A Study of mRNA-based Influenza and SARS-CoV-2 (COVID-19) Multi-component Vaccines in Healthy Adults

ModernaTX, Inc.1,758 enrolled

Overview

The study is divided into 2 parts: Part 1 and Part 2. The purpose of Part 1 of this study is to generate sufficient safety, reactogenicity, and immunogenicity data to enable selection of an mRNA-1083 vaccine composition and dose level to evaluate in a subsequent Phase 3 clinical trial in adults. The purpose of Part 2 of this study is to generate safety and immunogenicity data for additional mRNA-1083 compositions and dose levels in young adults ≥18 years and \<50 years of age.

Part 1: Participants will be enrolled into 1 of 2 age cohorts: Cohort A for adults ≥65 to \<80 years of age or Cohort B for adults ≥18 to \<65 year of age. In Cohort A, approximately 600 participants will be randomized (in equal allocation ratio) into the investigational treatment arms, stratified by influenza vaccine status in the most recent influenza season (received or not received since September 2022). In Cohort B, approximately 624 participants will be randomized (in equal allocation ratio) into the investigational treatment arms, stratified by 2 age groups: ≥18 to \<50 years and ≥50 to \<65 years of age and by influenza vaccine status in the most recent influenza season (received or not received since September 2022). Part 2: Approximately, 520 participants between ≥18 to \<50 years of age will be randomized (in equal allocation ratio) into the investigational treatment arms, stratified by influenza vaccine status in the most recent influenza season (received or not received since Sept 2023).

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

PREVENTION

Masking

TRIPLE

Enrollment

1,758

Conditions

SARS-CoV-2 Influenza

Interventions

Influenza Vaccine 1BIOLOGICAL

quadrivalent seasonal influenza vaccine

mRNA-1083.1BIOLOGICAL

Sterile liquid for injection

mRNA-1083.2BIOLOGICAL

Sterile liquid for injection

mRNA-1083.3

Eligibility

Sex: ALLMin age: 18 YearsMax age: 79 YearsHealthy volunteers:

Medical Language ↔ Plain English

Key Inclusion Criteria: Part 1 (Phase 1/2) * Adults ≥18 to \<80 years of age at the time of consent. * Body mass index (BMI) of 18 kilograms (kg)/square meter (m\^2) to 35 kg/m\^2 (inclusive) at the Screening Visit. * Healthy as determined by medical evaluation, including medical history, physical examination, and laboratory tests. * 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 90 days following vaccine administration, and not currently breastfeeding. * Fully vaccinated for COVID-19 primary series according to the locally authorized or approved regimen, and their last COVID-19 vaccine (primary series or booster) was ≥120 days prior to Day 1. Part 2 (Phase 2 Extension) * Adults ≥18 to \<50 years of age at the time of consent. * BMI of 18 kg/m\^2 to 35 kg/m\^2 (inclusive) at the Screening Visit. * Healthy as determined by medical evaluation, including medical history, and physical examination. * 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 90 days following vaccine administration, and not currently breastfeeding. * Have received at least 2 doses of locally authorized or approved COVID-19 vaccines and last dose was ≥90 days prior to Day 1. Key Exclusion Criteria: Part 1 (Phase 1/2) and Part 2 (Phase 2 Extension) * Participant is acutely ill or febrile (temperature ≥38.0 degrees Celsius \[°C\]/100.4 degrees Fahrenheit \[°F\]) 72 hours prior to or at the Screening Visit or Day 1. * Any medical, psychiatric, or occupational condition, including reported history of drug or alcohol abuse, that, in the opinion of the Investigator, might pose additional risk due to participation in the clinical trial or could interfere with the interpretation of study results. * Participant has received systemic immunosuppressants for \>14 days in total within 180 days prior to Screening Visit (for glucocorticoids ≥10 milligrams \[mg\]/day of prednisone or equivalent) or is anticipating the need for systemic immunosuppressive treatment at any time during participation in the clinical trial (including intra-articular steroid injections). Inhaled, nasal, and topical steroids are allowed. * Participant has received or plans to receive any vaccine authorized or approved by a local health agency ≤28 days prior to study intervention administration or plans to receive a vaccine authorized or approved by a local health agency within 28 days after study intervention administration. * Participant has received a seasonal influenza vaccine or any other investigational influenza vaccine within 150 days prior to Day 1. * Participant tested positive for influenza by local health authority-approved testing methods ≤150 days prior to Day 1. * Participant has had close contact to someone with COVID-19 as defined by the Centers for Disease Control and Prevention (CDC) in the past 10 days prior to Day 1. * Participant has donated ≥450 milliliters (mL) of blood products within 28 days prior to the Screening Visit or plans to donate blood products during the clinical trial. * Working or has worked as study personnel, is an immediate family member or household member of study personnel, study site staff, or Sponsor personnel, or resides in a nursing home. Part 2 (Phase 2 Extension) Only * Participants who enrolled in Part 1 of the mRNA-1083-P101 (Phase 1/2) study. Note: Other inclusion/exclusion criteria may apply.

