A Study of mRNA-1345 Vaccine Targeting Respiratory Syncytial Virus (RSV) in Adults ≥50 Years of Age

Study Overview
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Brief Summary
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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.

Official Title
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A Phase 3 Randomized, Observer-Blind, Study to Evaluate Safety, Tolerability, and Immunogenicity of mRNA-1345, an mRNA Vaccine Targeting Respiratory Syncytial Virus (RSV), When Given Alone or Coadministered With a Seasonal Influenza Vaccine or SARS-CoV-2 Vaccine and When Given as an Open-label Boost at 1 Year Following a Primary Dose in Adults ≥ 50 Years of Age

Conditions
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Respiratory Syncytial Virus

Intervention / Treatment
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* Biological: Placebo
* Biological: mRNA-1345
* Biological: Afluria® Quadrivalent
* Biological: mRNA-1273.214


Participation Criteria
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Eligibility Criteria
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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 exclusion criteria may apply.

Ages Eligible for Study
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Minimum Age: 50 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: Part A: mRNA-1345 + Placebo<br>Single injection of mRNA-1345 and placebo, administered intramuscularly (IM), one in each arm on Day 1. | Biological: Placebo<br>* 0.9% sodium chloride (normal saline) injection<br>Biological: mRNA-1345<br>* Sterile liquid for injection<br>|
| Experimental: Part A: mRNA-1345 + Afluria® Quadrivalent<br>Single injection of mRNA-1345 and Afluria® quadrivalent, administered IM, one in each arm on Day 1. | Biological: mRNA-1345<br>* Sterile liquid for injection<br>Biological: Afluria® Quadrivalent<br>* single-dose, pre-filled syringe for injection<br>|
| Active Comparator: Part A: Afluria® Quadrivalent + Placebo<br>Single injection of Afluria® quadrivalent and placebo, administered IM, one in each arm on Day 1. | Biological: Placebo<br>* 0.9% sodium chloride (normal saline) injection<br>Biological: Afluria® Quadrivalent<br>* single-dose, pre-filled syringe for injection<br>|
| Experimental: Part B: mRNA-1345 + Placebo<br>Single injection of mRNA-1345 and placebo, administered IM, one in each arm on Day 1. An additional injection of mRNA-1273.214, administered on Day 29. | Biological: Placebo<br>* 0.9% sodium chloride (normal saline) injection<br>Biological: mRNA-1345<br>* Sterile liquid for injection<br>Biological: mRNA-1273.214<br>* Sterile liquid for injection<br>|
| Experimental: Part B: mRNA-1345 + mRNA-1273.214<br>Single injection of mRNA-1345 and mRNA-1273.214, administered IM, one in each arm on Day 1. An additional injection of placebo administered on Day 29. | Biological: Placebo<br>* 0.9% sodium chloride (normal saline) injection<br>Biological: mRNA-1345<br>* Sterile liquid for injection<br>Biological: mRNA-1273.214<br>* Sterile liquid for injection<br>|
| Active Comparator: Part B: mRNA-1273.214 + Placebo<br>Single injection of mRNA-1273.214 and placebo, administered IM, one in each arm on Day 1. An additional injection of placebo administered on Day 29. | Biological: Placebo<br>* 0.9% sodium chloride (normal saline) injection<br>Biological: mRNA-1273.214<br>* Sterile liquid for injection<br>|
