Seasonal Influenza
Conditions
Keywords
Seasonal Influenza, Flu, mRNA-1010, Vaccine
Brief summary
The primary objectives of this study are to evaluate the safety and reactogenicity of mRNA-1010, and to evaluate relative vaccine efficacy (rVE) of mRNA-1010 versus an active comparator against reverse transcription polymerase chain reaction (RT-PCR)-confirmed protocol-defined influenza-like illness (ILI) caused by any influenza A or B strains.
Interventions
BIOLOGICALmRNA-1010
Intramuscular (IM) injection
BIOLOGICALFluarix®
IM injection
BIOLOGICALInflusplit® Tetra
IM injection
BIOLOGICALFluarix Tetra
IM injection
BIOLOGICALAlpharix® Tetra
IM injection
Sponsors
ModernaTX, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
50 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
* Capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in the protocol. * Participants who are assigned female at birth or can become pregnant are eligible to participate if: * The participant is a person of nonchildbearing potential (PONCBP) or * The participant is a person of childbearing potential (POCBP) who: * Is not breast/chest feeding. * Is using an acceptable contraceptive method at least 28 days prior to Day 1 (Baseline) to at least 90 days after Day 1 (Baseline). * Has a negative highly sensitive pregnancy test (urine or serum as required by local regulation or institutional review board \[IRB\]/independent ethics committee \[IEC\]) at the Screening Visit and before study intervention (if the Day 1 \[Baseline\] Visit is not on the same day as the Screening Visit).
Exclusion criteria
* Acutely ill or febrile (temperature ≥38.0 degrees Celsius (℃) \[100.4° Fahrenheit \[F\]\]) within 72 hours prior to Day 1 (Baseline). * Close contact with someone with laboratory-confirmed influenza infection or with someone who has been treated with antiviral therapies for influenza (for example, Tamiflu®/oseltamivir) within 5 days prior to Day 1 (Baseline). * History of a diagnosis or condition that, in the judgment of the Investigator, is clinically unstable or may affect participant safety, assessment of study endpoints, assessment of immune response, or adherence to study procedures. * Reported history of congenital or acquired immunodeficiency, immunosuppressive condition, asplenia, or recurrent severe infections disease. * Tested positive for influenza by local health authority-approved testing methods within 180 days prior to Day 1 (Baseline). * History of anaphylaxis or severe hypersensitivity reaction requiring medical intervention after receipt of any of the following: mRNA vaccine or therapeutic; components of an mRNA vaccine or therapeutic; influenza vaccine; or components of an influenza vaccine, including egg protein. * Malignancy within 2 years prior to Day 1 (Baseline) (adequately treated basal cell carcinoma and squamous cell carcinoma are allowed). * Received corticosteroids at ≥10 milligram (mg)/day of prednisone or equivalent for \>14 days in total within 90 days prior to Day 1 (Baseline) or is anticipating the need for corticosteroids at any time during the study. * Received systemic immunosuppressive treatment, including long-acting biological therapies that affect immune responses (for example, infliximab), within 180 days prior to Day 1 (Baseline) or plans to do so during the study. * Treated with antiviral therapies for influenza (for example, Tamiflu) within 180 days prior to Day 1 (Baseline). * Received any vaccine authorized or approved by local health agency within 28 days prior to Day 1 (Baseline) or plans to do so within 14 days after Day 1 (Baseline). * Received a licensed seasonal influenza vaccine within 180 days prior to Day 1 (Baseline) or plans to do so (outside of this study) at any time during the study. * Received an investigational seasonal influenza vaccine within 1 year prior to Day 1 (Baseline). Note: participants from mRNA-1010-P304 Season 1 are NOT eligible to re enroll into Season 2. * Participated in a clinical study with investigational treatment within 90 days prior to Day 1 (Baseline) based on the medical history interview or plans to do so while participating in this study. * Is working or has worked as study personnel or is an immediate family member or house member of study personnel, study staff, or Sponsor personnel.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Solicited Local and Systemic Adverse Reactions (ARs) | Day 1 up to Day 7 | Solicited ARs were recorded daily using electronic diaries (eDiaries). 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 all Serious Adverse Events (SAEs) and Other Adverse Events (nonserious) regardless of causality is located in the 'Reported Adverse Events' Section. |
| Number of Participants With Unsolicited Adverse Events (AEs) | Day 1 up to Day 28 | An unsolicited AE was defined as any AE reported by the participant that was not specified as a solicited AR in the protocol. An AE was defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. A summary of all SAEs and Other Adverse Events (nonserious) regardless of causality is located in the 'Reported Adverse Events' Section. |
