Respiratory Syncytial Virus
Conditions
Keywords
Viral Diseases, Messenger RNA, Moderna, mRNA-1345, Respiratory syncytial virus, Safety, Vaccines, SARS-CoV-2
Brief summary
The main purposes of Part A of this study are to evaluate the safety, tolerability, and immunogenicity of mRNA-1345 coadministered with a seasonal influenza vaccine (Afluria® Quadrivalent); to evaluate the impact of coadministered influenza vaccine on the immune response to RSV-A; and to evaluate the impact of coadministered RSV vaccine on the immune response to influenza. The main purposes of Part B of this study are to evaluate the safety, tolerability, and immunogenicity of mRNA-1345 coadministered with mRNA-1273.214; to evaluate the effect of coadministered mRNA-1273.214 on the immune response to RSV-A; and to evaluate the effect of coadministered RSV vaccine on the immune response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The main purposes of Part C (single arm, open-label) of this study are to evaluate the safety and tolerability of a booster dose (BD) of mRNA-1345 administered at 1 Year following a primary dose; to evaluate the immune response to RSV-A of a BD of mRNA 1345 administered at 1 Year following a primary dose; and to evaluate the immune response to RSV-B of a BD of mRNA-1345 administered at 1 Year following a primary dose.
Interventions
BIOLOGICALPlacebo
0.9% sodium chloride (normal saline) injection
BIOLOGICALmRNA-1345
Sterile liquid for injection
BIOLOGICALAfluria® Quadrivalent
single-dose, pre-filled syringe for injection
BIOLOGICALmRNA-1273.214
Sterile liquid for injection
Sponsors
ModernaTX, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Parts A and B are randomized, observer blind studies and Part C is a single-arm, open-label study.
Eligibility
Sex/Gender
ALL
Age
50 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
Key Inclusion Criteria: Parts A and B both: * Adults ≥50 years of age on the day of the Randomization Visit (Day 1) who are primarily responsible for self-care and activities of daily living. Participants may have one or more chronic medical diagnoses, but should be medically stable as assessed by: Absence of changes in medical therapy within 1 month due to treatment failure or toxicity; Absence of medical events qualifying as SAEs within 1 month of the planned vaccination on Day 1; and absence of known, current, and life-limiting diagnoses which, in the opinion of the investigator, would make completion of the protocol unlikely. * Able to comply with study requirements, including access to transportation for study visits. Part B only: * Fully vaccinated for COVID-19 with an approved primary series according to the locally authorized or approved regimen. If the most recent COVID-19 vaccine was part of a primary series, it must be ≥ 150 days before (or less per local guidance) Day 1. If the most recent COVID-19 vaccine was a booster dose, it must be ≥ 120 days before (or less per local guidance) Day 1. Part C: * Participants at Part C study sites who have been enrolled in Part B (Groups 4 and 5) of this study; have immunogenicity blood sampling at Part B baseline and Day 29; completed the Day 211/end-of-study visits for Part B; were included in the per-protocol (PP) set; and received 1 dose of mRNA-1345 at least 12 months (but no later than 15 months) prior to the time of enrollment. * Able to comply with study requirements, including access to transportation for study visits. Key
Exclusion criteria
Part A: * Participant has received or plans to receive any vaccine authorized or approved by a local health agency ≤28 days prior to study injections (Day 1) or plans to receive a vaccine authorized or approved by a local health agency within 28 days after the study injections. * Prior participation in research involving receipt of any investigational product (drug/biologic/device including any investigational RSV product) within 45 days before the planned date of the Day 1 study injection. * Participant has received a seasonal influenza vaccine or any other investigational influenza vaccine ≤180 days prior to the Randomization Visit (Day 1). * History of a serious reaction to any prior vaccination, or Guillain-Barré syndrome within 6 weeks of any prior influenza immunization. * Participated in an interventional clinical study within 28 days prior to the Screening Visit based on the medical history interview or plans to do so while participating in this study. Part B: * Participant has received or plans to receive any vaccine authorized or approved by a local health agency ≤ 28 days prior to study injections (Day 1) or plans to receive a vaccine authorized or approved by a local health agency within 28 days after the study injections (with the exception of SARS-Cov-2 vaccination). * Prior participation in research involving receipt of any investigational product (drug/biologic/device with the exception of RSV investigation products) within 45 days before the planned date of the Day 1 study injection. * Prior receipt of any investigational/approved RSV product within 1 year of the Day 1 study injection. * Has known history of SARS-CoV-2 infection within 90 days prior to enrollment. Parts A and B both: * Participant had significant exposure to someone with SARS-CoV-2 infection or COVID-19 in the past 10 days, as defined by the United States (US) Centers for Disease Control and Prevention (CDC) as a close contact of someone who has had COVID-19. Part C: * Participation in another interventional clinical research study where participant has received an investigational product (drug/biologic/device) within 6 months before the planned date of the BD Day 1 study injection. Any prior receipt of an investigational or approved vaccine against RSV, except as part of mRNA-1345 Study P302 Part B, is exclusionary. * Participant has received or plans to receive any vaccine authorized or approved by a local health agency ≤28 days prior to the study injection (BD Day 1) or plans to receive a vaccine authorized or approved by a local health agency within 28 days after the study injections. * History of a serious reaction to any prior vaccination or Guillain-Barré syndrome 6 weeks after any prior influenza immunization. Other inclusion and/or
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Part C: GMT of Serum RSV-A and RSV-B NAbs mRNA-1345 Revaccination Day 29 Compared to Primary Vaccination Day 29 | Primary Vaccination Day 29 to Revaccination Day 29 | Antibody values reported as below LLOQ were replaced by 0.5\*LLOQ. Values greater than the ULOQ were replaced by the ULOQ. LLOQ was 13 IU/mL and ULOQ was 259061 IU/mL for RSV-A. LLOQ was 10 IU/mL and ULOQ was 112476 IU/mL for RSV-B. mRNA-1345 Revaccination Day 29 and mRNA-1345 primary vaccination Day 29 (received in Part B) are presented. |
| Part A: Number of Participants With Solicited Local and Systemic Adverse Reactions (ARs) Within 7 Days After Day 1 Injection | Within 7 days after Day 1 injection | Solicited ARs were collected in an electronic diary (eDiary). Local ARs: injection site pain, erythema (redness), swelling/induration (hardness); and axillary (underarm) swelling or tenderness ipsilateral to the side of injection. Systemic ARs: fever, headache, fatigue, myalgia, arthralgia, nausea/vomiting, and chills. Note, not all solicited ARs were considered adverse events (AEs). 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. |
| Part A: Number of Participants With Unsolicited Adverse Events (AEs) After Day 1 Injection | Day 1 through Day 28 (28 days after Day 1 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. A summary of SAEs and all nonserious AEs (Other), regardless of causality, is located in the Reported Adverse Events section. |
| Part C: Number of Participants With MAAEs | Revaccination Day 1 through Day 181 | A MAAE is an AE that leads to an unscheduled visit to a healthcare practitioner. |
| Part A: Number of Participants With Medically Attended AEs (MAAEs), SAEs, Adverse Events of Special Interest (AESIs), and AEs Leading to Withdrawal | Day 1 through Day 181 (end of Study Part A) | A MAAE is an AE that leads to an unscheduled visit to a healthcare practitioner. An AESI is an AE (serious or nonserious) of scientific and medical concern specific to the Sponsor's product or program, for which ongoing monitoring and immediate notification by the Investigator to the Sponsor are required. 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, 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. |
| Part A: Geometric Mean Titer (GMT) of Serum Respiratory Syncytial Virus Subtype A (RSV-A) Neutralizing Antibodies (NAbs) at Day 29 | Day 29 | Antibody values reported as below lower limit of quantification (LLOQ) were replaced by 0.5\*LLOQ. Values greater than the upper limit of quantification (ULOQ) were replaced by the ULOQ. LLOQ was 13 international units (IU)/milliliter (mL) and ULOQ was 259061 IU/mL for RSV-A. As prespecified, only arms where participants received mRNA-1345 are presented for this outcome measure. |
| Part A: Percentage of Participants With Seroresponse in RSV-A NAbs at Day 29 | Day 29 | Seroresponse was defined as ≥4 × lower limit of quantification (LLOQ) if baseline was \<LLOQ or 4-fold or greater increase from baseline if baseline was ≥LLOQ. As prespecified, only arms where participants received mRNA-1345 are presented for this outcome measure. |
| Part A: GMT of Serum Anti-hemagglutination (HA) Ab Level, as Measured by Hemagglutination Inhibition (HAI) Assay for Influenza at Day 29 | Day 29 | Influenza A strains included H1N1 and H3N2 and influenza B strains included Washington and Phuket strains. Antibody values reported as below LLOQ were replaced by 0.5\*LLOQ. Values greater than the ULOQ were replaced by the ULOQ. LLOQ was 10 and ULOQ was 2560 for Influenza A. LLOQ was 10 and ULOQ was 640 for Influenza B. As prespecified, only arms where participants received Afluria® Quadrivalent are presented for this outcome measure. |
| Part B: Number of Participants With Solicited Local and Systemic ARs Within 7 Days After Day 1 Injection | Within 7 days after Day 1 injection | Solicited ARs were collected in an eDiary. Local ARs: injection site pain, erythema (redness), swelling/induration (hardness); and axillary (underarm) swelling or tenderness ipsilateral to the side of injection. Systemic ARs: fever, headache, fatigue, myalgia, arthralgia, nausea/vomiting, and chills. Note, not all solicited ARs were considered AEs. Investigator reviewed whether the solicited AR was also to be recorded as an AE. A Summary of SAEs and nonserious AEs (Other), regardless of causality, is located in the Reported Adverse Events section. |
| Part B: Number of Participants With Solicited Local and Systemic ARs Within 7 Days After Day 29 Injection | Within 7 days after Day 29 injection | Solicited ARs were collected in an eDiary. Local ARs: injection site pain, erythema (redness), swelling/induration (hardness); and axillary (underarm) swelling or tenderness ipsilateral to the side of injection. Systemic ARs: fever, headache, fatigue, myalgia, arthralgia, nausea/vomiting, and chills. Note, not all solicited ARs were considered AEs. Investigator reviewed whether the solicited AR was also to be recorded as an AE. A Summary of SAEs and nonserious AEs (Other), regardless of causality, is located in the Reported Adverse Events section. |
| Part B: Number of Participants With Unsolicited AEs After Day 1 Injection | Day 1 through Day 28 (28 days after Day 1 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 PT/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. A summary of SAEs and all nonserious AEs (Other), regardless of causality, is located in the Reported Adverse Events section. |
| Part B: Number of Participants With Unsolicited AEs After Day 29 Injection | Day 29 through Day 57 (28 days after Day 29 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. A summary of SAEs and all nonserious AEs (Other), regardless of causality, is located in the Reported Adverse Events section. |
| Part C: Number of Participants With SAEs, AESIs, and AEs Leading to Withdrawal | Revaccination Day 1 through Day 361 | 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, was a congenital anomaly/birth defect, or was an important medical event. An AESI is an AE (serious or nonserious) of scientific and medical concern specific to the Sponsor's product or program, for which ongoing monitoring and immediate notification by the Investigator to the Sponsor are required. A summary of SAEs and all nonserious AEs (Other), regardless of causality, is located in the Reported Adverse Events section. |
| Part B: Number of Participants With MAAEs, SAEs, AESIs, and AEs Leading to Withdrawal | Day 1 through Day 211 | A MAAE is an AE that leads to an unscheduled visit to a healthcare practitioner. An AESI is an AE (serious or nonserious) of scientific and medical concern specific to the Sponsor's product or program, for which ongoing monitoring and immediate notification by the Investigator to the Sponsor are required. 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, 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. |
| Part B: GMT of Serum RSV-A at Day 29 | Day 29 | Antibody values reported as below LLOQ were replaced by 0.5\*LLOQ. Values greater than the upper limit of quantification (ULOQ) were replaced by the ULOQ. LLOQ was 13 IU/mL and ULOQ was 259061 IU/mL for RSV-A. As prespecified, only arms where participants received mRNA-1345 are presented for this outcome measure. |
| Part B: Percentage of Participants With Seroresponse for RSV-A Neutralizing Abs From Baseline to Day 29 | Baseline to Day 29 | Seroresponse was defined as ≥4 × LLOQ if baseline was \<LLOQ or 4-fold or greater increase from baseline if baseline was ≥LLOQ. As prespecified, only arms where participants received mRNA-1345 are presented for this outcome measure. |
| Part B: Geometric Mean Concentration (GMC) of Serum Ab Level, as Measured by Neutralization Assay for SARS-Cov-2 at Day 29 | Day 29 | The model-based GM titer was estimated on ANCOVA model. SARS-CoV-2 variants included Wuhan-Hu-1 and B.1.1.529. Antibody values reported as below LLOQ were replaced by 0.5\*LLOQ. Values greater than the ULOQ were replaced by the ULOQ. LLOQ was 10 arbitrary units (AU)/milliliters (mL) and ULOQ was 111433 AU/mL for Wuhan-Hu-1. LLOQ was 8 and ULOQ was B.1.1.529 for B1.1.529. As prespecified, only arms where participants received mRNA-1273.214 are presented for this outcome measure. |
| Part B: Percentage of Participants With Seroresponse for SARS-Cov-2 NAbs From Baseline to Day 29 | Baseline to Day 29 | Seroresponse was defined as ≥4 × LLOQ if baseline was \<LLOQ or 4-fold or greater increase from baseline if baseline was ≥LLOQ. mRNA-As prespecified, only arms where participants received mRNA-1273.214 are presented for this outcome measure. |
