Placebo | Part A: Geometric Mean Fold Rise (GMFR) of SARS-CoV-2 Specific nAb | Baseline SARS-CoV-2 Positive, ID80 Day 57 | 0.66 Ratio |
| Part A (Blinded): mRNA-1273 | Part A: Geometric Mean Fold Rise (GMFR) of SARS-CoV-2 Specific nAb | Baseline SARS-CoV-2 Positive, ID80 Day 57 | 44.00 Ratio |
| Part A (Blinded): mRNA-1273 | Part A: Geometric Mean Fold Rise (GMFR) of SARS-CoV-2 Specific nAb | Baseline SARS-CoV-2 Negative, ID50 Day 29 | 5.69 Ratio |
| Part A (Blinded): mRNA-1273 | Part A: Geometric Mean Fold Rise (GMFR) of SARS-CoV-2 Specific nAb | Baseline SARS-CoV-2, Positive, ID50 Day 29 | 21.71 Ratio |
| Part A (Blinded): mRNA-1273 | Part A: Geometric Mean Fold Rise (GMFR) of SARS-CoV-2 Specific nAb | Baseline SARS-CoV-2 Negative, ID50 Day 57 | 112.30 Ratio |
| Part A (Blinded): mRNA-1273 | Part A: Geometric Mean Fold Rise (GMFR) of SARS-CoV-2 Specific nAb | Baseline SARS-CoV-2 Positive, ID80 Day 29 | 20.74 Ratio |
| Part A (Blinded): mRNA-1273 | Part A: Geometric Mean Fold Rise (GMFR) of SARS-CoV-2 Specific nAb | Baseline SARS-CoV-2, Negative, ID80 Day 29 | 2.68 Ratio |
| Part A (Blinded): mRNA-1273 | Part A: Geometric Mean Fold Rise (GMFR) of SARS-CoV-2 Specific nAb | Baseline SARS-CoV-2 Positive, ID50 Day 57 | 46.18 Ratio |
| Part A (Blinded): mRNA-1273 | Part A: Geometric Mean Fold Rise (GMFR) of SARS-CoV-2 Specific nAb | Baseline SARS-CoV-2 Negative, ID80 Day 57 | 45.62 Ratio |
Secondary
Part A: Geometric Mean Titer (GMT) of SARS-CoV-2 Specific Neutralizing Antibody (nAb)
GMT (50% inhibitory dose \[ID50\], 80% inhibitory dose \[ID80\]) of nAb against SARS-CoV-2 pseudotyped viruses as measured by pseudovirus nAb assay is reported. 95% CI was based on the t-distribution of log-transformed values for GM titer, then back transformed to original scale for presentation. Baseline SARS-CoV-2 Status: Positive if there is immunologic or virologic evidence of prior COVID-19, defined as positive RT-PCR test or positive Elecsys result at Day 1. Negative is defined as negative RT-PCR test and negative Elecsys result at Day 1.
Time frame: Day 1, Day 29, Day 57
Population: Part A PPRSI Set. Number analyzed=participants evaluable at specified timepoint. Immunogenicity samples from the Part B were not tested and no data were generated as results were not thought to provide additional information.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Part A (Blinded): Placebo | Part A: Geometric Mean Titer (GMT) of SARS-CoV-2 Specific Neutralizing Antibody (nAb) | Baseline SARS-CoV-2 Negative', ID50, Day 57 | 9.903 Titer |
| Part A (Blinded): Placebo | Part A: Geometric Mean Titer (GMT) of SARS-CoV-2 Specific Neutralizing Antibody (nAb) | Baseline SARS-CoV-2 Negative, ID50, Day 1 | NA Titer |
| Part A (Blinded): Placebo | Part A: Geometric Mean Titer (GMT) of SARS-CoV-2 Specific Neutralizing Antibody (nAb) | Baseline SARS-CoV-2 Negative', ID50, Day 29 | 9.515 Titer |
| Part A (Blinded): Placebo | Part A: Geometric Mean Titer (GMT) of SARS-CoV-2 Specific Neutralizing Antibody (nAb) | Baseline SARS-CoV-2 Negative', ID80, Day 1 | NA Titer |
| Part A (Blinded): Placebo | Part A: Geometric Mean Titer (GMT) of SARS-CoV-2 Specific Neutralizing Antibody (nAb) | Baseline SARS-CoV-2 Negative', ID80, Day 29 | 7.279 Titer |
