| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
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| E.1.1.1 | Medical condition in easily understood language |
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| E.1.1.2 | Therapeutic area | Diseases [C] - Virus Diseases [C02] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 20.0 |
| E.1.2 | Level | PT |
| E.1.2 | Classification code | 10022000 |
| E.1.2 | Term | Influenza |
| E.1.2 | System Organ Class | 10021881 - Infections and infestations |
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| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
- To evaluate the safety and reactogenicity of mRNA-1010 during the treatment period (28 days after study intervention) and follow-up period (period following the treatment period).
- To evaluate relative vaccine efficacy of mRNA-1010 as compared to an active comparator against influenza caused by any influenza A or B virus strains using protocol-defined ILI definition. |
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| E.2.2 | Secondary objectives of the trial |
To evaluate:
- relative vaccine efficacy of mRNA-1010 vaccine as compared to an active comparator against influenza caused by influenza A or B strains with similarity to the vaccine strains, using protocol defined ILI definition.
- relative vaccine efficacy of mRNA-1010 vaccine as compared to an active comparator against influenza caused by influenza A or B strains antigenically matched to the vaccine strains using protocol-defined ILI definition.
- relative vaccine efficacy of mRNA-1010 vaccine as compared to an active comparator against influenza caused by influenza A or B strains using CDC-defined ILI definition.
- relative vaccine efficacy of mRNA-1010 vaccine as compared to an active comparator against culture-confirmed influenza caused by any influenza A or B strains.
- relative vaccine efficacy of mRNA-1010 as compared to an active comparator to prevent hospitalizations associated with influenza illness. |
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| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
Participants are eligible to be included in the study only if all the following criteria apply:
1. At least 50 years of age at the time of consent (Screening visit).
2. Investigator has assessed that the participant understands and is willing and physically able to comply with protocol-mandated follow up, including all procedures.
3. Provide written informed consent for participation in this study, including all evaluations and procedures as specified by this protocol.
4. Females of nonchildbearing potential may be enrolled in the study. Nonchildbearing potential is defined as postmenopausal or permanently sterilized. Follicle-stimulating hormone may be measured at the discretion of the Investigator to confirm postmenopausal status.
5. Females of childbearing potential may be enrolled in the study if the participant fulfills all the following criteria:
- Has a negative pregnancy test at the Screening visit and on the day of vaccination prior to study vaccine dose being administered on Day 1.
- Has practiced adequate contraception or has abstained from all activities that could result in pregnancy for at least 28 days prior to the first dose (Day 1).
Adequate female contraception is defined as consistent and correct use of a local health authority-approved contraceptive method in accordance with the product label.
- Has agreed to continue adequate contraception through 90 days following study vaccine administration. |
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| E.4 | Principal exclusion criteria |
Participants are excluded from the study if any of the following criteria apply:
1. Close contact with someone with laboratory-confirmed influenza infection or with someone who has been treated with antiviral therapies for influenza within the past 5 days prior to the screening visit.
2. Close contact with someone with SARS-CoV-2 infection or COVID-19 as defined by the US CDC or has had a positive SARS-CoV-2 test in the past 10 days prior to the Screening visit.
3. Acutely ill or febrile (temperature ≥ 38.0°C [100.4°F]) 72 hours prior to or at the Screening visit or Day 1. Participants meeting this criterion may be rescheduled within the 28-day screening window and will retain their initially assigned participant number.
4. History of a diagnosis or condition that, in the judgment of the Investigator, is clinically unstable or may affect participant safety, assessment of safety endpoints, assessment of immune response, or adherence to study procedures. Clinically unstable is defined as a
diagnosis or condition requiring significant changes in management or medication within the 60 days prior to the Screening visit and includes ongoing workup of an undiagnosed illness that could lead to a new diagnosis or condition.
5. Reported history of congenital or acquired immunodeficiency, immunocompromising/ immunosuppressive condition, asplenia, or recurrent severe infections.
The following conditions are permitted at the discretion of the Investigator:
- Human immunodeficiency virus [HIV] positive participants on antiretroviral therapy with cluster of differentiation 4 count ≥ 350 cells/mm3 and HIV RNA ≤ 500 copies/mL within the past 12 months.
- Immune-mediated diseases that are stable, for example, Hashimoto's thyroiditis and type 1 diabetes mellitus or conditions such as asthma, psoriasis, vitiligo, gout, areata, autoimmune ovarian failure that do not require systemic immunosuppressants per Exclusion Criterion 10.
