NIH clinical trial examines investigational therapy for dengue

A clinical trial supported by the National Institutes of Health (NIH) is testing an experimental treatment designed to help people suffering the effects of dengue, a mosquito-borne viral disease. The study is supported by NIH's National Institute of Allergy and Infectious Diseases (NIAID), and will involve exposing adult volunteers to a weakened strain of dengue virus that causes a mild form of the disease and administering an investigational therapeutic at various doses to assess its safety and ability to lessen symptoms.

Dengue is transmitted via infected Aedes mosquitoes and sickens as many as 400 million people each year, primarily in tropical and subtropical parts of the world, according to the U.S. Centers for Disease Control and Prevention. In 2024, dengue cases surged to record levels in the Americas with local U.S. transmission reported in Arizona, California, Florida, Hawaii, and Texas. Dengue is endemic in Puerto Rico, which reported nearly 1,500 cases last year. Most people with dengue do not develop symptoms, but those who do commonly experience severe headache and body aches, nausea and vomiting, fever and rash. One in 20 people who get sick with dengue progress to severe illness, which may lead to shock, internal bleeding, and death. There is currently no Food and Drug Administration-approved treatment for dengue.

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."

Jeanne Marrazzo, M.D., M.P.H., NIAID Director

The new clinical trial will test the ability of AV-1, an investigational human monoclonal antibody therapeutic developed by AbViro (Bethesda, Maryland), to mitigate clinical symptoms when administered before and after dengue virus infection. The results of a previously completed NIAID-supported Phase 1 trial indicated that AV-1 is safe in humans, providing the basis for the new clinical trial to test its safety and efficacy.

The Phase 2 clinical trial will enroll at least 84 healthy adult volunteers at 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 an initial screening and physical examination, volunteers will be randomly assigned to one of two groups. One group will receive AV-1 one day prior to being challenged with a mild strain of dengue virus, and the other will receive AV-1 four days after being challenged with the dengue virus. Each group will be further subdivided to receive 100 mg, 300 mg, or 900 mg of AV-1, delivered in a 60-minute intravenous infusion. For each of the three dosage levels, 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 attenuated (weakened) dengue virus. In earlier studies using this challenge virus, most volunteers developed a rash, and some had other mild dengue symptoms, such as joint and muscle pain or headache. None of the volunteers developed dengue fever or severe dengue.

Volunteers will participate in regular follow-up visits with study staff for at least 155 days to carefully monitor the effects of the investigational monoclonal antibody. Through physical exams, diary cards and blood samples, researchers will document how the volunteers' immune systems respond to the dengue virus challenge, how quickly the virus vanishes from their bloodstream and any symptoms they may experience. The researchers will use this information 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 shows promising results in this clinical trial, researchers may pursue further clinical evaluations of its safety and efficacy against dengue virus. For more information about the study, visit ClinicalTrials.gov and search the identifier NCT05048875.

NIAID conducts and supports research—at NIH, throughout the United States, and worldwide—to study the causes of infectious and immune-mediated diseases, and to develop better means of preventing, diagnosing and treating these illnesses. News releases, fact sheets and other NIAID-related materials are available on the NIAID website.