| Part A (Blinded): Placebo | Part A: Geometric Mean Titer (GMT) of SARS-CoV-2 Specific Neutralizing Antibody (nAb) | Baseline SARS-CoV-2 Negative', ID80, Day 57 | 7.522 Titer |
| Part A (Blinded): Placebo | Part A: Geometric Mean Titer (GMT) of SARS-CoV-2 Specific Neutralizing Antibody (nAb) | Baseline SARS-CoV-2 Positive, ID50, Day 1 | 82.519 Titer |
| Part A (Blinded): Placebo | Part A: Geometric Mean Titer (GMT) of SARS-CoV-2 Specific Neutralizing Antibody (nAb) | Baseline SARS-CoV-2 Positive, ID50, Day 29 | 52.728 Titer |
| Part A (Blinded): Placebo | Part A: Geometric Mean Titer (GMT) of SARS-CoV-2 Specific Neutralizing Antibody (nAb) | Baseline SARS-CoV-2 Positive, ID50, Day 57 | 47.708 Titer |
| Part A (Blinded): Placebo | Part A: Geometric Mean Titer (GMT) of SARS-CoV-2 Specific Neutralizing Antibody (nAb) | Baseline SARS-CoV-2 Positive, ID80, Day 1 | 29.580 Titer |
| Part A (Blinded): Placebo | Part A: Geometric Mean Titer (GMT) of SARS-CoV-2 Specific Neutralizing Antibody (nAb) | Baseline SARS-CoV-2 Positive, ID80, Day 29 | 20.994 Titer |
| Part A (Blinded): Placebo | Part A: Geometric Mean Titer (GMT) of SARS-CoV-2 Specific Neutralizing Antibody (nAb) | Baseline SARS-CoV-2 Positive, ID80, Day 57 | 19.228 Titer |
| Part A (Blinded): mRNA-1273 | Part A: Geometric Mean Titer (GMT) of SARS-CoV-2 Specific Neutralizing Antibody (nAb) | Baseline SARS-CoV-2 Positive, ID80, Day 29 | 518.388 Titer |
| Part A (Blinded): mRNA-1273 | Part A: Geometric Mean Titer (GMT) of SARS-CoV-2 Specific Neutralizing Antibody (nAb) | Baseline SARS-CoV-2 Negative', ID50, Day 57 | 1081.124 Titer |
| Part A (Blinded): mRNA-1273 | Part A: Geometric Mean Titer (GMT) of SARS-CoV-2 Specific Neutralizing Antibody (nAb) | Baseline SARS-CoV-2 Positive, ID50, Day 1 | 68.117 Titer |
| Part A (Blinded): mRNA-1273 | Part A: Geometric Mean Titer (GMT) of SARS-CoV-2 Specific Neutralizing Antibody (nAb) | Baseline SARS-CoV-2 Negative, ID50, Day 1 | 9.624 Titer |
| Part A (Blinded): mRNA-1273 | Part A: Geometric Mean Titer (GMT) of SARS-CoV-2 Specific Neutralizing Antibody (nAb) | Baseline SARS-CoV-2 Positive, ID80, Day 1 | 24.996 Titer |
| Part A (Blinded): mRNA-1273 | Part A: Geometric Mean Titer (GMT) of SARS-CoV-2 Specific Neutralizing Antibody (nAb) | Baseline SARS-CoV-2 Negative', ID50, Day 29 | 54.866 Titer |
| Part A (Blinded): mRNA-1273 | Part A: Geometric Mean Titer (GMT) of SARS-CoV-2 Specific Neutralizing Antibody (nAb) | Baseline SARS-CoV-2 Positive, ID50, Day 29 | 1478.910 Titer |
| Part A (Blinded): mRNA-1273 | Part A: Geometric Mean Titer (GMT) of SARS-CoV-2 Specific Neutralizing Antibody (nAb) | Baseline SARS-CoV-2 Negative', ID80, Day 1 | 7.332 Titer |
| Part A (Blinded): mRNA-1273 | Part A: Geometric Mean Titer (GMT) of SARS-CoV-2 Specific Neutralizing Antibody (nAb) | Baseline SARS-CoV-2 Positive, ID80, Day 57 | 1099.847 Titer |
| Part A (Blinded): mRNA-1273 | Part A: Geometric Mean Titer (GMT) of SARS-CoV-2 Specific Neutralizing Antibody (nAb) | Baseline SARS-CoV-2 Negative', ID80, Day 29 | 19.684 Titer |
| Part A (Blinded): mRNA-1273 | Part A: Geometric Mean Titer (GMT) of SARS-CoV-2 Specific Neutralizing Antibody (nAb) | Baseline SARS-CoV-2 Positive, ID50, Day 57 | 3145.904 Titer |
