A Controlled Human Infection Model of Dengue

NCT07412483 | Recruiting DMC

• 1 other identifier: 2025/0743
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 1

Brief Summary

This study aims to conduct a safe human infection challenge using an attenuated serotype DEN3 dengue virus in adult volunteers. The clinical, viral and immune response characteristics of the model will be analysed to understand the pathophysiology of dengue fever. This data will be used to inform future studies, including a planned follow up study (DEN-CHIM-02) which will investigate the efficacy of an investigational dengue vaccine at protecting against DEN3 infection. Study conditions that result in a safe, reproducible infection in ≥80% of research participants (attack rate) with the DEN3 challenge agent have been identified during studies conducted by our collaborators in the US. This includes the inoculum dose, safety monitoring, and necessary participant pre-screening to exclude prior Orthoflavivrus infection or vaccinations. Study objectives are to:

1. 1.Establish in seronegative volunteers in Singapore a safe DENV controlled human infection (CHI) model, with an infection rate of ≥80%, suitable for future studies of interventions.
2. 2.Characterise the clinical, haematological and virological response following controlled inoculation of the attenuated DEN3 challenge agent.
3. 3.Conduct deep immunophenotyping to understand the cellular, humoral and innate immune response to dengue infection.
4. 4.Explore the longitudinal immune response in the 3 years after challenge, including following subsequent dengue vaccination.

Conditions

Dengue

Keywords

Human challenge study; controlled human infection model; dengue virus serotype 3; rDEN3delta30; dengue infection; dengue viremia; haematological response to dengue infection; neutralising antibodies to DEN-3

Outcome Measures

Primary Outcomes (4)

• Incidence of unsolicited Adverse Events (AEs) [Safety]

  Number of unsolicited AEs

  From day of viral challenge (Day 0) to Day 28 follow-up visit

• Severity of unsolicited AEs [Safety]

  Grading severity of AEs is guided by the FDA Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials: Grade 1 (Mild), Grade 2 (Moderate), Grade 3 (Severe), Grade 4 (Potentially life threatening)

  From day of viral challenge (Day 0) to Day 28 follow-up visit

• Incidence of Serious Adverse Events (SAEs) related to the viral challenge [Safety]

  Number of SAEs. Whether an adverse event is serious is determined by the outcome resulting from the event. An SAE is any untoward medical occurrence that: * Results in death * Is life-threatening (immediate risk of death) * Requires inpatient hospitalization or prolongation of existing hospitalization * Results in persistent or significant disability/incapacity * Results in congenital anomaly/birth defect * Is a medically important event

  Day of viral challenge (Day 0) to Day 28 follow-up visit

• Number of participants with lab confirmed infection [Infectivity]

  Laboratory confirmed infection is defined as at least one quantifiable (greater than lower limit of quantification, ≥LLOQ) qPCR measurement of DENV from blood

  From day of viral challenge (Day 0) to discharge from quarantine (Day 10).

Secondary Outcomes (12)

• Incidence of symptomatic DENV infection

  From day of viral challenge (Day 0) to 10 days post-inoculation

• Peak viral load in serum samples measured by qPCR

  Day 1 post-inoculation to Day 10 for uninfected participants or Day 14 for infected participants

• Duration of DENV viraemia measured by qCPR

  Day 1 post-inoculation to Day 10 for uninfected participants or Day 14 for infected participants

• Incubation period of DENV in serum samples measured by qPCR

  Day 1 post-inoculation to Day 10 for uninfected participants or Day 14 for infected participants

• Peak viral load in serum samples measured using viral culture

  Day 1 post-inoculation to Day 10 for uninfected participants or Day 14 for infected participants

Other Outcomes (13)

• Incidence of AEs as defined by clinically significant abnormal laboratory measurements during the quarantine period

  Day of inoculation (Day 0) to discharge from quarantine (Day 10)

• Severity of AEs as defined by clinically significant abnormal laboratory measurements during the quarantine period

  Day of inoculation (Day 0) to discharge from quarantine (Day 10)

• Incidence of concomitant medication usage

  Day 0 to Day 28 follow-up

Study Arms (1)

Attenuated dengue virus serotype 3 (rDEN3delta30) human infection challenge

EXPERIMENTAL

GMP-produced rDEN3delta30 virus will be administered to participants via subcutaneous injection.

Other: GMP-produced rDEN3delta30 virus

Interventions

GMP-produced rDEN3delta30 virus OTHER

The challenge virus used in DEN-CHIM-01 study (rDEN3delta30) is produced by the National Institutes of Health (NIH). The rDEN3delta30 strain has been tested in seronegative participants in two challenge studies and with two inoculum doses: 10\^3 and 10\^4 PFU. The wildtype parent (wildtype DEN3 strain) of the rDEN3Δ30 challenge agent was originally obtained from an infected patient in 1978, in Sleman, Yogyakarta, Indonesia. The Sleman/78 strain was a naturally occurring, partially attenuated dengue virus (DENV) suitable for development as a challenge agent. The NIH team made a contiguous 30-nucleotide deletion in the 3' untranslated region of the wildtype DENV genome and produced recombinant DENV via cDNA clone (rDEN3delta30).