6. Dermatologic conditions that could affect local solicited AR assessment of the injection site.
7. Reported history of anaphylaxis or severe hypersensitivity reaction after receipt of any mRNA or influenza vaccines or any components of the mRNA or influenza vaccines, including egg protein.
8. Reported history of coagulopathy or bleeding disorder that is considered a contraindication to IM injection or phlebotomy.
9. Any medical, psychiatric, or occupational condition, including reported history of substance abuse, that, in the opinion of the Investigator, may pose additional risk due to participation in the study or that could interfere with the interpretation of study results.
10. Received systemic immunosuppressants for > 14 days in total within 180 days prior to the Screening visit (for glucocorticosteroids, ≥ 10 mg/day of prednisone or equivalent) or is anticipating the need for systemic immunosuppressive treatment at any time during
participation in the study. Inhaled, nasal, intra-articular, and topical steroids are allowed.
11. Received any vaccine authorized or approved by local health agency ≤ 28 days prior to study intervention (Day 1) or plans to receive a vaccine authorized or approved by local health agency within 28 days before or after the study intervention.
12. Plans to receive a non-study influenza vaccine during the study from Day 1 to Day 181.
13. Is unaware whether they received an influenza vaccine in the previous influenza season.
14. Received a seasonal influenza vaccine or any other investigational influenza vaccine within 180 days prior to the Randomization Visit.
15. Tested positive for influenza by local health authority-approved testing methods within 180 days prior to the Randomization Visit.
16. Has been treated with antiviral therapies for influenza (eg, Tamiflu) within 180 days prior to the Randomization Visit.
17. History of myocarditis, pericarditis, or myopericarditis within 60 days prior to the Screening visit. Participants who have not returned to baseline after their convalescent period will also be excluded.
18. History of Guillain-Barre syndrome.
19. Received systemic immunoglobulins and long-acting biological therapies that affect immune responses (eg infliximab) or blood products within 90 days prior to the Screening visit or plans to receive them during the study.
20. Donated ≥ 450 mL of blood products within 28 days prior to the Screening visit or plans to donate blood products during the study.
21. 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.
Note: interventions such as counseling, biofeedback, and cognitive therapy are not exclusionary.
22. Participant is working or has worked as study personnel or is an immediate family member or household member of study personnel, study site staff, or Sponsor personnel. |
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| E.5 End points |
| E.5.1 | Primary end point(s) |
- Solicited local and systemic ARs through 7 days after study injection.
- Unsolicited AEs through 28 days after study injection.
- MAAEs from Day 1 to Day 361 (Month 12)/EoS.
- AESIs from Day 1 to Day 361 (Month 12)/EoS.
- SAEs from Day 1 to Day 361 (Month 12)/EoS.
- AEs leading to discontinuation from Day 1 to Day 361 (Month 12)/EoS.
|
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| E.5.1.1 | Timepoint(s) of evaluation of this end point |
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| E.5.2 | Secondary end point(s) |
- First episode of RT-PCR-confirmed ILI that begins at least 14 days post vaccination through Day 181 (Month 6)/end of influenza season caused by influenza A or B strains with similarity to those selected for the seasonal vaccine.
- First episode of RT-PCR confirmed ILI that begins at least 14 days after vaccination through Day 181 (Month 6)/end of influenza season caused by influenza A or B strains antigenically matched to the vaccine strains selected for the seasonal vaccine. |
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| E.5.2.1 | Timepoint(s) of evaluation of this end point |
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | No |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | No |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | Yes |
| E.6.13.1 | Other scope of the trial description |
|
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | No |
| E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | No |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | No |
| E.8.1.5 | Parallel group | No |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | Yes |
| E.8.1.7.1 | Other trial design description |
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| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | Yes |
| E.8.2.2 | Placebo | No |
| E.8.2.3 | Other | No |
| E.8.2.4 | Number of treatment arms in the trial | 2 |
| E.8.3 |
The trial involves single site in the Member State concerned
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 6 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 69 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | No |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
| Canada |
| Taiwan |
| United States |
| Bulgaria |
| Denmark |
| Estonia |
| Germany |
| Netherlands |
| Poland |
| Spain |
| United Kingdom |
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| E.8.7 | Trial has a data monitoring committee | Yes |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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| LVLS or last scheduled procedure for the last participant in the trial globally. |
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| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 2 |
| E.8.9.1 | In the Member State concerned months | 3 |
| E.8.9.1 | In the Member State concerned days | 0 |
| E.8.9.2 | In all countries concerned by the trial years | 2 |
| E.8.9.2 | In all countries concerned by the trial months | 3 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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