| Part A (Blinded): mRNA-1273 | Part A: Geometric Mean Titer (GMT) of SARS-CoV-2 Specific Neutralizing Antibody (nAb) | Baseline SARS-CoV-2 Negative', ID80, Day 57 | 334.867 Titer |
Secondary
Part A: Number of Participants With a First Occurrence of COVID-19 Starting 14 Days After First Dose
COVID-19 cases were defined as participants meeting clinical criteria based both on symptoms for COVID-19 and on RT-PCR detection of SARS-CoV-2 from samples collected within 72 hours of the study participant reporting symptoms that met the definition of COVID-19. An adjudication committee was assembled for the purpose of reviewing potential cases to determine if the criteria for COVID-19 were met.
Time frame: From 14 days after first dose up to approximately 8 months
Population: Part A PP Set. Number analyzed=participants evaluable at specified timepoint.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part A (Blinded): Placebo | Part A: Number of Participants With a First Occurrence of COVID-19 Starting 14 Days After First Dose | 769 Participants |
| Part A (Blinded): mRNA-1273 | Part A: Number of Participants With a First Occurrence of COVID-19 Starting 14 Days After First Dose | 56 Participants |
95% CI: [91.1, 94.9]
Secondary
Part A: Number of Participants With a First Occurrence of COVID-19 Starting 14 Days After Second Dose Regardless of Evidence of Prior SARS-CoV-2 Infection
COVID-19 cases were defined as participants meeting clinical criteria based both on symptoms for COVID-19 and on RT-PCR detection of SARS-CoV-2 from samples collected within 72 hours of the study participant reporting symptoms that met the definition of COVID-19. An adjudication committee was assembled for the purpose of reviewing potential cases to determine if the criteria for COVID-19 were met.
Time frame: From Day 43 (14 days after second dose) up to approximately 7 months after the second dose
Population: Part A FAS. Number analyzed=participants evaluable at specified timepoint.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part A (Blinded): Placebo | Part A: Number of Participants With a First Occurrence of COVID-19 Starting 14 Days After Second Dose Regardless of Evidence of Prior SARS-CoV-2 Infection | 754 Participants |
| Part A (Blinded): mRNA-1273 | Part A: Number of Participants With a First Occurrence of COVID-19 Starting 14 Days After Second Dose Regardless of Evidence of Prior SARS-CoV-2 Infection | 58 Participants |
95% CI: [79.5, 84.3]
Secondary
Part A: Number of Participants With a First Occurrence of Either COVID-19 or SARS-CoV-2 Infection Regardless of Symptomatology or Severity Starting 14 Days After Second Dose
COVID-19 cases were defined as participants meeting clinical criteria based both on symptoms for COVID-19 and on RT-PCR detection of SARS-CoV-2 from samples collected within 72 hours of the study participant reporting symptoms that met the definition of COVID-19. An adjudication committee was assembled for the purpose of reviewing potential cases to determine if the criteria for COVID-19 were met. SARS-CoV-2 infection was defined by seroconversion due to infection measured by binding antibody (bAb) levels against SARS-CoV-2 nucleocapsid or by positive RT-PCR at predefined timepoints. Seroconversion was defined by the participant's serostatus at baseline.
