A Study of mRNA-1010 Seasonal Influenza Vaccine in Healthy Adults

Study Overview
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Brief Summary
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The study comprises 3 parts: Phase 1/2, Phase 2 Northern Hemisphere (NH), and Phase 2 extension. The primary objective of this study is to evaluate the safety, reactogenicity, and humoral immunogenicity of mRNA-1010 vaccine.

Official Title
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A Phase 1/2, Randomized, Stratified, Observer-Blind, Dose-Ranging Study to Evaluate the Safety, Reactogenicity, and Immunogenicity of mRNA-1010 Seasonal Influenza Vaccine in Healthy Adults 18 Years and Older

Conditions
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Seasonal Influenza

Intervention / Treatment
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* Biological: mRNA-1010
* Biological: Placebo
* Biological: Active Comparator


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Phase 1/2: Participant has a body mass index (BMI) of 18 kilograms (kg)/square meter (m^2) to 35 kg/m^2 (inclusive) at the Screening Visit. Participant is in good health, in the opinion of the Investigator, based on review of medical history and physical examination performed at screening. For female participants of childbearing potential: negative pregnancy test, adequate contraception or has abstained from all activities that could result in pregnancy for at least 28 days prior to Day 1, agreement to continue adequate contraception through 3 months following vaccine administration, and not currently breastfeeding. Phase 2 NH and Phase 2 Extension: Participant is medically stable, in the opinion of the Investigator, based on review of medical history and physical examination performed at screening. For female participants of childbearing potential: negative pregnancy test, adequate contraception or has abstained from all activities that could result in pregnancy for at least 28 days prior to Day 1, agreement to continue adequate contraception through 3 months following vaccine administration, and not currently breastfeeding. Key Exclusion Criteria: Phase 1/2: Participant has had significant exposure to someone with laboratory-confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, COVID-19, or influenza-like illness (ILI) in the past 14 days prior to the Screening Visit, as defined by the United States Centers for Disease Control and Prevention (CDC) as close contact with someone who has COVID-19. Participant has a positive SARS-CoV-2 reverse transcriptase polymerase chain reaction (RT-PCR) or antigen test in the past 10 days prior to the Screening Visit. Participant is acutely ill or febrile (body temperature ≥ 38.0 degrees Celsius [°C]/100.4 degrees Fahrenheit [°F]) 72 hours prior to or at the Screening Visit or Day 1. Participant has a pre-existing medical condition that is not stable, at the discretion of the Investigator. Participant has a medical, psychiatric, or occupational condition that may pose additional risk as a result of participation or that could interfere with safety assessments or interpretation of results according to the Investigator's judgment. Participant has received systemic immunosuppressants or immune-modifying drugs for >14 days in total within 6 months prior to Screening Visit (for corticosteroids ≥10 milligrams [mg]/day of prednisone equivalent) or is anticipating the need for immunosuppressive treatment at any time during participation in the study. Participant has received or plans to receive any licensed vaccine ≤28 days prior to the investigational product (IP) injection (Day 1) or plans to receive a licensed vaccine within 28 days after the IP injection, with the exception of vaccines authorized or approved for the prevention of COVID-19 (regardless of type of vaccine) that become available to participants during the study. Efforts should be made to space study vaccination and COVID-19 vaccination by at least 7 and preferably 14 days, but COVID-19 vaccination should not be delayed. Participant has received a seasonal influenza vaccine or any other investigational influenza vaccine after 01 January 2021. Phase 2 NH: Participant has had close contact to someone with SARS-CoV-2 infection or COVID-19 as defined by the CDC (CDC 2021a) in the past 14 days prior to the Screening Visit, unless the participant has been