Influenza, SARS-CoV-2
Conditions
Keywords
mRNA-1083, mRNA-1083 Vaccine, SARS-CoV-2, SARS-CoV-2 Vaccine, Coronavirus, Virus Diseases, Messenger RNA, Influenza Vaccine, Moderna
Brief summary
The purpose of this study is to evaluate the immunogenicity, safety, and reactogenicity of mRNA-1083 as compared with active control, co-administered licensed influenza and severe acute respiratory syndrome coronavirus 2 (SARS CoV 2) vaccines, in 2 independent age-group sub-study cohorts, healthy adults 65 years and older (Cohort A) and healthy adults 50 to \<65 years of age (Cohort B).
Interventions
BIOLOGICALmRNA-1083
Suspension for injection
BIOLOGICALPlacebo
0.9% sodium chloride suspension for injection
BIOLOGICALInfluenza Vaccine
Commercially available formulation (Suspension for injection \[pre-filled syringe\])
BIOLOGICALCOVID-19 Vaccine
Commercially available formulation (Suspension for injection)
Sponsors
ModernaTX, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
50 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
Key Inclusion Criteria: * Healthy adults either ≥65 years of age (Cohort A) or 50 to \<65 years of age (Cohort B) at the time of consent (Screening Visit). * For female participants of childbearing potential: negative pregnancy test, adequate contraception or has abstained from all activities that could result in pregnancy for at least 28 days prior to Day 1, and agreement to continue adequate contraception through 3 months following vaccine administration. * Fully vaccinated for COVID-19 primary series according to the locally authorized or approved regimen, and their last COVID-19 vaccine (primary series or booster) was ≥90 days prior to Day 1.
Exclusion criteria
* Participant is acutely ill or febrile (temperature ≥38.0 degrees Celsius \[°C\]/100.4 degrees Fahrenheit \[°F\]) 72 hours prior to or at the Screening Visit or Day 1. * Any medical, psychiatric, or occupational condition, including reported history of drug or alcohol abuse, that, in the opinion of the Investigator, might pose additional risk due to participation in the study or could interfere with the interpretation of study results. * Participant has received systemic immunosuppressants for \>14 days in total within 180 days prior to Day 1 (for corticosteroids, ≥10 milligrams \[mg\]/day of prednisone or equivalent) or is anticipating the need for systemic immunosuppressive treatment at any time during participation in the study. Inhaled nasal and topical steroids are allowed. * Received or plans to receive any vaccine authorized or approved by a local health agency ≤28 days prior to study injections or plans to receive a vaccine authorized or approved by a local health agency within 28 days after the study injections. * Received a seasonal influenza vaccine ≤150 days prior to Day 1. * Tested positive for influenza by local health authority-approved testing methods ≤150 days prior to Day 1. * Has had close contact to someone with COVID-19 as defined by the Centers for Disease Control and Prevention (CDC) in the past 10 days prior to Day 1. * Has donated ≥450 milliliters (mL) of blood products within 28 days prior to the Screening Visit or plans to donate blood products during the study. Note: Other protocol-defined inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Medically Attended Adverse Events (MAAEs), Adverse Events of Special Interest (AESIs), Serious Adverse Events (SAEs), and AEs Leading to Discontinuation | Day 1 through Day 181 | An SAE was defined as any AE that resulted in death, was 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. AESIs included thrombocytopenia, new onset of or worsening of the protocol specified neurologic diseases, anaphylaxis, and myocarditis/pericarditis. An MAAE is an AE that lead to an unscheduled visit to an healthcare practitioner. This included visits to a study site for unscheduled assessments (for example, abnormal laboratory follow-up, and/or COVID-19 and visits to healthcare practitioners external to the study site. Number of participants with SAEs, AESIs, MAAEs, and AEs leading to discontinuation up to the end of study (Day 181) are reported in this outcome measure. A Summary of serious AEs (SAEs) and nonserious AEs (Other), regardless of causality, is located in the Reported Adverse Events section. |
| Geometric Mean (GM) Level of Antibodies for Influenza, as Measured by Hemagglutination Inhibition (HAI) Assay | Day 29 | Influenza A strains included H1N1 and H3N2 and influenza B strains included Victoria-lineage and Yamagata-lineage. The Per Protocol Immunogenicity Set (PPIS) included all randomized participants who received study intervention, complied with the timing of immunogenicity blood sample collections to have both Baseline and Day 29 assessments using a window of -7 to +14 days, had no major dosing error, had negative reverse transcription polymerase chain reaction (RT-PCR) test for influenza and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on Day 1, and had no major protocol deviations or conditions/medications that affected the immune response. |
| GM Level of Antibodies for SARS-CoV-2, as Measured by Pseudovirus Neutralization Assay (PsVNA) | Day 29 | SARS-CoV-2 strain included Omicron XBB.1.5 antibody. The PPIS included all randomized participants who received study intervention, complied with the timing of immunogenicity blood sample collections to have both Baseline and Day 29 assessments using a window of -7 to +14 days, had no major dosing error, had negative RT-PCR test for influenza and SARS-CoV-2 on Day 1, and had no major protocol deviations or conditions/medications that affected the immune response. |
| Influenza: Percentage of Participants With Seroconversion, as Measured by HAI Assay | Baseline to Day 29 | Influenza A strains included H1N1 and H3N2 and influenza B strains included Victoria-lineage and Yamagata-lineage. Seroconversion was defined as a Day 29 postinjection level ≥1:40 if Baseline was \<1:10 or a 4-fold or greater rise if Baseline was ≥1:10 in anti-hemagglutinin (HA) antibodies measured by HAI assay. The PPIS included all randomized participants who received study intervention, complied with the timing of immunogenicity blood sample collections to have both Baseline and Day 29 assessments using a window of -7 to +14 days, had no major dosing error, had negative RT-PCR test for influenza and SARS-CoV-2 on Day 1, and had no major protocol deviations or conditions/medications that affected the immune response. |
| SARS-CoV-2: Percentage of Participants With Seroresponse, as Measured by PsVNA | Baseline to Day 29 | SARS-CoV-2 strain included Omicron XBB.1.5 antibody. Seroresponse was defined as a Day 29 postinjection level ≥4-fold rise if Baseline was ≥lower limit of quantification (LLOQ) or ≥4×LLOQ if Baseline value was \<LLOQ in the nAb values measured by PsVNA. LLOQ was 38 arbitrary unit (AU)/milliliter (mL). The PPIS included all randomized participants who received study intervention, complied with the timing of immunogenicity blood sample collections to have both Baseline and Day 29 assessments using a window of -7 to +14 days, had no major dosing error, had negative RT-PCR test for influenza and SARS-CoV-2 on Day 1, and had no major protocol deviations or conditions/medications that affected the immune response. |
| Number of Participants With Solicited Local and Systemic Adverse Reactions (ARs) | Up to 7 days after study injection | Solicited ARs (local and systemic) were reported by participants an electronic diary (eDiary). Local ARs included: injection site pain, injection site erythema (redness), injection site swelling/induration (hardness), and axillary (underarm) swelling or tenderness ipsilateral to the side of injection. Systemic ARs included: fever, headache, fatigue, myalgia, arthralgia, nausea/vomiting, and chills. All solicited ARs considered causally related to injection were graded 0-4 (per Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials); lower score indicates lower severity, and a higher score indicates greater severity. The Investigator reviewed whether the solicited AR was also to be recorded as an AE. A Summary of serious AEs (SAEs) and nonserious AEs (Other), regardless of causality, is located in the Reported Adverse Events section. |
| Number of Participants With Unsolicited Adverse Events (AEs) | Up to 28 days after study injection | An AE was defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. Any abnormal laboratory test result (hematology, clinical chemistry, or prothrombin time \[PT\]/partial thromboplastin time \[PTT\]) or other safety assessment (for example, electrocardiogram, radiological scan, vital sign measurement), including one that worsened from baseline and was considered clinically significant in the medical and scientific judgment of the Investigator was recorded as an AE. Number of participants with unsolicited AEs (SAEs and non-serious AEs) up to 28 days post-vaccination are reported in this outcome measure. A Summary of serious AEs (SAEs) and nonserious AEs (Other), regardless of causality, is located in the Reported Adverse Events section. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Geometric Mean Fold-Rise (GMFR) of Antibodies for Influenza, as Measured by HAI Assay | Day 1, Day 29 | Influenza A strains included H1N1 and H3N2 and influenza B strains included Victoria-lineage and Yamagata-lineage. Fold-rise was calculated by dividing post-vaccination results by the baseline value. 95% CI for GMFR was calculated based on the t-distribution of the differences in the log-transformed values between analysis timepoint and baseline, then back transformed to the original scale for presentation. PPIS included all randomized participants who received study intervention, complied with the timing of immunogenicity blood sample collections to have both Baseline and Day 29 assessments using a window of -7 to +14 days, had no major dosing error, had negative RT-PCR test for influenza and SARS-CoV-2 on Day 1, and had no major protocol deviations or conditions/medications that affected the immune response. |