| Part C: Number of Participants With Solicited Local and Systemic Within 7 Days After Revaccination Day 1 | Within 7 days after Day 1 revaccination | Solicited ARs were collected in an electronic eDiary. Local ARs: injection site pain, erythema (redness), swelling/induration (hardness); and axillary (underarm) swelling or tenderness ipsilateral to the side of injection. Systemic ARs: fever, headache, fatigue, myalgia, arthralgia, nausea/vomiting, and chills. Note, not all solicited ARs were considered AEs. Investigator reviewed whether the solicited AR was also to be recorded as an AE. A Summary of SAEs and nonserious AEs (Other), regardless of causality, is located in the Reported Adverse Events section. |
| Part C: Number of Participants With Unsolicited AEs Within 28 Days After Revaccination Day 1 | Revaccination Day 1 through Day 28 (28 days after revaccination Day 1) | 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 PT/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. 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 B: GMFR of Serum RSV-A and RSV-B NAbs at Day 211 | Day 211 | Antibody values reported as below LLOQ were replaced by 0.5\*LLOQ. Values greater than the ULOQ were replaced by the ULOQ. As prespecified, only arms where participants received mRNA-1345 are presented for this outcome measure. |
| Part B: GMC of Serum Ab Level, as Measured by Neutralization Assay for SARS-Cov-2 at Day 211 | Day 211 | 95% CI for GM value was calculated based on the t-distribution of the log-transformed values between analysis timepoint and baseline, then back transformed to the original scale for presentation. SARS-CoV-2 variants included Wuhan-Hu-1 and B.1.1.529. Antibody values reported as below LLOQ were replaced by 0.5\*LLOQ. Values greater than the ULOQ were replaced by the ULOQ. LLOQ was 10 AU/mL and ULOQ was 111433 AU/mL for Wuhan-Hu-1. LLOQ was 8 AU/mL and ULOQ was 24503 for B1.1.529. |
| Part B: GMFR of Serum Ab Level, as Measured by Neutralization Assay for SARS-Cov-2 at Day 211 | Day 211 | 95% CI for GMFR (postinjection/baseline titers) 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. |
| Part B: Percentage of Participants With Seroresponse for SARS-Cov-2 NAbs at Day 211 | Day 211 | Seroresponse was defined as ≥4 × LLOQ if baseline was \<LLOQ or 4-fold or greater increase from baseline if baseline was ≥LLOQ. SARS-CoV-2 variants included Wuhan-Hu-1 and B.1.1.529. Antibody values reported as below LLOQ were replaced by 0.5\*LLOQ. Values greater than the ULOQ were replaced by the ULOQ. LLOQ was 10 and ULOQ was 111433 for Wuhan-Hu-1. LLOQ was 8 and ULOQ was B.1.1.529 for B1.1.529. |
| Part B: Percentage of Participants With Seroresponse in RSV-A and RSV-B NAb Titers at Day 211 | Day 211 | Seroresponse was defined as ≥4 × LLOQ if baseline was \<LLOQ or 4-fold or greater increase from baseline if baseline was ≥LLOQ. As prespecified, only arms where participants received mRNA-1345 are presented for this outcome measure. |
| Part C: Percentage of Participants With Seroresponse in RSV-A and RSV-B NAbs From Baseline (Before Primary Vaccination) to Revaccination Day 29 | Baseline (Before Primary Vaccination in Part B) to Revaccination Day 29 | Seroresponse was defined as ≥4 × LLOQ if baseline was \<LLOQ or 4-fold or greater increase from baseline if baseline was ≥LLOQ. Primary vaccination Day 29 (received in Part B) and Revaccination Day 29 are presented. |
| Part C: GMT of Serum RSV-A and RSV-B NAbs at Revaccination Day 361 | Revaccination Day 361 | Antibody values reported as below LLOQ were replaced by 0.5\*LLOQ. Values greater than the ULOQ were replaced by the ULOQ. LLOQ was 13 IU/mL and ULOQ was 259061 IU/mL for RSV-A. LLOQ was 10 IU/mL and ULOQ was 112476 IU/mL for RSV-B. |
| Part C: GMFR of Serum RSV-A and RSV-B NAbs at Revaccination Day 361 | Revaccination Day 361 | 95% CI for GMFR (postinjection/baseline titers) 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. |
| Part C: Percentage of Participants With Seroresponse in RSV-A and RSV-B NAbs at Revaccination Day 361 | Baseline to Revaccination Day 361 | Seroresponse was defined as ≥4 × LLOQ if baseline was \<LLOQ or 4-fold or greater increase from baseline if baseline was ≥LLOQ. |
| Part C: Percentage of Participants With ≥2-fold Increases From Baseline (Before Primary Vaccination) in RSV-A and RSV-B NAb Titers at Revaccination Day 361 | Baseline to Revaccination Day 361 | ≥2-fold increase from baseline at participant level was defined as a change from below the LLOQ to equal or above 2 \* LLOQ, or at least a 2-fold increase if baseline was equal to or above the LLOQ. LLOQ was 13 IU/mL and ULOQ was 259061 IU/mL for RSV-A. LLOQ was 10 IU/mL and ULOQ was 112476 IU/mL for RSV-B. |
| Part B: Percentage of Participants With ≥2-fold Increases From Baseline in RSV-A and RSV-B NAb Titers at Day 211 | Day 211 | ≥2-fold increase from baseline at participant level was defined as a change from below the LLOQ to equal or above 2 \* LLOQ, or at least a 2-fold increase if baseline was equal to or above the LLOQ. LLOQ was 13 IU/mL and ULOQ was 259061 IU/mL for RSV-A. LLOQ was 10 IU/mL and ULOQ was 112476 for RSV-B. As prespecified, only arms where participants received mRNA-1345 are presented for this outcome measure. |
| Part A: GMT of Serum RSV-B NAbs at Day 29 | Day 29 | Antibody values reported as below LLOQ were replaced by 0.5\*LLOQ. Values greater than the ULOQ were replaced by the ULOQ. LLOQ was 10 IU/mL and ULOQ was 112476 for RSV-B. As prespecified, only arms where participants received mRNA-1345 are presented for this outcome measure. |
| Part A: Percentage of Participants With Seroresponse in RSV-B NAbs at Day 29 | Day 29 | Seroresponse was defined as ≥4 × LLOQ if baseline was \<LLOQ or 4-fold or greater increase from baseline if baseline was ≥LLOQ. As prespecified, only arms where participants received mRNA-1345 are presented for this outcome measure. |
| Part A: Percentage of Participants With Seroconversion in Influenza A and B Strains at Day 181 | Day 181 | Influenza A strains included H1N1 and H3N2 and influenza B strains included Washington and Phuket strains. Seroconversion was defined as a titer ≥1:40 if baseline was \<1:10 or a 4-fold or greater rise from baseline in the titers if Baseline was ≥1:10. As prespecified, only arms where participants received Afluria® Quadrivalent are presented for this outcome measure. |
| Part A: GMT of Serum RSV-A and RSV-B NAbs at Day 181 | Day 181 | Antibody values reported as below LLOQ were replaced by 0.5\*LLOQ. Values greater than the ULOQ were replaced by the ULOQ. LLOQ was 13 IU/mL and ULOQ was 259061 IU/mL for RSV-A. LLOQ was 10 IU/mL and ULOQ was 112476 for RSV-B. As prespecified, only arms where participants received mRNA-1345 are presented for this outcome measure. |
| Part A: Geometric Mean Fold Rise (GMFR) of Serum RSV-A and RSV-B NAbs at Day 181 | Day 181 | 95% CI for GMFR (postinjection/baseline titers) 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. As prespecified, only arms where participants received mRNA-1345 are presented for this outcome measure. |
| Part A: Percentage of Participants With Seroresponse in RSV-A and RSV-B NAb Titers at Day 181 | Day 181 | Seroresponse was defined as ≥4 × LLOQ if baseline was \<LLOQ or 4-fold or greater increase from baseline if baseline was ≥LLOQ.As prespecified, only arms where participants received mRNA-1345 are presented for this outcome measure. |
| Part A: Percentage of Participants With ≥2-fold Increases From Baseline in RSV-A and RSV-B NAb Titers at Day 181 | Baseline to Day 181 | ≥2-fold increase from baseline at participant level was defined as a change from below the LLOQ to equal or above 2 \* LLOQ, or at least a 2-fold increase if baseline was equal to or above the LLOQ. As prespecified, only arms where participants received mRNA-1345 are presented for this outcome measure. |
| Part A: GMT of Serum Anti-HA Ab Level, as Measured by HAI Assay for Influenza at Day 181 | Day 181 | Influenza A strains included H1N1 and H3N2 and influenza B strains included Washington and Phuket strains. Antibody values reported as below LLOQ were replaced by 0.5\*LLOQ. Values greater than the ULOQ were replaced by the ULOQ. LLOQ was 10 and ULOQ was 2560 for Influenza A. LLOQ was 10 and ULOQ was 640 for Influenza B. As prespecified, only arms where participants received Afluria® Quadrivalent are presented for this outcome measure. |
| Part A: GMFR of Serum Anti-HA Ab Level, as Measured by HAI Assay for Influenza at Day 181 | Day 181 | Influenza A strains included H1N1 and H3N2 and influenza B strains included Washington and Phuket strains. Antibody values reported as below LLOQ were replaced by 0.5\*LLOQ. Values greater than the ULOQ were replaced by the ULOQ. LLOQ was 10 and ULOQ was 2560 for Influenza A. LLOQ was 10 and ULOQ was 640 for Influenza B. 95% CI for GMFR (postinjection/baseline titers) 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. As prespecified, only arms where participants received Afluria® Quadrivalent are presented for this outcome measure. |
| Part B: GMT of Serum RSV-B NAbs at Day 29 | Day 29 | Antibody values reported as below LLOQ were replaced by 0.5\*LLOQ. Values greater than the ULOQ were replaced by the ULOQ. LLOQ was 10 IU/mL and ULOQ was 112476 for RSV-B. As prespecified, only arms where participants received mRNA-1345 are presented for this outcome measure. |
| Part B: Percentage of Participants With Seroresponse in RSV-B NAbs From Baseline to Day 29 | Baseline to Day 29 | Seroresponse was defined as ≥4 × LLOQ if baseline was \<LLOQ or 4-fold or greater increase from baseline if baseline was ≥LLOQ. As prespecified, only arms where participants received mRNA-1345 are presented for this outcome measure. |
| Part B: GMT of Serum RSV-A and RSV-B NAbs at Day 181 | Day 181 | Antibody values reported as below LLOQ were replaced by 0.5\*LLOQ. Values greater than the ULOQ were replaced by the ULOQ. LLOQ was 13 IU/mL and ULOQ was 259061 IU/mL for RSV-A. LLOQ was 10 IU/mL and ULOQ was 112476 for RSV-B. As prespecified, only arms where participants received mRNA-1345 are presented for this outcome measure. |
| Part B: GMFR of Serum RSV-A and RSV-B NAbs at Day 181 | Day 181 | Antibody values reported as below LLOQ were replaced by 0.5\*LLOQ. Values greater than the ULOQ were replaced by the ULOQ. As prespecified, only arms where participants received mRNA-1345 are presented for this outcome measure. |
| Part B: GMC of Serum Ab Level, as Measured by Neutralization Assay for SARS-Cov-2 at Day 181 | Day 181 | 95% CI for GM value was calculated based on the t-distribution of the log-transformed values between analysis timepoint and baseline, then back transformed to the original scale for presentation. SARS-CoV-2 variants included Wuhan-Hu-1 and B.1.1.529. Antibody values reported as below LLOQ were replaced by 0.5\*LLOQ. Values greater than the ULOQ were replaced by the ULOQ. LLOQ was 10 AU/mL and ULOQ was 111433 AU/mL for Wuhan-Hu-1. LLOQ was 8 AU/mL and ULOQ was 24503 for B1.1.529. |
| Part B: GMFR of Serum Ab Level, as Measured by Neutralization Assay for SARS-Cov-2 at Day 181 | Day 181 | 95% CI for GMFR (postinjection/baseline titers) 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. |
| Part B: Percentage of Participants With Seroresponse for SARS-Cov-2 NAbs From Baseline to Day 181 | Baseline to Day 181 | Seroresponse was defined as ≥4 × LLOQ if baseline was \<LLOQ or 4-fold or greater increase from baseline if baseline was ≥LLOQ. SARS-CoV-2 variants included Wuhan-Hu-1 and B.1.1.529. Antibody values reported as below LLOQ were replaced by 0.5\*LLOQ. Values greater than the ULOQ were replaced by the ULOQ. LLOQ was 10 and ULOQ was 111433 for Wuhan-Hu-1. LLOQ was 8 and ULOQ was B.1.1.529 for B1.1.529. |
| Part B: Percentage of Participants With Seroresponse in RSV-A and RSV-B NAb Titers at Day 181 | Day 181 | Seroresponse was defined as ≥4 × LLOQ if baseline was \<LLOQ or 4-fold or greater increase from baseline if baseline was ≥LLOQ. As prespecified, only arms where participants received mRNA-1345 are presented for this outcome measure. |
| Part B: Percentage of Participants With ≥2-fold Increases From Baseline in RSV-A and RSV-B NAb Titers at Day 181 | Baseline to Day 181 | ≥2-fold increase from baseline at participant level was defined as a change from below the LLOQ to equal or above 2 \* LLOQ, or at least a 2-fold increase if baseline was equal to or above the LLOQ. LLOQ was 13 IU/mL and ULOQ was 259061 IU/mL for RSV-A. LLOQ was 10 IU/mL and ULOQ was 112476 for RSV-B. As prespecified, only arms where participants received mRNA-1345 are presented for this outcome measure. |
| Part B: GMT of Serum RSV-A and RSV-B NAbs at Day 211 | Day 211 | Antibody values reported as below LLOQ were replaced by 0.5\*LLOQ. Values greater than the ULOQ were replaced by the ULOQ. LLOQ was 13 IU/mL and ULOQ was 259061 IU/mL for RSV-A. LLOQ was 10 IU/mL and ULOQ was 112476 for RSV-B. As prespecified, only arms where participants received mRNA-1345 are presented for this outcome measure. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Number of Deaths During the Study | Up to Day 181 for Part A, up to Day 211 for Part B, and up to Day 361 for Part C | A death that occurred during the study or that came to the attention of the investigator during the study was reported to the Sponsor, whether or not it was considered related to study drug. The investigator assessed causality (that is, whether there is a reasonable possibility that the study drug caused the death). The relationship was characterized 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. The death was more likely explained by the study drug than by another cause. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Part A: mRNA-1345 + Placebo Participants received a single injection each of mRNA-1345 and placebo, administered IM on Day 1. | 249 |
| Part A: mRNA-1345 + Afluria® Quadrivalent Participants received a single injection each of mRNA-1345 and Afluria® quadrivalent, administered IM on Day 1. | 690 |
| Part A: Afluria® Quadrivalent + Placebo Participants received a single injection each of Afluria® quadrivalent and placebo, administered IM on Day 1. | 692 |
| Part B: mRNA-1345 + Placebo + mRNA-1273.214 Participants received a single injection of mRNA-1345 and placebo, administered IM on Day 1.
(Note: An additional injection of mRNA-1273.214 was administered on Day 29 to allow all study participants to receive an mRNA-1273.214 booster vaccination.) | 560 |
| Part B: mRNA-1345 + mRNA-1273.214 + Placebo Participants received a single injection each of mRNA-1345 and mRNA-1273.214, administered IM on Day 1.
(Note: An additional injection of placebo was administered on Day 29 to maintain blinding.) | 564 |
| Part B: mRNA-1273.214 + Placebo + Placebo Participants received a single injection each of mRNA-1273.214 and placebo, administered IM on Day 1.