fully vaccinated for COVID-19. Participant is acutely ill or febrile (body 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. Participant has a medical, psychiatric, occupational condition, or history of substance abuse that may pose additional risk as a result of participation or that could interfere with safety assessments or interpretation of results according to the Investigator's judgment. Participant has a current or previous diagnosis of immunocompromising/immunosuppressive condition, immune mediated disease requiring immune-modifying therapy, asplenia, recurrent severe infections (human immunodeficiency virus [HIV] positive participants on antiretroviral therapy with cluster of differentiation [CD] 4 count ≥ 350 cells/mm3 and HIV RNA ≤ 500 copies/mL within the past 12 months are permitted). Participant has received systemic immunosuppressants or immune-modifying drugs for > 14 days in total within 6 months prior to Screening Visit (for corticosteroids ≥ 10 mg/day of prednisone or equivalent) or is anticipating the need for systemic immunosuppressive treatment at any time during participation in the study. Participant has a history of anaphylaxis, urticaria, or other significant AR requiring medical intervention after receipt of a vaccine or any of the components contained in the mRNA 1010 or the comparator vaccine, which is an egg-based influenza vaccine. Participant has received or plans to receive any licensed vaccine ≤ 28 days prior to the IP injection (Day 1) or plans to receive a licensed vaccine within 28 days after the IP injection, with the exception of vaccines authorized or approved for the prevention of COVID-19 (regardless of type of vaccine) that become available to participants during the study. Efforts should be made to space study vaccination and COVID-19 vaccination by at least 7 and preferably 14 days, but COVID-19 vaccination should not be delayed. Participant has received a seasonal influenza vaccine or any other investigational influenza vaccine within 6 months prior to the Screening Visit. Participant has tested positive for influenza by CDC-recommended testing methods within 6 months prior to the Screening Visit. Participant has 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. Phase 2 Extension: Participant has had close contact to someone with SARS-CoV-2 infection or COVID-19 as defined by the CDC in the past 10 days prior to the Screening Visit. Participant is acutely ill or febrile (body 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. Participant has a medical, psychiatric, occupational condition, or history of substance abuse that may pose additional risk as a result of participation or that could interfere with safety assessments or interpretation of results according to the Investigator's judgment. Participant has a current or previous diagnosis of immunocompromising/immunosuppressive condition, immune-mediated disease requiring immune-modifying therapy, asplenia, recurrent severe infections (HIV-positive participants on antiretroviral therapy with CD 4 count ≥ 350 cells/mm^3 and HIV-RNA ≤ 500 copies/mL within the past 365 days are permitted). Participant has received systemic immunosuppressants or immune-modifying drugs for >14 days in total within 180 days prior to Screening Visit (for corticosteroids ≥ 10 mg/day of prednisone or equivalent) or is anticipating the need for systemic immunosuppressive treatment at any time during participation in the study. Participant has a history of anaphylaxis, urticaria, or other significant AR requiring medical intervention after receipt of a vaccine or any of the components contained in the mRNA-1010 or the comparator vaccine, which is an egg-based influenza vaccine. Participant has received or plans to receive any licensed vaccine ≤ 28 days prior to the IP injection (Day 1) or plans to receive a licensed vaccine within 28 days after the IP injection, with the exception of vaccines authorized or approved for the prevention of COVID-19 (regardless of type of vaccine) that become available to participants during the study. Efforts should be made to space study vaccination and COVID-19 vaccination by at least 7 and preferably 14 days, but COVID-19 vaccination should not be delayed. Participant has received a seasonal influenza vaccine or any other investigational influenza vaccine within 180 days prior to the randomization visit. Participant had tested positive for influenza by CDC-recommended testing methods within 180 days prior to the Screening Visit. Participant has 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. Other inclusion/exclusion criteria may apply.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Phase 1/2: mRNA-1010 Dose Level A<br>Participants will receive mRNA-1010 at dose level A by intramuscular (IM) injection on Day 1. | Biological: mRNA-1010<br>* Sterile liquid for injection<br>* Other names: Seasonal influenza vaccine;|
