A Study to Evaluate the Safety and Efficacy of mRNA-1345 Vaccine Targeting Respiratory Syncytial Virus (RSV) in Adults ≥60 Years of Age

Conditions

Respiratory Syncytial Virus

Keywords

Viral Diseases, Messenger RNA, Moderna, mRNA-1345, Respiratory syncytial virus, Safety, Vaccines

Brief summary

The main purpose of Part A of this study is to evaluate the safety and tolerability of mRNA-1345 vaccine and to demonstrate the efficacy of a single dose of mRNA-1345 vaccine in the prevention of a first episode of RSV-associated lower respiratory tract disease (RSV-LRTD) as compared with placebo from 14 days postinjection through 12 months. The main purpose of Part B of this study is to evaluate the safety, tolerability and immunogenicity of a booster dose (BD) of mRNA-1345 administered 24 months after the primary dose.

Detailed description

The study will be conducted in 2 phases: Phase 2 and Phase 3. In the Part A Phase 2 segment, up to 2,000 participants will be randomly assigned to receive a single injection of either mRNA-1345 vaccine at the selected dose or placebo in a 1:1 randomization ratio. In the Part A Phase 3 segment, approximately 35,000 participants will be randomly assigned to receive a single injection of either mRNA-1345 vaccine at the selected dose or placebo in a 1:1 randomization ratio. In the Part B substudy, 1500 participants who received a dose of mRNA-1345 in Part A Phase 3 will be randomly assigned in a 2:1 randomization ratio to receive a single BD injection of either mRNA-1345 at the selected dose or placebo.

Chong Ma, Jiejun Du, Lan Lan, Archana Kapoor, Gonzalo Pérez Marc et al. (18 authors)

Nature Communications2025-07-037 citations

10.1038/s41467-025-61153-x

Safety and Immunogenicity of an mRNA-Based RSV Vaccine Including a 12-Month Booster in a Phase 1 Clinical Trial in Healthy Older Adults.

Shaw CA, Essink B, Harper C, Mithani R, Kapoor A, Dhar R, Wilson L, Guo R, Panozzo CA, Wilson E, Simorellis AK, Reuter C, Stoszek SK, Chen GL, Das R, Goswami J.

2024-09-0140 citations

10.1093/infdis/jiae081

Safety, Tolerability, and Immunogenicity of an mRNA-Based Respiratory Syncytial Virus Vaccine in Healthy Young Adults in a Phase 1 Clinical Trial.

Shaw CA, Mithani R, Kapoor A, Dhar R, Wilson L, El Asmar L, Schnyder-Ghamloush S, Schaefers K, August A, Stoszek SK, Chen GL.

2024-09-0121 citations

10.1093/infdis/jiae035

Humoral Immunogenicity of mRNA-1345 RSV Vaccine in Older Adults

Jaya Goswami, Abdullah H Baqui, Pablo Alexis Doreski, Gonzalo Pérez Marc, Gilberto Jimenez et al. (27 authors)

The Journal of Infectious Diseases2024-06-1833 citations

10.1093/infdis/jiae316

Efficacy and Safety of an mRNA-Based RSV PreF Vaccine in Older Adults

Eleanor Wilson, Jaya Goswami, Abdullah H Baqui, Pablo Alexis Doreski, Gonzalo Perez-Marc et al. (33 authors)

New England Journal of Medicine2023-12-13366 citations

10.1056/nejmoa2307079

Papers published before 2007-09-01 may not appear yet. Historical indexing is in progress.

Interventions

DRUGPlacebo

0.9% sodium chloride (normal saline) injection

DRUGmRNA-1345

Sterile liquid for injection

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

PREVENTION

Masking

QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)

Eligibility

Sex/Gender

ALL

Age

60 Years to No maximum

Healthy volunteers

Yes

Inclusion criteria

Key Inclusion Criteria (Part A): * Adults ≥ 60 years of age who are primarily responsible for self-care and activities of daily living. Participants may have one or more chronic medical diagnoses (including chronic heart failure \[CHF\] and chronic obstructive pulmonary disease \[COPD\]), but should be medically stable * Body mass index from ≥18 kilograms (kg)/square meter (m\^2) to ≤35 kg/m\^2 Key Inclusion Criteria (Part B): * Randomized to and were subsequently vaccinated with the mRNA-1345 study injection in Part A at least 21 months prior to Screening. Key

Exclusion criteria

(Part A): * Participation in another clinical research study where participant has received an investigational product (drug/biologic/device) within 6 months before the planned date of the Day 1 study injection. * Current participation in research involving receipt of any investigational RSV product * History of a serious reaction to any prior vaccination or Guillain-Barré syndrome within 6 weeks of any prior influenza immunization. * Received or plans to receive any non-study vaccine within 28 days before or after the Day 1 study injection. Key

Design outcomes

Primary

Measure	Time frame	Description
Number of Participants with Solicited Local and Systemic Adverse Reactions (ARs)	Up to 7 days after each injection	—
Number of Participants with Unsolicited Adverse Events (AEs)	Up to 28 days after each injection	—
Number of Participants With Medically Attended AEs (MAAEs), Adverse Events of Special Interests (AESIs), Serious Adverse Events (SAEs), and AEs Leading to Withdrawal	Up to BD Day 181	—
Vaccine Efficacy (VE) of mRNA-1345 to Prevent a First Episode of RSV-LRTD with 2 or More Symptoms	From 14 days postinjection up to 12 months postinjection	VE of mRNA-1345 to prevent reverse transcription polymerase chain reaction (RT-PCR) confirmed protocol-defined RSV-LRTD, defined as 100\*(1-HR ratio), where HR is the hazard ratio (mRNA-1345 versus placebo).
VE of mRNA-1345 to Prevent a First Episode of RSV-LRTD with 3 or More Symptoms	From 14 days postinjection up to 12 months postinjection	VE of mRNA-1345 to prevent reverse transcription polymerase chain reaction (RT-PCR) confirmed protocol-defined RSV-LRTD, defined as 100\*(1-HR ratio), where HR is the hazard ratio (mRNA-1345 versus placebo).
Geometric Mean Titer (GMT) of Serum Respiratory Syncytial Virus Subtype A (RSV-A) and Respiratory Syncytial Virus Subtype B (RSV-B) Neutralizing Antibodies	BD Day 29	—
Geometric Mean Ratio (GMR) of Serum RSV-A and RSV-B Neutralizing Antibodies After BD Compared to After Initial Dose	BD Day 29	—

Secondary

Measure	Time frame	Description
Seroresponse Rate (SRR) Difference Between Serum RSV-A and RSV-B Neutralizing Antibodies After BD Compared to After Initial Dose	BD Day 29	—
GMT of Serum RSV-A and RSV-B Neutralizing Antibodies	BD Day 1 and Day 181	—
VE of mRNA-1345 to Prevent a First Episode of RSV-Associated Acute Respiratory Disease (RSV-ARD)	From 14 days postinjection up to 12 months postinjection	VE of mRNA-1345 to prevent RT-PCR confirmed protocol-defined RSV-ARD, defined as 100\*(1-HR ratio), where HR is the hazard ratio (mRNA-1345 versus placebo).
SRR of Serum RSV-A and RSV-B Neutralizing Antibodies from Pre-primary Dose (Baseline)	Baseline, BD Day 1, Day 29 and Day 181	—
GMFR of Serum RSV-A and RSV-B Neutralizing Antibodies from Pre-primary Dose (Baseline)	Baseline, BD Day 1, Day 29 and Day 181	—
VE of mRNA-1345 to Prevent First Hospitalization Associated with RSV-ARD or RSV-LRTD	From 14 days postinjection up to 12 months postinjection	VE of mRNA-1345 to prevent first hospitalization associated with RSV-ARD or RSV-LRTD, defined as 100\*(1-HR ratio), where HR is the hazard ratio (mRNA-1345 versus placebo).
GMT of Serum RSV Neutralizing Antibodies	Baseline through up to 24 months postinjection	—
Geometric Mean Concentration (GMC) of Serum RSV Binding Antibodies	Baseline through up to 24 months postinjection	—
Seroresponse Rate in RSV Neutralizing Antibodies	Baseline through up to 24 months postinjection	—
Geometric Mean Fold-Rise (GMFR) of Postbaseline/Baseline Antibody Titers	Baseline through up to 24 months postinjection	—
Proportion of Participants with ≥4-fold Increases in Antibody Titers from Baseline	Baseline through up to 24 months postinjection	—

Countries

Argentina, Australia, Bangladesh, Belgium, Canada, Chile, Colombia, Costa Rica, Finland, Germany, Japan, Mexico, New Zealand, Panama, Poland, Puerto Rico, Singapore, South Africa, South Korea, Spain, Taiwan, United Kingdom, United States

Outcome results

None listed