Chikungunya (CHIK) is a disease caused by the chikungunya virus (CHIKV). This can happen when a mosquito infected with this virus bites and injects CHIKV into a human. The signs may include hotness of body, joint pains, swollen joints and tiredness. The signs usually begin a few days after the bite. In most people, the illness is short lived and resolves on its own, but in some cases, joint pain and other signs can last for more than 12 weeks. Chikungunya poses a notable public health burden worldwide especially in areas where the disease is prominent. This includes the coastal region of Kenya, where outbreaks are common and have led to widespread illness, hospital strain, and economic disturbance. This includes Mombasa and Kilifi counties where several outbreaks have been experienced in 2018, 2023 and the currently ongoing outbreak that started in May 2025 where at least 89 confirmed positive cases were recorded as of 24 Jun 2025. The purpose of this trial is to determine the effectiveness and how safety of the VLA1553 vaccine (which has already been approved in some countries under the brand name IXCHIQ®) prevents signs and Chikungunya Virus infection confirmed by a blood test as compared with a placebo (an inactive material in an injection that will look identical to the vaccine but provides no benefit) in participants from different age groups and from various locations with active CHIKV transmission. Participants will be randomly (like a coin toss) selected and divided into in two groups, those receiving the investigational vaccine (VLA1553) and placebo . Each participant has an equal chance of receiving the vaccine or the placebo. Each enrolled participant will receive a single dose of 0.5 mL injection of either the vaccine or placebo on their upper arm (non-dominant arm).

Willing healthy individuals aged 12 to 65 years who live in areas where chikungunya is spreading may be eligible to join. Participants will be subject to a CHIKV virus test and should test negative for previous chikungunya infection. A sufficient number of participants will be screened to enroll at least 20,000 eligible participants across all the participating sites with KEMRI Mtwapa enrolling at least 700 participants. The participants will be assessed both during clinic visits and remotely via phone. Quality of life of the participants will be assessed using a set of questions (HRQoL). The trial will continue until the targeted number of positive cases of Chikungunya virus infection confirmed by a blood test are accumulated and 12 weeks of follow up for the last positive CHIKV case are reached and the safety

follow-up period for the last enrolled participant has been completed. The information collected in this trial will help determine how well the vaccine works, and

whether it can prevent CHIKV infection and its safety. The global burden of CHIKV is expected to grow due to climate change, globalization, demographic growth, and other factors playing a role in the expansion of mosquito vectors and population at risk of CHIKV infection. The development of a safe and effective vaccine

is a high priority. Through participation in this trial, participants will contribute to the confirmatory studies required to show how well the vaccine works following the FDA’s accelerated approval pathway.

Background: Chikungunya virus (CHIKV) is a mosquito-borne infection that causes acute fever and severe joint pain, with a risk of chronic complications lasting months or even years. The burden of chikungunya is particularly high in tropical and subtropical regions, including coastal areas of Kenya, where outbreaks frequently occur due to conducive ecological, environmental and socioeconomic factors. This includes Mombasa and Kilifi counties where several outbreaks have been experienced in 2018, 2023 and the currently ongoing outbreak that started in May 2025 where at least 89 confirmed positive cases were recorded as of 24

Jun 2025.

 

Purpose and rationale: This trial is being conducted to fulfill post-marketing requirements by evaluating Safety and the effectiveness of VLA1553 in preventing symptomatic, virologically confirmed chikungunya disease after a single dose of the vaccine.

 

Objective: A pragmatic randomized controlled trial to evaluate the effectiveness and safety of VLA1553 against Chikungunya Virus Disease.

 

Methodology: This is a Phase 3b, pragmatic, individual level randomized, observer-blind, placebo-controlled trial enrolling at least 20,000 healthy participants aged 12 years and above from chikungunya-endemic regions. It is a multicenter trial in approximately 2 to 3 countries where there is CHIKV transmission with KEMRI-Mtwapa site being one of the participating sites located in Kenya. A sufficient number of participants will be screened to randomize at least 20,000 across all participating sites with KEMRI-Mtwapa recruiting at least 700 of the total expected participants globally. The trial will be deemed complete when the targeted

number of virologically confirmed CHIKV cases and the subsequent 12 weeks of follow up for the last case are reached and the safety follow-up period for the last participant has been completed.

 

Expectation: The medical and economic burden of CHIKV is expected to grow with climate change as the mosquito vectors that transmit the disease continue to spread geographically. The development of a safe and effective vaccine is a high priority. This trial will contribute to the confirmatory studies required to show the clinical benefit and safety of VLA1553.