| GMFR of Antibodies for SARS-CoV-2, as Measured by PsVNA | Day 1, Day 29 | SARS-CoV-2 strain included Omicron XBB.1.5 antibody. Fold-rise was calculated by dividing post-vaccination results by the baseline value. 95% CI for GMFR was calculated based on the t-distribution of the differences in the log-transformed values between analysis timepoint and baseline, then back transformed to the original scale for presentation. PPIS included all randomized participants who received study intervention, complied with the timing of immunogenicity blood sample collections to have both Baseline and Day 29 assessments using a window of -7 to +14 days, had no major dosing error, had negative RT-PCR test for influenza and SARS-CoV-2 on Day 1, and had no major protocol deviations or conditions/medications that affected the immune response. |
| GM Level of Antibodies for Influenza, as Measured by Microneutralization (MN) Assay | Day 29 | Influenza A strains included H1N1 and H3N2 and influenza B strains included Victoria-lineage and Yamagata-lineage. The PPIS for MN assay included a subset of randomized participants who received study intervention to be tested for MN, complied with the timing of immunogenicity blood sampling collections to have both Baseline and Day 29 assessments using a window of -7 to +14 days, had no major dosing error, had negative RT-PCR test for influenza and SARS-CoV-2 on Day 1, and had no major protocol deviations or conditions/medications that affected the immune response. |
| GMFR of Antibodies for Influenza, as Measured by MN Assay | Day 1, Day 29 | Influenza A strains included H1N1 and H3N2 and influenza B strains included Victoria-lineage and Yamagata-lineage. Fold-rise was calculated by dividing post-vaccination results by the baseline value. 95% CI for GMFR was calculated based on the t-distribution of the differences in the log-transformed values between analysis timepoint and baseline, then back transformed to the original scale for presentation. The PPIS for MN assay included a subset of randomized participants who received study intervention to be tested for MN, complied with the timing of immunogenicity blood sampling collections to have both Baseline and Day 29 assessments using a window of -7 to +14 days, had no major dosing error, had negative RT-PCR test for influenza and SARS-CoV-2 on Day 1, and had no major protocol deviations or conditions/medications that affected the immune response. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Number of Deaths Related to Control Drug Influenza Vaccine and COVID-19 Vaccine | Day 1 through Day 181 | A death that occurred during the study or that came to the attention of the investigator during the study was reported to the Sponsor, irrespective of its perceived relationship to the study drug. The Investigator assessed the causality by determining whether there was a reasonable possibility that the death was related to the study drug, using the following classifications: Not related: There was not a reasonable possibility of a relationship to the study drug. The temporal sequence of the death relative to administration of the study drug was not reasonable AND/OR the death was more likely explained by a cause other than the study drug. Related: There was a reasonable possibility of a relationship to the study drug. There was evidence of exposure to the study drug. The temporal sequence of the death relative to the administration of the study drug was reasonable. |
| Number of Deaths Related to Study Drug mRNA-1083 and Placebo | Day 1 through Day 181 | A death that occurred during the study or that came to the attention of the investigator during the study was reported to the Sponsor, irrespective of its perceived relationship to the study drug. The Investigator assessed the causality by determining whether there was a reasonable possibility that the death was related to the study drug, using the following classifications: Not related: There was not a reasonable possibility of a relationship to the study drug. The temporal sequence of the death relative to administration of the study drug was not reasonable AND/OR the death was more likely explained by a cause other than the study drug. Related: There was a reasonable possibility of a relationship to the study drug. There was evidence of exposure to the study drug. The temporal sequence of the death relative to the administration of the study drug was reasonable. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Cohort A1: mRNA-1083 and Placebo Participants of age 65 years and older received mRNA-1083 and placebo administered as 2 IM injections (1 in each deltoid muscle) on Day 1. | 2,025 |
| Cohort A2: Influenza Vaccine and COVID-19 Vaccine Participants of age 65 years and older received age recommended influenza vaccine and COVID-19 vaccine administered as 2 IM injections (1 in each deltoid muscle) on Day 1. | 2,012 |
| Cohort B1: mRNA-1083 and Placebo Participants of age 50 to \<65 years received mRNA-1083 and placebo administered as 2 IM injections (1 in each deltoid muscle) on Day 1. | 2,009 |
| Cohort B2: Influenza Vaccine and COVID-19 Vaccine Participants of age 50 to \<65 years received age recommended influenza vaccine and COVID-19 vaccine administered as 2 IM injections (1 in each deltoid muscle) on Day 1. | 2,015 |
| Total | 8,061 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Death | 2 | 1 | 2 | 2 |
| Overall Study | Lost to Follow-up | 27 | 18 | 36 | 31 |
| Overall Study | Other Than Specified | 7 | 3 | 11 | 6 |
| Overall Study | Physician Decision | 0 | 1 | 0 | 3 |
| Overall Study | Protocol Violation | 1 | 1 | 2 | 1 |
| Overall Study | Withdrawal by Subject | 14 | 11 | 14 | 15 |
Baseline characteristics
| Characteristic | Total | Cohort B2: Influenza Vaccine and COVID-19 Vaccine | Cohort B1: mRNA-1083 and Placebo | Cohort A2: Influenza Vaccine and COVID-19 Vaccine | Cohort A1: mRNA-1083 and Placebo |
|---|---|---|---|---|---|
| Age, Continuous | 64.1 years STANDARD_DEVIATION 8.06 | 57.4 years STANDARD_DEVIATION 4.21 | 57.5 years STANDARD_DEVIATION 4.25 | 70.7 years STANDARD_DEVIATION 4.7 | 70.9 years STANDARD_DEVIATION 4.96 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1333 Participants | 381 Participants | 393 Participants | 275 Participants | 284 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 6600 Participants | 1613 Participants | 1591 Participants | 1695 Participants | 1701 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 128 Participants | 21 Participants | 25 Participants | 42 Participants | 40 Participants |
| Race/Ethnicity, Customized Race American Indian or Alaska Native | 46 Participants | 13 Participants | 12 Participants | 12 Participants | 9 Participants |
| Race/Ethnicity, Customized Race Asian | 153 Participants | 39 Participants | 52 Participants | 37 Participants | 25 Participants |
| Race/Ethnicity, Customized Race Black or African American | 1820 Participants | 555 Participants | 522 Participants | 370 Participants | 373 Participants |
| Race/Ethnicity, Customized Race Multiple | 58 Participants | 21 Participants | 19 Participants | 4 Participants | 14 Participants |
| Race/Ethnicity, Customized Race Native Hawaiian or Other Pacific Islander | 13 Participants | 5 Participants | 3 Participants | 4 Participants | 1 Participants |
| Race/Ethnicity, Customized Race Other | 19 Participants | 8 Participants | 4 Participants | 3 Participants | 4 Participants |
| Race/Ethnicity, Customized Race Unknown/Not Reported | 62 Participants | 24 Participants | 15 Participants | 12 Participants | 11 Participants |
| Race/Ethnicity, Customized Race White | 5890 Participants | 1350 Participants | 1382 Participants | 1570 Participants | 1588 Participants |
| Sex: Female, Male Female | 4550 Participants | 1201 Participants | 1165 Participants | 1100 Participants | 1084 Participants |
| Sex: Female, Male Male | 3511 Participants | 814 Participants | 844 Participants | 912 Participants | 941 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 2 / 2,025 | 1 / 2,012 | 2 / 2,009 | 2 / 2,015 |
| other Total, other adverse events | 0 / 2,011 | 0 / 2,006 | 0 / 1,993 | 0 / 2,005 |
| serious Total, serious adverse events | 71 / 2,011 | 52 / 2,006 | 29 / 1,993 | 27 / 2,005 |
Outcome results
Primary
Geometric Mean (GM) Level of Antibodies for Influenza, as Measured by Hemagglutination Inhibition (HAI) Assay
Influenza A strains included H1N1 and H3N2 and influenza B strains included Victoria-lineage and Yamagata-lineage. The Per Protocol Immunogenicity Set (PPIS) included all randomized participants who received study intervention, complied with the timing of immunogenicity blood sample collections to have both Baseline and Day 29 assessments using a window of -7 to +14 days, had no major dosing error, had negative reverse transcription polymerase chain reaction (RT-PCR) test for influenza and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on Day 1, and had no major protocol deviations or conditions/medications that affected the immune response.
Time frame: Day 29
Population: The PPIS. Overall number of participants analyzed = participants evaluable for this outcome measure. Number Analyzed = participants evaluable for specified categories.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Cohort A1: mRNA-1083 and Placebo | Geometric Mean (GM) Level of Antibodies for Influenza, as Measured by Hemagglutination Inhibition (HAI) Assay | Influenza A H1N1 Antibody | 120.5 titer |
| Cohort A1: mRNA-1083 and Placebo | Geometric Mean (GM) Level of Antibodies for Influenza, as Measured by Hemagglutination Inhibition (HAI) Assay | Influenza A H3N2 Antibody | 114.7 titer |
| Cohort A1: mRNA-1083 and Placebo | Geometric Mean (GM) Level of Antibodies for Influenza, as Measured by Hemagglutination Inhibition (HAI) Assay | Influenza B Victoria-lineage Antibody | 245.3 titer |
| Cohort A1: mRNA-1083 and Placebo | Geometric Mean (GM) Level of Antibodies for Influenza, as Measured by Hemagglutination Inhibition (HAI) Assay | Influenza B Yamagata-lineage Antibody | 93.3 titer |
| Cohort A2: Influenza Vaccine and COVID-19 Vaccine | Geometric Mean (GM) Level of Antibodies for Influenza, as Measured by Hemagglutination Inhibition (HAI) Assay | Influenza A H3N2 Antibody | 107.9 titer |
| Cohort A2: Influenza Vaccine and COVID-19 Vaccine | Geometric Mean (GM) Level of Antibodies for Influenza, as Measured by Hemagglutination Inhibition (HAI) Assay | Influenza B Victoria-lineage Antibody | 219.4 titer |
| Cohort A2: Influenza Vaccine and COVID-19 Vaccine | Geometric Mean (GM) Level of Antibodies for Influenza, as Measured by Hemagglutination Inhibition (HAI) Assay | Influenza B Yamagata-lineage Antibody | 92.6 titer |
| Cohort A2: Influenza Vaccine and COVID-19 Vaccine | Geometric Mean (GM) Level of Antibodies for Influenza, as Measured by Hemagglutination Inhibition (HAI) Assay | Influenza A H1N1 Antibody | 104.3 titer |
| Cohort B1: mRNA-1083 and Placebo | Geometric Mean (GM) Level of Antibodies for Influenza, as Measured by Hemagglutination Inhibition (HAI) Assay | Influenza B Victoria-lineage Antibody | 224.9 titer |
| Cohort B1: mRNA-1083 and Placebo | Geometric Mean (GM) Level of Antibodies for Influenza, as Measured by Hemagglutination Inhibition (HAI) Assay | Influenza A H3N2 Antibody | 111.5 titer |
| Cohort B1: mRNA-1083 and Placebo | Geometric Mean (GM) Level of Antibodies for Influenza, as Measured by Hemagglutination Inhibition (HAI) Assay | Influenza B Yamagata-lineage Antibody | 101.7 titer |
| Cohort B1: mRNA-1083 and Placebo | Geometric Mean (GM) Level of Antibodies for Influenza, as Measured by Hemagglutination Inhibition (HAI) Assay | Influenza A H1N1 Antibody | 137.7 titer |
| Cohort B2: Influenza Vaccine and COVID-19 Vaccine | Geometric Mean (GM) Level of Antibodies for Influenza, as Measured by Hemagglutination Inhibition (HAI) Assay | Influenza B Yamagata-lineage Antibody | 88.1 titer |
| Cohort B2: Influenza Vaccine and COVID-19 Vaccine | Geometric Mean (GM) Level of Antibodies for Influenza, as Measured by Hemagglutination Inhibition (HAI) Assay | Influenza A H3N2 Antibody | 80.8 titer |
| Cohort B2: Influenza Vaccine and COVID-19 Vaccine | Geometric Mean (GM) Level of Antibodies for Influenza, as Measured by Hemagglutination Inhibition (HAI) Assay | Influenza A H1N1 Antibody | 97.3 titer |
| Cohort B2: Influenza Vaccine and COVID-19 Vaccine | Geometric Mean (GM) Level of Antibodies for Influenza, as Measured by Hemagglutination Inhibition (HAI) Assay | Influenza B Victoria-lineage Antibody | 185.0 titer |
Comparison: GMR (Cohort A1 vs Cohort A2) for Influenza A H1N1 Antibody97.5% CI: [1.086, 1.229]
Comparison: GMR (Cohort A1 vs Cohort A2) for Influenza A H1N1 Antibody95% CI: [1.094, 1.22]
Comparison: GMR (Cohort A1 vs Cohort A2) for Influenza A H3N2 Antibody97.5% CI: [0.999, 1.13]
Comparison: GMR (Cohort A1 vs Cohort A2) for Influenza A H3N2 Antibody95% CI: [1.007, 1.122]
Comparison: GMR (Cohort B1 vs Cohort B2) for Influenza A H1N1 Antibody97.5% CI: [1.322, 1.513]
Comparison: GMR (Cohort B1 vs Cohort B2) for Influenza A H1N1 Antibody95% CI: [1.333, 1.5]
Comparison: GMR (Cohort B1 vs Cohort B2) for Influenza A H3N2 Antibody97.5% CI: [1.3, 1.465]
Comparison: GMR (Cohort B1 vs Cohort B2) for Influenza A H3N2 Antibody95% CI: [1.31, 1.454]
Comparison: GMR (Cohort A1 vs Cohort A2) for Influenza B Victoria-lineage Antibody97.5% CI: [1.063, 1.175]
Comparison: GMR (Cohort A1 vs Cohort A2) for Influenza B Victoria-lineage Antibody95% CI: [1.07, 1.167]
Comparison: GMR (Cohort A1 vs Cohort A2) for Influenza B Yamagata-lineage Antibody97.5% CI: [0.969, 1.047]
Comparison: GMR (Cohort A1 vs Cohort A2) for Influenza B Yamagata-lineage Antibody95% CI: [0.973, 1.042]
Comparison: GMR (Cohort B1 vs Cohort B2) for Influenza B Victoria-lineage Antibody97.5% CI: [1.156, 1.278]
Comparison: GMR (Cohort B1 vs Cohort B2) for Influenza B Victoria-lineage Antibody95% CI: [1.163, 1.27]
Comparison: GMR (Cohort B1 vs Cohort B2) for Influenza B Yamagata-lineage Antibody97.5% CI: [1.109, 1.201]
Comparison: GMR (Cohort B1 vs Cohort B2) for Influenza B Yamagata-lineage Antibody95% CI: [1.115, 1.195]
Primary
GM Level of Antibodies for SARS-CoV-2, as Measured by Pseudovirus Neutralization Assay (PsVNA)
SARS-CoV-2 strain included Omicron XBB.1.5 antibody. The PPIS included all randomized participants who received study intervention, complied with the timing of immunogenicity blood sample collections to have both Baseline and Day 29 assessments using a window of -7 to +14 days, had no major dosing error, had negative RT-PCR test for influenza and SARS-CoV-2 on Day 1, and had no major protocol deviations or conditions/medications that affected the immune response.
Time frame: Day 29
Population: The PPIS. Overall number of participants analyzed = participants evaluable for this outcome measure.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Cohort A1: mRNA-1083 and Placebo | GM Level of Antibodies for SARS-CoV-2, as Measured by Pseudovirus Neutralization Assay (PsVNA) | 1396.7 titer |
| Cohort A2: Influenza Vaccine and COVID-19 Vaccine | GM Level of Antibodies for SARS-CoV-2, as Measured by Pseudovirus Neutralization Assay (PsVNA) | 851.1 titer |
| Cohort B1: mRNA-1083 and Placebo | GM Level of Antibodies for SARS-CoV-2, as Measured by Pseudovirus Neutralization Assay (PsVNA) | 1551.6 titer |
| Cohort B2: Influenza Vaccine and COVID-19 Vaccine | GM Level of Antibodies for SARS-CoV-2, as Measured by Pseudovirus Neutralization Assay (PsVNA) | 1186.1 titer |
Comparison: GMR (Cohort A1 vs Cohort A2) for SARS-CoV-2 Antibody95% CI: [1.526, 1.765]
Comparison: GMR (Cohort A1 vs Cohort A2) for SARS-CoV-2 Antibody97.5% CI: [1.51, 1.783]
Comparison: GMR (Cohort B1 vs Cohort B2) for SARS-CoV-2 Antibody95% CI: [1.219, 1.404]
Comparison: GMR (Cohort B1 vs Cohort B2) for SARS-CoV-2 Antibody97.5% CI: [1.207, 1.418]
Primary
Influenza: Percentage of Participants With Seroconversion, as Measured by HAI Assay
Influenza A strains included H1N1 and H3N2 and influenza B strains included Victoria-lineage and Yamagata-lineage. Seroconversion was defined as a Day 29 postinjection level ≥1:40 if Baseline was \<1:10 or a 4-fold or greater rise if Baseline was ≥1:10 in anti-hemagglutinin (HA) antibodies measured by HAI assay. The PPIS included all randomized participants who received study intervention, complied with the timing of immunogenicity blood sample collections to have both Baseline and Day 29 assessments using a window of -7 to +14 days, had no major dosing error, had negative RT-PCR test for influenza and SARS-CoV-2 on Day 1, and had no major protocol deviations or conditions/medications that affected the immune response.
Time frame: Baseline to Day 29
Population: The PPIS. Overall number of participants analyzed = participants evaluable for this outcome measure. Number Analyzed = participants evaluable for specified categories.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cohort A1: mRNA-1083 and Placebo | Influenza: Percentage of Participants With Seroconversion, as Measured by HAI Assay | Influenza B Yamagata-lineage Antibody | 8.8 percentage of participants |
| Cohort A1: mRNA-1083 and Placebo | Influenza: Percentage of Participants With Seroconversion, as Measured by HAI Assay | Influenza A H3N2 Antibody | 38.7 percentage of participants |
| Cohort A1: mRNA-1083 and Placebo | Influenza: Percentage of Participants With Seroconversion, as Measured by HAI Assay | Influenza B Victoria-lineage Antibody | 23.9 percentage of participants |
| Cohort A1: mRNA-1083 and Placebo | Influenza: Percentage of Participants With Seroconversion, as Measured by HAI Assay | Influenza A H1N1 Antibody | 36.4 percentage of participants |
| Cohort A2: Influenza Vaccine and COVID-19 Vaccine | Influenza: Percentage of Participants With Seroconversion, as Measured by HAI Assay | Influenza B Victoria-lineage Antibody | 19.4 percentage of participants |
| Cohort A2: Influenza Vaccine and COVID-19 Vaccine | Influenza: Percentage of Participants With Seroconversion, as Measured by HAI Assay | Influenza A H1N1 Antibody | 31.1 percentage of participants |
| Cohort A2: Influenza Vaccine and COVID-19 Vaccine | Influenza: Percentage of Participants With Seroconversion, as Measured by HAI Assay | Influenza A H3N2 Antibody | 34.6 percentage of participants |
| Cohort A2: Influenza Vaccine and COVID-19 Vaccine | Influenza: Percentage of Participants With Seroconversion, as Measured by HAI Assay | Influenza B Yamagata-lineage Antibody | 10.2 percentage of participants |
| Cohort B1: mRNA-1083 and Placebo | Influenza: Percentage of Participants With Seroconversion, as Measured by HAI Assay | Influenza A H1N1 Antibody | 50.6 percentage of participants |
| Cohort B1: mRNA-1083 and Placebo | Influenza: Percentage of Participants With Seroconversion, as Measured by HAI Assay | Influenza A H3N2 Antibody | 41.9 percentage of participants |
| Cohort B1: mRNA-1083 and Placebo | Influenza: Percentage of Participants With Seroconversion, as Measured by HAI Assay | Influenza B Victoria-lineage Antibody | 25.8 percentage of participants |
| Cohort B1: mRNA-1083 and Placebo | Influenza: Percentage of Participants With Seroconversion, as Measured by HAI Assay | Influenza B Yamagata-lineage Antibody | 13.0 percentage of participants |
| Cohort B2: Influenza Vaccine and COVID-19 Vaccine | Influenza: Percentage of Participants With Seroconversion, as Measured by HAI Assay | Influenza A H1N1 Antibody | 32.7 percentage of participants |
| Cohort B2: Influenza Vaccine and COVID-19 Vaccine | Influenza: Percentage of Participants With Seroconversion, as Measured by HAI Assay | Influenza B Yamagata-lineage Antibody | 10.3 percentage of participants |
| Cohort B2: Influenza Vaccine and COVID-19 Vaccine | Influenza: Percentage of Participants With Seroconversion, as Measured by HAI Assay | Influenza A H3N2 Antibody | 27.4 percentage of participants |
| Cohort B2: Influenza Vaccine and COVID-19 Vaccine | Influenza: Percentage of Participants With Seroconversion, as Measured by HAI Assay | Influenza B Victoria-lineage Antibody | 17.2 percentage of participants |
Comparison: Percentage Difference (Cohort A1 vs Cohort A2) for Influenza A H1N1 Antibody95% CI: [2.4, 8.4]
Comparison: Percentage Difference (Cohort A1 vs Cohort A2) for Influenza A H1N1 Antibody97.5% CI: [1.9, 8.8]
Comparison: Percentage Difference (Cohort A1 vs Cohort A2) for Influenza A H3N2 Antibody95% CI: [1, 7.1]
Comparison: Percentage Difference (Cohort A1 vs Cohort A2) for Influenza A H3N2 Antibody97.5% CI: [0.5, 7.6]
Comparison: Percentage Difference (Cohort A1 vs Cohort A2) for Victoria-lineage Antibody95% CI: [1.9, 7.2]
Comparison: Percentage Difference (Cohort A1 vs Cohort A2) for Victoria-lineage Antibody95% CI: [1.5, 7.5]
Comparison: Percentage Difference (Cohort A1 vs Cohort A2) for Yamagata-lineage Antibody95% CI: [-3.3, 0.4]
Comparison: Percentage Difference (Cohort A1 vs Cohort A2) for Yamagata-lineage Antibody97.5% CI: [-3.6, 0.7]
Comparison: Percentage Difference (Cohort B1 vs Cohort B2) for Influenza A H1N1 Antibody95% CI: [14.8, 21]
Comparison: Percentage Difference (Cohort B1 vs Cohort B2) for Influenza A H1N1 Antibody97.5% CI: [14.3, 21.4]
Comparison: Percentage Difference (Cohort B1 vs Cohort B2) for Influenza A H3N2 Antibody95% CI: [11.6, 17.6]
Comparison: Percentage Difference (Cohort B1 vs Cohort B2) for Influenza A H3N2 Antibody97.5% CI: [11.1, 18]