(Note: An additional injection of placebo was administered on Day 29 to maintain blinding.) | 562 |
| Total | 3,317 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 |
|---|---|---|---|---|---|---|---|---|
| Primary | Adverse Event | 0 | 0 | 0 | 1 | 0 | 0 | 0 |
| Primary | Death | 0 | 3 | 1 | 1 | 0 | 0 | 0 |
| Primary | Lost to Follow-up | 12 | 21 | 38 | 30 | 25 | 28 | 0 |
| Primary | Other Than Specified | 0 | 1 | 2 | 1 | 2 | 2 | 0 |
| Primary | Physician Decision | 0 | 0 | 0 | 0 | 1 | 0 | 0 |
| Primary | Protocol Violation | 0 | 2 | 0 | 4 | 0 | 3 | 0 |
| Primary | Withdrawal by Subject | 4 | 11 | 8 | 23 | 20 | 19 | 0 |
| Revaccination | Adverse Event | 0 | 0 | 0 | 0 | 0 | 0 | 3 |
| Revaccination | Death | 0 | 0 | 0 | 0 | 0 | 0 | 3 |
| Revaccination | Lost to Follow-up | 0 | 0 | 0 | 0 | 0 | 0 | 10 |
| Revaccination | Withdrawal by Subject | 0 | 0 | 0 | 0 | 0 | 0 | 2 |
Baseline characteristics
| Characteristic | Part B: mRNA-1273.214 + Placebo + Placebo | Total | Part B: mRNA-1345 + mRNA-1273.214 + Placebo | Part A: mRNA-1345 + Placebo | Part A: mRNA-1345 + Afluria® Quadrivalent | Part A: Afluria® Quadrivalent + Placebo | Part B: mRNA-1345 + Placebo + mRNA-1273.214 |
|---|---|---|---|---|---|---|---|
| Age, Customized ≥50 years of age | 562 years | 3317 years | 564 years | 249 years | 690 years | 692 years | 560 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 223 Participants | 1230 Participants | 214 Participants | 91 Participants | 240 Participants | 249 Participants | 213 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 333 Participants | 2069 Participants | 349 Participants | 158 Participants | 445 Participants | 442 Participants | 342 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 6 Participants | 18 Participants | 1 Participants | 0 Participants | 5 Participants | 1 Participants | 5 Participants |
| Race/Ethnicity, Customized Race American Indian or Alaska Native | 2 Participants | 18 Participants | 4 Participants | 1 Participants | 1 Participants | 4 Participants | 6 Participants |
| Race/Ethnicity, Customized Race Asian | 1 Participants | 22 Participants | 8 Participants | 0 Participants | 4 Participants | 3 Participants | 6 Participants |
| Race/Ethnicity, Customized Race Black or African American | 111 Participants | 718 Participants | 113 Participants | 59 Participants | 157 Participants | 166 Participants | 112 Participants |
| Race/Ethnicity, Customized Race Multiple | 3 Participants | 6 Participants | 0 Participants | 0 Participants | 2 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Race Native Hawaiian or Other Pacific Islander | 0 Participants | 8 Participants | 3 Participants | 0 Participants | 1 Participants | 3 Participants | 1 Participants |
| Race/Ethnicity, Customized Race Not Reported | 4 Participants | 16 Participants | 8 Participants | 0 Participants | 0 Participants | 1 Participants | 3 Participants |
| Race/Ethnicity, Customized Race Other | 3 Participants | 6 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Race White | 438 Participants | 2523 Participants | 428 Participants | 189 Participants | 524 Participants | 514 Participants | 430 Participants |
| Sex: Female, Male Female | 296 Participants | 1811 Participants | 317 Participants | 141 Participants | 367 Participants | 375 Participants | 315 Participants |
| Sex: Female, Male Male | 266 Participants | 1506 Participants | 247 Participants | 108 Participants | 323 Participants | 317 Participants | 245 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 | EG006 affected / at risk |
|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 249 | 3 / 690 | 1 / 692 | 1 / 560 | 0 / 564 | 0 / 562 | 3 / 543 |
| other Total, other adverse events | 0 / 249 | 0 / 685 | 0 / 689 | 0 / 554 | 0 / 562 | 0 / 560 | 0 / 543 |
| serious Total, serious adverse events | 4 / 249 | 28 / 685 | 24 / 689 | 18 / 554 | 13 / 562 | 10 / 560 | 28 / 543 |
Outcome results
Primary
Part A: Geometric Mean Titer (GMT) of Serum Respiratory Syncytial Virus Subtype A (RSV-A) Neutralizing Antibodies (NAbs) at Day 29
Antibody values reported as below lower limit of quantification (LLOQ) were replaced by 0.5\*LLOQ. Values greater than the upper limit of quantification (ULOQ) were replaced by the ULOQ. LLOQ was 13 international units (IU)/milliliter (mL) and ULOQ was 259061 IU/mL for RSV-A. As prespecified, only arms where participants received mRNA-1345 are presented for this outcome measure.
Time frame: Day 29
Population: PP Set: All participants who received the assigned study injections according to protocol, complied with immunogenicity sampling (baseline and at least 1 Day 29 post-injection assessment), and had no major protocol deviations affecting the immune response. 'Overall number of participants analyzed' = participants evaluable for this endpoint.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Part A: mRNA-1345 + Placebo | Part A: Geometric Mean Titer (GMT) of Serum Respiratory Syncytial Virus Subtype A (RSV-A) Neutralizing Antibodies (NAbs) at Day 29 | 17271.72 IU/mL |
| Part A: mRNA-1345 + Afluria® Quadrivalent | Part A: Geometric Mean Titer (GMT) of Serum Respiratory Syncytial Virus Subtype A (RSV-A) Neutralizing Antibodies (NAbs) at Day 29 | 13929.98 IU/mL |
95% CI: [0.668, 0.974]
Primary
Part A: GMT of Serum Anti-hemagglutination (HA) Ab Level, as Measured by Hemagglutination Inhibition (HAI) Assay for Influenza at Day 29
Influenza A strains included H1N1 and H3N2 and influenza B strains included Washington and Phuket strains. Antibody values reported as below LLOQ were replaced by 0.5\*LLOQ. Values greater than the ULOQ were replaced by the ULOQ. LLOQ was 10 and ULOQ was 2560 for Influenza A. LLOQ was 10 and ULOQ was 640 for Influenza B. As prespecified, only arms where participants received Afluria® Quadrivalent are presented for this outcome measure.
Time frame: Day 29
Population: PP Set: All participants who received the assigned study injections according to protocol, complied with immunogenicity sampling (baseline and at least 1 Day 29 post-injection assessment), and had no major protocol deviations affecting the immune response. 'Overall number of participants analyzed' = participants evaluable for this endpoint. 'Number analyzed' = participants evaluable for specified category.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Part A: mRNA-1345 + Placebo | Part A: GMT of Serum Anti-hemagglutination (HA) Ab Level, as Measured by Hemagglutination Inhibition (HAI) Assay for Influenza at Day 29 | Influenza A H1N1 Antibody | 271.27 titer |
| Part A: mRNA-1345 + Placebo | Part A: GMT of Serum Anti-hemagglutination (HA) Ab Level, as Measured by Hemagglutination Inhibition (HAI) Assay for Influenza at Day 29 | Influenza A H3N2 Antibody | 144.14 titer |
| Part A: mRNA-1345 + Placebo | Part A: GMT of Serum Anti-hemagglutination (HA) Ab Level, as Measured by Hemagglutination Inhibition (HAI) Assay for Influenza at Day 29 | Influenza B Washington Antibody | 57.59 titer |
| Part A: mRNA-1345 + Placebo | Part A: GMT of Serum Anti-hemagglutination (HA) Ab Level, as Measured by Hemagglutination Inhibition (HAI) Assay for Influenza at Day 29 | Influenza B Phuket Antibody | 38.52 titer |
| Part A: mRNA-1345 + Afluria® Quadrivalent | Part A: GMT of Serum Anti-hemagglutination (HA) Ab Level, as Measured by Hemagglutination Inhibition (HAI) Assay for Influenza at Day 29 | Influenza B Phuket Antibody | 42.40 titer |
| Part A: mRNA-1345 + Afluria® Quadrivalent | Part A: GMT of Serum Anti-hemagglutination (HA) Ab Level, as Measured by Hemagglutination Inhibition (HAI) Assay for Influenza at Day 29 | Influenza A H1N1 Antibody | 303.92 titer |
| Part A: mRNA-1345 + Afluria® Quadrivalent | Part A: GMT of Serum Anti-hemagglutination (HA) Ab Level, as Measured by Hemagglutination Inhibition (HAI) Assay for Influenza at Day 29 | Influenza B Washington Antibody | 62.13 titer |
| Part A: mRNA-1345 + Afluria® Quadrivalent | Part A: GMT of Serum Anti-hemagglutination (HA) Ab Level, as Measured by Hemagglutination Inhibition (HAI) Assay for Influenza at Day 29 | Influenza A H3N2 Antibody | 148.69 titer |
Comparison: Influenza A H1N1 Antibody95% CI: [0.772, 1.032]
Comparison: Influenza A H3N2 Antibody95% CI: [0.861, 1.091]
Comparison: Influenza B Washington Antibody95% CI: [0.822, 1.045]
Comparison: Influenza B Phuket Antibody95% CI: [0.809, 1.02]
Primary
Part A: Number of Participants With Medically Attended AEs (MAAEs), SAEs, Adverse Events of Special Interest (AESIs), and AEs Leading to Withdrawal
A MAAE is an AE that leads to an unscheduled visit to a healthcare practitioner. An AESI is an AE (serious or nonserious) of scientific and medical concern specific to the Sponsor's product or program, for which ongoing monitoring and immediate notification by the Investigator to the Sponsor are required. 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, 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 through Day 181 (end of Study Part A)
Population: The Safety Set included all randomized participants who received any study intervention. Participants were included in the treatment arm corresponding to the study drug they actually received.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part A: mRNA-1345 + Placebo | Part A: Number of Participants With Medically Attended AEs (MAAEs), SAEs, Adverse Events of Special Interest (AESIs), and AEs Leading to Withdrawal | MAAE | 41 Participants |
| Part A: mRNA-1345 + Placebo | Part A: Number of Participants With Medically Attended AEs (MAAEs), SAEs, Adverse Events of Special Interest (AESIs), and AEs Leading to Withdrawal | SAE | 4 Participants |
| Part A: mRNA-1345 + Placebo | Part A: Number of Participants With Medically Attended AEs (MAAEs), SAEs, Adverse Events of Special Interest (AESIs), and AEs Leading to Withdrawal | AESI | 0 Participants |
| Part A: mRNA-1345 + Placebo | Part A: Number of Participants With Medically Attended AEs (MAAEs), SAEs, Adverse Events of Special Interest (AESIs), and AEs Leading to Withdrawal | AEs Leading to Withdrawal | 0 Participants |
| Part A: mRNA-1345 + Afluria® Quadrivalent | Part A: Number of Participants With Medically Attended AEs (MAAEs), SAEs, Adverse Events of Special Interest (AESIs), and AEs Leading to Withdrawal | AEs Leading to Withdrawal | 3 Participants |
| Part A: mRNA-1345 + Afluria® Quadrivalent | Part A: Number of Participants With Medically Attended AEs (MAAEs), SAEs, Adverse Events of Special Interest (AESIs), and AEs Leading to Withdrawal | MAAE | 136 Participants |
| Part A: mRNA-1345 + Afluria® Quadrivalent | Part A: Number of Participants With Medically Attended AEs (MAAEs), SAEs, Adverse Events of Special Interest (AESIs), and AEs Leading to Withdrawal | AESI | 1 Participants |
| Part A: mRNA-1345 + Afluria® Quadrivalent | Part A: Number of Participants With Medically Attended AEs (MAAEs), SAEs, Adverse Events of Special Interest (AESIs), and AEs Leading to Withdrawal | SAE | 28 Participants |
| Part B: mRNA-1273.214 + Placebo + Placebo | Part A: Number of Participants With Medically Attended AEs (MAAEs), SAEs, Adverse Events of Special Interest (AESIs), and AEs Leading to Withdrawal | AEs Leading to Withdrawal | 1 Participants |
| Part B: mRNA-1273.214 + Placebo + Placebo | Part A: Number of Participants With Medically Attended AEs (MAAEs), SAEs, Adverse Events of Special Interest (AESIs), and AEs Leading to Withdrawal | SAE | 24 Participants |
| Part B: mRNA-1273.214 + Placebo + Placebo | Part A: Number of Participants With Medically Attended AEs (MAAEs), SAEs, Adverse Events of Special Interest (AESIs), and AEs Leading to Withdrawal | AESI | 1 Participants |
| Part B: mRNA-1273.214 + Placebo + Placebo | Part A: Number of Participants With Medically Attended AEs (MAAEs), SAEs, Adverse Events of Special Interest (AESIs), and AEs Leading to Withdrawal | MAAE | 114 Participants |
Primary
Part A: Number of Participants With Solicited Local and Systemic Adverse Reactions (ARs) Within 7 Days After Day 1 Injection
Solicited ARs were collected in an electronic diary (eDiary). Local ARs: injection site pain, erythema (redness), swelling/induration (hardness); and axillary (underarm) swelling or tenderness ipsilateral to the side of injection. Systemic ARs: fever, headache, fatigue, myalgia, arthralgia, nausea/vomiting, and chills. Note, not all solicited ARs were considered adverse events (AEs). 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: Within 7 days after Day 1 injection
Population: Solicited Safety Set included all randomized participants who received any study intervention and contributed any solicited ARs data from the time of study injection on Day 1 through the following 6 days. Participants were included in the treatment arm corresponding to the study drug they actually received.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part A: mRNA-1345 + Placebo | Part A: Number of Participants With Solicited Local and Systemic Adverse Reactions (ARs) Within 7 Days After Day 1 Injection | 147 Participants |
| Part A: mRNA-1345 + Afluria® Quadrivalent | Part A: Number of Participants With Solicited Local and Systemic Adverse Reactions (ARs) Within 7 Days After Day 1 Injection | 395 Participants |
| Part B: mRNA-1273.214 + Placebo + Placebo | Part A: Number of Participants With Solicited Local and Systemic Adverse Reactions (ARs) Within 7 Days After Day 1 Injection | 291 Participants |
Primary
Part A: Number of Participants With Unsolicited Adverse Events (AEs) After Day 1 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. A summary of SAEs and all nonserious AEs (Other), regardless of causality, is located in the Reported Adverse Events section.
