DengueDEN-CHIM-01NCT07412483
A Controlled Human Infection Model of Dengue
A study testing GMP-produced rDEN3delta30 virus in people with Dengue, run by Tan Tock Seng Hospital at 1 site in Singapore.
Trial 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. Read more about this study
- Who is it for?
- Ages 21 to 45 yearsHealthy volunteers can take part
- Conditions the study is for
- Dengue
- What is being tested?
- GMP-produced rDEN3delta30 virus
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 5 participants
- Where
- 1 siteSingapore
- Study dates
- 5 Mar 2026to Apr 2029
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 21 to 45 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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.
Show all 9Show fewer
- 6b 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.
- 7 In good health with no history of clinically significant medical conditions (as described in Exclusion criteria) that would interfere with subject safety, as defined by medical history, physical examination and routine laboratory tests, ECG, and Chest X-Ray and determined by the Investigator at an admission evaluation.
- 8 Willing and able to commit to participation in the study.
Who cannot join
- 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
Show all 26Show fewer
- 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.
- 11 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.
- 12 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.
- 14 Medications:
- Receipt of any investigational drug within 3 months prior to the planned date of viral challenge
- Receipt of systemic (intravenous and/or oral) glucocorticoids or systemic antiviral drugs within 6 months prior to the planned date of viral challenge.
- Over the counter medications (e.g., paracetamol or ibuprofen) where the dose taken over the preceding 7 days prior to the planned date of viral challenge had exceeded the maximum permissible 24-hour dose (e.g., >4g per day of paracetamol over the preceding week).
- Participants who have received any systemic chemotherapy agent, immunoglobulins, or other cytotoxic or immunosuppressive drugs at any time.
- 15 Participant is mentally or legally incapacitated in the opinion of the Investigator.
- 16 Females who:
- Are breastfeeding within 6 months of study commencement, or
- Had been pregnant within 6 months prior to the study, or
- Had a positive pregnancy test at any point during screening or prior to inoculation with challenge virus 17 Anyone who is first degree related to anyone who is a delegated member of the research team.
- 18 Any other reason that the Investigator considered made the participant unsuitable to participate.
- 19 Presence of symptoms and/or fever (defined as participant presenting with a temperature reading of >37.9ºC) suggesting an infection at pre-challenge on Day 0.
Trial locations and contacts
1 site in 1 country.
About this study
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 collaborators in the US. This includes the inoculum dose, safety monitoring, and necessary participant pre-screening to exclude prior Orthoflavivrus infection or vaccinations.
Read more
Study objectives are to:
- 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.
- Characterise the clinical, haematological and virological response following controlled inoculation of the attenuated DEN3 challenge agent.
- Conduct deep immunophenotyping to understand the cellular, humoral and innate immune response to dengue infection.
- Explore the longitudinal immune response in the 3 years after challenge, including following subsequent dengue vaccination.
Read the detailed description
Dengue fever is a mosquito-transmitted infection, with an escalating geographic distribution and disease burden because of factors including climate change, urbanisation and globalisation. Despite ongoing and often intensive vector control efforts implemented in many endemic countries, the incidence of dengue has increased thirty-fold worldwide over the past half-century, establishing it as the most rapidly spreading vector-borne disease. The rising burden of disease from dengue is further compounded by the absence of specific antiviral treatments, and the limitations of currently available vaccines.
In light of these challenges, innovative strategies to enhance the understanding of dengue and accelerate the development of effective countermeasures are urgently needed. Controlled human infection (CHI) studies have emerged as a valuable tool in this endeavour, offering a unique platform for investigating the natural history of infectious diseases and evaluating the potential of novel interventions.
CHI studies involve the deliberate inoculation of human volunteers with an infectious agent such as a virus, bacteria, or parasite. The strength of this study design is a result of their highly controlled nature, whereby carefully selected volunteers are exposed to standardised amounts of a well-characterised infectious agent. This enables exact longitudinal measurement of challenge agent replication kinetics, infectious shedding, immunological responses and clinical features, and contrasts with what is achievable through field trials of natural infection, including household contact studies. By inoculating all study participants with the same agent at the same dose and under the same conditions, confounding by strain, dose, and exposure is controlled. Host factors associated with inter-individual differences in clinical outcome and the effect of interventions can then be robustly inferred, along with the ability to connect detailed longitudinal data to the earliest time points after exposure, including prior to the onset of symptoms.
Singapore, an equatorial city-state, is highly endemic for dengue, with the co-circulation of all four serotypes. The country boasts a well-established research infrastructure and considerable expertise in infectious diseases at institutions like NCID. Singapore also has a globally recognized vector control program and maintains extensive dengue surveillance data, providing a rich context for studying the disease. The strong research infrastructure and expertise at NCID, coupled with Singapore's commitment to public health and its history of effective disease surveillance and control, create a conducive environment for conducting high-quality and impactful dengue CHI studies.
