Phase 1 Challenge Study Using rDEN2delta30-7169 to Evaluate Host-Pathogen Interactions in Primary, Homotypic, and Heterotypic Dengue Virus Infection

NCT07706686 | Recruiting Phase 1 FDA Drug

• 2 other identifiers: 10002606002606-I
• Study Type: interventional
• Target: 200
• Locations: 1 country
• Sites: 1

Brief Summary

Background: Dengue is a viral disease spread by mosquitoes. Most people bitten by mosquitoes carrying dengue viruses do not get sick, but severe cases can cause shock, internal bleeding, and death. There are no treatments for dengue. To develop treatments, researchers need to understand more about what dengue viruses do in the body. Objective: To infect healthy people with a mild dengue virus to study how their body responds. Eligibility: People ages 18 to 50 years with or without a history of dengue virus infection. Design: Participants will be screened. They will have a physical exam with blood tests. The tests will show whether they have ever been infected with dengue or related viruses in the past. At their first study visit, participants will receive an injection of dengue virus into the arm. The injected virus is weaker than the natural virus, so any symptoms should be milder. Participants will have a total of 11 study visits over 6 months; 8 of those visits will be in the first month. Blood will be drawn at each visit. Some visits will include ultrasound exams of their internal organs. They will discuss any symptoms they are having. Any rashes they develop may be photographed. Two procedures are optional: Participants may have up to 5 lymph node aspirations and 3 bone marrow biopsies during the study. For both procedures, a needle will be inserted into the tissues to draw out immune cells. Two more visits are optional: 1 visit up to 2 months before receiving the virus, for lymph node or bone marrow samples, and 1 about a year after for a blood draw.

Conditions

Healthy Volunteers; Dengue; Human Challenge Trial

Keywords

Dengue; Viruses; Healthy Volunteers; Human challenge trial; Antibody dependent enhancement; Bone marrow examination; Host pathogen interactions; Immunology; Lymph node aspiration

Outcome Measures

Primary Outcomes (3)

• The frequency and severity of AEs through day 28 and SAEs through day 180.

  Evaluate the safety of the challenge strain in all groups.

  Through Day 180

• Fold difference between groups in peak viral RNAemia titers on any day from days 2 to 19.

  Evaluate viral replication by qRT-PCR and compare the peak replication among groups.

  Through Day 19

• Fold change in DENV1-4 neutralizing antibody GMTs between days 0 and 28 within each group.

  Evaluate the immunogenicity of the challenge by examining the change in antibody titers in each group.

  Through Day 28

Secondary Outcomes (3)

• Differences in the change in IP-10 signaling between day 0 and days 2 to 19 among groups.

  Through Day 19

• Difference between the bone marrow cellularity at day 5 versus the reference range within each group.

  At Day 5

• The magnitude of bone marrow DENV-specific antibody-secreting cells at day 57.

  At Day 57

Study Arms (3)

Heterotypic

EXPERIMENTAL

Those with their highest titer to a non-DENV2.

Biological: rDEN2delta30-7169

Homotypic

EXPERIMENTAL

Those with a DENV2-dominant serotype.

Biological: rDEN2delta30-7169

Naive

EXPERIMENTAL

Those with no exposures to flaviviruses

Biological: rDEN2delta30-7169

Interventions

rDEN2delta30-7169 BIOLOGICAL

The rDEN2delta30-7169 strain is a live attenuated recombinant virus constructed by introducing a 30-nucleotide deletion (delta30) in 3 UTR of the wild type DEN-2 Tonga/74.

