A clinical trial supported by the National Institutes of Health (NIH) is underway to evaluate AV-1, an experimental treatment for dengue fever, a mosquito-borne viral disease affecting millions globally. The study, backed by the NIH’s National Institute of Allergy and Infectious Diseases (NIAID), involves exposing adult volunteers to a weakened strain of the dengue virus and administering the investigational therapeutic at various doses to assess its safety and ability to lessen symptoms.
Dengue, transmitted by infected Aedes mosquitoes, sickens approximately 400 million people annually, primarily in tropical and subtropical regions. In 2024, the Americas saw a surge in dengue cases, with local transmission reported in several U.S. states. While most individuals with dengue remain asymptomatic, those who develop symptoms commonly experience severe headaches, body aches, nausea, vomiting, fever, and rash. In a subset of patients, the disease progresses to severe illness, potentially leading to shock, internal bleeding, and death. Currently, there is no FDA-approved treatment for dengue.
AV-1: A Novel Monoclonal Antibody
AV-1, developed by AbViro (Bethesda, Maryland), is an investigational human monoclonal antibody therapeutic. The Phase 2 clinical trial will assess its ability to mitigate clinical symptoms when administered both before and after dengue virus infection. Previous NIAID-supported Phase 1 trials indicated that AV-1 is safe in humans, providing the rationale for this trial to test its safety and efficacy further.
NIAID Director Jeanne Marrazzo, M.D., M.P.H., stated, "When caring for a patient who is critically ill with dengue, healthcare providers have few options other than providing supportive care. We must find safe and effective therapeutics to provide much-needed relief to people suffering from dengue."
Trial Design and Methodology
The Phase 2 clinical trial will enroll at least 84 healthy adult volunteers across two sites: the Johns Hopkins Bloomberg School of Public Health Center for Immunization Research in Baltimore, and the University of Vermont Vaccine Testing Center in Burlington. Following initial screening and physical examinations, volunteers will be randomly assigned to one of two groups. One group will receive AV-1 one day before being challenged with a mild strain of dengue virus, while the other group will receive AV-1 four days after the viral challenge. Each group will be further subdivided to receive 100 mg, 300 mg, or 900 mg of AV-1, administered via a 60-minute intravenous infusion. For each dosage level, 12 participants will receive the investigational monoclonal antibody, and two will receive a placebo.
Before or after AV-1 dosing, each volunteer will receive an injection of an attenuated dengue virus. Previous studies using this challenge virus resulted in most volunteers developing a rash and some experiencing mild dengue symptoms such as joint and muscle pain or headache. Notably, none of the volunteers developed dengue fever or severe dengue.
Monitoring and Evaluation
Volunteers will participate in regular follow-up visits with study staff for at least 155 days to monitor the effects of the investigational monoclonal antibody. Researchers will document the volunteers’ immune system responses to the dengue virus challenge, the rate of viral clearance from their bloodstream, and any symptoms experienced through physical exams, diary cards, and blood samples. This data will be used to determine how AV-1 affects the volunteers' ability to recover from dengue compared to placebo and to determine the dosages at which AV-1 may be effective.
If AV-1 demonstrates promising results in this clinical trial, further clinical evaluations of its safety and efficacy against dengue virus may be pursued. Additional information about the study can be found at ClinicalTrials.gov, identifier NCT05048875.