Findings from CHI studies conducted in Singapore are likely to be highly relevant to other endemic areas in Southeast Asia and globally. The specific dengue serotype dynamics in Singapore, including recent switches involving DEN1 and DEN3, make research on these serotypes particularly timely. Furthermore, Singapore has observed a shift in the average age of dengue patients towards older adults, who may be at higher risk of severe disease, making research in this context especially important.
By developing a dengue controlled human infection model in Singapore through the DEN-CHIM-01 study the investigators intend to enable:
- A model of infection that can be used to assess the efficacy of new vaccines, treatments, and diagnostics in a dengue endemic setting.
- Identification of the immune and other host factors, including ethnicity, associated with viral kinetics and dengue symptoms.
- Provide the foundation for future development of a unique model of secondary dengue.
The DEN-CHIM-01 study will use the optimised conditions established by collaborators in the US to conduct a GMP rDEN3delta30 challenge study in seronegative volunteers. This study aims to investigate in the Singapore context the clinical, virologic and immunologic features of DEN3 infection and what immune, transcriptomic and genomic markers correlate with symptomology, viral kinetics and the immune response.
The DEN-CHIM-01 study forms part of a wider programme of work in Singapore, both in dengue fever and using CHI studies as an experimental model to advance the development of therapeutics and vaccines. Experience from the Sing-CoV controlled human infection study (PI: A/Prof Barnaby Young) has informed development of this protocol, and agreements for sharing of samples and data with scientific collaborators are in place.
The DEN-CHIM-01 is a critical first step to conducting a follow up pilot clinical trial, DEN-CHIM-02, funded by the same grant. In DEN-CHIM-02 the investigators plan to investigate the efficacy of a dengue vaccine at protecting against challenge with rDEN3delta30.
- Conditions
- Dengue
- Being tested
- GMP-produced rDEN3delta30 virus
- 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
- Medical subject headings
- Dengue
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GMP-produced rDEN3delta30 virusOther
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).
| Study group | Role | What they receive |
|---|---|---|
| Attenuated dengue virus serotype 3 (rDEN3delta30) human infection challenge | Experimental | GMP-produced rDEN3delta30 virus will be administered to participants via subcutaneous injection. Receives: Other: GMP-produced rDEN3delta30 virus |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of unsolicited Adverse Events (AEs) [Safety]
Number of unsolicited AEs
Measured: 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)
Measured: 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
Measured: 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
Measured: From day of viral challenge (Day 0) to discharge from quarantine (Day 10).
Secondary outcomes (12)
Incidence of symptomatic DENV infection
Number of participants with lab confirmed symptomatic DENV infection
Measured: From day of viral challenge (Day 0) to 10 days post-inoculation
Peak viral load in serum samples measured by qPCR
Peak viral load of DENV as defined by the maximum viral load determined by qPCR measurements
Measured: Day 1 post-inoculation to Day 10 for uninfected participants or Day 14 for infected participants
Duration of DENV viraemia measured by qCPR
Duration is defined as the day of first quantifiable viral detection until first confirmed undetectable assessment after their peak measure and after which no further virus is detected.
Measured: 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
Incubation period is defined as the time from inoculation to the first quantifiable viral detection, and up to discharge from quarantine.
Measured: 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
Peak viral load of DENV as defined by the maximum viral load determined by plaque assay
Measured: Day 1 post-inoculation to Day 10 for uninfected participants or Day 14 for infected participants
Duration of DENV viraemia measured using viral culture
Duration is defined as the day of first quantifiable viral detection until first confirmed undetectable assessment after their peak measure and after which no further virus is detected.
Measured: Day 1 post-inoculation to Day 10 for uninfected participants or Day 14 for infected participants
Incubation period of DENV in serum samples measured using viral culture
Incubation period is defined as the time from inoculation to the first quantifiable viral detection, and up to discharge from quarantine.
Measured: Day 1 post-inoculation to Day 10 for uninfected participants or Day 14 for infected participants
Peak viral load in serum samples measured using quantitative NS1 antigen
Peak viral load of DENV as defined by the maximum NS1 antigen measurement
Measured: Day 1 post-inoculation to Day 10 for uninfected participants or Day 14 for infected participants
Duration of DENV viraemia measured using quantitative NS1 antigen
Duration is defined as the day of first quantifiable viral detection using quantitative NS1 antigen measurement until first confirmed undetectable assessment after their peak measure and after which no further virus is detected.
Measured: Day 1 post-inoculation to Day 10 for uninfected participants or Day 14 for infected participants
Incubation period of DENV in serum samples measured using quantitative NS1 antigen
Incubation period is defined as the time from inoculation to the first quantifiable viral detection using quantitative NS1 antigen measurements, and up to discharge from quarantine.