Attenuated dengue virus serotype 3 (rDEN3delta30) human infection challenge

Eligibility Criteria

• Age: 21 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• An informed consent form (ICF) has been signed and dated by the participant, an investigator, and a witness
• Adult, aged between 21 and 45 years, inclusive (at the time of consent)
• No known history of prior dengue, zika or other Orthoflavivirus infection
• No history of prior dengue, yellow fever, Japanese encephalitis virus, or other Orthoflavivirus vaccination
• Sero-suitable based on the pre-screening serology result
• a Female participants must be willing and able to use contraception from 2 weeks before the scheduled date of viral challenge until 1 month after receipt of the final dose of study virus. Negative urine pregnancy tests will be required at screening, and on admission to the quarantine unit a negative serum beta human chorionic gonadotropin (β-hCG) is required prior to inoculation.
• b Male participants who are willing to use one of the contraception methods described in the study protocol, from the date of viral challenge, for 1 month. In addition to the contraceptive requirements above, male participants must agree not to donate sperm following discharge from quarantine until 1 month after the date of viral challenge.

You may not qualify if:

• Willing and able to commit to participation in the study.
• History or evidence of any clinically significant or currently active neurologic, cardiac, pulmonary, hepatic, rheumatologic, autoimmune, or renal disease.
• History of active depression and/or anxiety with associated severe psychiatric comorbidities, for example psychosis.
• Behavioural, cognitive, or psychiatric disease that in the opinion of the investigator affects the ability of the subject to understand and cooperate with the requirements of the study protocol.
• Significant history or presence of drug or alcohol misuse
• History of anaphylaxis and/or a history of severe allergic reaction or significant intolerance to any food or drug, as assessed by the PI.
• Family history of 1st degree relative aged 50 years or less with sudden cardiac or unexplained death
• A total body weight of ≤ 45kg and a Body Mass Index (BMI) ≤18 kg/m2 and ≥30 kg/m2.
• Venous access deemed inadequate for the phlebotomy demands of the study.
• Any clinically significant abnormal finding on screening biochemistry, haematology and microbiology blood tests or urinalysis apart from minor deviations which are clinically acceptable and approved by the investigator.
• Any of the following:
• Elevated HbA1C
• Positive HIV, active/chronic hepatitis B or hepatitis C test. 10 Twelve-lead ECG recording with clinically relevant abnormalities as judged by the study investigator.
• Receipt of a live vaccine within 60 days prior to the planned date of viral challenge, a non-live vaccine within 30 days prior to the planned date of viral challenge or intention to receive any vaccination(s) before the day 28 follow-up visit.
• Previous receipt of a flavivirus vaccine (licensed or experimental). 13 Receipt of blood or blood products, or loss (including blood donations) of 550 mL or more of blood during the 3 months prior to the planned date of viral challenge or planned during the 3 months after the final visit.

Sponsors & Collaborators

• Tan Tock Seng Hospital: lead
• A*Star: collaborator
• Duke-NUS Graduate Medical School: collaborator
• Nanyang Technological University: collaborator

Study Sites (1)

National Centre for Infectious Diseases (NCID)

Singapore, Singapore

RECRUITING

Related Publications (3)

• Blaney JE, Hanson CT, Firestone C-Y, Hanley KA, Murphy BR, Whitehead SS. Genetically modified, live attenuated dengue virus type 3 vaccine candidates. Am J Trop Med Hyg 2004; 71: 811-21.

  BACKGROUND

• Pierce KK, Whitehead SS, Diehl SA, et al. Evaluation of a new dengue 3 controlled human infection model for use in the evaluation of candidate dengue vaccines. MedRxiv Prepr Serv Health Sci 2024; : 2023.06.07.23291100.

  BACKGROUND

• Pierce KK, Durbin AP, Walsh M-CR, et al. TV005 dengue vaccine protects against dengue serotypes 2 and 3 in two controlled human infection studies. J Clin Invest 2024; 134: e173328.

  BACKGROUND

MeSH Terms

Conditions

Dengue

Condition Hierarchy (Ancestors)

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

Study Officials

• Barnaby E Young, MB BChir, PhD

  National Centre for Infectious Diseases (NCID)

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Xuan Ying Poh, PhD

CONTACT

+65 6511 5090; poh.xuan.ying@nhghealth.com.sg

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 25, 2025
• First Posted: February 17, 2026
• Study Start: March 1, 2026
• Primary Completion: May 1, 2026
• Study Completion (Estimated): April 1, 2029
• Last Updated: February 17, 2026

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

SG (1)