| Experimental: Phase 1/2: mRNA-1010 Dose Level B<br>Participants will receive mRNA-1010 at dose level B by IM injection on Day 1. | Biological: mRNA-1010<br>* Sterile liquid for injection<br>* Other names: Seasonal influenza vaccine;|
| Experimental: Phase 1/2: mRNA-1010 Dose Level C<br>Participants will receive mRNA-1010 at dose level C by IM injection on Day 1. | Biological: mRNA-1010<br>* Sterile liquid for injection<br>* Other names: Seasonal influenza vaccine;|
| Experimental: Phase 1/2: Placebo<br>Participants will receive placebo matching to mRNA-1010 by IM injection on Day 1. | Biological: Placebo<br>* 0.9% sodium chloride solution for injection<br>|
| Active Comparator: Phase 2 NH: Active Comparator Dose Level A<br>Participants will receive active comparator at dose level A by IM injection on Day 1. | Biological: Active Comparator<br>* 0.5 milliliter (mL) intramuscular (IM) injection<br>* Other names: Licensed quadrivalent seasonal influenza;|
| Experimental: Phase 2 NH: mRNA-1010 Dose Level D<br>Participants will receive mRNA-1010 at dose level D by IM injection on Day 1. | Biological: mRNA-1010<br>* Sterile liquid for injection<br>* Other names: Seasonal influenza vaccine;|
| Experimental: Phase 2 NH: mRNA-1010 Dose Level A<br>Participants will receive mRNA-1010 at dose level A by IM injection on Day 1. | Biological: mRNA-1010<br>* Sterile liquid for injection<br>* Other names: Seasonal influenza vaccine;|
| Experimental: Phase 2 NH: mRNA-1010 Dose Level B<br>Participants will receive mRNA-1010 at dose level B by IM injection on Day 1. | Biological: mRNA-1010<br>* Sterile liquid for injection<br>* Other names: Seasonal influenza vaccine;|
| Active Comparator: Phase 2 Extension: Active Comparator Dose Level A<br>Participants will receive active comparator at dose level A by IM injection on Day 1. | Biological: Active Comparator<br>* 0.5 milliliter (mL) intramuscular (IM) injection<br>* Other names: Licensed quadrivalent seasonal influenza;|
| Experimental: Phase 2 Extension: mRNA-1010 Dose Level D<br>Participants will receive mRNA-1010 at dose level D by IM injection on Day 1. | Biological: mRNA-1010<br>* Sterile liquid for injection<br>* Other names: Seasonal influenza vaccine;|
| Experimental: Phase 2 Extension: mRNA-1010 Dose Level E<br>Participants will receive mRNA-1010 at dose level E by IM injection on Day 1. | Biological: mRNA-1010<br>* Sterile liquid for injection<br>* Other names: Seasonal influenza vaccine;|
| Experimental: Phase 2 Extension: mRNA-1010 Dose Level F<br>Participants will receive mRNA-1010 at dose level F by IM injection on Day 1. | Biological: mRNA-1010<br>* Sterile liquid for injection<br>* Other names: Seasonal influenza vaccine;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Solicited Local and Systemic ARs | Solicited ARs (local and systemic) were collected in the electronic diary (eDiary). Local ARs included: pain at injection site, erythema (redness) at injection site, swelling/induration (hardness) at injection site, and localized axillary swelling or tenderness ipsilateral to the injection arm. Systemic ARs included: headache, fatigue, myalgia (muscle aches all over the body), arthralgia (aching in several joints), nausea/vomiting, rash, body temperature (potentially fever), and chills. Solicited ARs (local and systemic) considered causally related to injection were graded 0-4; lower score indicates lower severity and a higher score indicates greater severity. Note, not all solicited ARs were considered adverse events (AEs). The Investigator reviewed whether the solicited AR was also to be recorded as an AE. Summary of serious AEs (SAEs) and nonserious AEs (Other), regardless of causality, is in Reported Adverse Events section and presented by Phase/dose group. | 7 days after vaccination | 