Measured: Day 1 post-inoculation to Day 10 for uninfected participants or Day 14 for infected participants
Severity of DENV-induced symptoms during quarantine period
Severity of DENV-related symptoms are reported and assessed by participants three times daily during quarantine using the Symptom Diary Card. Symptoms are graded on a scale of 0-3:
- Grade 0: No symptoms.
- Grade 1: Just noticeable.
- Grade 2: Clearly bothersome from time to time but does not interfere with me doing my normal daily activities.
- Grade 3: Quite bothersome most or all the time, and it stops me participating in activities.
The sum total symptoms diary card score, peak symptoms diary card score and peak daily symptom score can be calculated.
Measured: Day 1 post-viral challenge to Day 10.
Incidence of DENV illness
The incidence of:
- Febrile illness (FI)
- Symptomatic illness (SI)
- Rash
- Proportion of participants with Grade 3 symptoms on any occasion at any time from Day 0 to Day 14.
- Proportion of participants with Grade 2 or higher symptoms on any occasion at any time from Day 0 to Day 14.
- Proportion of participants with Grade 2 or higher Symptoms on two separate occasions at any time from Day 0 to Day 14.
- Proportion of participants with any symptom (grade >=1) on any occasion at any time from Day 0 to Day 14.
- Proportion of participants with any symptom (grade >=1) on two separate occasions at any time from Day 0 to Day 14.
Measured: Day of inoculation (Day 0) to Day 14
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Feb 2026
- Study start5 Mar 2026
- Primary completion2 Jun 2026
- Study completionApr 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for DengueStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 5 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Tan Tock Seng Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- A*Star, Duke-NUS Graduate Medical School, Nanyang Technological University
- Responsible party
- Sponsor
- Investigators
- Barnaby E Young, MB BChir, PhD, Principal investigator, National Centre for Infectious Diseases (NCID)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07412483
- Sponsor's protocol ID
- 2025/0743
- Acronym
- DEN-CHIM-01
- Status last verified
- Dec 2025
- First submitted
- 25 Dec 2025
- Last updated
- 16 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: All study findings and documents will be regarded as confidential. The investigators and other study personnel must not disclose such information without prior written approval from the PI. Participant confidentiality will be strictly maintained to the extent possible under the law and local hospital policy. Identifiable information will be removed from any published data.
Publications
Blaney JE Jr, Hanson CT, Firestone CY, Hanley KA, Murphy BR, Whitehead SS. Genetically modified, live attenuated dengue virus type 3 vaccine candidates. Am J Trop Med Hyg. 2004 Dec;71(6):811-21.
PubMed 15642976Pierce 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.
Pierce KK, Durbin AP, Walsh MR, Carmolli M, Sabundayo BP, Dickson DM, Diehl SA, Whitehead SS, Kirkpatrick BD. TV005 dengue vaccine protects against dengue serotypes 2 and 3 in two controlled human infection studies. J Clin Invest. 2024 Feb 1;134(3):e173328. doi: 10.1172/JCI173328.
PubMed 37971871
Study at a glance
From the registry record, last updated by the sponsor on 16 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Controlled Human Infection Model of Dengue
- ClinicalTrials.gov ID
- NCT07412483
- Acronym / sponsor ID
- DEN-CHIM-01 / 2025/0743
- 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
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 5 participants (estimated)
- Lead sponsor
- Tan Tock Seng HospitalUniversity, hospital or other
- Collaborators
- A*Star, Duke-NUS Graduate Medical School, Nanyang Technological University
- Study start
- 5 Mar 2026 (actual)
- Primary completion
- 2 Jun 2026 (actual)
- Study completion
- Apr 2029 (estimated)
- First posted
- 17 Feb 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 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:
- 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.
- Characterise the clinical, haematological and virological response following controlled inoculation of the attenuated DEN3 challenge agent.
- Conduct deep immunophenotyping to understand the cellular, humoral and innate immune response to dengue infection.
- Explore the longitudinal immune response in the 3 years after challenge, including following subsequent dengue vaccination.
Detailed description
Dengue fever is a mosquito-transmitted infection, with an escalating geographic distribution and disease burden because of factors including climate change, urbanisation and globalisation. Despite ongoing and often intensive vector control efforts implemented in many endemic countries, the incidence of dengue has increased thirty-fold worldwide over the past half-century, establishing it as the most rapidly spreading vector-borne disease. The rising burden of disease from dengue is further compounded by the absence of specific antiviral treatments, and the limitations of currently available vaccines.
In light of these challenges, innovative strategies to enhance the understanding of dengue and accelerate the development of effective countermeasures are urgently needed. Controlled human infection (CHI) studies have emerged as a valuable tool in this endeavour, offering a unique platform for investigating the natural history of infectious diseases and evaluating the potential of novel interventions.