Locations (69)

Outcomes

Primary Outcomes

Parts 1 and 2: Number of Participants With Solicited Local and Systemic Adverse Reactions (ARs)

Solicited ARs (local and systemic) were reported by participants an electronic diary (eDiary). Local ARs included: injection site pain, injection site erythema (redness), injection site swelling/induration (hardness), and axillary (underarm) swelling or tenderness ipsilateral to the side of injection. Systemic ARs included: fever, headache, fatigue, myalgia, arthralgia, nausea/vomiting, and chills.

Time frame: Up to 7 days after study injection

Parts 1 and 2: Number of Participants With Unsolicited Adverse Events (AEs) and Severe AEs

An AE was defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. Any abnormal laboratory test result (hematology, clinical chemistry, or prothrombin time \[PT\]/partial thromboplastin time \[PTT\]) or other safety assessment (for example, electrocardiogram, radiological scan, vital sign measurement), including one that worsened from baseline and was considered clinically significant in the medical and scientific judgment of the Investigator was recorded as an AE. Severity for all unsolicited AEs was determined by the Investigator based upon medical judgment and graded as Mild, Moderate or Severe. Number of participants with unsolicited AEs (SAEs and non-serious AEs) and severe AEs up to 28 days post-vaccination are reported in this outcome measure. A Summary of serious AEs (SAEs) and nonserious AEs ("Other"), regardless of causality, is located in the "Reported Adverse Events" section.

Time frame: Up to 28 days after study injection

Parts 1 and 2: Number of Participants With Unsolicited Medically Attended Adverse Events (MAAEs), Adverse Events of Special Interest (AESIs), Serious Adverse Events (SAEs), and AEs Leading to Study Discontinuation

An SAE was defined as any AE that resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in disability/permanent damage, was a congenital anomaly/birth defect, or was an important medical event. AESIs were protocol-defined medical concepts. An MAAE is an AE that lead to an unscheduled visit to an healthcare practitioner. This included visits to a study site for unscheduled assessments (for example, abnormal laboratory follow-up, and/or COVID-19 and visits to healthcare practitioners external to the study site. Number of participants with SAEs, AESIs, MAAEs, and AEs leading to study discontinuation up to Day 181 are reported in this outcome measure. A Summary of serious AEs (SAEs) and nonserious AEs ("Other"), regardless of causality, is located in the "Reported Adverse Events" section.

Data from ClinicalTrials.gov

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Secondary Outcomes

Part 1: GMT of Antibodies for Influenza, as Measured by HAI Assay

Influenza A strains included H1N1 and H3N2 and influenza B strains included Victoria-lineage and Yamagata-lineage. Antibody values reported as below LLOQ were replaced by 0.5 \* LLOQ. Values greater than ULOQ were converted to ULOQ. LLOQ = 10 and ULOQ = 640 for Influenza A H1N1 and Influenza A H3N2 antibody, LLOQ = 10 and ULOQ = 320 for Influenza B/ Victoria, and LLOQ = 10 and ULOQ = 640 for Influenza B/Yamagata antibody. 95% CI was calculated based on t-distribution of log-transformed values for GM titer, then back transformed to original scale for presentation. PP Set: all randomized participants who received study drug, complied with injection schedule, complied with timings of immunogenicity blood sampling to have a Baseline and at least 1 post-injection assessment at Day 29, had no documented infection of either influenza or SARS-CoV-2 on Day 1 and up to Day 29, had no major dosing error, and had no major protocol deviations or conditions/medications that affected immune response.

Time frame: Baseline (Day 1), Day 29, and Day 181

Part 1: GMT of Antibodies for SARS-CoV-2, as Measured by PsVNA

SARS-CoV-2 strain included BA.4/5 and D614G antibody. Antibody values reported as below LLOQ were replaced by 0.5 \* LLOQ. Values greater than ULOQ were converted to ULOQ. LLOQ = 53 and ULOQ = 71376 for SARS-CoV-2 BA.4/5 antibody and LLOQ = 74.1 and ULOQ = 184317 for SARS-CoV-2 D614G antibody. 95% CI was calculated based on t-distribution of log-transformed values for GM titer, then back transformed to original scale for presentation. PP Set: all randomized participants who received study drug, complied with injection schedule, complied with timings of immunogenicity blood sampling to have a Baseline and at least 1 post-injection assessment at Day 29, had no documented infection of either influenza or SARS-CoV-2 on Day 1 and up to Day 29, had no major dosing error, and had no major protocol deviations or conditions/medications that affected immune response.