| Number of Participants With Unsolicited AEs | An AE was defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. A treatment-emergent AE (TEAE) was defined as any event not present before exposure to vaccine or any event already present that worsens in intensity or frequency after exposure. 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 worsens from baseline and is considered clinically significant in the medical and scientific judgment of the Investigator. A summary of SAEs and all nonserious AEs (Other) reported up to the end of the study, regardless of causality, is located in the Reported Adverse Events section and presented by each Phase and dose group separately. | Up to 28 days after vaccination | 
| Number of Participants With SAEs, AEs of Special Interest (AESIs), Medically Attended AEs (MAAEs) | An SAE was defined as any AE that resulted in death, is life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in disability/permanent damage, was a congenital anomaly/birth defect, or was an important medical event. AESIs included thrombocytopenia, new onset of or worsening of the protocol specified neurologic diseases, anaphylaxis, and myocarditis/pericarditis. An MAAE is an AE that leads to an unscheduled visit to an healthcare practitioner. This would include visits to a study site for unscheduled assessments (for example, abnormal laboratory follow-up, and/or COVID-19 and visits to healthcare practitioners external to the study site (for example, urgent care, primary care physician). A summary of SAEs and all nonserious AEs (Other), regardless of causality, is located in the Reported Adverse Events section and presented by each Phase and dose group separately. | Up to 6 months (end of study) | 
| Phase 1/2: Geometric Mean Titer (GMT) of Anti-Hemagglutinin (HA) Antibodies at Day 29, as Measured by Hemagglutination Inhibition (HAI) Assay for Vaccine-Matched Seasonal Influenza A and B Strains | Seasonal influenza A included H1N1 and H3N2 and seasonal influenza B strains included Victoria-lineage and Yamagata-lineage. GMT 95% confidence interval (CI) was calculated based on the t-distribution of the log-transformed values then back transformed to the original scale for presentation. | Day 29 | 
| Phase 2 NH: GMT of HA Antibodies at Day 29, as Measured by HAI Assay for Vaccine-Matched Seasonal Influenza A and B Strains | Humoral immunogenicity relative to that of the active comparator (afluria quadrivalent) was assessed against vaccine-matched Influenza A and B strains at Day 29. Seasonal influenza A included H1N1 and H3N2 and seasonal influenza B strains included Victoria-lineage and Yamagata-lineage. GMT 95% CI was calculated based on the t-distribution of the log-transformed values then back transformed to the original scale for presentation. | Day 29 | 
| Phase 2 Extension: GMT of HA Antibodies at Day 29, as Measured by HAI Assay for Vaccine-Matched Seasonal Influenza A and B Strains | Humoral immunogenicity relative to that of the active comparator (afluria quadrivalent) was assessed against vaccine-matched Influenza A and B strains at Day 29. Seasonal influenza A included H1N1 and H3N2 and seasonal influenza B strains included Victoria-lineage and Yamagata-lineage. GMT 95% CI was calculated based on the t-distribution of the log-transformed values then back transformed to the original scale for presentation. | Day 29 | 
| Phase 1/2: Percentage of Participants With Seroconversion, as Measured by HAI Assay for Vaccine-Matched Seasonal Influenza A and B | Seasonal influenza A included H1N1 and H3N2 and seasonal influenza B strains included Victoria-lineage and Yamagata-lineage. Seroconversion at a participant level was defined as (a) if lower limit of quantification (LLOQ) was 1:10, a post-baseline titer ≥1:40 if baseline was <1:10 or a 4-fold or greater rise from baseline if baseline was ≥1:10 in anti-HA antibodies; or (b) if LLOQ was >1:10, a post-baseline titer ≥4 x LLOQ if baseline was <LLOQ, or 4-fold or greater increase from baseline if baseline was ≥LLOQ in anti-HA antibodies. | Day 29 | 
| Phase 1/2: Geometric Mean Fold-Rise (GMFR) of Anti-HA Antibodies at Day 29, as Measured by HAI Assay for Vaccine-Matched Seasonal Influenza A and B Strains | The GMFR measures the changes in immunogenicity titers or levels from Baseline within participants. Seasonal influenza A included H1N1 and H3N2 and seasonal influenza B strains included Victoria-lineage and Yamagata-lineage. 95% CI was calculated based on the difference in the log-transformed values for GMFR, then back transformed to the original scale for presentation. | Day 1 (Baseline), Day 29 | 