| Number of Participants With Medically Attended AEs (MAAEs), AEs Leading to Study Discontinuation, SAEs, or Adverse Events of Special Interests (AESIs) | Day 1 up to Day 181 | MAAEs were AEs that led to an unscheduled visit to a healthcare provider. SAEs were AEs that resulted in death, were life threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions, a congenital anomaly or birth defect, or was a medically important event. AESIs were AEs (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 was required. A summary of all SAEs and Other Adverse Events (nonserious) regardless of causality is located in the 'Reported Adverse Events' Section. |
| Number of Participants With First Episode of Reverse Tanscription Polymerase Chain Reaction (RT-PCR) Confirmed Protocol Defined Influenza-like Illness (ILI) Caused by Any Influenza A or B Strains | Day 14 up to end of influenza season (up to 7.5 months) | Protocol-defined ILI: At least 1 systemic symptom (temperature \>37.2 degrees celsius \[°C\] \[\>99.0 degrees Fahrenheit {°F}\], chills, feverish, tiredness, headaches, or myalgia) and at least 1 respiratory symptom (sore throat, cough, sputum production, wheezing, or difficulty breathing). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With First Episode of RT-PCR Confirmed Modified United States (US) Centers for Disease Control and Prevention (CDC)-Defined ILI Caused by Any Influenza A or B Strains | Day 14 up to end of influenza season (up to 7.5 months) | Modified CDC-defined ILI: Body temperature ≥37.2°C (≥99.0°F) accompanied by cough and/or sore throat. |
| Number of Participants With First Episode of RT-PCR-confirmed Protocol-defined ILI or Modified CDC-defined ILI Caused by Any Influenza A or B Strains With Antigenic Match to the Vaccine Strains | Day 14 up to end of influenza season (up to 7.5 months) | Protocol-defined ILI: At least 1 systemic symptom (temperature \>37.2°C \[\>99.0°F\], chills, feverish, tiredness, headaches, or myalgia) and at least 1 respiratory symptom (sore throat, cough, sputum production, wheezing, or difficulty breathing). Modified CDC-defined ILI: Body temperature \>37.2°C (\>99.0°F) accompanied by cough and/or sore throat. The confirmed RT-PCR test of influenza A or B strains with antigentic match to the vaccine strains. |
| Geometric Mean Titer (GMT) of Hemagglutination Inhibition (HAI) | Day 29 | Seasonal influenza A strains included H1N1 and H3N2 and seasonal influenza B strain included Victoria. Antibody values reported as below lower limit of quantification (LLOQ) were replaced by 0.5 \* LLOQ. Values greater than upper limit of quantification (ULOQ) were converted to ULOQ. LLOQ = 10, ULOQ = 3620 for H1N1. LLOQ = 10, ULOQ = 2560 for H3N2. LLOQ = 10, ULOQ = 1356. 95% confidence interval (CI) was calculated based on the t-distribution of log-transformed values for geometric mean (GM) titer, then back transformed to original scale for presentation. |
| Number of Participants Reaching Seroconversion as Measured by HAI | Day 29 | Seroconversion was defined as either a Baseline HAI titer \<1:10 and a post-baseline titer ≥1:40 or a Baseline HAI titer ≥1:10 and a minimum 4-fold rise in post-baseline HAI antibody titer. Seasonal influenza A strains included H1N1 and H3N2 and seasonal influenza B strain included Victoria. |
| Number of Participants With an HAI Titer ≥1:40 | Day 29 | Seasonal influenza A strains included H1N1 and H3N2 and seasonal influenza B strain included Victoria. |
| Geometric Mean Fold Rise (GMFR) of HAI Titers | Baseline, Day 29 | Seasonal influenza A strains included H1N1 and H3N2 and seasonal influenza B strain included Victoria. 95% CI was calculated based on the t-distribution of the difference in the log-transformed values for GM fold rise, then back transformed to the original scale for presentation. |
Countries
Belgium, Bulgaria, Canada, Estonia, Finland, Georgia, Germany, South Korea, Taiwan, United Kingdom, United States
Participant flow
Pre-assignment details
A total of 40805 participants were randomized; 20402 participants to the mRNA-1010 group and 20403 participants to the standard dose comparator group. Participants were followed up for up to Day 181 for safety assessment and for up to 7.5 months (up to end of influenza season) for efficacy assessment.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 64.2 years STANDARD_DEVIATION 8.28 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2072 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 18029 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 597 Participants |
| Race/Ethnicity, Customized Race American Indian or Alaska Native | 158 Participants |
| Race/Ethnicity, Customized Race Asian | 483 Participants |
| Race/Ethnicity, Customized Race Black or African American | 5404 Participants |
| Race/Ethnicity, Customized Race Multiple | 110 Participants |
| Race/Ethnicity, Customized Race Native Hawaiian or Other Pacific Islander | 19 Participants |
| Race/Ethnicity, Customized Race Not Reported | 167 Participants |
| Race/Ethnicity, Customized Race Other | 55 Participants |
| Race/Ethnicity, Customized Race Unknown | 16 Participants |
| Race/Ethnicity, Customized Race White | 33704 Participants |
| Sex: Female, Male Female | 23207 Participants |
| Sex: Female, Male Male | 8857 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 40 / 20,402 | 34 / 20,403 |
| other Total, other adverse events | 0 / 20,350 | 0 / 20,353 |
| serious Total, serious adverse events | 455 / 20,350 | 392 / 20,353 |
Outcome results
None listed