Time frame: Baseline (Day 1), Day 29, and Day 181

Part 1: GMFR of Antibodies for Influenza, as Measured by HAI Assay

Influenza A strains included H1N1 and H3N2 and influenza B strains included Victoria-lineage and Yamagata-lineage. Antibody values reported as below LLOQ were replaced by 0.5 \* LLOQ. Values greater than ULOQ were converted to ULOQ. LLOQ = 10 and ULOQ = 640 for Influenza A H1N1 and Influenza A H3N2 antibody, LLOQ = 10 and ULOQ = 320 for Influenza B/Victoria, and LLOQ = 10 and ULOQ = 640 for Influenza B/Yamagata antibody. 95% CI was calculated based on t-distribution of log-transformed values for GMFR, then back transformed to original scale for presentation. PP Set: all randomized participants who received study drug, complied with injection schedule, complied with timings of immunogenicity blood sampling to have a Baseline and at least 1 post-injection assessment at Day 29, had no documented infection of either influenza or SARS-CoV-2 on Day 1 and up to Day 29, had no major dosing error, and had no major protocol deviations or conditions/medications that affected immune response.

Time frame: Day 29 and Day 181

Part 1: GMFR of Antibodies for SARS-CoV-2, as Measured by PsVNA

SARS-CoV-2 strain included BA.4/5 and D614G antibody. Antibody values reported as below LLOQ were replaced by 0.5 \* LLOQ. Values greater than ULOQ were converted to ULOQ. LLOQ = 53 and ULOQ = 71376 for SARS-CoV-2 BA.4/5 antibody and LLOQ = 74.1 and ULOQ = 184317 for SARS-CoV-2 D614G antibody. 95% CI was calculated based on t-distribution of log-transformed values for GMFR, then back transformed to original scale for presentation. PP Set: all randomized participants who received study drug, complied with injection schedule, complied with timings of immunogenicity blood sampling to have a Baseline and at least 1 post-injection assessment at Day 29, had no documented infection of either influenza or SARS-CoV-2 on Day 1 and up to Day 29, had no major dosing error, and had no major protocol deviations or conditions/medications that affected immune response.

Time frame: Day 29 and Day 181

Part 1: Influenza: Percentage of Participants With Seroconversion, as Measured by HAI Assay

Influenza A strains included H1N1 and H3N2 and influenza B strains included Victoria-lineage and Yamagata-lineage. Seroconversion was defined as a pre-vaccination HAI titer \< 1:10 and a post-vaccination HAI titer ≥1:40 or a pre-vaccination HAI titer ≥1:10 and a minimum 4-fold rise in post vaccination HAI antibody titer. PP Set: all randomized participants who received study drug, complied with injection schedule, complied with timings of immunogenicity blood sampling to have a Baseline and at least 1 post-injection assessment at Day 29, had no documented infection of either influenza or SARS-CoV-2 on Day 1 and up to Day 29, had no major dosing error, and had no major protocol deviations or conditions/medications that affected immune response.

Time frame: Baseline (Day 1) to Day 29, and Day 181

Part 1: SARS-CoV-2: Percentage of Participants With Seroresponse, as Measured by PsVNA

SARS-CoV-2 strain included BA.4/5 and D614G antibody. Seroresponse was defined as an increase from below the LLOQ to ≥4 x LLOQ if baseline nAb level was \<LLOQ, or ≥4 fold rise if baseline nAb level was ≥LLOQ. PP Set: all randomized participants who received study drug, complied with injection schedule, complied with timings of immunogenicity blood sampling to have a Baseline and at least 1 post-injection assessment at Day 29, had no documented infection of either influenza or SARS-CoV-2 on Day 1 and up to Day 29, had no major dosing error, and had no major protocol deviations or conditions/medications that affected immune response.

Time frame: Baseline (Day 1) to Day 29, and Day 181

Part 2: GMT of Antibodies for Influenza, as Measured by HAI Assay

Influenza A strains included H1N1 and H3N2 and influenza B strains included Victoria-lineage and Yamagata-lineage. Antibody values reported as below the LLOQ were replaced by 0.5 \* LLOQ. Values greater than the ULOQ were converted to the ULOQ. LLOQ = 10 and ULOQ = 3620 for Influenza A H1N1 antibody, LLOQ = 10 and ULOQ = 5120 for Influenza A H3N2 antibody, LLOQ = 10 and ULOQ = 1356 for Influenza B/Victoria-lineage antibody, and LLOQ = 10 and ULOQ = 1280 for Influenza B/Yamagata-lineage antibody. 95% CI was calculated based on the t-distribution of the log-transformed values for GM titer, then back transformed to the original scale for presentation. Arms based on the applicable vaccine for this Outcome Measure.

Time frame: Baseline (Day 1), Day 181

Part 2: GM Concentration of Antibodies for SARS-CoV-2, as Measured by PsVNA

Time frame: Baseline (Day 1), Day 181

Part 2: GMFR of Antibodies for Influenza, as Measured by HAI Assay

Influenza A strains included H1N1 and H3N2 and influenza B strains included Victoria-lineage and Yamagata-lineage. Antibody values reported as below LLOQ replaced by 0.5 \* LLOQ. Values greater than ULOQ converted to ULOQ. LLOQ= 10, ULOQ= 3620 for Influenza A H1N1, LLOQ= 10, ULOQ= 5120 for Influenza A H3N2, LLOQ= 10, ULOQ= 1356 for Influenza B/Victoria-lineage, and LLOQ= 10, ULOQ= 1280 for Influenza B/Yamagata-lineage. 95% CI was calculated based on t-distribution of log-transformed values for GMFR, then back transformed to original scale for presentation. PP Set: all randomized participants who received study drug, complied with injection schedule, complied with timings of immunogenicity blood sampling to have a Baseline and at least 1 post-injection assessment at Day 29, had no documented infection of either influenza or SARS-CoV-2 on Day 1 and up to Day 29, had no major dosing error, and had no major protocol deviations or conditions/medications that affected immune response.

Time frame: Day 181

Part 2: GMFR of Antibodies for SARS-CoV-2, as Measured by PsVNA

SARS-CoV-2 strain included Omicron XBB.1.5 antibody. Antibody values reported as below the LLOQ are replaced by 0.5 \* LLOQ. Values greater than the ULOQ are converted to the ULOQ. LLOQ = 38 and ULOQ = 6960 AU/mL for SARS-CoV-2 Omicron XBB.1.5 antibody. 95% CI was calculated based on the t-distribution of the log-transformed values for GMFR values, then back transformed to the original scale for presentation. PP Set: all randomized participants who received study drug, complied with injection schedule, complied with timings of immunogenicity blood sampling to have a Baseline and at least 1 post-injection assessment at Day 29, had no documented infection of either influenza or SARS-CoV-2 on Day 1 and up to Day 29, had no major dosing error, and had no major protocol deviations or conditions/medications that affected immune response.

Time frame: Day 181

Part 2: Influenza: Percentage of Participants With Seroconversion, as Measured by HAI Assay

Influenza A strains included H1N1 and H3N2 and influenza B strains included Victoria-lineage and Yamagata-lineage. Seroconversion was defined as a pre-vaccination HAI titer \<1:10 and a post-vaccination HAI titer ≥1:40 or a pre-vaccination HAI titer ≥1:10 and a minimum 4-fold rise in post-vaccination HAI antibody titer. PP Set included all randomized participants who received the study intervention, complied with the injection schedule, complied with the timings of immunogenicity blood sampling to have a Baseline and at least 1 post-injection assessment at Day 29, had no documented infection of either influenza or SARS-CoV-2 on Day 1 and up to Day 29, had no major dosing error, and had no major protocol deviations or conditions/medications that affected the immune response.

Time frame: Baseline (Day 1) to Day 181

Part 2: SARS-CoV-2: Percentage of Participants With Seroresponse, as Measured by PsVNA

SARS-CoV-2 strain included Omicron XBB.1.5 antibody. Seroresponse was defined as an increase from below the LLOQ to ≥4 \* LLOQ if Baseline nAb level was \< LLOQ, or ≥4-fold rise if Baseline nAb level was ≥ LLOQ. PP Set included all randomized participants who received the study intervention, complied with the injection schedule, complied with the timings of immunogenicity blood sampling to have a Baseline and at least 1 post-injection assessment at Day 29, had no documented infection of either influenza or SARS-CoV-2 on Day 1 and up to Day 29, had no major dosing error, and had no major protocol deviations or conditions/medications that affected the immune response.

Time frame: Baseline (Day 1) to Day 181