Evaluation of Modified Vaccinia Ankara-Bavarian Nordic Live Virus Vaccine for Immunogenicity and Durability in Preventing Mpox Infection

The primary objective of the MPOX-VAX Study is to assess the **rate of change** and durability of MVA-specific antibodies at week 48 post-vaccination with the Modified Vaccinia Ankara (MVA) vaccine. This evaluation is clinically relevant as it provides insights into the long-term efficacy of the vaccine in preventing **Mpox infection**, which is crucial for understanding its potential role in public health strategies.

Secondary objectives include:

• Development of MVA-specific antibodies at week 6 after the first dose.
• Neutralizing capacity of the vaccine-induced immune response for the Mpox virus in vitro culture at weeks 6 and 48.
• Prevalence of Mpox seroconversion.
• Prevalence of active Mpox infection.
• Prevalence of active sexually transmitted infections (STIs) at inclusion, including HAV, HBV, HCV, Syphilis, Chlamydia, and Gonorrhoea, and prevalence of participants with chronic HIV infection, HBV, HCV.
• Incidence of STIs at weeks 6, 12, and 48.

The clinical trial involves participants who are **18 years or older**, encompassing both male and female subjects. The study population is not restricted to any specific vulnerable groups. The trial focuses on individuals who have either received one or two doses of the Modified Vaccinia Ankara (MVA) vaccine for the prevention of **Mpox infection** or have received their first dose less than 28 days prior, in accordance with NIAC guidelines. The sponsor has not provided information regarding the total number of participants. Participants are expected to understand and comply with study procedures and provide informed consent. The trial does not specify any particular lifestyle considerations such as diet or physical activity. The selection criteria ensure that participants are eligible for the MVA vaccination as per the outlined guidelines.

The clinical trial is designed to evaluate the **immune response** to the Modified Vaccinia Ankara (MVA) vaccine in preventing **Mpox infection**. This trial is structured as a randomized, double-blind, controlled study, ensuring that neither the participants nor the researchers know who receives the vaccine or a placebo, thus minimizing bias. The trial is expected to last until May 1, 2025, with recruitment starting on February 15, 2024. Participants will be involved for a maximum treatment period of four weeks, with the possibility of early termination if they do not comply with the study procedures or if adverse effects occur.

The study visits are sequenced to include an initial screening visit, where eligibility is confirmed based on criteria such as being 18 years or older and understanding the study procedures. Following the screening, participants will receive one or two doses of the MVA vaccine, depending on their eligibility as per NIAC guidelines. Follow-up visits are scheduled at weeks 0, 2, 6, 12, and 48 to monitor the **antibody titres** and assess the vaccine's neutralizing capacity against the Mpox virus. The end-of-study visit will occur at week 48, where the primary endpoint of mean geometric MVA-specific antibody titres will be evaluated.

Participants are expected to adhere to the study schedule and procedures, with the primary objective being to assess the durability and factors associated with MVA-specific antibodies at week 48 post-vaccination. Secondary endpoints include the detection of Mpox-specific antibodies and DNA, as well as the incidence of sexually transmitted infections (STIs) at various intervals. The trial's design and methodology are aimed at providing robust data on the vaccine's efficacy and safety in preventing Mpox infection.

The clinical trial involves the administration of **IMVANEX**, a **suspension for injection** designed as a vaccine for smallpox and monkeypox. The active substance in this vaccine is the **Modified Vaccinia Ankara – Bavarian Nordic Live Virus**, classified under the ATC code J07BX, which pertains to other viral vaccines. The pharmaceutical form of the vaccine is a suspension for injection, and it is administered via injection. The dosage is set at a maximum of 0.5 ml per administration, with a total maximum dose of 0.5 ml. The treatment period is limited to a maximum of four weeks. The vaccine is not formulated for pediatric use and is not classified as an orphan drug. The vaccine is produced by Bavarian Nordic A/S and is authorized for use in the European Union under the marketing authorization number EU/1/13/855/002.

In this study, no non-experimental treatments such as standard-of-care therapy, placebo, or comparator treatments are specified. The focus is solely on the administration of the IMVANEX vaccine. Participant compliance with the dosing schedule will be monitored throughout the trial to ensure adherence to the protocol. The trial aims to assess the rate of change and durability of MVA-specific antibodies at 48 weeks post-vaccination, as well as factors associated with these antibodies.

Efficacy in the clinical trial titled "Vaccination to prevent Mpox Infection (MPOX-VAX Study)" will be assessed through a series of primary and secondary endpoints. The primary endpoints include the evaluation of mean geometric **MVA-specific antibody** titres at week 48 and the mean rate of change in these antibody titres from post week 6 to week 48. Secondary endpoints will focus on the absolute mean change from baseline in MVA-specific antibody levels 6 weeks after the first vaccine dose, as well as the neutralizing capacity of the vaccine-induced immune response for the Mpox virus in vitro culture at weeks 6 and 48. Additionally, the detection of Mpox-specific antibodies will be measured at weeks 0, 2, 6, 12, and 48, alongside the detection of Mpox DNA on anorectal, throat, or vaginal swabs at the same timepoints.

Further secondary endpoints include the frequency of active sexually transmitted infections (STIs) at inclusion, specifically HAV (IgM), HBV, HCV, Syphilis, Chlamydia, and Gonorrhoea, as well as the frequency of participants with chronic HIV infection, HBV, or HCV. The incidence of STIs will also be assessed at weeks 6, 12, and 48. These efficacy parameters will be collected and analyzed at specified timepoints to determine the vaccine's effectiveness in preventing Mpox infection and its impact on the immune response.