| Phase 2 NH: Percentage of Participants With Seroconversion, as Measured by HAI Assay for Vaccine-Matched Seasonal Influenza A and B | Humoral immunogenicity relative to that of the active comparator (afluria quadrivalent) was assessed against vaccine-matched Influenza A and B strains at Day 29. Seasonal influenza A included H1N1 and H3N2 and seasonal influenza B strains included Victoria-lineage and Yamagata-lineage. Seroconversion at a participant level was defined as (a) if LLOQ was 1:10, a post-baseline titer ≥1:40 if baseline was <1:10 or a 4-fold or greater rise from baseline if baseline was ≥1:10 in anti-HA antibodies; or (b) if LLOQ was >1:10, a post-baseline titer ≥4 x LLOQ if baseline was <LLOQ, or 4-fold or greater increase from baseline if baseline was ≥LLOQ in anti-HA antibodies. 95% CI was calculated using the Clopper-Pearson method | Day 29 | 
| Phase 2 Extension: Percentage of Participants With Seroconversion, as Measured by HAI Assay for Vaccine-Matched Seasonal Influenza A and B | Humoral immunogenicity relative to that of the active comparator (afluria quadrivalent) was assessed against vaccine-matched Influenza A and B strains at Day 29. Seasonal influenza A included H1N1 and H3N2 and seasonal influenza B strains included Victoria-lineage and Yamagata-lineage. Seroconversion at a participant level was defined as (a) if LLOQ was 1:10, a post-baseline titer ≥1:40 if baseline was <1:10 or a 4-fold or greater rise from baseline if baseline was ≥1:10 in anti-HA antibodies; or (b) if LLOQ was >1:10, a post-baseline titer ≥4 x LLOQ if baseline was <LLOQ, or 4-fold or greater increase from baseline if baseline was ≥LLOQ in anti-HA antibodies. 95% CI was calculated using the Clopper-Pearson method | Day 29 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Phase 1/2: GMT of Anti-HA Antibodies at Days 1, 8 and 181, as Measured by HAI Assay for Vaccine-Matched Seasonal Influenza A and B Strains | Seasonal influenza A included H1N1 and H3N2 and seasonal influenza B strains included Victoria-lineage and Yamagata-lineage. GMT 95% CI was calculated based on the t-distribution of the log-transformed values then back transformed to the original scale for presentation. | Day 1 (Baseline), Day 8 and Day 181 | 
| Phase 1/2: GMFR of Anti-HA Antibodies at Days 8 and 181, as Measured by HAI Assay for Vaccine-Matched Seasonal Influenza A and B Strains | The GMFR measures the changes in immunogenicity titers or levels from Baseline within participants. Seasonal influenza A included H1N1 and H3N2 and seasonal influenza B strains included Victoria-lineage and Yamagata-lineage. 95% CI was calculated based on the difference in the log-transformed values for GMT, then back transformed to the original scale for presentation. | Day 1 (Baseline), Day 8 and Day 181 | 
| Phase 2 NH and Phase 2 Extension: Percentage of Participants With Seroconversion, as Measured by HAI Assay for Vaccine-Matched Seasonal Influenza A and B | Seasonal influenza A included H1N1 and H3N2 and seasonal influenza B strains included Victoria-lineage and Yamagata-lineage. Seroconversion at a participant level was defined as (a) if lower limit of quantification (LLOQ) was 1:10, a post-baseline titer ≥1:40 if baseline was <1:10 or a 4-fold or greater rise from baseline if baseline was ≥1:10 in anti-HA antibodies; or (b) if LLOQ was >1:10, a post-baseline titer ≥4 x LLOQ if baseline was <LLOQ, or 4-fold or greater increase from baseline if baseline was ≥LLOQ in anti-HA antibodies. | Day 29 | 
| Phase 2 NH and Phase 2 Extension: GMFR of Anti-HA Antibodies at Day 29, as Measured by HAI Assay for Vaccine-Matched Seasonal Influenza A and B Strains | The GMFR measures the changes in immunogenicity titers or levels from Baseline within participants. Seasonal influenza A included H1N1 and H3N2 and seasonal influenza B strains included Victoria-lineage and Yamagata-lineage. 95% CI was calculated based on the difference in the log-transformed values for GMFR, then back transformed to the original scale for presentation. | Day 29 | 
| Phase 2 NH and Phase 2 Extension: Percentage of Participants With HAI Titer ≥1:40 at Day 29 |  | Day 29 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Influenza vaccine, mRNA-1010, Moderna