Comparison: Percentage Difference (Cohort B1 vs Cohort B2) for Victoria-lineage Antibody95% CI: [6, 11.2]
Comparison: Percentage Difference (Cohort B1 vs Cohort B2) for Victoria-lineage Antibody97.5% CI: [5.6, 11.6]
Comparison: Percentage Difference (Cohort B1 vs Cohort B2) for Yamagata-lineage Antibody95% CI: [0.6, 4.7]
Comparison: Percentage Difference (Cohort B1 vs Cohort B2) for Yamagata-lineage Antibody97.5% CI: [0.3, 5]
Primary
Number of Participants With Medically Attended Adverse Events (MAAEs), Adverse Events of Special Interest (AESIs), Serious Adverse Events (SAEs), and AEs Leading to Discontinuation
An SAE was defined as any AE that resulted in death, was 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. AESIs included thrombocytopenia, new onset of or worsening of the protocol specified neurologic diseases, anaphylaxis, and myocarditis/pericarditis. An MAAE is an AE that lead to an unscheduled visit to an healthcare practitioner. This included visits to a study site for unscheduled assessments (for example, abnormal laboratory follow-up, and/or COVID-19 and visits to healthcare practitioners external to the study site. Number of participants with SAEs, AESIs, MAAEs, and AEs leading to discontinuation up to the end of study (Day 181) are reported in this outcome measure. A Summary of serious AEs (SAEs) and nonserious AEs (Other), regardless of causality, is located in the Reported Adverse Events section.
Time frame: Day 1 through Day 181
Population: The Safety Set included all participants who were randomized and received any study vaccination.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cohort A1: mRNA-1083 and Placebo | Number of Participants With Medically Attended Adverse Events (MAAEs), Adverse Events of Special Interest (AESIs), Serious Adverse Events (SAEs), and AEs Leading to Discontinuation | SAEs | 70 Participants |
| Cohort A1: mRNA-1083 and Placebo | Number of Participants With Medically Attended Adverse Events (MAAEs), Adverse Events of Special Interest (AESIs), Serious Adverse Events (SAEs), and AEs Leading to Discontinuation | AESIs | 18 Participants |
| Cohort A1: mRNA-1083 and Placebo | Number of Participants With Medically Attended Adverse Events (MAAEs), Adverse Events of Special Interest (AESIs), Serious Adverse Events (SAEs), and AEs Leading to Discontinuation | MAAEs | 426 Participants |
| Cohort A1: mRNA-1083 and Placebo | Number of Participants With Medically Attended Adverse Events (MAAEs), Adverse Events of Special Interest (AESIs), Serious Adverse Events (SAEs), and AEs Leading to Discontinuation | AEs Leading to Discontinuation | 0 Participants |
| Cohort A2: Influenza Vaccine and COVID-19 Vaccine | Number of Participants With Medically Attended Adverse Events (MAAEs), Adverse Events of Special Interest (AESIs), Serious Adverse Events (SAEs), and AEs Leading to Discontinuation | SAEs | 52 Participants |
| Cohort A2: Influenza Vaccine and COVID-19 Vaccine | Number of Participants With Medically Attended Adverse Events (MAAEs), Adverse Events of Special Interest (AESIs), Serious Adverse Events (SAEs), and AEs Leading to Discontinuation | MAAEs | 428 Participants |
| Cohort A2: Influenza Vaccine and COVID-19 Vaccine | Number of Participants With Medically Attended Adverse Events (MAAEs), Adverse Events of Special Interest (AESIs), Serious Adverse Events (SAEs), and AEs Leading to Discontinuation | AEs Leading to Discontinuation | 0 Participants |
| Cohort A2: Influenza Vaccine and COVID-19 Vaccine | Number of Participants With Medically Attended Adverse Events (MAAEs), Adverse Events of Special Interest (AESIs), Serious Adverse Events (SAEs), and AEs Leading to Discontinuation | AESIs | 13 Participants |
| Cohort B1: mRNA-1083 and Placebo | Number of Participants With Medically Attended Adverse Events (MAAEs), Adverse Events of Special Interest (AESIs), Serious Adverse Events (SAEs), and AEs Leading to Discontinuation | MAAEs | 301 Participants |
| Cohort B1: mRNA-1083 and Placebo | Number of Participants With Medically Attended Adverse Events (MAAEs), Adverse Events of Special Interest (AESIs), Serious Adverse Events (SAEs), and AEs Leading to Discontinuation | AEs Leading to Discontinuation | 1 Participants |
| Cohort B1: mRNA-1083 and Placebo | Number of Participants With Medically Attended Adverse Events (MAAEs), Adverse Events of Special Interest (AESIs), Serious Adverse Events (SAEs), and AEs Leading to Discontinuation | SAEs | 29 Participants |
| Cohort B1: mRNA-1083 and Placebo | Number of Participants With Medically Attended Adverse Events (MAAEs), Adverse Events of Special Interest (AESIs), Serious Adverse Events (SAEs), and AEs Leading to Discontinuation | AESIs | 4 Participants |
| Cohort B2: Influenza Vaccine and COVID-19 Vaccine | Number of Participants With Medically Attended Adverse Events (MAAEs), Adverse Events of Special Interest (AESIs), Serious Adverse Events (SAEs), and AEs Leading to Discontinuation | AEs Leading to Discontinuation | 0 Participants |
| Cohort B2: Influenza Vaccine and COVID-19 Vaccine | Number of Participants With Medically Attended Adverse Events (MAAEs), Adverse Events of Special Interest (AESIs), Serious Adverse Events (SAEs), and AEs Leading to Discontinuation | AESIs | 9 Participants |
| Cohort B2: Influenza Vaccine and COVID-19 Vaccine | Number of Participants With Medically Attended Adverse Events (MAAEs), Adverse Events of Special Interest (AESIs), Serious Adverse Events (SAEs), and AEs Leading to Discontinuation | SAEs | 27 Participants |
| Cohort B2: Influenza Vaccine and COVID-19 Vaccine | Number of Participants With Medically Attended Adverse Events (MAAEs), Adverse Events of Special Interest (AESIs), Serious Adverse Events (SAEs), and AEs Leading to Discontinuation | MAAEs | 304 Participants |
Primary
Number of Participants With Solicited Local and Systemic Adverse Reactions (ARs)
Solicited ARs (local and systemic) were reported by participants an electronic diary (eDiary). Local ARs included: injection site pain, injection site erythema (redness), injection site swelling/induration (hardness), and axillary (underarm) swelling or tenderness ipsilateral to the side of injection. Systemic ARs included: fever, headache, fatigue, myalgia, arthralgia, nausea/vomiting, and chills. All solicited ARs considered causally related to injection were graded 0-4 (per Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials); lower score indicates lower severity, and a higher score indicates greater severity. The Investigator reviewed whether the solicited AR was also to be recorded as an AE. A Summary of serious AEs (SAEs) and nonserious AEs (Other), regardless of causality, is located in the Reported Adverse Events section.
