Merck has launched the MOBILIZE-1 Phase 3 clinical trial for V181, an investigational single-dose quadrivalent vaccine designed to prevent dengue disease caused by all four dengue virus serotypes, marking a significant milestone in the fight against one of the world's most widespread mosquito-borne diseases. The trial represents the first Phase 3 study in Merck's clinical development program for V181, with recruitment beginning in Singapore.
Global Health Impact and Unmet Medical Need
Dengue disease poses a critical public health challenge, with approximately half of the world's population—four billion people—living in areas at risk for dengue infection. According to the company's announcement, around 105 million dengue viral infections occur annually worldwide, with approximately 50-60 million being symptomatic on average per year. The disease burden extends beyond individual health impacts, with an average of 4-11 million cases resulting in hospitalizations annually and approximately 29,000 dengue-related deaths worldwide each year.
"Approximately half of the world's population live in areas with a risk for dengue, making it a serious public health threat," said Dr. Paula Annunziato, senior vice president, infectious diseases and vaccines, global clinical development, Merck Research Laboratories. "The initiation of the MOBILIZE-1 study, the first Phase 3 trial in our clinical development program, marks a key milestone in our work to help address this widespread mosquito-borne disease."
Trial Design and Scope
The MOBILIZE-1 study (NCT07013487), also designated as V181-005, is a randomized, double-blind, placebo-controlled Phase 3 trial evaluating the safety, immunogenicity, and efficacy of V181. The study aims to enroll approximately 12,000 healthy individuals aged 2 to 17 years who will be randomized to receive either a single dose of V181 or placebo.
The trial is planned to include more than 30 trial sites across dengue-endemic areas in the Asia-Pacific region, including Indonesia, Malaysia, Philippines, Singapore, Thailand, and Vietnam. This geographic distribution reflects the regions where dengue poses the greatest health threat and where the vaccine's impact could be most significant.
Primary and Secondary Endpoints
The study's primary endpoints focus on evaluating both safety and efficacy of a single dose of V181 in preventing symptomatic virologically confirmed dengue (VCD) of any severity, caused by any of the four dengue serotypes (DENV-1, DENV-2, DENV-3, and DENV-4), regardless of prior dengue exposure.
The key secondary efficacy endpoint will evaluate V181's effectiveness in preventing symptomatic VCD of any severity due to each individual dengue serotype, maintaining the approach of including participants regardless of previous dengue exposure. Additional secondary endpoints include assessing the vaccine's ability to prevent symptomatic VCD with warning signs, severe VCD, and hospitalization—outcomes that represent the most serious clinical manifestations of dengue disease.
Vaccine Technology and Design
V181 is a live attenuated quadrivalent vaccine specifically designed as a single-dose vaccination. The vaccine is being studied to provide protection against dengue disease, including severe forms, whether individuals have been previously infected with the dengue virus or have had no prior infections. This approach addresses a critical challenge in dengue prevention, as the disease's complex immunology can sometimes lead to more severe illness upon reinfection with different serotypes.
The single-dose design represents a potential advantage in public health implementation, particularly in resource-limited settings where multiple-dose vaccination schedules can present logistical challenges and reduced compliance rates.
Disease Characteristics and Clinical Progression
Dengue disease is characterized as one of the fastest-growing mosquito-borne diseases, affecting not only individual health but often the economic stability of communities globally. The disease represents a rapidly emerging cause of serious and sometimes debilitating illness in tropical and subtropical countries.
Clinical presentation can range from mild to severe manifestations. Symptoms of mild dengue fever may include high fever, rash, and muscle and joint pain. However, dengue fever can progress to severe dengue, formerly known as dengue hemorrhagic fever, which can cause severe bleeding, sudden drops in blood pressure, and in rare cases, death. While the majority of infections are uncomplicated, the potential for severe outcomes underscores the importance of effective prevention strategies.
Clinical Development Strategy
Merck has committed to establishing a comprehensive program of clinical trials for V181, including conducting trials globally in areas where dengue represents a significant health threat. The MOBILIZE-1 trial represents the cornerstone of this development program, designed to generate the pivotal efficacy and safety data needed for regulatory submissions.
"If successful, V181 could provide an important single-dose option for at-risk populations, regardless of previous exposure to dengue, to help reduce the significant burden around the globe," Dr. Annunziato noted, highlighting the vaccine's potential to address current gaps in dengue prevention.
The company's approach reflects recognition of dengue's global impact and the need for vaccination strategies that can be effectively implemented across diverse healthcare systems and resource settings. The focus on a single-dose regimen that works regardless of prior exposure represents a potentially significant advancement in dengue prevention strategy.
