NIH clinical trial examines investigational therapy for dengue

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 from the effects of dengue, a mosquito-borne viral disease. The study is supported by the NIH National Institute of Allergy and Infectious Diseases (NIAID) and will expose adult volunteers to a weakened strain of dengue virus that causes a mild form of the disease and administer an investigational therapeutic drug at various doses to evaluate its safety and ability to reduce symptoms.

Dengue is transmitted through infected peopleAedesMosquitoes and sicken up to 400 million people each year, mostly in tropical and subtropical parts of the world, according to the U.S. Centers for Disease Control and Prevention. In 2024, dengue cases rose to record in America. U.S. U.S. cases reported in Arizona, California, Florida, Hawaii and Texas increased. 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 usually have severe headaches and body aches, nausea and vomiting, fever and rash. One in 20 people who become ill with dengue causes serious illness, which can lead to shock, internal bleeding and death. Currently, there is no Food and Drug Administration-approved treatment for dengue.

When caring for a patient sick with dengue, healthcare providers have few options other than to provide supportive care. We must find safe and effective therapeutics to provide much-needed relief to people suffering from dengue. “

Jeanne Marrazzo, MD, MPH, NIAID -Director

The new clinical trial will test the ability of AV-1, a monoclonal antibody-antibody therapeutic developed by Abviro (Bethesda, Maryland), to mitigate clinical symptoms when administered before and after dengue virus infection. Results from a previously completed NIAID-supported Phase 1 study demonstrated that AV-1 is safe in humans and form the basis for the new clinical trial testing its safety and effectiveness.

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. After an initial screening and physical examination, volunteers will be randomly assigned to one of two groups. One group will receive AV-1 one day before being challenged with mild dengue virus, and the other will receive AV-1 four days after challenge with dengue virus. Each group will be further divided 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 the attenuated (weakened) dengue virus. In previous studies using this challenge virus, most volunteers developed a rash, and some had other mild symptoms of dengue, such as joint and muscle pain or headaches. None of the volunteers developed dengue fever or severe dengue.

Volunteers will attend 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 volunteers' immune systems respond to the dengue virus challenge, how quickly the virus clears from their bloodstream and any symptoms they may experience. Researchers will use this information to determine how AV-1 affects 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 can conduct further clinical evaluations of its safety and effectiveness against the dengue virus. For more information about the study, visit clinicaltrials.gov and search identifier NCT05048875.

NIAID conducts and supports research—at NIH, in the United States, and worldwide—to investigate the causes of infectious and immune-mediated diseases and to develop better means of preventing, diagnosing, and treating these diseases. The NIAID website contains news publications, fact sheets, and other NIAID materials.

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