Clinical trial NCT05330975: A Study of mRNA-1345 Vaccine Targeting Respiratory Syncytial Virus (RSV) in Adults ≥50 Years of Age
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Respiratory Syncytial Virus
Keywords: Viral Diseases
Messenger RNA
Moderna
mRNA-1345
Respiratory syncytial virus
Safety
Vaccines
SARS-CoV-2
Lead sponsor: ModernaTX, Inc.
Sponsor class: INDUSTRY
First posted: 2022-04-15
Enrollment: 3317
Sex: ALL
Minimum age (years): 50
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Parts A and B: Number of Participants with Solicited Local and Systemic Adverse Reactions (ARs)
timeFrame: Day 1 through Day 7 (7 days post-injection)
measure: Part C: Number of Participants with Solicited Local and Systemic ARs 7 Days post-BD
timeFrame: BD Day 1 through Day 7 (7 days post-BD)
measure: Parts A and B: Number of Participants with Unsolicited Adverse Events (AEs)
timeFrame: Day 1 through Day 28 (28 days post-injection)
measure: Part C: Number of Participants with Unsolicited AEs 28 Days post-BD Day 1
timeFrame: BD Day 1 through Day 28 (28 days post-BD Day 1)
measure: 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
timeFrame: Day 1 through Day 181
measure: Part C: Number of Participants With MAAEs From BD Day 1 Through BD Day 181
timeFrame: BD Day 1 through BD Day 181
measure: Part C: Number of Participants With SAEs, AESIs, and AEs Leading to Withdrawal From BD Day 1 Through BD Day 361
timeFrame: BD Day 1 through BD Day 361
measure: Parts A and B: Geometric Mean Titer (GMT) of Serum RSV-A Neutralizing Antibodies (Abs) at Day 29
timeFrame: Day 29
measure: 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
timeFrame: Day 29 to BD Day 29
measure: 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
timeFrame: Day 29 to BD Day 29
measure: Part A: GMT of Serum Ab Level, as Measured by Hemagglutination Inhibition (HAI) Assay for Influenza at Day 29
timeFrame: Day 29
measure: Part B: Geometric Mean Concentration (GMC) of Serum Ab Level, as Measured by Neutralization Assay for SARS-Cov-2 at Day 29
timeFrame: Day 29
measure: Parts A and B: Percentage of Participants With Seroresponse in RSV-A Neutralizing Abs From Baseline to Day 29
timeFrame: Baseline to Day 29
measure: Part B: Percentage of Participants With Seroresponse for SARS-Cov-2 Neutralizing Abs From Baseline to Day 29
timeFrame: Baseline to Day 29
Secondary outcomes:
measure: Parts A and B: GMT of Serum RSV-B Neutralizing Abs at Day 29
timeFrame: Day 29
measure: Part C: Percentage of Participants With Seroresponse in RSV-A Neutralizing Abs From Baseline (Defined as Before Primary Dose) to BD Day 29
timeFrame: Baseline to BD Day 29
measure: Parts A and B: Percentage of Participants With Seroresponse in RSV-B Neutralizing Abs From Baseline to Day 29
timeFrame: Baseline to Day 29
measure: Part C: Percentage of Participants With Seroresponse in RSV-B Neutralizing Abs From Baseline (Defined as Before Primary Dose) to BD Day 29
timeFrame: Baseline to BD Day 29
measure: Part A: Percentage of Participants With Seroconversion in Influenza A and B Strains From Baseline to Day 29
timeFrame: Baseline to Day 29
measure: Parts A and B: GMT of Serum RSV-A Neutralizing Abs up to Day 181
timeFrame: up to Day 181
measure: Part C: GMT of Serum RSV-A Neutralizing Abs up to BD Day 361
timeFrame: up to BD Day 361
measure: Parts A and B: Geometric Mean Fold Rise (GMFR) of Serum RSV-A Neutralizing Abs up to Day 181
timeFrame: up to Day 181
measure: Part C: GMFR of Serum RSV-A Neutralizing Abs up to BD Day 361
timeFrame: up to BD Day 361
measure: Parts A and B: GMT of Serum RSV-B Neutralizing Abs up to Day 181
timeFrame: up to Day 181
measure: Part C: GMT of Serum RSV-B Neutralizing Abs up to BD Day 361
timeFrame: up to BD Day 361
measure: Parts A and B: GMFR of Serum RSV-B Neutralizing Abs up to Day 181
timeFrame: up to Day 181
measure: Part C: GMFR of Serum RSV-B Neutralizing Abs up to BD Day 361
timeFrame: up to BD Day 361
measure: Part C: Percentage of Participants With Seroresponse in RSV-A Neutralizing Abs From Baseline to BD Day 361