Time frame: Day 1 through Day 28 (28 days after Day 1 injection)
Population: The Safety Set included all randomized participants who received any study intervention. Participants were included in the treatment arm corresponding to the study drug they actually received.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part A: mRNA-1345 + Placebo | Part A: Number of Participants With Unsolicited Adverse Events (AEs) After Day 1 Injection | 21 Participants |
| Part A: mRNA-1345 + Afluria® Quadrivalent | Part A: Number of Participants With Unsolicited Adverse Events (AEs) After Day 1 Injection | 57 Participants |
| Part B: mRNA-1273.214 + Placebo + Placebo | Part A: Number of Participants With Unsolicited Adverse Events (AEs) After Day 1 Injection | 46 Participants |
Primary
Part A: Percentage of Participants With Seroresponse in RSV-A NAbs at Day 29
Seroresponse was defined as ≥4 × lower limit of quantification (LLOQ) if baseline was \<LLOQ or 4-fold or greater increase from baseline if baseline was ≥LLOQ. As prespecified, only arms where participants received mRNA-1345 are presented for this outcome measure.
Time frame: Day 29
Population: PP Set: All participants who received the assigned study injections according to protocol, complied with immunogenicity sampling (baseline and at least 1 Day 29 post-injection assessment), and had no major protocol deviations affecting the immune response. 'Overall number of participants analyzed' = participants evaluable for this endpoint.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part A: mRNA-1345 + Placebo | Part A: Percentage of Participants With Seroresponse in RSV-A NAbs at Day 29 | 72.4 percentage of participants |
| Part A: mRNA-1345 + Afluria® Quadrivalent | Part A: Percentage of Participants With Seroresponse in RSV-A NAbs at Day 29 | 61.2 percentage of participants |
95% CI: [-17.9, -4.1]
Primary
Part B: Geometric Mean Concentration (GMC) of Serum Ab Level, as Measured by Neutralization Assay for SARS-Cov-2 at Day 29
The model-based GM titer was estimated on ANCOVA model. SARS-CoV-2 variants included Wuhan-Hu-1 and B.1.1.529. Antibody values reported as below LLOQ were replaced by 0.5\*LLOQ. Values greater than the ULOQ were replaced by the ULOQ. LLOQ was 10 arbitrary units (AU)/milliliters (mL) and ULOQ was 111433 AU/mL for Wuhan-Hu-1. LLOQ was 8 and ULOQ was B.1.1.529 for B1.1.529. As prespecified, only arms where participants received mRNA-1273.214 are presented for this outcome measure.
Time frame: Day 29
Population: PP Set: All participants who received the assigned study injections according to protocol, complied with immunogenicity sampling (baseline and at least 1 Day 29 post-injection assessment), and had no major protocol deviations affecting the immune response. 'Overall number of participants analyzed' = participants evaluable for this endpoint. 'Number analyzed' = participants evaluable for specified category.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Part A: mRNA-1345 + Placebo | Part B: Geometric Mean Concentration (GMC) of Serum Ab Level, as Measured by Neutralization Assay for SARS-Cov-2 at Day 29 | Wuhan-Hu-1 | 9881.69 AU/mL |
| Part A: mRNA-1345 + Placebo | Part B: Geometric Mean Concentration (GMC) of Serum Ab Level, as Measured by Neutralization Assay for SARS-Cov-2 at Day 29 | B.1.1.529 | 2353.15 AU/mL |
| Part A: mRNA-1345 + Afluria® Quadrivalent | Part B: Geometric Mean Concentration (GMC) of Serum Ab Level, as Measured by Neutralization Assay for SARS-Cov-2 at Day 29 | Wuhan-Hu-1 | 10300.49 AU/mL |
| Part A: mRNA-1345 + Afluria® Quadrivalent | Part B: Geometric Mean Concentration (GMC) of Serum Ab Level, as Measured by Neutralization Assay for SARS-Cov-2 at Day 29 | B.1.1.529 | 2342.87 AU/mL |
Comparison: GMR for Wuhan-Hu-195% CI: [0.872, 1.056]
Comparison: GMR for B.1.1.52995% CI: [0.888, 1.137]
Primary
Part B: GMT of Serum RSV-A at Day 29
Antibody values reported as below LLOQ were replaced by 0.5\*LLOQ. Values greater than the upper limit of quantification (ULOQ) were replaced by the ULOQ. LLOQ was 13 IU/mL and ULOQ was 259061 IU/mL for RSV-A. As prespecified, only arms where participants received mRNA-1345 are presented for this outcome measure.
Time frame: Day 29
Population: PP Set: All participants who received the assigned study injections according to protocol, complied with immunogenicity sampling (baseline and at least 1 Day 29 post-injection assessment), and had no major protocol deviations affecting the immune response. 'Overall number of participants analyzed' = participants evaluable for this endpoint.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Part A: mRNA-1345 + Placebo | Part B: GMT of Serum RSV-A at Day 29 | 19071.03 IU/mL |
| Part A: mRNA-1345 + Afluria® Quadrivalent | Part B: GMT of Serum RSV-A at Day 29 | 15171.23 IU/mL |
95% CI: [0.702, 0.901]
Primary
Part B: Number of Participants With MAAEs, SAEs, AESIs, and AEs Leading to Withdrawal
A MAAE is an AE that leads to an unscheduled visit to a healthcare practitioner. An AESI is an AE (serious or nonserious) of scientific and medical concern specific to the Sponsor's product or program, for which ongoing monitoring and immediate notification by the Investigator to the Sponsor are required. 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, 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 through Day 211
Population: Safety Set included all randomized participants who received any study intervention. Participants were included in the treatment arm corresponding to the study drug they actually received.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part A: mRNA-1345 + Placebo | Part B: Number of Participants With MAAEs, SAEs, AESIs, and AEs Leading to Withdrawal | MAAEs | 109 Participants |
| Part A: mRNA-1345 + Placebo | Part B: Number of Participants With MAAEs, SAEs, AESIs, and AEs Leading to Withdrawal | SAEs | 18 Participants |
| Part A: mRNA-1345 + Placebo | Part B: Number of Participants With MAAEs, SAEs, AESIs, and AEs Leading to Withdrawal | AESIs | 5 Participants |
| Part A: mRNA-1345 + Placebo | Part B: Number of Participants With MAAEs, SAEs, AESIs, and AEs Leading to Withdrawal | AEs Leading to Withdrawal | 1 Participants |
| Part A: mRNA-1345 + Afluria® Quadrivalent | Part B: Number of Participants With MAAEs, SAEs, AESIs, and AEs Leading to Withdrawal | AEs Leading to Withdrawal | 0 Participants |
| Part A: mRNA-1345 + Afluria® Quadrivalent | Part B: Number of Participants With MAAEs, SAEs, AESIs, and AEs Leading to Withdrawal | MAAEs | 107 Participants |
| Part A: mRNA-1345 + Afluria® Quadrivalent | Part B: Number of Participants With MAAEs, SAEs, AESIs, and AEs Leading to Withdrawal | AESIs | 2 Participants |
| Part A: mRNA-1345 + Afluria® Quadrivalent | Part B: Number of Participants With MAAEs, SAEs, AESIs, and AEs Leading to Withdrawal | SAEs | 13 Participants |
| Part B: mRNA-1273.214 + Placebo + Placebo | Part B: Number of Participants With MAAEs, SAEs, AESIs, and AEs Leading to Withdrawal | AEs Leading to Withdrawal | 0 Participants |
| Part B: mRNA-1273.214 + Placebo + Placebo | Part B: Number of Participants With MAAEs, SAEs, AESIs, and AEs Leading to Withdrawal | SAEs | 10 Participants |
| Part B: mRNA-1273.214 + Placebo + Placebo | Part B: Number of Participants With MAAEs, SAEs, AESIs, and AEs Leading to Withdrawal | AESIs | 7 Participants |
| Part B: mRNA-1273.214 + Placebo + Placebo | Part B: Number of Participants With MAAEs, SAEs, AESIs, and AEs Leading to Withdrawal | MAAEs | 97 Participants |
Primary
Part B: Number of Participants With Solicited Local and Systemic ARs Within 7 Days After Day 1 Injection
Solicited ARs were collected in an eDiary. Local ARs: injection site pain, erythema (redness), swelling/induration (hardness); and axillary (underarm) swelling or tenderness ipsilateral to the side of injection. Systemic ARs: fever, headache, fatigue, myalgia, arthralgia, nausea/vomiting, and chills. Note, not all solicited ARs were considered AEs. Investigator reviewed whether the solicited AR was also to be recorded as an AE. A Summary of SAEs and nonserious AEs (Other), regardless of causality, is located in the Reported Adverse Events section.
Time frame: Within 7 days after Day 1 injection
Population: Solicited Safety Set included all randomized participants who received any study intervention and contributed any solicited ARs data from the time of study injection on Day 1 through the following 6 days. Participants were included in the treatment arm corresponding to the study drug they actually received. 'Overall number of participants analyzed' = participants evaluable for this endpoint.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part A: mRNA-1345 + Placebo | Part B: Number of Participants With Solicited Local and Systemic ARs Within 7 Days After Day 1 Injection | 358 Participants |
| Part A: mRNA-1345 + Afluria® Quadrivalent | Part B: Number of Participants With Solicited Local and Systemic ARs Within 7 Days After Day 1 Injection | 394 Participants |
| Part B: mRNA-1273.214 + Placebo + Placebo | Part B: Number of Participants With Solicited Local and Systemic ARs Within 7 Days After Day 1 Injection | 361 Participants |
Primary
Part B: Number of Participants With Solicited Local and Systemic ARs Within 7 Days After Day 29 Injection
Solicited ARs were collected in an eDiary. Local ARs: injection site pain, erythema (redness), swelling/induration (hardness); and axillary (underarm) swelling or tenderness ipsilateral to the side of injection. Systemic ARs: fever, headache, fatigue, myalgia, arthralgia, nausea/vomiting, and chills. Note, not all solicited ARs were considered AEs. Investigator reviewed whether the solicited AR was also to be recorded as an AE. A Summary of SAEs and nonserious AEs (Other), regardless of causality, is located in the Reported Adverse Events section.
Time frame: Within 7 days after Day 29 injection
Population: Part B Solicited Safety Set Day 29 Injection consisted of all randomized participants who received any study injection on Day 29 and contributed any solicited ARs. Participants were included in the treatment arm corresponding to the study drug they actually received. 'Overall number of participants analyzed' = participants evaluable for this endpoint.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part A: mRNA-1345 + Placebo | Part B: Number of Participants With Solicited Local and Systemic ARs Within 7 Days After Day 29 Injection | 265 Participants |
| Part A: mRNA-1345 + Afluria® Quadrivalent | Part B: Number of Participants With Solicited Local and Systemic ARs Within 7 Days After Day 29 Injection | 147 Participants |
| Part B: mRNA-1273.214 + Placebo + Placebo | Part B: Number of Participants With Solicited Local and Systemic ARs Within 7 Days After Day 29 Injection | 148 Participants |
Primary
Part B: Number of Participants With Unsolicited AEs After Day 1 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 PT/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. A summary of SAEs and all nonserious AEs (Other), regardless of causality, is located in the Reported Adverse Events section.
Time frame: Day 1 through Day 28 (28 days after Day 1 injection)
Population: Safety Set Day 1 injection included all randomized participants who received any study intervention. Participants were included in the treatment arm corresponding to the study drug they actually received.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part A: mRNA-1345 + Placebo | Part B: Number of Participants With Unsolicited AEs After Day 1 Injection | 41 Participants |
| Part A: mRNA-1345 + Afluria® Quadrivalent | Part B: Number of Participants With Unsolicited AEs After Day 1 Injection | 54 Participants |
| Part B: mRNA-1273.214 + Placebo + Placebo | Part B: Number of Participants With Unsolicited AEs After Day 1 Injection | 44 Participants |
Primary
Part B: Number of Participants With Unsolicited AEs After Day 29 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. A summary of SAEs and all nonserious AEs (Other), regardless of causality, is located in the Reported Adverse Events section.
Time frame: Day 29 through Day 57 (28 days after Day 29 injection)
Population: Safety Set Day 29 injection included all randomized participants who received any study intervention. Participants were included in the treatment arm corresponding to the study drug they actually received.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part A: mRNA-1345 + Placebo | Part B: Number of Participants With Unsolicited AEs After Day 29 Injection | 31 Participants |
| Part A: mRNA-1345 + Afluria® Quadrivalent | Part B: Number of Participants With Unsolicited AEs After Day 29 Injection | 25 Participants |
| Part B: mRNA-1273.214 + Placebo + Placebo | Part B: Number of Participants With Unsolicited AEs After Day 29 Injection | 26 Participants |
Primary
Part B: Percentage of Participants With Seroresponse for RSV-A Neutralizing Abs From Baseline to Day 29
Seroresponse was defined as ≥4 × LLOQ if baseline was \<LLOQ or 4-fold or greater increase from baseline if baseline was ≥LLOQ. As prespecified, only arms where participants received mRNA-1345 are presented for this outcome measure.
Time frame: Baseline to Day 29
Population: PP Set: All participants who received the assigned study injections according to protocol, complied with immunogenicity sampling (baseline and at least 1 Day 29 post-injection assessment), and had no major protocol deviations affecting the immune response. 'Overall number of participants analyzed' = participants evaluable for this endpoint.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part A: mRNA-1345 + Placebo | Part B: Percentage of Participants With Seroresponse for RSV-A Neutralizing Abs From Baseline to Day 29 | 75.4 percentage of participants |
| Part A: mRNA-1345 + Afluria® Quadrivalent | Part B: Percentage of Participants With Seroresponse for RSV-A Neutralizing Abs From Baseline to Day 29 | 70.9 percentage of participants |
95% CI: [-9.9, 1]
Primary
Part B: Percentage of Participants With Seroresponse for SARS-Cov-2 NAbs From Baseline to Day 29
Seroresponse was defined as ≥4 × LLOQ if baseline was \<LLOQ or 4-fold or greater increase from baseline if baseline was ≥LLOQ. mRNA-As prespecified, only arms where participants received mRNA-1273.214 are presented for this outcome measure.
