Prospective Evaluation of Chikungunya Virus Strain CHIKV LR2006-OPY1 Live Attenuated Vaccine Efficacy, Safety, and Immunogenicity in At-Risk Populations

The primary objective of this study is to evaluate the **vaccine effectiveness** (EV) at 6 months of the chikungunya vaccine in preventing the occurrence of confirmed chikungunya in vulnerable populations. This is clinically relevant as it aims to assess the vaccine's ability to reduce the incidence of chikungunya, a significant infectious disease, particularly in populations at risk of severe or complicated forms.

Secondary objectives include:

• Measuring the EV in preventing hospitalization of more than 24 hours in vaccinated patients.
• Assessing the EV in preventing intensive care unit (ICU) hospitalization or death in vaccinated participants.
• Evaluating the EV to prevent disabling complications.

The clinical trial focuses on evaluating the effectiveness of a vaccine against **Chikungunya**, an infectious disease. The study population includes both male and female participants, aged 18 years and older, who are considered part of a vulnerable population. Participants are required to be eligible for anti-chikungunya vaccination as per HAS recommendations and must be beneficiaries of social security coverage. The trial does not specify the total number of participants, as this information was not provided by the sponsor. The selection of participants is based on their agreement to participate in the study and the signing of an informed consent form. The trial does not specify any particular lifestyle considerations such as diet or physical activity. The sponsor has not provided additional details regarding the general health status of the participants.

The clinical trial is designed to evaluate the **effectiveness**, safety, and immunogenicity of a **chikungunya** vaccine in populations at risk of severe or complicated forms of the disease. This is a prospective, phase IV, low-intervention study, conducted under real-life conditions. The trial employs a randomized, double-blind, controlled design to ensure the reliability and validity of the results. The study is expected to commence on April 14, 2025, and conclude by April 13, 2026, with a total duration of approximately 12 months.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as informed consent, eligibility for vaccination, and social security coverage. Following the initial vaccination, participants will be monitored through follow-up visits at 3 months and 12 months post-vaccination. These visits aim to assess the primary endpoint, which is the vaccine's effectiveness in reducing the attack rate of confirmed chikungunya cases. Secondary endpoints include hospitalization rates, ICU admissions, and the occurrence of disabling complications such as arthralgia and chronic fatigue.

The expected length of participant involvement is up to 12 months, with interim analyses conducted at 3 months. Conditions that may lead to early termination from the study include withdrawal of consent or any adverse events that compromise participant safety. The study involves minimal risks and constraints, primarily limited to blood sampling in addition to vaccination, aligning with the low-intervention nature of the trial. The vaccine is administered via intramuscular injection, with a maximum daily and total dose of 0.50 ml. The trial is conducted in accordance with health authority recommendations, ensuring that only individuals meeting the criteria for vulnerable populations are included.

The clinical trial involves the administration of **IXCHIQ**, a **Chikungunya vaccine (live)**, which is formulated as a **powder and solvent for solution for injection**. The active substance in this experimental medication is the **Chikungunya virus, strain CHIKV LR2006-OPY1, live attenuated**. The vaccine is administered via **intramuscular injection**. The dosage is set at a maximum of **0.50 ml** per administration, with a total treatment period limited to a single dose. The pharmaceutical form of the vaccine is a **solution for injection**, and it is not a pediatric formulation. The vaccine is classified under the ATC code **J07BX**, which denotes it as an "other viral vaccine".

In this study, no non-experimental treatments such as standard-of-care therapy, placebo, or comparator treatments are utilized. The focus is solely on evaluating the effectiveness, safety, and immunogenicity of the **IXCHIQ** vaccine in populations at risk of severe or complicated forms of Chikungunya. Participant compliance with the dosing schedule is monitored to ensure adherence to the single-dose regimen. The trial aims to measure the vaccine's effectiveness at six months post-administration in preventing confirmed cases of Chikungunya, as indicated by PCR+ or IgM+ results in participants who were not previously immunized during the epidemic phase.

Efficacy in this clinical trial will be assessed by evaluating the **vaccine effectiveness (EV)** of the chikungunya vaccine in preventing confirmed chikungunya cases in vulnerable populations. The primary endpoint is defined as the EV, calculated as the quotient of the difference in attack rate between unvaccinated and vaccinated participants divided by the attack rate in unvaccinated participants. This is expressed as a percentage: EV (%) = (λ_nv - λ_v) × 100 / λ_nv, where λ represents the cumulative incidence at the end of the study follow-up period. Interim analysis will occur at 3 months, with full follow-up at 12 months, starting from day 7 post-vaccination for the vaccinated group.

Secondary endpoints include the rate of hospitalization over 24 hours and the preventive fraction of hospitalization in both vaccinated and unvaccinated participants. Additionally, the rate of ICU hospitalization or death and the preventive fraction will be assessed at day 30 and at the end of the study. The rate of disabling complications, such as arthralgia and chronic phenotypes (fatigue/anxiety-depression), will be evaluated at 3 months of inclusion and at the study's conclusion. These parameters will be measured and analyzed to determine the vaccine's efficacy in real-world conditions.