Time frame: From Day 43 (14 days after second dose) up to approximately 7 months after the second dose
Population: Part A PP Set. Number analyzed=participants evaluable at specified timepoint.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part A (Blinded): Placebo | Part A: Number of Participants With a First Occurrence of Either COVID-19 or SARS-CoV-2 Infection Regardless of Symptomatology or Severity Starting 14 Days After Second Dose | 1339 Participants |
| Part A (Blinded): mRNA-1273 | Part A: Number of Participants With a First Occurrence of Either COVID-19 or SARS-CoV-2 Infection Regardless of Symptomatology or Severity Starting 14 Days After Second Dose | 280 Participants |
95% CI: [79.5, 84.2]
Secondary
Part A: Number of Participants With a First Occurrence of SARS-CoV-2 Infection in the Absence of Symptoms Defining COVID-19 Starting 14 Days After Second Dose
SARS-CoV-2 infection was defined by seroconversion due to infection measured by binding antibody (bAb) levels against SARS-CoV-2 nucleocapsid or by positive RT-PCR at predefined timepoints. Seroconversion was defined by the participant's serostatus at baseline.
Time frame: From Day 43 (14 days after second dose) up to approximately 7 months after the second dose
Population: Part A PP Set. Number analyzed=participants evaluable at specified timepoint.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part A (Blinded): Placebo | Part A: Number of Participants With a First Occurrence of SARS-CoV-2 Infection in the Absence of Symptoms Defining COVID-19 Starting 14 Days After Second Dose | 498 Participants |
| Part A (Blinded): mRNA-1273 | Part A: Number of Participants With a First Occurrence of SARS-CoV-2 Infection in the Absence of Symptoms Defining COVID-19 Starting 14 Days After Second Dose | 214 Participants |
95% CI: [56.6, 68.5]
Secondary
Part A: Number of Participants With a Secondary Case Definition of COVID-19 Starting 14 Days After Second Dose
Secondary case definition of COVID-19 was defined as the presence of at least 1 of the following systemic symptoms: fever (temperature ≥38ºC), or chills, cough, shortness of breath or difficulty breathing, fatigue, muscle aches or body aches, headache, new loss of taste or smell, sore throat, nasal congestion or rhinorrhea, nausea or vomiting, or diarrhea and a positive nasopharyngeal swab, nasal swab, or saliva sample (or respiratory sample, if hospitalized) for SARS-CoV-2 by RT-PCR.
Time frame: From Day 43 (14 days after second dose) up to approximately 7 months after the second dose
Population: Part A PP Set. Number analyzed=participants evaluable at specified timepoint.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part A (Blinded): Placebo | Part A: Number of Participants With a Secondary Case Definition of COVID-19 Starting 14 Days After Second Dose | 807 Participants |
| Part A (Blinded): mRNA-1273 | Part A: Number of Participants With a Secondary Case Definition of COVID-19 Starting 14 Days After Second Dose | 58 Participants |
95% CI: [91.4, 94.9]
Secondary
Part A: Number of Participants With Unsolicited AEs up to 28 Days After Any Injection Dose
Unsolicited AE was any AE reported by the participant that was not specified as an AR or was specified as a solicited AR in the protocol but started outside the protocol-defined, post-injection period for reporting solicited ARs. Unsolicited AEs were collected for the 28 days after any injection. An AE was as any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. A summary of all SAEs and all nonserious AEs (Other) reported up to the end of the study, regardless of causality, is located in the Reported Adverse Events section.
Time frame: Up to 28 days after any dose
Population: Safety Set: All randomized participants who received at least 1 dose. Participants were included in the treatment group corresponding to dose they actually received. For a participant who was randomized to placebo but received any dose of mRNA-1273 at any injection, the participant was included in the mRNA-1273 group in the Safety Set.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part A (Blinded): Placebo | Part A: Number of Participants With Unsolicited AEs up to 28 Days After Any Injection Dose | 4338 Participants |
| Part A (Blinded): mRNA-1273 | Part A: Number of Participants With Unsolicited AEs up to 28 Days After Any Injection Dose | 4752 Participants |
Secondary
Part A: Percentage of Participants With Seroresponse Against SARS-CoV-2
Seroresponse to pseudovirus neutralizing antibody ID50 titer at a participant level is defined as a change from below the LLOQ to equal or above the LLOQ, or at least a 3.3-fold rise if baseline is equal to or above the LLOQ. Seroresponse to pseudovirus neutralizing antibody ID80 titer at a participant level is defined as a change from below the LLOQ to equal or above the LLOQ, or at least a 2.3-fold rise if baseline is equal to or above the LLOQ. Baseline SARS-CoV-2 Status: Positive if there is immunologic or virologic evidence of prior COVID-19, defined as positive RT-PCR test or positive Elecsys result at Day 1. Negative is defined as negative RT-PCR test and negative Elecsys result at Day 1.
Time frame: Day 29, Day 57
Population: Part A PPRSI Set. Number analyzed=participants evaluable at specified timepoint. Immunogenicity samples from the Part B were not tested and no data were generated as results were not thought to provide additional information.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Part A (Blinded): Placebo | Part A: Percentage of Participants With Seroresponse Against SARS-CoV-2 | Baseline SARS-CoV-2 Negative, ID50, Day 29 | 0.7 percentage of participants |
| Part A (Blinded): Placebo | Part A: Percentage of Participants With Seroresponse Against SARS-CoV-2 | Baseline SARS-CoV-2 Negative, ID50, Day 57 | 1.4 percentage of participants |
| Part A (Blinded): Placebo | Part A: Percentage of Participants With Seroresponse Against SARS-CoV-2 | Baseline SARS-CoV-2 Negative, ID80, Day 29 | 0.7 percentage of participants |
| Part A (Blinded): Placebo | Part A: Percentage of Participants With Seroresponse Against SARS-CoV-2 | Baseline SARS-CoV-2 Negative, ID80, Day 57 | 1.4 percentage of participants |
| Part A (Blinded): Placebo | Part A: Percentage of Participants With Seroresponse Against SARS-CoV-2 | Baseline SARS-CoV-2 Positive, ID50, Day 29 | 0.8 percentage of participants |
| Part A (Blinded): Placebo | Part A: Percentage of Participants With Seroresponse Against SARS-CoV-2 | Baseline SARS-CoV-2 Positive, ID50, Day 57 | 1.6 percentage of participants |
| Part A (Blinded): Placebo | Part A: Percentage of Participants With Seroresponse Against SARS-CoV-2 | Baseline SARS-CoV-2 Positive, ID80, Day 29 | 3.1 percentage of participants |
| Part A (Blinded): Placebo | Part A: Percentage of Participants With Seroresponse Against SARS-CoV-2 | Baseline SARS-CoV-2 Positive, ID80, Day 57 | 2.3 percentage of participants |
| Part A (Blinded): mRNA-1273 | Part A: Percentage of Participants With Seroresponse Against SARS-CoV-2 | Baseline SARS-CoV-2 Positive, ID80, Day 57 | 96.2 percentage of participants |
| Part A (Blinded): mRNA-1273 | Part A: Percentage of Participants With Seroresponse Against SARS-CoV-2 | Baseline SARS-CoV-2 Negative, ID50, Day 29 | 81.4 percentage of participants |
| Part A (Blinded): mRNA-1273 | Part A: Percentage of Participants With Seroresponse Against SARS-CoV-2 | Baseline SARS-CoV-2 Positive, ID50, Day 29 | 87.7 percentage of participants |
| Part A (Blinded): mRNA-1273 | Part A: Percentage of Participants With Seroresponse Against SARS-CoV-2 | Baseline SARS-CoV-2 Negative, ID50, Day 57 | 98.9 percentage of participants |
| Part A (Blinded): mRNA-1273 | Part A: Percentage of Participants With Seroresponse Against SARS-CoV-2 | Baseline SARS-CoV-2 Positive, ID80, Day 29 | 90.0 percentage of participants |
| Part A (Blinded): mRNA-1273 | Part A: Percentage of Participants With Seroresponse Against SARS-CoV-2 | Baseline SARS-CoV-2 Negative, ID80, Day 29 | 63.0 percentage of participants |
| Part A (Blinded): mRNA-1273 | Part A: Percentage of Participants With Seroresponse Against SARS-CoV-2 | Baseline SARS-CoV-2 Positive, ID50, Day 57 | 94.6 percentage of participants |
| Part A (Blinded): mRNA-1273 | Part A: Percentage of Participants With Seroresponse Against SARS-CoV-2 | Baseline SARS-CoV-2 Negative, ID80, Day 57 | 98.9 percentage of participants |
Secondary
Part C: Geometric Mean Concentration (GMC) of SARS-CoV-2 Specific nAb After BD Compared to After Second Dose in Part A Measured by Pseudovirus (VAC62)
95% CI is calculated based on the t-distribution of the log-transformed values for GMC, then back transformed to the original scale for presentation.
Time frame: Part C BD Day 29 and Part A Day 57
Population: Part C PPIS Set pre-booster SARS-CoV-2 negative. Number analyzed=participants evaluable at specified timepoint.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Part A (Blinded): Placebo | Part C: Geometric Mean Concentration (GMC) of SARS-CoV-2 Specific nAb After BD Compared to After Second Dose in Part A Measured by Pseudovirus (VAC62) | Part C BD Day 29 | 7739.680 arbitrary units (AU)/milliliters (mL) |
| Part A (Blinded): mRNA-1273 | Part C: Geometric Mean Concentration (GMC) of SARS-CoV-2 Specific nAb After BD Compared to After Second Dose in Part A Measured by Pseudovirus (VAC62) | Part A Day 57 | 1111.274 arbitrary units (AU)/milliliters (mL) |
Comparison: Ratio of GMC 28 days following the booster dose (BD-Day 29) compared with 28 days following second dose (Part A-Day 57).95% CI: [6.509, 7.52]
Secondary
Part C: GMT of SARS-CoV-2 Specific nAb Measured by Pseudovirus (VAC62)
95% CI is calculated based on the t-distribution of the log-transformed values for GM value, then back transformed to the original scale for presentation.
Time frame: Pre-booster (Baseline), post-booster Day 29 and post-booster Day 181
Population: Part C PPIS Set. Number analyzed=participants evaluable at specified timepoint.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Part A (Blinded): Placebo | Part C: GMT of SARS-CoV-2 Specific nAb Measured by Pseudovirus (VAC62) | Pre-booster (Baseline) | 163.848 Titer |
| Part A (Blinded): Placebo | Part C: GMT of SARS-CoV-2 Specific nAb Measured by Pseudovirus (VAC62) | BD Day 29 | 8122.189 Titer |
| Part A (Blinded): Placebo | Part C: GMT of SARS-CoV-2 Specific nAb Measured by Pseudovirus (VAC62) | BD Day 181 | 2951.123 Titer |
Secondary
Part C: Percentage of Participants With Seroresponse Against SARS-CoV-2 After BD Compared to After Second Dose in Part A
Pseudovirus neutralizing antibody (VAC62) are presented. Seroresponse at a participant level is defined as a change from below the LLOQ to equal or above 4 x LLOQ, or at least a4-fold rise if baseline (Pre- Dose 1) is equal to or above the LLOQ.
Time frame: Part C BD Day 29 and Part A Day 57
Population: Part C PPIS Set pre-booster SARS-CoV-2 negative. Number analyzed=participants evaluable at specified timepoint.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Part A (Blinded): Placebo | Part C: Percentage of Participants With Seroresponse Against SARS-CoV-2 After BD Compared to After Second Dose in Part A | Part C BD Day 29 | 100 percentage of participants |
| Part A (Blinded): mRNA-1273 | Part C: Percentage of Participants With Seroresponse Against SARS-CoV-2 After BD Compared to After Second Dose in Part A | Part A Day 57 | 98.8 percentage of participants |
Comparison: Seroresponse 28 days following the booster dose (BD-Day 29) compared with 28 days following second dose (Part A-Day 57)95% CI: [0.1, 1.8]
Secondary
Part C: Percentage of Participants With Seroresponse Against SARS-CoV-2 Measured by Pseudovirus (VAC62)
Pseudovirus neutralizing antibody (VAC62) from pre-booster is presented. Seroresponse at a participant level is defined as a change from below the LLOQ to \>= 4 x LLOQ, or at least a 4-fold rise if pre-booster is equal to or above the LLOQ.
Time frame: Post-booster Day 29 and post-booster Day 181
Population: Part C PPIS Set. Number analyzed=participants evaluable at specified timepoint.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Part A (Blinded): Placebo | Part C: Percentage of Participants With Seroresponse Against SARS-CoV-2 Measured by Pseudovirus (VAC62) | BD Day 29 | 94.5 percentage of participants |
| Part A (Blinded): Placebo | Part C: Percentage of Participants With Seroresponse Against SARS-CoV-2 Measured by Pseudovirus (VAC62) | BD Day 181 | 89.2 percentage of participants |
Secondary
Parts A and B: Number of Participants Who Died Due to a Cause Directly Attributed to a Complication of COVID-19 Starting 14 Days After Second Dose
Time frame: From Day 43 (14 days after second dose) up to approximately 8 months for Part A and from PDV/unblinding (at 4 months) to up to 8 months for Part B
Population: Parts A and B PP Set. Number analyzed=participants evaluable at specified timepoint.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part A (Blinded): Placebo | Parts A and B: Number of Participants Who Died Due to a Cause Directly Attributed to a Complication of COVID-19 Starting 14 Days After Second Dose | 3 Participants |
| Part A (Blinded): mRNA-1273 | Parts A and B: Number of Participants Who Died Due to a Cause Directly Attributed to a Complication of COVID-19 Starting 14 Days After Second Dose | 0 Participants |
| Part B (Open-label): Placebo | Parts A and B: Number of Participants Who Died Due to a Cause Directly Attributed to a Complication of COVID-19 Starting 14 Days After Second Dose | 0 Participants |
| Part B (Open-label): Placebo/mRNA-1273 | Parts A and B: Number of Participants Who Died Due to a Cause Directly Attributed to a Complication of COVID-19 Starting 14 Days After Second Dose | 0 Participants |
| Part B (Open-label): mRNA-1273 | Parts A and B: Number of Participants Who Died Due to a Cause Directly Attributed to a Complication of COVID-19 Starting 14 Days After Second Dose | 0 Participants |
Secondary
Parts A and B: Number of Participants With a First Occurrence of Severe COVID-19 Starting 14 Days After Second Dose
COVID-19 cases were defined as participants meeting clinical criteria based on symptoms for COVID-19 and reverse transcriptase polymerase chain reaction (RT-PCR) detection of SARS-CoV-2 from samples collected within 72 hours of the participant reporting symptoms meeting the definition of COVID-19. An adjudication committee reviewed potential cases to determine if the criteria for COVID-19 were met. Clinical signs indicative of severe COVID-19 systemic illness included any of the following: respiratory rate ≥30 per minute, heart rate ≥125 beats per minute, oxygen saturation (SpO2) ≤93% on room air at sea level, or partial pressure of oxygen (PaO2)/fraction of inspired oxygen (FIO2) \<300 millimeter of mercury (mm Hg), or respiratory failure or acute respiratory distress syndrome (ARDS), evidence of shock, or significant acute renal, hepatic, or neurologic dysfunction, or admission to an intensive care unit or death.
Time frame: From Day 43 (14 days after second dose) up to approximately 8 months for Part A and from PDV/unblinding (at 4 months) to up to 8 months for Part B
Population: Parts A and B PP Sets. Number analyzed=participants evaluable at specified timepoint.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part A (Blinded): Placebo | Parts A and B: Number of Participants With a First Occurrence of Severe COVID-19 Starting 14 Days After Second Dose | 106 Participants |
| Part A (Blinded): mRNA-1273 | Parts A and B: Number of Participants With a First Occurrence of Severe COVID-19 Starting 14 Days After Second Dose | 2 Participants |
| Part B (Open-label): Placebo | Parts A and B: Number of Participants With a First Occurrence of Severe COVID-19 Starting 14 Days After Second Dose | 1 Participants |
| Part B (Open-label): Placebo/mRNA-1273 | Parts A and B: Number of Participants With a First Occurrence of Severe COVID-19 Starting 14 Days After Second Dose | 8 Participants |
| Part B (Open-label): mRNA-1273 | Parts A and B: Number of Participants With a First Occurrence of Severe COVID-19 Starting 14 Days After Second Dose | 1 Participants |
95% CI: [92.8, 99.6]VE