Heterotypic; Homotypic; Naive

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• To be eligible to participate in this study, an individual must meet all the following criteria:
• Aged 18 to 50 years.
• In good general health as evidenced by medical history, physical examination, and laboratory screening results
• Willing to allow storage of samples and data for future research.
• Willing to forgo receipt of any vaccine in the 28 days preceding the challenge strain through the 28 days following administration of the challenge strain. For participants opting for LN FNA or bone marrow sampling on day 57, they must be willing to forgo any vaccine through day 57. For those opting for FNA or bone marrow sampling on day 180, they must be willing to forgo any vaccine for at least 28 days before sampling.
• For individuals who can become pregnant: use of at least one method of effective contraception (see below) from at least 28 days prior to challenge through 60 days after challenge.
• Able to provide informed consent.
• Willing to adhere to lifestyle considerations for the duration of the study.
• Willing to avoid travel to a dengue-endemic area as defined by the CDC from 1 month before administration of challenge through day 28. For participants opting for LN FNA or bone marrow sampling on day 57, they must be willing to forgo travel through day 57.
• Serologic evidence of previous dengue virus infection consistent with our serology criteria.
• a. For the flavivirus-naive group, they must have no history of flavivirus vaccination or medical illness concerning for a flavivirus infection. If there is uncertainty about a previous flavivirus exposure, then confirmatory antibody testing against the virus of interest must be negative.
• Agree to avoid participation in other clinical studies requiring investigational interventions through day 180.
• Agree to avoid blood and plasma donation outside this study through day 57.
• Contraceptive requirements: Participants who can become pregnant must agree to use at least one method of effective contraception as outlined below from at least 28 days before through 60 days after challenge to avoid any potential risk from the product on the pregnancy or fetus. Participants who can become pregnant must have a negative serum pregnancy test on day 0 before receiving rDEN2delta30-7169. If a participant becomes pregnant or suspects they are pregnant during the study, they should inform the study staff and their primary care physician immediately. Acceptable forms of contraception are listed below and are consistent with prior studies using this product:
• Intrauterine device or equivalent.

You may not qualify if:

• An individual who meets any of the following criteria will be excluded from participation in this study:
• Pregnancy.
• Lactation during the first 28 days of the study.
• Baseline absolute neutrophil count (ANC) \<=750 cells/microL.
• Baseline creatinine \>=1.5 mg/dL.
• Baseline ALT \>=1.25 x upper limit of normal.
• Requiring a potent anticoagulator like a direct acting oral agent or warfarin during the first 28 days of the study.
• History of or positive test result for HIV, hepatitis B, or hepatitis C.
• History of a tetravalent, chimeric, or subunit dengue vaccine.
• Has any of the following:
• More than 10 days of systemic immunosuppressive medications (\>=10 mg prednisone dose or its equivalent) or cytotoxic medication within the 30 days prior to administration of challenge strain or immunomodulating therapy within 180 days prior to administration of challenge strain.
• Received blood products, including immunoglobulin products, within 120 days prior to administration of challenge strain.
• History of serious reactions to vaccines.
• Hereditary, acquired, or idiopathic forms of angioedema.
• Idiopathic urticaria within the past year.

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

RECRUITING

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Dengue; Virus Diseases

Condition Hierarchy (Ancestors)

Mosquito-Borne Diseases; Vector Borne Diseases; Infections; Arbovirus Infections; Flavivirus Infections; Flaviviridae Infections; RNA Virus Infections; Hemorrhagic Fevers, Viral

Study Officials

• Camila D Odio, M.D.

  National Institute of Allergy and Infectious Diseases (NIAID)

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Camila D Odio, M.D.

CONTACT

(240) 338-4945; camila.odio@nih.gov

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 15, 2026
• First Posted: July 16, 2026
• Study Start (Estimated): August 5, 2026
• Primary Completion (Estimated): November 3, 2028
• Study Completion (Estimated): May 3, 2029
• Last Updated: July 31, 2026

Record last verified: 2026-07-13

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
• Time Frame: Scientific data will be made available no later than the time of publication, when possible. We place no restrictions on the length of time data will be made available.
• Access Criteria: IPD used in publications will be de-identified, generalized, and shared as supplemental material, which can be accessed by any person reading the article. De-identified, generalized IPD will also be deposited in ImmPort. Data are available on ImmPort to qualified researchers after a brief registration and approval process. Users must accept a data sharing and access agreement before approval is granted. Genetic data will be deposited in dbGap with only the minimal associated metadata needed for interpretation to reduce any possibility of de-identification. To gain access to data on dbGap, researchers must agree to follow the NIH Genomic Data Sharing (GDS) Policy, and be approved by the NIH Data Access Committee or appropriate Data Access Committee. They must describe the proposed use of the data and ensure all researchers involved in the request will adhere to this project outline. Investigators gain access to the data for one year with the ability to extend to additional years.

Locations

US (1)