Phase 3 Randomized Study on Efficacy and Safety of IVX-A12 Vaccine for RSV and hMPV in Adults Aged 60+

The primary objective of this study is to demonstrate the efficacy of a single intramuscular vaccination with **IVX-A12** in preventing confirmed lower respiratory tract disease (LRTD) caused by **Respiratory Syncytial Virus (RSV)** and **Human Metapneumovirus (hMPV)** of any severity in adults aged 60 years and older during the first season, compared to placebo. This is clinically relevant as it addresses the prevention of respiratory infections that can lead to significant morbidity in the elderly population.

Secondary objectives include:

• To demonstrate the efficacy of IVX-A12 in preventing confirmed RSV LRTD and hMPV LRTD in adults aged 60 years and older over two seasons compared to placebo.
• To demonstrate the efficacy of IVX-A12 in preventing confirmed severe RSV LRTD and severe hMPV LRTD in adults aged 60 years and older over two seasons compared to placebo.

The clinical trial involves a total of **25,736 participants** who are adults aged **60 years and older**. The study population includes both **male and female** subjects who are medically stable, as determined by the investigator. Participants with chronic stable medical conditions, such as diabetes, hypertension, or cardiac disease, are eligible to participate if deemed stable. The trial focuses on individuals who can understand and comply with study requirements, including attending scheduled visits, with assistance if necessary. The study does not include a vulnerable population. The primary objective is to assess the efficacy of a single intramuscular vaccination with IVX-A12 in preventing confirmed lower respiratory tract disease (LRTD) caused by **Respiratory Syncytial Virus (RSV)** and **Human Metapneumovirus (hMPV)** in this age group during the first season compared to a placebo. The selection of participants was based on their ability to meet these criteria, ensuring a representative sample of the target demographic.

The clinical trial is designed as a **randomized**, modified **double-blind**, placebo-controlled study to evaluate the efficacy, immunogenicity, and safety of the investigational vaccine IVX-A12 in adults aged 60 years and older. The trial aims to assess the vaccine's ability to prevent confirmed lower respiratory tract disease (LRTD) caused by **Respiratory Syncytial Virus** (RSV) and **Human Metapneumovirus** (hMPV). The study will span over two seasons, with an estimated recruitment start date in September 2025 and an expected completion by September 2027.

Participants will be involved in the study for a maximum of two years. The trial will include several key visits: an initial screening visit to determine eligibility based on inclusion criteria such as age and medical stability, followed by a baseline visit where the investigational product or placebo will be administered via **intramuscular injection**. Subsequent follow-up visits will be scheduled to monitor the occurrence of RSV and hMPV-confirmed LRTD, starting from Day 15 post-vaccination. The end-of-study visit will conclude the participant's involvement, assessing the long-term safety and efficacy outcomes.

Participants may be withdrawn from the study early if they experience significant adverse events, fail to comply with study procedures, or withdraw consent. The primary endpoints focus on the occurrence of the first RSV and hMPV-confirmed LRTD during the first season, while secondary endpoints extend this assessment over two seasons, including severe cases. The trial's methodology ensures rigorous evaluation through its controlled and blinded design, providing robust data on the vaccine's performance in the target population.

The clinical trial involves the administration of **IVX-A12**, an investigational vaccine designed to prevent respiratory syncytial virus (RSV) and human metapneumovirus (hMPV) lower respiratory tract disease (LRTD) in adults aged 60 years and older. **IVX-A12** is formulated as a **solution for injection** and is administered via **intramuscular injection**. The active substances in **IVX-A12** include **IVX-121**, a protein of other origin, and a **human metapneumovirus virus-like protein**, classified as a structurally diverse substance and vaccine. The maximum daily dose is 300 micrograms, with a total maximum dose of 600 micrograms over a treatment period of up to two days. The vaccine is provided by AstraZeneca AB and is not a pediatric formulation.

The comparator treatment in this study is a **placebo**, consisting of 0.9% (w/v) sodium chloride (NaCl) for injection. The placebo is also administered via **intramuscular injection** and is provided by the study sites. The use of a placebo allows for a controlled evaluation of the efficacy and safety of the investigational vaccine, **IVX-A12**. Participant compliance with the dosing schedule will be monitored throughout the trial to ensure adherence to the protocol.

The efficacy of the investigational vaccine IVX-A12 will be assessed in a Phase 3, global, randomized, modified double-blind, placebo-controlled clinical trial. The primary endpoints for evaluating efficacy include the occurrence of the first **RSV-confirmed LRTD** (Lower Respiratory Tract Disease) and the first **hMPV-confirmed LRTD** starting on Day 15 during the first season. Secondary endpoints will assess the occurrence of these conditions over two seasons, as well as the occurrence of severe cases of RSV-confirmed and hMPV-confirmed LRTD starting on Day 15 over two seasons.

The trial aims to demonstrate the efficacy of a single intramuscular vaccination with IVX-A12 in preventing confirmed RSV and hMPV LRTD of any severity in adults aged 60 years and older. The efficacy parameters will be measured and collected at specified timepoints, starting from Day 15, and will continue to be monitored over the course of one or two seasons, depending on the endpoint. The analysis will focus on the first occurrence of the specified conditions, providing a clear measure of the vaccine's protective effect against these viral infections.