Time frame: Up to 7 days after study injection
Population: The Solicited Safety Set included all randomized participants who received any study vaccination and contributed any solicited AR data.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cohort A1: mRNA-1083 and Placebo | Number of Participants With Solicited Local and Systemic Adverse Reactions (ARs) | Any | 1681 Participants |
| Cohort A1: mRNA-1083 and Placebo | Number of Participants With Solicited Local and Systemic Adverse Reactions (ARs) | Grade 3 or Grade 4 | 183 Participants |
| Cohort A2: Influenza Vaccine and COVID-19 Vaccine | Number of Participants With Solicited Local and Systemic Adverse Reactions (ARs) | Any | 1565 Participants |
| Cohort A2: Influenza Vaccine and COVID-19 Vaccine | Number of Participants With Solicited Local and Systemic Adverse Reactions (ARs) | Grade 3 or Grade 4 | 84 Participants |
| Cohort B1: mRNA-1083 and Placebo | Number of Participants With Solicited Local and Systemic Adverse Reactions (ARs) | Any | 1698 Participants |
| Cohort B1: mRNA-1083 and Placebo | Number of Participants With Solicited Local and Systemic Adverse Reactions (ARs) | Grade 3 or Grade 4 | 246 Participants |
| Cohort B2: Influenza Vaccine and COVID-19 Vaccine | Number of Participants With Solicited Local and Systemic Adverse Reactions (ARs) | Grade 3 or Grade 4 | 127 Participants |
| Cohort B2: Influenza Vaccine and COVID-19 Vaccine | Number of Participants With Solicited Local and Systemic Adverse Reactions (ARs) | Any | 1640 Participants |
Primary
Number of Participants With Unsolicited Adverse Events (AEs)
An AE was defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. Any abnormal laboratory test result (hematology, clinical chemistry, or prothrombin time \[PT\]/partial thromboplastin time \[PTT\]) or other safety assessment (for example, electrocardiogram, radiological scan, vital sign measurement), including one that worsened from baseline and was considered clinically significant in the medical and scientific judgment of the Investigator was recorded as an AE. Number of participants with unsolicited AEs (SAEs and non-serious AEs) up to 28 days post-vaccination are reported in this outcome measure. A Summary of serious AEs (SAEs) and nonserious AEs (Other), regardless of causality, is located in the Reported Adverse Events section.
Time frame: Up to 28 days after study injection
Population: The Safety Set included all participants who were randomized and received any study vaccination.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cohort A1: mRNA-1083 and Placebo | Number of Participants With Unsolicited Adverse Events (AEs) | 239 Participants |
| Cohort A2: Influenza Vaccine and COVID-19 Vaccine | Number of Participants With Unsolicited Adverse Events (AEs) | 250 Participants |
| Cohort B1: mRNA-1083 and Placebo | Number of Participants With Unsolicited Adverse Events (AEs) | 195 Participants |
| Cohort B2: Influenza Vaccine and COVID-19 Vaccine | Number of Participants With Unsolicited Adverse Events (AEs) | 191 Participants |
Primary
SARS-CoV-2: Percentage of Participants With Seroresponse, as Measured by PsVNA
SARS-CoV-2 strain included Omicron XBB.1.5 antibody. Seroresponse was defined as a Day 29 postinjection level ≥4-fold rise if Baseline was ≥lower limit of quantification (LLOQ) or ≥4×LLOQ if Baseline value was \<LLOQ in the nAb values measured by PsVNA. LLOQ was 38 arbitrary unit (AU)/milliliter (mL). The PPIS included all randomized participants who received study intervention, complied with the timing of immunogenicity blood sample collections to have both Baseline and Day 29 assessments using a window of -7 to +14 days, had no major dosing error, had negative RT-PCR test for influenza and SARS-CoV-2 on Day 1, and had no major protocol deviations or conditions/medications that affected the immune response.
Time frame: Baseline to Day 29
Population: The PPIS. Overall number of participants analyzed = participants evaluable for this outcome measure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort A1: mRNA-1083 and Placebo | SARS-CoV-2: Percentage of Participants With Seroresponse, as Measured by PsVNA | 82.3 percentage of participants |
| Cohort A2: Influenza Vaccine and COVID-19 Vaccine | SARS-CoV-2: Percentage of Participants With Seroresponse, as Measured by PsVNA | 69.6 percentage of participants |
| Cohort B1: mRNA-1083 and Placebo | SARS-CoV-2: Percentage of Participants With Seroresponse, as Measured by PsVNA | 84.6 percentage of participants |
| Cohort B2: Influenza Vaccine and COVID-19 Vaccine | SARS-CoV-2: Percentage of Participants With Seroresponse, as Measured by PsVNA | 76.5 percentage of participants |
Comparison: Percentage Difference (Cohort A1 vs Cohort A2) for SARS-CoV-2 Antibody95% CI: [10, 15.5]
Comparison: Percentage Difference (Cohort A1 vs Cohort A2) for SARS-CoV-2 Antibody97.5% CI: [9.6, 15.9]
Comparison: Percentage Difference (Cohort B1 vs Cohort B2) for SARS-CoV-2 Antibody95% CI: [5.5, 10.6]
Comparison: Percentage Difference (Cohort B1 vs Cohort B2) for SARS-CoV-2 Antibody97.5% CI: [5.2, 11]
Secondary
Geometric Mean Fold-Rise (GMFR) of Antibodies for Influenza, as Measured by HAI Assay
Influenza A strains included H1N1 and H3N2 and influenza B strains included Victoria-lineage and Yamagata-lineage. Fold-rise was calculated by dividing post-vaccination results by the baseline value. 95% CI for GMFR was calculated based on the t-distribution of the differences in the log-transformed values between analysis timepoint and baseline, then back transformed to the original scale for presentation. PPIS included all randomized participants who received study intervention, complied with the timing of immunogenicity blood sample collections to have both Baseline and Day 29 assessments using a window of -7 to +14 days, had no major dosing error, had negative RT-PCR test for influenza and SARS-CoV-2 on Day 1, and had no major protocol deviations or conditions/medications that affected the immune response.