| Experimental: Part C: mRNA-1345<br>Single injection of mRNA-1345 administered IM on BD Day 1. | Biological: mRNA-1345<br>* Sterile liquid for injection<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Parts A and B: Number of Participants with Solicited Local and Systemic Adverse Reactions (ARs) |  | Day 1 through Day 7 (7 days post-injection) | 
| Part C: Number of Participants with Solicited Local and Systemic ARs 7 Days post-BD |  | BD Day 1 through Day 7 (7 days post-BD) | 
| Parts A and B: Number of Participants with Unsolicited Adverse Events (AEs) |  | Day 1 through Day 28 (28 days post-injection) | 
| Part C: Number of Participants with Unsolicited AEs 28 Days post-BD Day 1 |  | BD Day 1 through Day 28 (28 days post-BD Day 1) | 
| Parts A and B: Number of Participants With Medically Attended AEs (MAAEs), Serious Adverse Events (SAEs), Adverse Events of Special Interest (AESIs), and AEs Leading to Withdrawal |  | Day 1 through Day 181 | 
| Part C: Number of Participants With MAAEs From BD Day 1 Through BD Day 181 |  | BD Day 1 through BD Day 181 | 
| Part C: Number of Participants With SAEs, AESIs, and AEs Leading to Withdrawal From BD Day 1 Through BD Day 361 |  | BD Day 1 through BD Day 361 | 
| Parts A and B: Geometric Mean Titer (GMT) of Serum RSV-A Neutralizing Antibodies (Abs) at Day 29 |  | Day 29 | 
| Part C: GMT Ratio of Serum RSV-A Neutralizing Abs at BD Day 29 Over GMT of serum RSV-A Neutralizing Abs at Day 29 Post Primary Dose |  | Day 29 to BD Day 29 | 
| Part C: GMT Ratio of Serum RSV-B Neutralizing Abs at BD Day 29 Over GMT of serum RSV-B Neutralizing Abs at Day 29 Post Primary Dose |  | Day 29 to BD Day 29 | 
| Part A: GMT of Serum Ab Level, as Measured by Hemagglutination Inhibition (HAI) Assay for Influenza at Day 29 |  | Day 29 | 
| Part B: Geometric Mean Concentration (GMC) of Serum Ab Level, as Measured by Neutralization Assay for SARS-Cov-2 at Day 29 |  | Day 29 | 
| Parts A and B: Percentage of Participants With Seroresponse in RSV-A Neutralizing Abs From Baseline to Day 29 | Seroresponse is defined as ≥4 × lower limit of quantification (LLOQ) if baseline is <LLOQ or 4-fold or greater increase from baseline if baseline is ≥LLOQ in RSV-A neutralizing Ab titers at Day 29. | Baseline to Day 29 | 
| Part B: Percentage of Participants With Seroresponse for SARS-Cov-2 Neutralizing Abs From Baseline to Day 29 | Seroresponse is defined as ≥4 × LLOQ if baseline is <LLOQ or 4-fold or greater increase from baseline if baseline is ≥LLOQ in SARS-CoV-2 neutralizing Ab titers at Day 29. | Baseline to Day 29 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Parts A and B: GMT of Serum RSV-B Neutralizing Abs at Day 29 |  | Day 29 | 
| Part C: Percentage of Participants With Seroresponse in RSV-A Neutralizing Abs From Baseline (Defined as Before Primary Dose) to BD Day 29 | Seroresponse is defined as ≥4 × LLOQ if baseline is <LLOQ or 4-fold or greater increase from baseline if baseline is ≥LLOQ in RSV-A neutralizing Ab titers at BD Day 29. | Baseline to BD Day 29 | 
| Parts A and B: Percentage of Participants With Seroresponse in RSV-B Neutralizing Abs From Baseline to Day 29 | Seroresponse is defined as ≥4 × LLOQ if baseline is <LLOQ or 4-fold or greater increase from baseline if baseline is ≥LLOQ in RSV-B neutralizing Ab titers at BD Day 29. | Baseline to Day 29 | 
| Part C: Percentage of Participants With Seroresponse in RSV-B Neutralizing Abs From Baseline (Defined as Before Primary Dose) to BD Day 29 | Seroresponse is defined as ≥4 × LLOQ if baseline is <LLOQ or 4-fold or greater increase from baseline if baseline is ≥LLOQ in RSV-B neutralizing Ab titers at BD Day 29. | Baseline to BD Day 29 | 