timeFrame: Baseline to BD Day 361
measure: Part C: Percentage of Participants With Seroresponse in RSV-B Neutralizing Abs From Baseline to BD Day 361
timeFrame: Baseline to BD Day 361
measure: Parts A and B: Percentage of Participants With ≥2-fold Increases From Baseline in RSV-A Neutralizing Ab Titers up to Day 181
timeFrame: Baseline up to Day 181
measure: 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
timeFrame: Baseline up to BD Day 361
measure: 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
timeFrame: Baseline up to Day 181
measure: 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
timeFrame: Baseline up to BD Day 361
measure: Part A: Percentage of Participants With Seroconversion in Influenza A and B Strains From Baseline up to Day 181
timeFrame: Baseline up to Day 181
measure: Part A: GMT of Serum Ab Level, as Measured by HAI Assay for Influenza up to Day 181
timeFrame: up to Day 181
measure: Part A: GMFR of Serum Ab Level, as Measured by HAI Assay for Influenza up to Day 181
timeFrame: up to Day 181
measure: Part B: GMC of Serum Ab Level, as Measured by Neutralization Assay for SARS-Cov-2 up to Day 181
timeFrame: up to Day 181
measure: Part B: GMFR of Serum Ab Level, as Measured by Neutralization Assay for SARS-Cov-2 up to Day 181
timeFrame: up to Day 181
measure: Part B: Percentage of Participants With Seroresponse for SARS-Cov-2 Neutralizing Abs From Baseline to Day 181
timeFrame: Baseline up to Day 181
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Central Research Associates Inc
state: Alabama
city: Tucson
country: United States
facility: Del Sol Research Management - Clinedge - PPDS
state: Arizona
city: Garden Grove
country: United States
facility: Paragon Rx Clinical, Inc
state: California
city: Long Beach
country: United States
facility: Ark Clinical Research
state: California
city: Long Beach
country: United States
facility: Long Beach Clinical Trials, LLC (Site 1)
state: California
city: Long Beach
country: United States
facility: Long Beach Clinical Trials, LLC (Site 2)
state: California
city: Modesto
country: United States
facility: Central Valley Research, LLC
state: California
city: Panorama City
country: United States
facility: Velocity Clinical Research - Panorama City
state: California
city: Pomona
country: United States
facility: Empire Clinical Research
state: California
city: San Diego
country: United States
facility: Acclaim Clinical Research
state: California
city: San Diego
country: United States
facility: Medical Center For Clinical Research - M3 WR - ERN - PPDS
state: California
city: Tustin
country: United States
facility: Ark Clinical Research
state: California
city: Waterbury
country: United States
facility: Chase Medical Research LLC
state: Connecticut
city: Brandon
country: United States
facility: Teradan Clinical Trials
state: Florida
city: Doral
country: United States
facility: Revival Research Corporation - Clinedge - PPDS
state: Florida
city: Doral
country: United States
facility: Dolphin Medical Research
state: Florida
city: Hialeah
country: United States
facility: Indago Research and Health Center
state: Florida
city: Jacksonville
country: United States
facility: Westside Center for Clinical Research - ERN - PPDS
state: Florida
city: Miami Lakes
country: United States
facility: Floridian Clinical Research - ClinEdge - PPDS
state: Florida
city: Miami
country: United States
facility: Suncoast Research Group LLC - ERN-PPDS
state: Florida
city: Miami
country: United States
facility: Suncoast Research Associates LLC - ERN - PPDS
state: Florida
city: Chamblee
country: United States
facility: Tekton Research - Georgia - Platinum - PPDS
state: Georgia
city: Lilburn
country: United States
facility: Lifeline Primary Care / CCT Research
state: Georgia
city: Norcross
country: United States
facility: Georgia Clinic / CCT Research
state: Georgia
city: Savannah
country: United States
facility: Meridian Clinical Research (Savannah Georgia) - Platinum - PPDS
state: Georgia
city: Honolulu
country: United States