Time frame: Day 1, Day 29
Population: The PPIS. Overall number of participants analyzed = participants evaluable for this outcome measure. Number Analyzed = participants evaluable for specified categories.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Cohort A1: mRNA-1083 and Placebo | Geometric Mean Fold-Rise (GMFR) of Antibodies for Influenza, as Measured by HAI Assay | Influenza A H1N1 Antibody | 2.70 ratio |
| Cohort A1: mRNA-1083 and Placebo | Geometric Mean Fold-Rise (GMFR) of Antibodies for Influenza, as Measured by HAI Assay | Influenza A H3N2 Antibody | 2.78 ratio |
| Cohort A1: mRNA-1083 and Placebo | Geometric Mean Fold-Rise (GMFR) of Antibodies for Influenza, as Measured by HAI Assay | Influenza B Victoria-lineage | 2.05 ratio |
| Cohort A1: mRNA-1083 and Placebo | Geometric Mean Fold-Rise (GMFR) of Antibodies for Influenza, as Measured by HAI Assay | Influenza B Yamagata-lineage | 1.52 ratio |
| Cohort A2: Influenza Vaccine and COVID-19 Vaccine | Geometric Mean Fold-Rise (GMFR) of Antibodies for Influenza, as Measured by HAI Assay | Influenza A H3N2 Antibody | 2.59 ratio |
| Cohort A2: Influenza Vaccine and COVID-19 Vaccine | Geometric Mean Fold-Rise (GMFR) of Antibodies for Influenza, as Measured by HAI Assay | Influenza B Yamagata-lineage | 1.52 ratio |
| Cohort A2: Influenza Vaccine and COVID-19 Vaccine | Geometric Mean Fold-Rise (GMFR) of Antibodies for Influenza, as Measured by HAI Assay | Influenza A H1N1 Antibody | 2.36 ratio |
| Cohort A2: Influenza Vaccine and COVID-19 Vaccine | Geometric Mean Fold-Rise (GMFR) of Antibodies for Influenza, as Measured by HAI Assay | Influenza B Victoria-lineage | 1.84 ratio |
| Cohort B1: mRNA-1083 and Placebo | Geometric Mean Fold-Rise (GMFR) of Antibodies for Influenza, as Measured by HAI Assay | Influenza B Victoria-lineage | 2.13 ratio |
| Cohort B1: mRNA-1083 and Placebo | Geometric Mean Fold-Rise (GMFR) of Antibodies for Influenza, as Measured by HAI Assay | Influenza B Yamagata-lineage | 1.71 ratio |
| Cohort B1: mRNA-1083 and Placebo | Geometric Mean Fold-Rise (GMFR) of Antibodies for Influenza, as Measured by HAI Assay | Influenza A H1N1 Antibody | 3.70 ratio |
| Cohort B1: mRNA-1083 and Placebo | Geometric Mean Fold-Rise (GMFR) of Antibodies for Influenza, as Measured by HAI Assay | Influenza A H3N2 Antibody | 3.07 ratio |
| Cohort B2: Influenza Vaccine and COVID-19 Vaccine | Geometric Mean Fold-Rise (GMFR) of Antibodies for Influenza, as Measured by HAI Assay | Influenza B Yamagata-lineage | 1.48 ratio |
| Cohort B2: Influenza Vaccine and COVID-19 Vaccine | Geometric Mean Fold-Rise (GMFR) of Antibodies for Influenza, as Measured by HAI Assay | Influenza A H1N1 Antibody | 2.54 ratio |
| Cohort B2: Influenza Vaccine and COVID-19 Vaccine | Geometric Mean Fold-Rise (GMFR) of Antibodies for Influenza, as Measured by HAI Assay | Influenza A H3N2 Antibody | 2.22 ratio |
| Cohort B2: Influenza Vaccine and COVID-19 Vaccine | Geometric Mean Fold-Rise (GMFR) of Antibodies for Influenza, as Measured by HAI Assay | Influenza B Victoria-lineage | 1.75 ratio |
Secondary
GMFR of Antibodies for Influenza, as Measured by MN Assay
Influenza A strains included H1N1 and H3N2 and influenza B strains included Victoria-lineage and Yamagata-lineage. Fold-rise was calculated by dividing post-vaccination results by the baseline value. 95% CI for GMFR was calculated based on the t-distribution of the differences in the log-transformed values between analysis timepoint and baseline, then back transformed to the original scale for presentation. The PPIS for MN assay included a subset of randomized participants who received study intervention to be tested for MN, complied with the timing of immunogenicity blood sampling collections to have both Baseline and Day 29 assessments using a window of -7 to +14 days, had no major dosing error, had negative RT-PCR test for influenza and SARS-CoV-2 on Day 1, and had no major protocol deviations or conditions/medications that affected the immune response.
Time frame: Day 1, Day 29
Population: The PPIS for MN assay.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Cohort A1: mRNA-1083 and Placebo | GMFR of Antibodies for Influenza, as Measured by MN Assay | Influenza A H1N1 Antibody | 4.89 ratio |
| Cohort A1: mRNA-1083 and Placebo | GMFR of Antibodies for Influenza, as Measured by MN Assay | Influenza A H3N2 Antibody | 2.88 ratio |
| Cohort A1: mRNA-1083 and Placebo | GMFR of Antibodies for Influenza, as Measured by MN Assay | Influenza B Yamagata-lineage | 2.98 ratio |
| Cohort A1: mRNA-1083 and Placebo | GMFR of Antibodies for Influenza, as Measured by MN Assay | Influenza B Victoria-lineage | 3.22 ratio |
| Cohort A2: Influenza Vaccine and COVID-19 Vaccine | GMFR of Antibodies for Influenza, as Measured by MN Assay | Influenza A H3N2 Antibody | 2.46 ratio |
| Cohort A2: Influenza Vaccine and COVID-19 Vaccine | GMFR of Antibodies for Influenza, as Measured by MN Assay | Influenza B Yamagata-lineage | 3.38 ratio |
| Cohort A2: Influenza Vaccine and COVID-19 Vaccine | GMFR of Antibodies for Influenza, as Measured by MN Assay | Influenza A H1N1 Antibody | 4.68 ratio |
| Cohort A2: Influenza Vaccine and COVID-19 Vaccine | GMFR of Antibodies for Influenza, as Measured by MN Assay | Influenza B Victoria-lineage | 3.02 ratio |
| Cohort B1: mRNA-1083 and Placebo | GMFR of Antibodies for Influenza, as Measured by MN Assay | Influenza B Victoria-lineage | 3.87 ratio |
| Cohort B1: mRNA-1083 and Placebo | GMFR of Antibodies for Influenza, as Measured by MN Assay | Influenza A H1N1 Antibody | 8.74 ratio |
| Cohort B1: mRNA-1083 and Placebo | GMFR of Antibodies for Influenza, as Measured by MN Assay | Influenza B Yamagata-lineage | 3.66 ratio |
| Cohort B1: mRNA-1083 and Placebo | GMFR of Antibodies for Influenza, as Measured by MN Assay | Influenza A H3N2 Antibody | 3.33 ratio |
| Cohort B2: Influenza Vaccine and COVID-19 Vaccine | GMFR of Antibodies for Influenza, as Measured by MN Assay | Influenza B Yamagata-lineage | 3.42 ratio |
| Cohort B2: Influenza Vaccine and COVID-19 Vaccine | GMFR of Antibodies for Influenza, as Measured by MN Assay | Influenza A H1N1 Antibody | 5.14 ratio |
| Cohort B2: Influenza Vaccine and COVID-19 Vaccine | GMFR of Antibodies for Influenza, as Measured by MN Assay | Influenza A H3N2 Antibody | 1.94 ratio |
| Cohort B2: Influenza Vaccine and COVID-19 Vaccine | GMFR of Antibodies for Influenza, as Measured by MN Assay | Influenza B Victoria-lineage | 3.27 ratio |
Secondary
GMFR of Antibodies for SARS-CoV-2, as Measured by PsVNA
SARS-CoV-2 strain included Omicron XBB.1.5 antibody. Fold-rise was calculated by dividing post-vaccination results by the baseline value. 95% CI for GMFR was calculated based on the t-distribution of the differences in the log-transformed values between analysis timepoint and baseline, then back transformed to the original scale for presentation. PPIS included all randomized participants who received study intervention, complied with the timing of immunogenicity blood sample collections to have both Baseline and Day 29 assessments using a window of -7 to +14 days, had no major dosing error, had negative RT-PCR test for influenza and SARS-CoV-2 on Day 1, and had no major protocol deviations or conditions/medications that affected the immune response.
Time frame: Day 1, Day 29
Population: The PPIS. Overall number of participants analyzed = participants evaluable for this outcome measure.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Cohort A1: mRNA-1083 and Placebo | GMFR of Antibodies for SARS-CoV-2, as Measured by PsVNA | 16.86 ratio |
| Cohort A2: Influenza Vaccine and COVID-19 Vaccine | GMFR of Antibodies for SARS-CoV-2, as Measured by PsVNA | 10.32 ratio |
| Cohort B1: mRNA-1083 and Placebo | GMFR of Antibodies for SARS-CoV-2, as Measured by PsVNA | 17.83 ratio |
| Cohort B2: Influenza Vaccine and COVID-19 Vaccine | GMFR of Antibodies for SARS-CoV-2, as Measured by PsVNA | 13.56 ratio |
Secondary
GM Level of Antibodies for Influenza, as Measured by Microneutralization (MN) Assay
Influenza A strains included H1N1 and H3N2 and influenza B strains included Victoria-lineage and Yamagata-lineage. The PPIS for MN assay included a subset of randomized participants who received study intervention to be tested for MN, complied with the timing of immunogenicity blood sampling collections to have both Baseline and Day 29 assessments using a window of -7 to +14 days, had no major dosing error, had negative RT-PCR test for influenza and SARS-CoV-2 on Day 1, and had no major protocol deviations or conditions/medications that affected the immune response.
Time frame: Day 29
Population: The PPIS for MN assay.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Cohort A1: mRNA-1083 and Placebo | GM Level of Antibodies for Influenza, as Measured by Microneutralization (MN) Assay | Influenza A H1N1 Antibody | 676.4 titer |
| Cohort A1: mRNA-1083 and Placebo | GM Level of Antibodies for Influenza, as Measured by Microneutralization (MN) Assay | Influenza A H3N2 Antibody | 587.6 titer |
| Cohort A1: mRNA-1083 and Placebo | GM Level of Antibodies for Influenza, as Measured by Microneutralization (MN) Assay | Influenza B Yamagata-lineage Antibody | 1118.8 titer |
| Cohort A1: mRNA-1083 and Placebo | GM Level of Antibodies for Influenza, as Measured by Microneutralization (MN) Assay | Influenza B Victoria-lineage Antibody | 2845.4 titer |
| Cohort A2: Influenza Vaccine and COVID-19 Vaccine | GM Level of Antibodies for Influenza, as Measured by Microneutralization (MN) Assay | Influenza A H3N2 Antibody | 668.8 titer |
| Cohort A2: Influenza Vaccine and COVID-19 Vaccine | GM Level of Antibodies for Influenza, as Measured by Microneutralization (MN) Assay | Influenza B Yamagata-lineage Antibody | 1434.4 titer |
| Cohort A2: Influenza Vaccine and COVID-19 Vaccine | GM Level of Antibodies for Influenza, as Measured by Microneutralization (MN) Assay | Influenza A H1N1 Antibody | 635.9 titer |
| Cohort A2: Influenza Vaccine and COVID-19 Vaccine | GM Level of Antibodies for Influenza, as Measured by Microneutralization (MN) Assay | Influenza B Victoria-lineage Antibody | 3072.5 titer |
| Cohort B1: mRNA-1083 and Placebo | GM Level of Antibodies for Influenza, as Measured by Microneutralization (MN) Assay | Influenza B Victoria-lineage Antibody | 2901.5 titer |
| Cohort B1: mRNA-1083 and Placebo | GM Level of Antibodies for Influenza, as Measured by Microneutralization (MN) Assay | Influenza A H1N1 Antibody | 946.8 titer |
| Cohort B1: mRNA-1083 and Placebo | GM Level of Antibodies for Influenza, as Measured by Microneutralization (MN) Assay | Influenza B Yamagata-lineage Antibody | 1449.6 titer |
| Cohort B1: mRNA-1083 and Placebo | GM Level of Antibodies for Influenza, as Measured by Microneutralization (MN) Assay | Influenza A H3N2 Antibody | 645.8 titer |
| Cohort B2: Influenza Vaccine and COVID-19 Vaccine | GM Level of Antibodies for Influenza, as Measured by Microneutralization (MN) Assay | Influenza B Yamagata-lineage Antibody | 1071.3 titer |
| Cohort B2: Influenza Vaccine and COVID-19 Vaccine | GM Level of Antibodies for Influenza, as Measured by Microneutralization (MN) Assay | Influenza A H1N1 Antibody | 428.1 titer |
| Cohort B2: Influenza Vaccine and COVID-19 Vaccine | GM Level of Antibodies for Influenza, as Measured by Microneutralization (MN) Assay | Influenza A H3N2 Antibody | 393.9 titer |
| Cohort B2: Influenza Vaccine and COVID-19 Vaccine | GM Level of Antibodies for Influenza, as Measured by Microneutralization (MN) Assay | Influenza B Victoria-lineage Antibody | 1883.1 titer |
Other Pre-specified
Number of Deaths Related to Control Drug Influenza Vaccine and COVID-19 Vaccine
A death that occurred during the study or that came to the attention of the investigator during the study was reported to the Sponsor, irrespective of its perceived relationship to the study drug. The Investigator assessed the causality by determining whether there was a reasonable possibility that the death was related to the study drug, using the following classifications: Not related: There was not a reasonable possibility of a relationship to the study drug. The temporal sequence of the death relative to administration of the study drug was not reasonable AND/OR the death was more likely explained by a cause other than the study drug. Related: There was a reasonable possibility of a relationship to the study drug. There was evidence of exposure to the study drug. The temporal sequence of the death relative to the administration of the study drug was reasonable.
Time frame: Day 1 through Day 181
Population: Safety set included all participants who were randomized and received any study vaccination.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cohort A1: mRNA-1083 and Placebo | Number of Deaths Related to Control Drug Influenza Vaccine and COVID-19 Vaccine | Deaths | 1 Participants |
| Cohort A1: mRNA-1083 and Placebo | Number of Deaths Related to Control Drug Influenza Vaccine and COVID-19 Vaccine | Deaths Related to Control Drug | 0 Participants |
| Cohort A2: Influenza Vaccine and COVID-19 Vaccine | Number of Deaths Related to Control Drug Influenza Vaccine and COVID-19 Vaccine | Deaths | 2 Participants |
| Cohort A2: Influenza Vaccine and COVID-19 Vaccine | Number of Deaths Related to Control Drug Influenza Vaccine and COVID-19 Vaccine | Deaths Related to Control Drug | 0 Participants |
Other Pre-specified
Number of Deaths Related to Study Drug mRNA-1083 and Placebo
A death that occurred during the study or that came to the attention of the investigator during the study was reported to the Sponsor, irrespective of its perceived relationship to the study drug. The Investigator assessed the causality by determining whether there was a reasonable possibility that the death was related to the study drug, using the following classifications: Not related: There was not a reasonable possibility of a relationship to the study drug. The temporal sequence of the death relative to administration of the study drug was not reasonable AND/OR the death was more likely explained by a cause other than the study drug. Related: There was a reasonable possibility of a relationship to the study drug. There was evidence of exposure to the study drug. The temporal sequence of the death relative to the administration of the study drug was reasonable.
Time frame: Day 1 through Day 181
Population: Safety set included all participants who were randomized and received any study vaccination.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cohort A1: mRNA-1083 and Placebo | Number of Deaths Related to Study Drug mRNA-1083 and Placebo | Deaths | 2 Participants |
| Cohort A1: mRNA-1083 and Placebo | Number of Deaths Related to Study Drug mRNA-1083 and Placebo | Deaths Related to Study Drug mRNA-1083 | 0 Participants |
| Cohort A2: Influenza Vaccine and COVID-19 Vaccine | Number of Deaths Related to Study Drug mRNA-1083 and Placebo | Deaths | 2 Participants |
| Cohort A2: Influenza Vaccine and COVID-19 Vaccine | Number of Deaths Related to Study Drug mRNA-1083 and Placebo | Deaths Related to Study Drug mRNA-1083 | 0 Participants |