| Part A: Percentage of Participants With Seroconversion in Influenza A and B Strains From Baseline to Day 29 | Seroconversion is defined as a Day 29 titer ≥1:40 if baseline is <1:10 or a 4-fold or greater rise if baseline is ≥1:10 in anti-hemagglutinin (anti-HA) Abs measured by HAI assay. | Baseline to Day 29 | 
| Parts A and B: GMT of Serum RSV-A Neutralizing Abs up to Day 181 |  | up to Day 181 | 
| Part C: GMT of Serum RSV-A Neutralizing Abs up to BD Day 361 |  | up to BD Day 361 | 
| Parts A and B: Geometric Mean Fold Rise (GMFR) of Serum RSV-A Neutralizing Abs up to Day 181 |  | up to Day 181 | 
| Part C: GMFR of Serum RSV-A Neutralizing Abs up to BD Day 361 |  | up to BD Day 361 | 
| Parts A and B: GMT of Serum RSV-B Neutralizing Abs up to Day 181 |  | up to Day 181 | 
| Part C: GMT of Serum RSV-B Neutralizing Abs up to BD Day 361 |  | up to BD Day 361 | 
| Parts A and B: GMFR of Serum RSV-B Neutralizing Abs up to Day 181 |  | up to Day 181 | 
| Part C: GMFR of Serum RSV-B Neutralizing Abs up to BD Day 361 |  | up to BD Day 361 | 
| Part C: Percentage of Participants With Seroresponse in RSV-A Neutralizing Abs From Baseline to BD Day 361 | Seroresponse is defined as ≥4 × LLOQ if baseline is <LLOQ or 4-fold or greater increase from baseline if baseline is ≥LLOQ in RSV-A neutralizing Ab titers at BD Day 361. | Baseline to BD Day 361 | 
| Part C: Percentage of Participants With Seroresponse in RSV-B Neutralizing Abs From Baseline to BD Day 361 | Seroresponse is defined as ≥4 × LLOQ if baseline is <LLOQ or 4-fold or greater increase from baseline if baseline is ≥LLOQ in RSV-B neutralizing Ab titers at BD Day 361. | Baseline to BD Day 361 | 
| Parts A and B: Percentage of Participants With ≥2-fold Increases From Baseline in RSV-A Neutralizing Ab Titers up to Day 181 |  | Baseline up to Day 181 | 
| Part C: Percentage of Participants With ≥2-fold Increases From Baseline (Defined as Before Primary Dose) in RSV-A Neutralizing Ab Titers up to BD Day 361 |  | Baseline up to BD Day 361 | 
| Parts A and B: Percentage of Participants With ≥2-fold and ≥4- fold Increases From Baseline in RSV-B Neutralizing Ab Titers up to Day 181 |  | Baseline up to Day 181 | 
| Part C: Percentage of Participants With ≥2-fold Increases From Baseline (Defined as Before Primary Dose) in RSV-B Neutralizing Ab Titers up to BD Day 361 |  | Baseline up to BD Day 361 | 
| Part A: Percentage of Participants With Seroconversion in Influenza A and B Strains From Baseline up to Day 181 | Seroconversion is defined as a Day 181/EOS titer ≥1:40 if baseline is <1:10 or a 4-fold or greater rise if baseline is ≥1:10 in anti-HA Abs measured by HAI assay. | Baseline up to Day 181 | 
| Part A: GMT of Serum Ab Level, as Measured by HAI Assay for Influenza up to Day 181 |  | up to Day 181 | 
| Part A: GMFR of Serum Ab Level, as Measured by HAI Assay for Influenza up to Day 181 |  | up to Day 181 | 
| Part B: GMC of Serum Ab Level, as Measured by Neutralization Assay for SARS-Cov-2 up to Day 181 |  | up to Day 181 | 
| Part B: GMFR of Serum Ab Level, as Measured by Neutralization Assay for SARS-Cov-2 up to Day 181 |  | up to Day 181 | 
| Part B: Percentage of Participants With Seroresponse for SARS-Cov-2 Neutralizing Abs From Baseline to Day 181 | Seroresponse is defined as ≥4 × LLOQ if baseline is <LLOQ or 4-fold or greater increase from baseline if baseline is ≥LLOQ in SARS-CoV-2 strain neutralizing Ab titers at Day 181. | Baseline up to Day 181 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Viral Diseases, Messenger RNA, Moderna, mRNA-1345, Respiratory syncytial virus, Safety, Vaccines, SARS-CoV-2