facility: East-West Medical Research Institute
state: Hawaii
city: Sioux City
country: United States
facility: Meridian Clinical Research (Sioux City - Iowa)
state: Iowa
city: Overland Park
country: United States
facility: Meridian Clinical Research, LLC (Overland Park, Kansas) - Platinum - PPDS
state: Kansas
city: Baton Rouge
country: United States
facility: Meridian Clinical Research (Baton Rouge-Louisiana) - Platinum - PPDS
state: Louisiana
city: Lake Charles
country: United States
facility: Clinical Trials of SWLA, LLC
state: Louisiana
city: Rockville
country: United States
facility: Meridian Clinical Research (Rockville Maryland) - Platinum - PPDS
state: Maryland
city: Minneapolis
country: United States
facility: Clinical Research Institute, Inc - CRN - PPDS
state: Minnesota
city: Grand Island
country: United States
facility: Meridian Clinical Research (Grand Island) - Platinum - PPDS
state: Nebraska
city: Lincoln
country: United States
facility: Meridian Clinical Research, LLC (Lincoln Nebraska) - Platinum - PPDS
state: Nebraska
city: Lincoln
country: United States
facility: Be Well Clinical Studies, LLC
state: Nebraska
city: Norfolk
country: United States
facility: Meridian Clinical Research
state: Nebraska
city: Omaha
country: United States
facility: Meridian Clinical Research (Omaha-Nebraska) - Platinum - PPDS
state: Nebraska
city: Omaha
country: United States
facility: Midwest Regional Health Services - CCT Research
state: Nebraska
city: Las Vegas
country: United States
facility: Clinical Research Center of Nevada - ERN - PPDS
state: Nevada
city: Las Vegas
country: United States
facility: Santa Rosa Medical Centers of Nevada - CCT Research
state: Nevada
city: Bronx
country: United States
facility: CHEAR Center LLC - ClinEdge - PPDS
state: New York
city: Endwell
country: United States
facility: Meridian Clinical Research (Endwell-New York) - Platinum - PPDS
state: New York
city: New York
country: United States
facility: IMA Medical Research, PC.
state: New York
city: Charlotte
country: United States
facility: Javara Research Inc. - Charlotte - Javara - PPDS
state: North Carolina
city: Raleigh
country: United States
facility: M3 Wake Research, Inc - M3 WR - ERN - PPDS
state: North Carolina
city: Cleveland
country: United States
facility: Velocity Clinical Research - Cleveland - ERN - PPDS
state: Ohio
city: Springdale
country: United States
facility: Meridian Clinical Research - Cincinnati - Platinum - PPDS
state: Ohio
city: Moore
country: United States
facility: Tekton Research
state: Oklahoma
city: Anderson
country: United States
facility: Velocity Clinical Research - Anderson - ERN - PPDS
state: South Carolina
city: Greenville
country: United States
facility: Velocity Clinical Research - Greenville - ERN - PPDS
state: South Carolina
city: Myrtle Beach
country: United States
facility: Trial Management Associates LLC - ERN - PPDS
state: South Carolina
city: Spartanburg
country: United States
facility: Velocity Clinical Research - Spartanburg - ERN - PPDS
state: South Carolina
city: Knoxville
country: United States
facility: New Phase Research &amp; Development
state: Tennessee
city: Austin
country: United States
facility: Benchmark Research - Austin - HyperCore - PPDS
state: Texas
city: Beaumont
country: United States
facility: Tekton Research - Beaumont - Platinum - PPDS
state: Texas
city: Dallas
country: United States
facility: Zenos Clinical Research
state: Texas
city: Laredo
country: United States
facility: Milton Haber, M.D.
state: Texas
city: San Antonio
country: United States
facility: Sun Research Institute
state: Texas
city: Bountiful
country: United States
facility: Cope Family Medicine - Ogden Clinic
state: Utah
city: Springville
country: United States
facility: CCT Research at Springville Dermatology
state: Utah
city: Forest
country: United States
facility: Javara Inc./Privia Medical Group INC
state: Virginia
city: Portsmouth
country: United States
facility: Meridian Clinical Research - Family Practice Ports - Portsmouth - Platinum - PPDS
state: Virginia
Study officials:
References: