In short
Researchers are currently evaluating an investigational vaccine called mRNA-1345 that targets Respiratory Syncytial Virus (RSV) in adults aged 60 and older. RSV is a common respiratory virus that can cause serious lower respiratory tract infections, especially in older adults. The clinical trial is designed in two parts: Part A aims to assess the safety, tolerability, and effectiveness of a single dose of the vaccine in preventing RSV-associated lower respiratory tract disease, while Part B evaluates a booster dose administered 24 months after the initial vaccination. This large-scale study involves approximately 37,000 participants and uses advanced methods to measure immune responses and protection against RSV infection.
Key points
- The mRNA-1345 vaccine is being evaluated in a large Phase 2/3 clinical trial involving approximately 37,000 adults aged 60 and older to prevent Respiratory Syncytial Virus (RSV) infection. The study is divided into two parts: Part A assesses a single dose of the vaccine compared to placebo, while Part B examines a booster dose given 24 months later to a subset of participants. Researchers are measuring both the safety profile of the vaccine and its effectiveness in preventing RSV-associated lower respiratory tract disease. The trial is tracking several outcomes, including prevention of RSV illness with varying symptom severity, prevention of hospitalizations, and detailed measurements of immune responses through antibody production. Results will help determine if this mRNA vaccine can provide protection against RSV in older adults.
At a glance
- Vaccine Name
- mRNA-1345
- Target Disease
- Respiratory Syncytial Virus (RSV)
- Target Population
- Adults aged 60 years and older
- Study Design
- Phase 2/3, randomized, observer-blind, placebo-controlled
- Total Participants
- Approximately 37,000 (up to 2,000 in Phase 2, about 35,000 in Phase 3)
- Treatment Schedule
- Part A: Single injection of mRNA-1345 or placebo; Part B: Booster dose at 24 months for selected participants
- Primary Outcomes
- • Safety and tolerability; • Prevention of first episode of RSV-LRTD with 2+ or 3+ symptoms; • Immune response measurements
- Secondary Outcomes
- • Prevention of RSV-ARD; • Prevention of RSV-related hospitalizations; • Detailed antibody response measurements
- Safety Monitoring
- • Local and systemic reactions (7 days); • Unsolicited adverse events (28 days); • Serious adverse events (up to 181 days after booster)
What is MRNA-1345?
MRNA-1345 is an investigational vaccine that is being developed to protect against Respiratory Syncytial Virus (RSV). It is administered as a sterile liquid injection. This vaccine uses mRNA technology, which instructs your cells to produce proteins that trigger an immune response against RSV. Unlike traditional vaccines that use weakened or inactivated viruses, mRNA vaccines contain genetic instructions that teach your body how to recognize and fight the actual virus if you're exposed to it later.
What is RSV?
Respiratory Syncytial Virus is a common respiratory virus that usually causes mild, cold-like symptoms. However, it can be serious, especially for older adults and people with weakened immune systems. RSV can lead to more severe respiratory conditions like lower respiratory tract disease (LRTD), which affects the lungs and can cause significant breathing problems. The virus has two main subtypes: RSV-A and RSV-B, both of which are targeted by the mRNA-1345 vaccine.
Clinical Trial Overview
The clinical trial for mRNA-1345 (identified as NCT05127434) is designed to evaluate whether this vaccine is safe and effective in preventing RSV infections in adults who are 60 years of age and older. This is an important age group to study because older adults are at higher risk for severe RSV disease.
Trial Design
The study is being conducted in two main parts with different phases:
Part A
Part A consists of:
- Phase 2 segment: Up to 2,000 participants receive either a single injection of mRNA-1345 or a placebo (a harmless substance with no active ingredients - in this case, normal saline solution).
- Phase 3 segment: Approximately 35,000 participants receive either a single injection of mRNA-1345 or a placebo.
Part B
In Part B:
- 1,500 participants who received mRNA-1345 in Part A's Phase 3 will receive either a booster dose of mRNA-1345 or a placebo 24 months after their initial dose.
This study is "observer-blind" and "placebo-controlled," which means that the people evaluating the outcomes don't know which participants received the vaccine and which received the placebo. This helps prevent bias in assessing the results.
Purpose of the Study
The main goals of this clinical trial are:
For Part A:
- To evaluate the safety and tolerability of the mRNA-1345 vaccine.
- To demonstrate the effectiveness of a single dose of mRNA-1345 in preventing the first episode of RSV-associated lower respiratory tract disease (RSV-LRTD) compared to placebo. This effectiveness is measured from 14 days after injection through 12 months.
For Part B:
- To evaluate the safety, tolerability, and immune response (immunogenicity) of a booster dose of mRNA-1345 given 24 months after the primary dose.
Outcomes Being Measured
The study is measuring several important outcomes to determine whether the vaccine is safe and effective:
Safety Outcomes:
- Solicited adverse reactions: These are expected side effects that are specifically monitored after vaccination, such as pain at the injection site, fatigue, or headache. These are tracked for up to 7 days after each injection.
- Unsolicited adverse events: These are unexpected side effects that are reported by participants. These are monitored for up to 28 days after each injection.
- Medically attended adverse events: These are side effects that require medical attention.
- Serious adverse events: These are severe side effects that may require hospitalization or cause significant disability.
- Adverse events of special interest: These are specific medical events that researchers are particularly interested in monitoring.
Effectiveness Outcomes:
- Vaccine efficacy against RSV-LRTD: The study measures how effective the vaccine is at preventing RSV-related lower respiratory tract disease with either 2 or more symptoms or 3 or more symptoms. This is confirmed through laboratory testing (RT-PCR) that detects the virus.
- Vaccine efficacy against RSV-ARD: The study also looks at how effective the vaccine is at preventing RSV-associated acute respiratory disease, which is a broader category of respiratory illness caused by RSV.
- Prevention of hospitalization: Researchers are measuring whether the vaccine prevents hospitalizations related to RSV infections.
Immune Response Outcomes:
- Antibody levels: The study measures the levels of antibodies that participants develop against both RSV-A and RSV-B subtypes.
- Seroresponse rate: This is the percentage of participants who develop a significant increase in antibody levels after vaccination.
- Geometric mean titer: This is a mathematical way to measure the average concentration of antibodies in participants' blood.
- Fold-increase in antibodies: The study tracks how many times higher the antibody levels are after vaccination compared to before vaccination.
Potential Benefits
If proven effective, the mRNA-1345 vaccine could provide important protection against RSV for older adults. The study is specifically looking at whether the vaccine can:
- Prevent RSV-related lower respiratory tract disease, which can be serious or even life-threatening in older adults.
- Reduce hospitalizations due to RSV infections.
- Provide long-lasting protection, with researchers monitoring antibody levels for up to 24 months after vaccination.
- Potentially offer additional protection through a booster dose given 24 months after the initial vaccination.
Safety Monitoring
The study includes comprehensive safety monitoring to identify any potential side effects or adverse reactions to the vaccine:
- Participants are closely monitored for immediate reactions after receiving the injection.
- Specific expected side effects (like pain at the injection site, fever, or fatigue) are tracked for 7 days after vaccination.
- Any unexpected side effects are monitored for 28 days after vaccination.
- Serious adverse events and medically attended adverse events are tracked throughout the study period (up to 181 days after the booster dose).
- The study design includes "blinding" to ensure unbiased assessment of safety outcomes.