Time frame: Baseline to Day 29
Population: PP Set: All participants who received the assigned study injections according to protocol, complied with immunogenicity sampling (baseline and at least 1 Day 29 post-injection assessment), and had no major protocol deviations affecting the immune response. 'Overall number of participants analyzed' = participants evaluable for this endpoint. 'Number analyzed' = participants evaluable for specified category.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Part A: mRNA-1345 + Placebo | Part B: Percentage of Participants With Seroresponse for SARS-Cov-2 NAbs From Baseline to Day 29 | Wuhan-Hu-1 | 52.7 percentage of participants |
| Part A: mRNA-1345 + Placebo | Part B: Percentage of Participants With Seroresponse for SARS-Cov-2 NAbs From Baseline to Day 29 | B.1.1.529 | 68.4 percentage of participants |
| Part A: mRNA-1345 + Afluria® Quadrivalent | Part B: Percentage of Participants With Seroresponse for SARS-Cov-2 NAbs From Baseline to Day 29 | Wuhan-Hu-1 | 52.5 percentage of participants |
| Part A: mRNA-1345 + Afluria® Quadrivalent | Part B: Percentage of Participants With Seroresponse for SARS-Cov-2 NAbs From Baseline to Day 29 | B.1.1.529 | 69.4 percentage of participants |
Comparison: SRR difference for Wuhan-Hu-195% CI: [-6, 6.3]
Comparison: SRR difference for B.1.1.52995% CI: [-6.6, 4.7]
Primary
Part C: GMT of Serum RSV-A and RSV-B NAbs mRNA-1345 Revaccination Day 29 Compared to Primary Vaccination Day 29
Antibody values reported as below LLOQ were replaced by 0.5\*LLOQ. Values greater than the ULOQ were replaced by the ULOQ. LLOQ was 13 IU/mL and ULOQ was 259061 IU/mL for RSV-A. LLOQ was 10 IU/mL and ULOQ was 112476 IU/mL for RSV-B. mRNA-1345 Revaccination Day 29 and mRNA-1345 primary vaccination Day 29 (received in Part B) are presented.
Time frame: Primary Vaccination Day 29 to Revaccination Day 29
Population: PP Set: participants received mRNA-1345 revaccination, had prerevaccination and at least 1 postinjection assessment of immunogenicity after revaccination, complied with immunogenicity testing schedule, and had no major protocol derivations. 'Overall number of participants analyzed' = participants evaluable for this endpoint. 'Number analyzed' = participants evaluable for specified category.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Part A: mRNA-1345 + Placebo | Part C: GMT of Serum RSV-A and RSV-B NAbs mRNA-1345 Revaccination Day 29 Compared to Primary Vaccination Day 29 | RSV-A | 18190.30 IU/mL |
| Part A: mRNA-1345 + Placebo | Part C: GMT of Serum RSV-A and RSV-B NAbs mRNA-1345 Revaccination Day 29 Compared to Primary Vaccination Day 29 | RSV-B | 6746.41 IU/mL |
| Part A: mRNA-1345 + Afluria® Quadrivalent | Part C: GMT of Serum RSV-A and RSV-B NAbs mRNA-1345 Revaccination Day 29 Compared to Primary Vaccination Day 29 | RSV-A | 19649.18 IU/mL |
| Part A: mRNA-1345 + Afluria® Quadrivalent | Part C: GMT of Serum RSV-A and RSV-B NAbs mRNA-1345 Revaccination Day 29 Compared to Primary Vaccination Day 29 | RSV-B | 6123.47 IU/mL |
Comparison: GMR of RSV-A. GMR was calculated by back transforming the mean of paired difference of antibody levels on the logarithmic scale between revaccination Day 29 and primary vaccination Day 29.95% CI: [0.995, 1.166]
Comparison: GMR of RSV-B. GMR was calculated by back transforming the mean of paired difference of antibody levels on the logarithmic scale between revaccination Day 29 and primary vaccination Day 29.95% CI: [0.839, 0.984]
Primary
Part C: Number of Participants With MAAEs
A MAAE is an AE that leads to an unscheduled visit to a healthcare practitioner.
Time frame: Revaccination Day 1 through Day 181
Population: Safety Set included all participants who received any revaccination with mRNA-1345. Participants were included in the treatment arm corresponding to the study drug they actually received.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part A: mRNA-1345 + Placebo | Part C: Number of Participants With MAAEs | 105 Participants |
Primary
Part C: Number of Participants With SAEs, AESIs, and AEs Leading to Withdrawal
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, was a congenital anomaly/birth defect, or was an important medical event. An AESI is an AE (serious or nonserious) of scientific and medical concern specific to the Sponsor's product or program, for which ongoing monitoring and immediate notification by the Investigator to the Sponsor are required. A summary of SAEs and all nonserious AEs (Other), regardless of causality, is located in the Reported Adverse Events section.
Time frame: Revaccination Day 1 through Day 361
Population: Safety Set included all participants who received any revaccination with mRNA-1345. Participants were included in the treatment arm corresponding to the study drug they actually received.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part A: mRNA-1345 + Placebo | Part C: Number of Participants With SAEs, AESIs, and AEs Leading to Withdrawal | SAEs | 28 Participants |
| Part A: mRNA-1345 + Placebo | Part C: Number of Participants With SAEs, AESIs, and AEs Leading to Withdrawal | AESIs | 2 Participants |
| Part A: mRNA-1345 + Placebo | Part C: Number of Participants With SAEs, AESIs, and AEs Leading to Withdrawal | AEs Leading to Withdrawal | 5 Participants |
Primary
Part C: Number of Participants With Solicited Local and Systemic Within 7 Days After Revaccination Day 1
Solicited ARs were collected in an electronic eDiary. Local ARs: injection site pain, erythema (redness), swelling/induration (hardness); and axillary (underarm) swelling or tenderness ipsilateral to the side of injection. Systemic ARs: fever, headache, fatigue, myalgia, arthralgia, nausea/vomiting, and chills. Note, not all solicited ARs were considered AEs. Investigator reviewed whether the solicited AR was also to be recorded as an AE. A Summary of SAEs and nonserious AEs (Other), regardless of causality, is located in the Reported Adverse Events section.
Time frame: Within 7 days after Day 1 revaccination
Population: Solicited Safety Set included all participants who received revaccination with mRNA-1345 and contributed any solicited AR data. Participants were included in the treatment arm corresponding to the study drug they actually received.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part A: mRNA-1345 + Placebo | Part C: Number of Participants With Solicited Local and Systemic Within 7 Days After Revaccination Day 1 | 338 Participants |
Primary
Part C: Number of Participants With Unsolicited AEs Within 28 Days After Revaccination Day 1
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 PT/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. A summary of SAEs and all nonserious AEs (Other), regardless of causality, is located in the Reported Adverse Events section.
Time frame: Revaccination Day 1 through Day 28 (28 days after revaccination Day 1)
Population: Safety Set included all participants who received any revaccination with mRNA-1345. Participants were included in the treatment arm corresponding to the study drug they actually received.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part A: mRNA-1345 + Placebo | Part C: Number of Participants With Unsolicited AEs Within 28 Days After Revaccination Day 1 | 31 Participants |
Secondary
Part A: Geometric Mean Fold Rise (GMFR) of Serum RSV-A and RSV-B NAbs at Day 181
95% CI for GMFR (postinjection/baseline titers) 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. As prespecified, only arms where participants received mRNA-1345 are presented for this outcome measure.
Time frame: Day 181
Population: PP Set: All participants who received the assigned study injections according to protocol, complied with immunogenicity sampling (baseline and at least 1 Day 29 post-injection assessment), and had no major protocol deviations affecting the immune response. 'Overall number of participants analyzed' = participants evaluable for this endpoint. 'Number analyzed' = participants evaluable for specified category.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Part A: mRNA-1345 + Placebo | Part A: Geometric Mean Fold Rise (GMFR) of Serum RSV-A and RSV-B NAbs at Day 181 | RSV-A | 3.46 ratio |
| Part A: mRNA-1345 + Placebo | Part A: Geometric Mean Fold Rise (GMFR) of Serum RSV-A and RSV-B NAbs at Day 181 | RSV-B | 1.32 ratio |
| Part A: mRNA-1345 + Afluria® Quadrivalent | Part A: Geometric Mean Fold Rise (GMFR) of Serum RSV-A and RSV-B NAbs at Day 181 | RSV-A | 2.19 ratio |
| Part A: mRNA-1345 + Afluria® Quadrivalent | Part A: Geometric Mean Fold Rise (GMFR) of Serum RSV-A and RSV-B NAbs at Day 181 | RSV-B | 0.94 ratio |
Secondary
Part A: GMFR of Serum Anti-HA Ab Level, as Measured by HAI Assay for Influenza at Day 181
Influenza A strains included H1N1 and H3N2 and influenza B strains included Washington and Phuket strains. Antibody values reported as below LLOQ were replaced by 0.5\*LLOQ. Values greater than the ULOQ were replaced by the ULOQ. LLOQ was 10 and ULOQ was 2560 for Influenza A. LLOQ was 10 and ULOQ was 640 for Influenza B. 95% CI for GMFR (postinjection/baseline titers) 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. As prespecified, only arms where participants received Afluria® Quadrivalent are presented for this outcome measure.
Time frame: Day 181
Population: PP Set: All participants who received the assigned study injections according to protocol, complied with immunogenicity sampling (baseline and at least 1 Day 29 post-injection assessment), and had no major protocol deviations affecting the immune response. 'Overall number of participants analyzed' = participants evaluable for this endpoint.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Part A: mRNA-1345 + Placebo | Part A: GMFR of Serum Anti-HA Ab Level, as Measured by HAI Assay for Influenza at Day 181 | Influenza A H1N1 Antibody | 3.21 ratio |
| Part A: mRNA-1345 + Placebo | Part A: GMFR of Serum Anti-HA Ab Level, as Measured by HAI Assay for Influenza at Day 181 | Influenza A H3N2 Antibody | 2.28 ratio |
| Part A: mRNA-1345 + Placebo | Part A: GMFR of Serum Anti-HA Ab Level, as Measured by HAI Assay for Influenza at Day 181 | Influenza B Washington Antibody | 1.80 ratio |
| Part A: mRNA-1345 + Placebo | Part A: GMFR of Serum Anti-HA Ab Level, as Measured by HAI Assay for Influenza at Day 181 | Influenza B Phuket Antibody | 1.76 ratio |
| Part A: mRNA-1345 + Afluria® Quadrivalent | Part A: GMFR of Serum Anti-HA Ab Level, as Measured by HAI Assay for Influenza at Day 181 | Influenza B Phuket Antibody | 1.79 ratio |
| Part A: mRNA-1345 + Afluria® Quadrivalent | Part A: GMFR of Serum Anti-HA Ab Level, as Measured by HAI Assay for Influenza at Day 181 | Influenza A H1N1 Antibody | 3.08 ratio |
| Part A: mRNA-1345 + Afluria® Quadrivalent | Part A: GMFR of Serum Anti-HA Ab Level, as Measured by HAI Assay for Influenza at Day 181 | Influenza B Washington Antibody | 1.95 ratio |
| Part A: mRNA-1345 + Afluria® Quadrivalent | Part A: GMFR of Serum Anti-HA Ab Level, as Measured by HAI Assay for Influenza at Day 181 | Influenza A H3N2 Antibody | 2.23 ratio |
Secondary
Part A: GMT of Serum Anti-HA Ab Level, as Measured by HAI Assay for Influenza at Day 181
Influenza A strains included H1N1 and H3N2 and influenza B strains included Washington and Phuket strains. Antibody values reported as below LLOQ were replaced by 0.5\*LLOQ. Values greater than the ULOQ were replaced by the ULOQ. LLOQ was 10 and ULOQ was 2560 for Influenza A. LLOQ was 10 and ULOQ was 640 for Influenza B. As prespecified, only arms where participants received Afluria® Quadrivalent are presented for this outcome measure.
Time frame: Day 181
Population: PP Set: All participants who received the assigned study injections according to protocol, complied with immunogenicity sampling (baseline and at least 1 Day 29 post-injection assessment), and had no major protocol deviations affecting the immune response. 'Overall number of participants analyzed' = participants evaluable for this endpoint. 'Number analyzed' = participants evaluable for specified category.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Part A: mRNA-1345 + Placebo | Part A: GMT of Serum Anti-HA Ab Level, as Measured by HAI Assay for Influenza at Day 181 | Influenza B Washington Antibody | 32.11 titer |
| Part A: mRNA-1345 + Placebo | Part A: GMT of Serum Anti-HA Ab Level, as Measured by HAI Assay for Influenza at Day 181 | Influenza A H1N1 Antibody | 155.59 titer |
| Part A: mRNA-1345 + Placebo | Part A: GMT of Serum Anti-HA Ab Level, as Measured by HAI Assay for Influenza at Day 181 | Influenza B Phuket Antibody | 25.64 titer |
| Part A: mRNA-1345 + Placebo | Part A: GMT of Serum Anti-HA Ab Level, as Measured by HAI Assay for Influenza at Day 181 | Influenza A H3N2 Antibody | 113.58 titer |
| Part A: mRNA-1345 + Afluria® Quadrivalent | Part A: GMT of Serum Anti-HA Ab Level, as Measured by HAI Assay for Influenza at Day 181 | Influenza B Phuket Antibody | 26.43 titer |
| Part A: mRNA-1345 + Afluria® Quadrivalent | Part A: GMT of Serum Anti-HA Ab Level, as Measured by HAI Assay for Influenza at Day 181 | Influenza A H1N1 Antibody | 156.47 titer |
| Part A: mRNA-1345 + Afluria® Quadrivalent | Part A: GMT of Serum Anti-HA Ab Level, as Measured by HAI Assay for Influenza at Day 181 | Influenza B Washington Antibody | 35.03 titer |
| Part A: mRNA-1345 + Afluria® Quadrivalent | Part A: GMT of Serum Anti-HA Ab Level, as Measured by HAI Assay for Influenza at Day 181 | Influenza A H3N2 Antibody | 109.36 titer |
Secondary
Part A: GMT of Serum RSV-A and RSV-B NAbs at Day 181
Antibody values reported as below LLOQ were replaced by 0.5\*LLOQ. Values greater than the ULOQ were replaced by the ULOQ. LLOQ was 13 IU/mL and ULOQ was 259061 IU/mL for RSV-A. LLOQ was 10 IU/mL and ULOQ was 112476 for RSV-B. As prespecified, only arms where participants received mRNA-1345 are presented for this outcome measure.
Time frame: Day 181
Population: PP Set: All participants who received the assigned study injections according to protocol, complied with immunogenicity sampling (baseline and at least 1 Day 29 post-injection assessment), and have no major protocol deviations affecting the immune response. 'Overall number of participants analyzed' = participants evaluable for this endpoint. Number analyzed' = participants evaluable for specified category.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Part A: mRNA-1345 + Placebo | Part A: GMT of Serum RSV-A and RSV-B NAbs at Day 181 | RSV-A | 7551.13 IU/mL |
| Part A: mRNA-1345 + Placebo | Part A: GMT of Serum RSV-A and RSV-B NAbs at Day 181 | RSV-B | 2402.86 IU/mL |
| Part A: mRNA-1345 + Afluria® Quadrivalent | Part A: GMT of Serum RSV-A and RSV-B NAbs at Day 181 | RSV-A | 6429.48 IU/mL |
| Part A: mRNA-1345 + Afluria® Quadrivalent | Part A: GMT of Serum RSV-A and RSV-B NAbs at Day 181 | RSV-B | 2301.47 IU/mL |
Secondary
Part A: GMT of Serum RSV-B NAbs at Day 29
Antibody values reported as below LLOQ were replaced by 0.5\*LLOQ. Values greater than the ULOQ were replaced by the ULOQ. LLOQ was 10 IU/mL and ULOQ was 112476 for RSV-B. As prespecified, only arms where participants received mRNA-1345 are presented for this outcome measure.
Time frame: Day 29
Population: PP Set: All participants who received the assigned study injections according to protocol, complied with immunogenicity sampling (baseline and at least 1 Day 29 post-injection assessment), and have no major protocol deviations affecting the immune response. 'Overall number of participants analyzed' = participants evaluable for this endpoint.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Part A: mRNA-1345 + Placebo | Part A: GMT of Serum RSV-B NAbs at Day 29 | 10436.03 IU/mL |
| Part A: mRNA-1345 + Afluria® Quadrivalent | Part A: GMT of Serum RSV-B NAbs at Day 29 | 8909.80 IU/mL |
95% CI: [0.728, 1.002]
Secondary
Part A: Percentage of Participants With ≥2-fold Increases From Baseline in RSV-A and RSV-B NAb Titers at Day 181
≥2-fold increase from baseline at participant level was defined as a change from below the LLOQ to equal or above 2 \* LLOQ, or at least a 2-fold increase if baseline was equal to or above the LLOQ. As prespecified, only arms where participants received mRNA-1345 are presented for this outcome measure.
Time frame: Baseline to Day 181
Population: PP Set: All participants who received the assigned study injections according to protocol, complied with immunogenicity sampling (baseline and at least 1 Day 29 post-injection assessment), and had no major protocol deviations affecting the immune response. 'Overall number of participants analyzed' = participants evaluable for this endpoint. 'Number analyzed' = participants evaluable for specified category.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Part A: mRNA-1345 + Placebo | Part A: Percentage of Participants With ≥2-fold Increases From Baseline in RSV-A and RSV-B NAb Titers at Day 181 | RSV-A | 67.0 percentage of participants |
| Part A: mRNA-1345 + Placebo | Part A: Percentage of Participants With ≥2-fold Increases From Baseline in RSV-A and RSV-B NAb Titers at Day 181 | RSV-B | 32.1 percentage of participants |
| Part A: mRNA-1345 + Afluria® Quadrivalent | Part A: Percentage of Participants With ≥2-fold Increases From Baseline in RSV-A and RSV-B NAb Titers at Day 181 | RSV-A | 54.1 percentage of participants |
| Part A: mRNA-1345 + Afluria® Quadrivalent | Part A: Percentage of Participants With ≥2-fold Increases From Baseline in RSV-A and RSV-B NAb Titers at Day 181 | RSV-B | 21.0 percentage of participants |
Secondary
Part A: Percentage of Participants With Seroconversion in Influenza A and B Strains at Day 181
Influenza A strains included H1N1 and H3N2 and influenza B strains included Washington and Phuket strains. Seroconversion was defined as a titer ≥1:40 if baseline was \<1:10 or a 4-fold or greater rise from baseline in the titers if Baseline was ≥1:10. As prespecified, only arms where participants received Afluria® Quadrivalent are presented for this outcome measure.
Time frame: Day 181
Population: PP Set: All participants who received the assigned study injections according to protocol, complied with immunogenicity sampling (baseline and at least 1 Day 29 post-injection assessment), and have no major protocol deviations affecting the immune response. 'Overall number of participants analyzed' = participants evaluable for this endpoint.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Part A: mRNA-1345 + Placebo | Part A: Percentage of Participants With Seroconversion in Influenza A and B Strains at Day 181 | Influenza A H1N1 Antibody | 41.1 percentage of participants |
| Part A: mRNA-1345 + Placebo | Part A: Percentage of Participants With Seroconversion in Influenza A and B Strains at Day 181 | Influenza A H3N2 Antibody | 29.4 percentage of participants |
| Part A: mRNA-1345 + Placebo | Part A: Percentage of Participants With Seroconversion in Influenza A and B Strains at Day 181 | Influenza B Washington Antibody | 19.5 percentage of participants |
| Part A: mRNA-1345 + Placebo | Part A: Percentage of Participants With Seroconversion in Influenza A and B Strains at Day 181 | Influenza B Phuket Antibody | 17.2 percentage of participants |
| Part A: mRNA-1345 + Afluria® Quadrivalent | Part A: Percentage of Participants With Seroconversion in Influenza A and B Strains at Day 181 | Influenza B Phuket Antibody | 18.8 percentage of participants |
| Part A: mRNA-1345 + Afluria® Quadrivalent | Part A: Percentage of Participants With Seroconversion in Influenza A and B Strains at Day 181 | Influenza A H1N1 Antibody | 38.8 percentage of participants |
| Part A: mRNA-1345 + Afluria® Quadrivalent | Part A: Percentage of Participants With Seroconversion in Influenza A and B Strains at Day 181 | Influenza B Washington Antibody | 19.7 percentage of participants |
| Part A: mRNA-1345 + Afluria® Quadrivalent | Part A: Percentage of Participants With Seroconversion in Influenza A and B Strains at Day 181 | Influenza A H3N2 Antibody | 28.7 percentage of participants |
Secondary
Part A: Percentage of Participants With Seroresponse in RSV-A and RSV-B NAb Titers at Day 181
Seroresponse was defined as ≥4 × LLOQ if baseline was \<LLOQ or 4-fold or greater increase from baseline if baseline was ≥LLOQ.As prespecified, only arms where participants received mRNA-1345 are presented for this outcome measure.
Time frame: Day 181
Population: PP Set: All participants who received the assigned study injections according to protocol, complied with immunogenicity sampling (baseline and at least 1 Day 29 post-injection assessment), and had no major protocol deviations affecting the immune response. 'Overall number of participants analyzed' = participants evaluable for this endpoint. 'Number analyzed' = participants evaluable for specified category.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Part A: mRNA-1345 + Placebo | Part A: Percentage of Participants With Seroresponse in RSV-A and RSV-B NAb Titers at Day 181 | RSV-A | 46.8 percentage of participants |
| Part A: mRNA-1345 + Placebo | Part A: Percentage of Participants With Seroresponse in RSV-A and RSV-B NAb Titers at Day 181 | RSV-B | 13.3 percentage of participants |
| Part A: mRNA-1345 + Afluria® Quadrivalent | Part A: Percentage of Participants With Seroresponse in RSV-A and RSV-B NAb Titers at Day 181 | RSV-A | 29.9 percentage of participants |
| Part A: mRNA-1345 + Afluria® Quadrivalent | Part A: Percentage of Participants With Seroresponse in RSV-A and RSV-B NAb Titers at Day 181 | RSV-B | 6.7 percentage of participants |
Secondary
Part A: Percentage of Participants With Seroresponse in RSV-B NAbs at Day 29
Seroresponse was defined as ≥4 × LLOQ if baseline was \<LLOQ or 4-fold or greater increase from baseline if baseline was ≥LLOQ. As prespecified, only arms where participants received mRNA-1345 are presented for this outcome measure.
Time frame: Day 29
Population: PP Set: All participants who received the assigned study injections according to protocol, complied with immunogenicity sampling (baseline and at least 1 Day 29 post-injection assessment), and have no major protocol deviations affecting the immune response. 'Overall number of participants analyzed' = participants evaluable for this endpoint.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part A: mRNA-1345 + Placebo | Part A: Percentage of Participants With Seroresponse in RSV-B NAbs at Day 29 | 63.8 percentage of participants |
| Part A: mRNA-1345 + Afluria® Quadrivalent | Part A: Percentage of Participants With Seroresponse in RSV-B NAbs at Day 29 | 49.5 percentage of participants |
95% CI: [-21.5, -6.9]
Secondary
Part B: GMC of Serum Ab Level, as Measured by Neutralization Assay for SARS-Cov-2 at Day 181
95% CI for GM value was calculated based on the t-distribution of the log-transformed values between analysis timepoint and baseline, then back transformed to the original scale for presentation. SARS-CoV-2 variants included Wuhan-Hu-1 and B.1.1.529. Antibody values reported as below LLOQ were replaced by 0.5\*LLOQ. Values greater than the ULOQ were replaced by the ULOQ. LLOQ was 10 AU/mL and ULOQ was 111433 AU/mL for Wuhan-Hu-1. LLOQ was 8 AU/mL and ULOQ was 24503 for B1.1.529.
Time frame: Day 181
Population: PP Set: All participants who received the assigned study injections according to protocol, complied with immunogenicity sampling (baseline and at least 1 Day 29 post-injection assessment), and had no major protocol deviations affecting the immune response. 'Overall number of participants analyzed' = participants evaluable for this endpoint.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Part A: mRNA-1345 + Placebo | Part B: GMC of Serum Ab Level, as Measured by Neutralization Assay for SARS-Cov-2 at Day 181 | Wuhan-Hu-1 | 4075.34 AU/mL |
| Part A: mRNA-1345 + Placebo | Part B: GMC of Serum Ab Level, as Measured by Neutralization Assay for SARS-Cov-2 at Day 181 | B.1.1.529 | 1002.35 AU/mL |
| Part A: mRNA-1345 + Afluria® Quadrivalent | Part B: GMC of Serum Ab Level, as Measured by Neutralization Assay for SARS-Cov-2 at Day 181 | Wuhan-Hu-1 | 3615.45 AU/mL |
| Part A: mRNA-1345 + Afluria® Quadrivalent | Part B: GMC of Serum Ab Level, as Measured by Neutralization Assay for SARS-Cov-2 at Day 181 | B.1.1.529 | 889.75 AU/mL |
| Part B: mRNA-1273.214 + Placebo + Placebo | Part B: GMC of Serum Ab Level, as Measured by Neutralization Assay for SARS-Cov-2 at Day 181 | Wuhan-Hu-1 | 3665.39 AU/mL |
| Part B: mRNA-1273.214 + Placebo + Placebo | Part B: GMC of Serum Ab Level, as Measured by Neutralization Assay for SARS-Cov-2 at Day 181 | B.1.1.529 | 919.49 AU/mL |
Secondary
Part B: GMC of Serum Ab Level, as Measured by Neutralization Assay for SARS-Cov-2 at Day 211
95% CI for GM value was calculated based on the t-distribution of the log-transformed values between analysis timepoint and baseline, then back transformed to the original scale for presentation. SARS-CoV-2 variants included Wuhan-Hu-1 and B.1.1.529. Antibody values reported as below LLOQ were replaced by 0.5\*LLOQ. Values greater than the ULOQ were replaced by the ULOQ. LLOQ was 10 AU/mL and ULOQ was 111433 AU/mL for Wuhan-Hu-1. LLOQ was 8 AU/mL and ULOQ was 24503 for B1.1.529.
Time frame: Day 211
Population: PP Set: All participants who received the assigned study injections according to protocol, complied with immunogenicity sampling (baseline and at least 1 Day 29 post-injection assessment), and had no major protocol deviations affecting the immune response. 'Overall number of participants analyzed' = participants evaluable for this endpoint.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Part A: mRNA-1345 + Placebo | Part B: GMC of Serum Ab Level, as Measured by Neutralization Assay for SARS-Cov-2 at Day 211 | Wuhan-Hu-1 | 3551.74 AU/mL |
| Part A: mRNA-1345 + Placebo | Part B: GMC of Serum Ab Level, as Measured by Neutralization Assay for SARS-Cov-2 at Day 211 | B.1.1.529 | 923.10 AU/mL |
| Part A: mRNA-1345 + Afluria® Quadrivalent | Part B: GMC of Serum Ab Level, as Measured by Neutralization Assay for SARS-Cov-2 at Day 211 | Wuhan-Hu-1 | 3034.11 AU/mL |
| Part A: mRNA-1345 + Afluria® Quadrivalent | Part B: GMC of Serum Ab Level, as Measured by Neutralization Assay for SARS-Cov-2 at Day 211 | B.1.1.529 | 797.17 AU/mL |
| Part B: mRNA-1273.214 + Placebo + Placebo | Part B: GMC of Serum Ab Level, as Measured by Neutralization Assay for SARS-Cov-2 at Day 211 | Wuhan-Hu-1 | 3123.69 AU/mL |
| Part B: mRNA-1273.214 + Placebo + Placebo | Part B: GMC of Serum Ab Level, as Measured by Neutralization Assay for SARS-Cov-2 at Day 211 | B.1.1.529 | 795.90 AU/mL |
Secondary
Part B: GMFR of Serum Ab Level, as Measured by Neutralization Assay for SARS-Cov-2 at Day 181
95% CI for GMFR (postinjection/baseline titers) 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.
Time frame: Day 181
Population: PP Set: All participants who received the assigned study injections according to protocol, complied with immunogenicity sampling (baseline and at least 1 Day 29 post-injection assessment), and had no major protocol deviations affecting the immune response. 'Overall number of participants analyzed' = participants evaluable for this endpoint. 'Number analyzed' = participants evaluable for specified category.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Part A: mRNA-1345 + Placebo | Part B: GMFR of Serum Ab Level, as Measured by Neutralization Assay for SARS-Cov-2 at Day 181 | Wuhan-Hu-1 | 2.12 ratio |
| Part A: mRNA-1345 + Placebo | Part B: GMFR of Serum Ab Level, as Measured by Neutralization Assay for SARS-Cov-2 at Day 181 | B.1.1.529 | 3.57 ratio |
| Part A: mRNA-1345 + Afluria® Quadrivalent | Part B: GMFR of Serum Ab Level, as Measured by Neutralization Assay for SARS-Cov-2 at Day 181 | Wuhan-Hu-1 | 1.94 ratio |
| Part A: mRNA-1345 + Afluria® Quadrivalent | Part B: GMFR of Serum Ab Level, as Measured by Neutralization Assay for SARS-Cov-2 at Day 181 | B.1.1.529 | 3.27 ratio |
| Part B: mRNA-1273.214 + Placebo + Placebo | Part B: GMFR of Serum Ab Level, as Measured by Neutralization Assay for SARS-Cov-2 at Day 181 | Wuhan-Hu-1 | 1.84 ratio |
| Part B: mRNA-1273.214 + Placebo + Placebo | Part B: GMFR of Serum Ab Level, as Measured by Neutralization Assay for SARS-Cov-2 at Day 181 | B.1.1.529 | 3.13 ratio |
Secondary
Part B: GMFR of Serum Ab Level, as Measured by Neutralization Assay for SARS-Cov-2 at Day 211
95% CI for GMFR (postinjection/baseline titers) 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.
Time frame: Day 211
Population: PP Set: All participants who received the assigned study injections according to protocol, complied with immunogenicity sampling (baseline and at least 1 Day 29 post-injection assessment), and had no major protocol deviations affecting the immune response. 'Overall number of participants analyzed' = participants evaluable for this endpoint. 'Number analyzed' = participants evaluable for specified category.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Part A: mRNA-1345 + Placebo | Part B: GMFR of Serum Ab Level, as Measured by Neutralization Assay for SARS-Cov-2 at Day 211 | Wuhan-Hu-1 | 1.87 ratio |
| Part A: mRNA-1345 + Placebo | Part B: GMFR of Serum Ab Level, as Measured by Neutralization Assay for SARS-Cov-2 at Day 211 | B.1.1.529 | 3.31 ratio |
| Part A: mRNA-1345 + Afluria® Quadrivalent | Part B: GMFR of Serum Ab Level, as Measured by Neutralization Assay for SARS-Cov-2 at Day 211 | Wuhan-Hu-1 | 1.64 ratio |
| Part A: mRNA-1345 + Afluria® Quadrivalent | Part B: GMFR of Serum Ab Level, as Measured by Neutralization Assay for SARS-Cov-2 at Day 211 | B.1.1.529 | 2.95 ratio |
| Part B: mRNA-1273.214 + Placebo + Placebo | Part B: GMFR of Serum Ab Level, as Measured by Neutralization Assay for SARS-Cov-2 at Day 211 | Wuhan-Hu-1 | 1.59 ratio |
| Part B: mRNA-1273.214 + Placebo + Placebo | Part B: GMFR of Serum Ab Level, as Measured by Neutralization Assay for SARS-Cov-2 at Day 211 | B.1.1.529 | 2.72 ratio |
Secondary
Part B: GMFR of Serum RSV-A and RSV-B NAbs at Day 181
Antibody values reported as below LLOQ were replaced by 0.5\*LLOQ. Values greater than the ULOQ were replaced by the ULOQ. As prespecified, only arms where participants received mRNA-1345 are presented for this outcome measure.
Time frame: Day 181
Population: PP Set: All participants who received the assigned study injections according to protocol, complied with immunogenicity sampling (baseline and at least 1 Day 29 post-injection assessment), and had no major protocol deviations affecting the immune response. 'Overall number of participants analyzed' = participants evaluable for this endpoint. 'Number analyzed' = participants evaluable for specified category.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Part A: mRNA-1345 + Placebo | Part B: GMFR of Serum RSV-A and RSV-B NAbs at Day 181 | RSV-A | 2.91 ratio |
| Part A: mRNA-1345 + Placebo | Part B: GMFR of Serum RSV-A and RSV-B NAbs at Day 181 | RSV-B | 1.61 ratio |
| Part A: mRNA-1345 + Afluria® Quadrivalent | Part B: GMFR of Serum RSV-A and RSV-B NAbs at Day 181 | RSV-A | 2.58 ratio |
| Part A: mRNA-1345 + Afluria® Quadrivalent | Part B: GMFR of Serum RSV-A and RSV-B NAbs at Day 181 | RSV-B | 1.49 ratio |
Secondary
Part B: GMFR of Serum RSV-A and RSV-B NAbs at Day 211
Antibody values reported as below LLOQ were replaced by 0.5\*LLOQ. Values greater than the ULOQ were replaced by the ULOQ. As prespecified, only arms where participants received mRNA-1345 are presented for this outcome measure.
Time frame: Day 211
Population: PP Set: All participants who received the assigned study injections according to protocol, complied with immunogenicity sampling (baseline and at least 1 Day 29 post-injection assessment), and had no major protocol deviations affecting the immune response. 'Overall number of participants analyzed' = participants evaluable for this endpoint. 'Number analyzed' = participants evaluable for specified category.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Part A: mRNA-1345 + Placebo | Part B: GMFR of Serum RSV-A and RSV-B NAbs at Day 211 | RSV-A | 2.71 ratio |
| Part A: mRNA-1345 + Placebo | Part B: GMFR of Serum RSV-A and RSV-B NAbs at Day 211 | RSV-B | 1.50 ratio |
| Part A: mRNA-1345 + Afluria® Quadrivalent | Part B: GMFR of Serum RSV-A and RSV-B NAbs at Day 211 | RSV-A | 2.35 ratio |
| Part A: mRNA-1345 + Afluria® Quadrivalent | Part B: GMFR of Serum RSV-A and RSV-B NAbs at Day 211 | RSV-B | 1.40 ratio |
Secondary
Part B: GMT of Serum RSV-A and RSV-B NAbs at Day 181
Antibody values reported as below LLOQ were replaced by 0.5\*LLOQ. Values greater than the ULOQ were replaced by the ULOQ. LLOQ was 13 IU/mL and ULOQ was 259061 IU/mL for RSV-A. LLOQ was 10 IU/mL and ULOQ was 112476 for RSV-B. As prespecified, only arms where participants received mRNA-1345 are presented for this outcome measure.
Time frame: Day 181
Population: PP Set: All participants who received the assigned study injections according to protocol, complied with immunogenicity sampling (baseline and at least 1 Day 29 post-injection assessment), and had no major protocol deviations affecting the immune response. 'Overall number of participants analyzed' = participants evaluable for this endpoint.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Part A: mRNA-1345 + Placebo | Part B: GMT of Serum RSV-A and RSV-B NAbs at Day 181 | RSV-A | 6456.32 IU/mL |
| Part A: mRNA-1345 + Placebo | Part B: GMT of Serum RSV-A and RSV-B NAbs at Day 181 | RSV-B | 2447.67 IU/mL |
| Part A: mRNA-1345 + Afluria® Quadrivalent | Part B: GMT of Serum RSV-A and RSV-B NAbs at Day 181 | RSV-A | 5221.87 IU/mL |
| Part A: mRNA-1345 + Afluria® Quadrivalent | Part B: GMT of Serum RSV-A and RSV-B NAbs at Day 181 | RSV-B | 2274.83 IU/mL |
Secondary
Part B: GMT of Serum RSV-A and RSV-B NAbs at Day 211
Antibody values reported as below LLOQ were replaced by 0.5\*LLOQ. Values greater than the ULOQ were replaced by the ULOQ. LLOQ was 13 IU/mL and ULOQ was 259061 IU/mL for RSV-A. LLOQ was 10 IU/mL and ULOQ was 112476 for RSV-B. As prespecified, only arms where participants received mRNA-1345 are presented for this outcome measure.
Time frame: Day 211
Population: PP Set: All participants who received the assigned study injections according to protocol, complied with immunogenicity sampling (baseline and at least 1 Day 29 post-injection assessment), and had no major protocol deviations affecting the immune response. 'Overall number of participants analyzed' = participants evaluable for this endpoint. 'Number analyzed' = participants evaluable for specified category.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Part A: mRNA-1345 + Placebo | Part B: GMT of Serum RSV-A and RSV-B NAbs at Day 211 | RSV-A | 5921.09 IU/mL |
| Part A: mRNA-1345 + Placebo | Part B: GMT of Serum RSV-A and RSV-B NAbs at Day 211 | RSV-B | 2261.26 IU/mL |
| Part A: mRNA-1345 + Afluria® Quadrivalent | Part B: GMT of Serum RSV-A and RSV-B NAbs at Day 211 | RSV-A | 4696.74 IU/mL |
| Part A: mRNA-1345 + Afluria® Quadrivalent | Part B: GMT of Serum RSV-A and RSV-B NAbs at Day 211 | RSV-B | 2132.70 IU/mL |
Secondary
Part B: GMT of Serum RSV-B NAbs at Day 29
Antibody values reported as below LLOQ were replaced by 0.5\*LLOQ. Values greater than the ULOQ were replaced by the ULOQ. LLOQ was 10 IU/mL and ULOQ was 112476 for RSV-B. As prespecified, only arms where participants received mRNA-1345 are presented for this outcome measure.
Time frame: Day 29
Population: PP Set: All participants who received the assigned study injections according to protocol, complied with immunogenicity sampling (baseline and at least 1 Day 29 post-injection assessment), and had no major protocol deviations affecting the immune response. 'Overall number of participants analyzed' = participants evaluable for this endpoint.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Part A: mRNA-1345 + Placebo | Part B: GMT of Serum RSV-B NAbs at Day 29 | 6584.54 IU/mL |
| Part A: mRNA-1345 + Afluria® Quadrivalent | Part B: GMT of Serum RSV-B NAbs at Day 29 | 5843.94 IU/mL |
95% CI: [0.791, 0.995]
Secondary
Part B: Percentage of Participants With ≥2-fold Increases From Baseline in RSV-A and RSV-B NAb Titers at Day 181
≥2-fold increase from baseline at participant level was defined as a change from below the LLOQ to equal or above 2 \* LLOQ, or at least a 2-fold increase if baseline was equal to or above the LLOQ. LLOQ was 13 IU/mL and ULOQ was 259061 IU/mL for RSV-A. LLOQ was 10 IU/mL and ULOQ was 112476 for RSV-B. As prespecified, only arms where participants received mRNA-1345 are presented for this outcome measure.
Time frame: Baseline to Day 181
Population: PP Set: All participants who received the assigned study injections according to protocol, complied with immunogenicity sampling (baseline and at least 1 Day 29 post-injection assessment), and had no major protocol deviations affecting the immune response. 'Overall number of participants analyzed' = participants evaluable for this endpoint. 'Number analyzed' = participants evaluable for specified category.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Part A: mRNA-1345 + Placebo | Part B: Percentage of Participants With ≥2-fold Increases From Baseline in RSV-A and RSV-B NAb Titers at Day 181 | RSV-A | 62.8 percentage of participants |
| Part A: mRNA-1345 + Placebo | Part B: Percentage of Participants With ≥2-fold Increases From Baseline in RSV-A and RSV-B NAb Titers at Day 181 | RSV-B | 36.4 percentage of participants |
| Part A: mRNA-1345 + Afluria® Quadrivalent | Part B: Percentage of Participants With ≥2-fold Increases From Baseline in RSV-A and RSV-B NAb Titers at Day 181 | RSV-A | 58.3 percentage of participants |
| Part A: mRNA-1345 + Afluria® Quadrivalent | Part B: Percentage of Participants With ≥2-fold Increases From Baseline in RSV-A and RSV-B NAb Titers at Day 181 | RSV-B | 35.7 percentage of participants |
Secondary
Part B: Percentage of Participants With ≥2-fold Increases From Baseline in RSV-A and RSV-B NAb Titers at Day 211
≥2-fold increase from baseline at participant level was defined as a change from below the LLOQ to equal or above 2 \* LLOQ, or at least a 2-fold increase if baseline was equal to or above the LLOQ. LLOQ was 13 IU/mL and ULOQ was 259061 IU/mL for RSV-A. LLOQ was 10 IU/mL and ULOQ was 112476 for RSV-B. As prespecified, only arms where participants received mRNA-1345 are presented for this outcome measure.
Time frame: Day 211
Population: PP Set: All participants who received the assigned study injections according to protocol, complied with immunogenicity sampling (baseline and at least 1 Day 29 post-injection assessment), and had no major protocol deviations affecting the immune response. 'Overall number of participants analyzed' = participants evaluable for this endpoint. 'Number analyzed' = participants evaluable for specified category.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Part A: mRNA-1345 + Placebo | Part B: Percentage of Participants With ≥2-fold Increases From Baseline in RSV-A and RSV-B NAb Titers at Day 211 | RSV-A | 57.8 percentage of participants |
| Part A: mRNA-1345 + Placebo | Part B: Percentage of Participants With ≥2-fold Increases From Baseline in RSV-A and RSV-B NAb Titers at Day 211 | RSV-B | 33.7 percentage of participants |
| Part A: mRNA-1345 + Afluria® Quadrivalent | Part B: Percentage of Participants With ≥2-fold Increases From Baseline in RSV-A and RSV-B NAb Titers at Day 211 | RSV-A | 53.7 percentage of participants |
| Part A: mRNA-1345 + Afluria® Quadrivalent | Part B: Percentage of Participants With ≥2-fold Increases From Baseline in RSV-A and RSV-B NAb Titers at Day 211 | RSV-B | 30.6 percentage of participants |
Secondary
Part B: Percentage of Participants With Seroresponse for SARS-Cov-2 NAbs at Day 211
Seroresponse was defined as ≥4 × LLOQ if baseline was \<LLOQ or 4-fold or greater increase from baseline if baseline was ≥LLOQ. SARS-CoV-2 variants included Wuhan-Hu-1 and B.1.1.529. Antibody values reported as below LLOQ were replaced by 0.5\*LLOQ. Values greater than the ULOQ were replaced by the ULOQ. LLOQ was 10 and ULOQ was 111433 for Wuhan-Hu-1. LLOQ was 8 and ULOQ was B.1.1.529 for B1.1.529.
Time frame: Day 211
Population: PP Set: All participants who received the assigned study injections according to protocol, complied with immunogenicity sampling (baseline and at least 1 Day 29 post-injection assessment), and had no major protocol deviations affecting the immune response. 'Overall number of participants analyzed' = participants evaluable for this endpoint. Number analyzed' = participants evaluable for specified category.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Part A: mRNA-1345 + Placebo | Part B: Percentage of Participants With Seroresponse for SARS-Cov-2 NAbs at Day 211 | Wuhan-Hu-1 | 21.1 percentage of participants |
| Part A: mRNA-1345 + Placebo | Part B: Percentage of Participants With Seroresponse for SARS-Cov-2 NAbs at Day 211 | B.1.1.529 | 41.4 percentage of participants |
| Part A: mRNA-1345 + Afluria® Quadrivalent | Part B: Percentage of Participants With Seroresponse for SARS-Cov-2 NAbs at Day 211 | Wuhan-Hu-1 | 20.3 percentage of participants |
| Part A: mRNA-1345 + Afluria® Quadrivalent | Part B: Percentage of Participants With Seroresponse for SARS-Cov-2 NAbs at Day 211 | B.1.1.529 | 38.8 percentage of participants |
| Part B: mRNA-1273.214 + Placebo + Placebo | Part B: Percentage of Participants With Seroresponse for SARS-Cov-2 NAbs at Day 211 | Wuhan-Hu-1 | 17.8 percentage of participants |
| Part B: mRNA-1273.214 + Placebo + Placebo | Part B: Percentage of Participants With Seroresponse for SARS-Cov-2 NAbs at Day 211 | B.1.1.529 | 37.0 percentage of participants |
Secondary
Part B: Percentage of Participants With Seroresponse for SARS-Cov-2 NAbs From Baseline to Day 181
Seroresponse was defined as ≥4 × LLOQ if baseline was \<LLOQ or 4-fold or greater increase from baseline if baseline was ≥LLOQ. SARS-CoV-2 variants included Wuhan-Hu-1 and B.1.1.529. Antibody values reported as below LLOQ were replaced by 0.5\*LLOQ. Values greater than the ULOQ were replaced by the ULOQ. LLOQ was 10 and ULOQ was 111433 for Wuhan-Hu-1. LLOQ was 8 and ULOQ was B.1.1.529 for B1.1.529.
Time frame: Baseline to Day 181
Population: PP Set: All participants who received the assigned study injections according to protocol, complied with immunogenicity sampling (baseline and at least 1 Day 29 post-injection assessment), and had no major protocol deviations affecting the immune response. 'Overall number of participants analyzed' = participants evaluable for this endpoint. Number analyzed' = participants evaluable for specified category.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Part A: mRNA-1345 + Placebo | Part B: Percentage of Participants With Seroresponse for SARS-Cov-2 NAbs From Baseline to Day 181 | Wuhan-Hu-1 | 24.1 percentage of participants |
| Part A: mRNA-1345 + Placebo | Part B: Percentage of Participants With Seroresponse for SARS-Cov-2 NAbs From Baseline to Day 181 | B.1.1.529 | 44.7 percentage of participants |
| Part A: mRNA-1345 + Afluria® Quadrivalent | Part B: Percentage of Participants With Seroresponse for SARS-Cov-2 NAbs From Baseline to Day 181 | Wuhan-Hu-1 | 23.6 percentage of participants |
| Part A: mRNA-1345 + Afluria® Quadrivalent | Part B: Percentage of Participants With Seroresponse for SARS-Cov-2 NAbs From Baseline to Day 181 | B.1.1.529 | 41.0 percentage of participants |
| Part B: mRNA-1273.214 + Placebo + Placebo | Part B: Percentage of Participants With Seroresponse for SARS-Cov-2 NAbs From Baseline to Day 181 | Wuhan-Hu-1 | 19.8 percentage of participants |
| Part B: mRNA-1273.214 + Placebo + Placebo | Part B: Percentage of Participants With Seroresponse for SARS-Cov-2 NAbs From Baseline to Day 181 | B.1.1.529 | 40.5 percentage of participants |
Secondary
Part B: Percentage of Participants With Seroresponse in RSV-A and RSV-B NAb Titers at Day 181
Seroresponse was defined as ≥4 × LLOQ if baseline was \<LLOQ or 4-fold or greater increase from baseline if baseline was ≥LLOQ. As prespecified, only arms where participants received mRNA-1345 are presented for this outcome measure.
Time frame: Day 181
Population: PP Set: All participants who received the assigned study injections according to protocol, complied with immunogenicity sampling (baseline and at least 1 Day 29 post-injection assessment), and had no major protocol deviations affecting the immune response. 'Overall number of participants analyzed' = participants evaluable for this endpoint. 'Number analyzed' = participants evaluable for specified category.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Part A: mRNA-1345 + Placebo | Part B: Percentage of Participants With Seroresponse in RSV-A and RSV-B NAb Titers at Day 181 | RSV-A | 34.9 percentage of participants |
| Part A: mRNA-1345 + Placebo | Part B: Percentage of Participants With Seroresponse in RSV-A and RSV-B NAb Titers at Day 181 | RSV-B | 14.9 percentage of participants |
| Part A: mRNA-1345 + Afluria® Quadrivalent | Part B: Percentage of Participants With Seroresponse in RSV-A and RSV-B NAb Titers at Day 181 | RSV-A | 30.2 percentage of participants |
| Part A: mRNA-1345 + Afluria® Quadrivalent | Part B: Percentage of Participants With Seroresponse in RSV-A and RSV-B NAb Titers at Day 181 | RSV-B | 12.7 percentage of participants |
Secondary
Part B: Percentage of Participants With Seroresponse in RSV-A and RSV-B NAb Titers at Day 211
Seroresponse was defined as ≥4 × LLOQ if baseline was \<LLOQ or 4-fold or greater increase from baseline if baseline was ≥LLOQ. As prespecified, only arms where participants received mRNA-1345 are presented for this outcome measure.
Time frame: Day 211
Population: PP Set: All participants who received the assigned study injections according to protocol, complied with immunogenicity sampling (baseline and at least 1 Day 29 post-injection assessment), and had no major protocol deviations affecting the immune response. 'Overall number of participants analyzed' = participants evaluable for this endpoint. 'Number analyzed' = participants evaluable for specified category.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Part A: mRNA-1345 + Placebo | Part B: Percentage of Participants With Seroresponse in RSV-A and RSV-B NAb Titers at Day 211 | RSV-A | 32.5 percentage of participants |
| Part A: mRNA-1345 + Placebo | Part B: Percentage of Participants With Seroresponse in RSV-A and RSV-B NAb Titers at Day 211 | RSV-B | 12.3 percentage of participants |
| Part A: mRNA-1345 + Afluria® Quadrivalent | Part B: Percentage of Participants With Seroresponse in RSV-A and RSV-B NAb Titers at Day 211 | RSV-A | 26.5 percentage of participants |
| Part A: mRNA-1345 + Afluria® Quadrivalent | Part B: Percentage of Participants With Seroresponse in RSV-A and RSV-B NAb Titers at Day 211 | RSV-B | 10.1 percentage of participants |
Secondary
Part B: Percentage of Participants With Seroresponse in RSV-B NAbs From Baseline to Day 29
Seroresponse was defined as ≥4 × LLOQ if baseline was \<LLOQ or 4-fold or greater increase from baseline if baseline was ≥LLOQ. As prespecified, only arms where participants received mRNA-1345 are presented for this outcome measure.
Time frame: Baseline to Day 29
Population: PP Set: All participants who received the assigned study injections according to protocol, complied with immunogenicity sampling (baseline and at least 1 Day 29 post-injection assessment), and had no major protocol deviations affecting the immune response. 'Overall number of participants analyzed' = participants evaluable for this endpoint. 'Number analyzed' = participants evaluable for specified category.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part A: mRNA-1345 + Placebo | Part B: Percentage of Participants With Seroresponse in RSV-B NAbs From Baseline to Day 29 | 51.9 percentage of participants |
| Part A: mRNA-1345 + Afluria® Quadrivalent | Part B: Percentage of Participants With Seroresponse in RSV-B NAbs From Baseline to Day 29 | 46.0 percentage of participants |
95% CI: [-11.9, 0.3]
Secondary
Part C: GMFR of Serum RSV-A and RSV-B NAbs at Revaccination Day 361
95% CI for GMFR (postinjection/baseline titers) 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.
Time frame: Revaccination Day 361
Population: PP Set: All participants received mRNA-1345 revaccination, had prerevaccination and at least 1 postinjection assessment of immunogenicity after revaccination, complied with immunogenicity testing schedule, and had no major protocol derivations. 'Overall number of participants analyzed' = participants evaluable for this endpoint. 'Number analyzed' = participants evaluable for specified category.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Part A: mRNA-1345 + Placebo | Part C: GMFR of Serum RSV-A and RSV-B NAbs at Revaccination Day 361 | RSV-A | 2.26 ratio |
| Part A: mRNA-1345 + Placebo | Part C: GMFR of Serum RSV-A and RSV-B NAbs at Revaccination Day 361 | RSV-B | 1.42 ratio |
Secondary
Part C: GMT of Serum RSV-A and RSV-B NAbs at Revaccination Day 361
Antibody values reported as below LLOQ were replaced by 0.5\*LLOQ. Values greater than the ULOQ were replaced by the ULOQ. LLOQ was 13 IU/mL and ULOQ was 259061 IU/mL for RSV-A. LLOQ was 10 IU/mL and ULOQ was 112476 IU/mL for RSV-B.
Time frame: Revaccination Day 361
Population: PP Set: All participants who received mRNA-1345 revaccination, had prerevaccination and at least 1 postinjection assessment of immunogenicity after revaccination, complied with immunogenicity testing schedule, and had no major protocol derivations. 'Overall number of participants analyzed' = participants evaluable for this endpoint. 'Number analyzed' = participants evaluable for specified category.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Part A: mRNA-1345 + Placebo | Part C: GMT of Serum RSV-A and RSV-B NAbs at Revaccination Day 361 | RSV-A | 4708.27 IU/mL |
| Part A: mRNA-1345 + Placebo | Part C: GMT of Serum RSV-A and RSV-B NAbs at Revaccination Day 361 | RSV-B | 2251.24 IU/mL |
Secondary
Part C: Percentage of Participants With ≥2-fold Increases From Baseline (Before Primary Vaccination) in RSV-A and RSV-B NAb Titers at Revaccination Day 361
≥2-fold increase from baseline at participant level was defined as a change from below the LLOQ to equal or above 2 \* LLOQ, or at least a 2-fold increase if baseline was equal to or above the LLOQ. LLOQ was 13 IU/mL and ULOQ was 259061 IU/mL for RSV-A. LLOQ was 10 IU/mL and ULOQ was 112476 IU/mL for RSV-B.
Time frame: Baseline to Revaccination Day 361
Population: PP Set: All participants received mRNA-1345 revaccination, had prerevaccination and at least 1 postinjection assessment of immunogenicity after revaccination, complied with immunogenicity testing schedule, and had no major protocol derivations. 'Overall number of participants analyzed' = participants evaluable for this endpoint. 'Number analyzed' = participants evaluable for specified category.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Part A: mRNA-1345 + Placebo | Part C: Percentage of Participants With ≥2-fold Increases From Baseline (Before Primary Vaccination) in RSV-A and RSV-B NAb Titers at Revaccination Day 361 | RSV-A | 53.0 percentage of participants |
| Part A: mRNA-1345 + Placebo | Part C: Percentage of Participants With ≥2-fold Increases From Baseline (Before Primary Vaccination) in RSV-A and RSV-B NAb Titers at Revaccination Day 361 | RSV-B | 32.7 percentage of participants |
Secondary
Part C: Percentage of Participants With Seroresponse in RSV-A and RSV-B NAbs at Revaccination Day 361
Seroresponse was defined as ≥4 × LLOQ if baseline was \<LLOQ or 4-fold or greater increase from baseline if baseline was ≥LLOQ.
Time frame: Baseline to Revaccination Day 361
Population: PP Set: All participants received mRNA-1345 revaccination, had prerevaccination and at least 1 postinjection assessment of immunogenicity after revaccination, complied with immunogenicity testing schedule, and had no major protocol derivations. 'Overall number of participants analyzed' = participants evaluable for this endpoint. 'Number analyzed' = participants evaluable for specified category.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Part A: mRNA-1345 + Placebo | Part C: Percentage of Participants With Seroresponse in RSV-A and RSV-B NAbs at Revaccination Day 361 | RSV-A | 25.8 percentage of participants |
| Part A: mRNA-1345 + Placebo | Part C: Percentage of Participants With Seroresponse in RSV-A and RSV-B NAbs at Revaccination Day 361 | RSV-B | 11.5 percentage of participants |
Secondary
Part C: Percentage of Participants With Seroresponse in RSV-A and RSV-B NAbs From Baseline (Before Primary Vaccination) to Revaccination Day 29
Seroresponse was defined as ≥4 × LLOQ if baseline was \<LLOQ or 4-fold or greater increase from baseline if baseline was ≥LLOQ. Primary vaccination Day 29 (received in Part B) and Revaccination Day 29 are presented.
Time frame: Baseline (Before Primary Vaccination in Part B) to Revaccination Day 29
Population: PP Set: All participants received mRNA-1345 revaccination, had prerevaccination and at least 1 postinjection assessment of immunogenicity after revaccination, complied with immunogenicity testing schedule, and had no major protocol derivations. 'Overall number of participants analyzed' = participants evaluable for this endpoint. 'Number analyzed' = participants evaluable for specified category.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Part A: mRNA-1345 + Placebo | Part C: Percentage of Participants With Seroresponse in RSV-A and RSV-B NAbs From Baseline (Before Primary Vaccination) to Revaccination Day 29 | RSV-A | 75.3 percentage of participants |
| Part A: mRNA-1345 + Placebo | Part C: Percentage of Participants With Seroresponse in RSV-A and RSV-B NAbs From Baseline (Before Primary Vaccination) to Revaccination Day 29 | RSV-B | 48.2 percentage of participants |
| Part A: mRNA-1345 + Afluria® Quadrivalent | Part C: Percentage of Participants With Seroresponse in RSV-A and RSV-B NAbs From Baseline (Before Primary Vaccination) to Revaccination Day 29 | RSV-A | 77.5 percentage of participants |
| Part A: mRNA-1345 + Afluria® Quadrivalent | Part C: Percentage of Participants With Seroresponse in RSV-A and RSV-B NAbs From Baseline (Before Primary Vaccination) to Revaccination Day 29 | RSV-B | 47.5 percentage of participants |
Other Pre-specified
Number of Deaths During the Study
A death that occurred during the study or that came to the attention of the investigator during the study was reported to the Sponsor, whether or not it was considered related to study drug. The investigator assessed causality (that is, whether there is a reasonable possibility that the study drug caused the death). The relationship was characterized 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. The death was more likely explained by the study drug than by another cause.
Time frame: Up to Day 181 for Part A, up to Day 211 for Part B, and up to Day 361 for Part C
Population: Randomized Set included all participants who were randomized in the study, regardless of the participant's treatment status in the study.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part A: mRNA-1345 + Placebo | Number of Deaths During the Study | Deaths | 0 Participants |
| Part A: mRNA-1345 + Placebo | Number of Deaths During the Study | Deaths related to study drug | 0 Participants |
| Part A: mRNA-1345 + Afluria® Quadrivalent | Number of Deaths During the Study | Deaths | 3 Participants |
| Part A: mRNA-1345 + Afluria® Quadrivalent | Number of Deaths During the Study | Deaths related to study drug | 0 Participants |
| Part B: mRNA-1273.214 + Placebo + Placebo | Number of Deaths During the Study | Deaths related to study drug | 0 Participants |
| Part B: mRNA-1273.214 + Placebo + Placebo | Number of Deaths During the Study | Deaths | 1 Participants |
| Part B: mRNA-1345 + Placebo + mRNA-1273.214 | Number of Deaths During the Study | Deaths related to study drug | 0 Participants |
| Part B: mRNA-1345 + Placebo + mRNA-1273.214 | Number of Deaths During the Study | Deaths | 1 Participants |
| Part B: mRNA-1345 + mRNA-1273.214 + Placebo | Number of Deaths During the Study | Deaths | 0 Participants |
| Part B: mRNA-1345 + mRNA-1273.214 + Placebo | Number of Deaths During the Study | Deaths related to study drug | 0 Participants |
| Part B: mRNA-1273.214 + Placebo + Placebo | Number of Deaths During the Study | Deaths | 0 Participants |
| Part B: mRNA-1273.214 + Placebo + Placebo | Number of Deaths During the Study | Deaths related to study drug | 0 Participants |
| Part C: mRNA-1345 Revaccination | Number of Deaths During the Study | Deaths related to study drug | 0 Participants |
| Part C: mRNA-1345 Revaccination | Number of Deaths During the Study | Deaths | 3 Participants |