CHI studies involve the deliberate inoculation of human volunteers with an infectious agent such as a virus, bacteria, or parasite. The strength of this study design is a result of their highly controlled nature, whereby carefully selected volunteers are exposed to standardised amounts of a well-characterised infectious agent. This enables exact longitudinal measurement of challenge agent replication kinetics, infectious shedding, immunological responses and clinical features, and contrasts with what is achievable through field trials of natural infection, including household contact studies. By inoculating all study participants with the same agent at the same dose and under the same conditions, confounding by strain, dose, and exposure is controlled. Host factors associated with inter-individual differences in clinical outcome and the effect of interventions can then be robustly inferred, along with the ability to connect detailed longitudinal data to the earliest time points after exposure, including prior to the onset of symptoms.
Singapore, an equatorial city-state, is highly endemic for dengue, with the co-circulation of all four serotypes. The country boasts a well-established research infrastructure and considerable expertise in infectious diseases at institutions like NCID. Singapore also has a globally recognized vector control program and maintains extensive dengue surveillance data, providing a rich context for studying the disease. The strong research infrastructure and expertise at NCID, coupled with Singapore's commitment to public health and its history of effective disease surveillance and control, create a conducive environment for conducting high-quality and impactful dengue CHI studies.
Findings from CHI studies conducted in Singapore are likely to be highly relevant to other endemic areas in Southeast Asia and globally. The specific dengue serotype dynamics in Singapore, including recent switches involving DEN1 and DEN3, make research on these serotypes particularly timely. Furthermore, Singapore has observed a shift in the average age of dengue patients towards older adults, who may be at higher risk of severe disease, making research in this context especially important.
By developing a dengue controlled human infection model in Singapore through the DEN-CHIM-01 study the investigators intend to enable:
- A model of infection that can be used to assess the efficacy of new vaccines, treatments, and diagnostics in a dengue endemic setting.
- Identification of the immune and other host factors, including ethnicity, associated with viral kinetics and dengue symptoms.
- Provide the foundation for future development of a unique model of secondary dengue.
The DEN-CHIM-01 study will use the optimised conditions established by collaborators in the US to conduct a GMP rDEN3delta30 challenge study in seronegative volunteers. This study aims to investigate in the Singapore context the clinical, virologic and immunologic features of DEN3 infection and what immune, transcriptomic and genomic markers correlate with symptomology, viral kinetics and the immune response.
The DEN-CHIM-01 study forms part of a wider programme of work in Singapore, both in dengue fever and using CHI studies as an experimental model to advance the development of therapeutics and vaccines. Experience from the Sing-CoV controlled human infection study (PI: A/Prof Barnaby Young) has informed development of this protocol, and agreements for sharing of samples and data with scientific collaborators are in place.
The DEN-CHIM-01 is a critical first step to conducting a follow up pilot clinical trial, DEN-CHIM-02, funded by the same grant. In DEN-CHIM-02 the investigators plan to investigate the efficacy of a dengue vaccine at protecting against challenge with rDEN3delta30.
Study design
- Primary purpose
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Attenuated dengue virus serotype 3 (rDEN3delta30) human infection challenge | Experimental | Other: GMP-produced rDEN3delta30 virusGMP-produced rDEN3delta30 virus will be administered to participants via subcutaneous injection. |
Who may qualify
- Ages
- 21 to 45 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (9 listed)
- 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
Key exclusion criteria (26 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| GMP-produced rDEN3delta30 virusThe 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). | Other | Attenuated dengue virus serotype 3 (rDEN3delta30) human infection challenge |
Primary outcome
Incidence of unsolicited Adverse Events (AEs) [Safety]
Time frame: From day of viral challenge (Day 0) to Day 28 follow-up visit
Number of unsolicited AEs
Severity of unsolicited AEs [Safety]
Time frame: From day of viral challenge (Day 0) to Day 28 follow-up visit
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)
Incidence of Serious Adverse Events (SAEs) related to the viral challenge [Safety]
Time frame: Day of viral challenge (Day 0) to Day 28 follow-up visit
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
Number of participants with lab confirmed infection [Infectivity]
Time frame: From day of viral challenge (Day 0) to discharge from quarantine (Day 10).
Laboratory confirmed infection is defined as at least one quantifiable (greater than lower limit of quantification, ≥LLOQ) qPCR measurement of DENV from blood
12 secondary outcomes
Incidence of symptomatic DENV infection
Time frame: From day of viral challenge (Day 0) to 10 days post-inoculation
Peak viral load in serum samples measured by qPCR
Time frame: Day 1 post-inoculation to Day 10 for uninfected participants or Day 14 for infected participants
Duration of DENV viraemia measured by qCPR
Time frame: 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
Time frame: 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
Time frame: Day 1 post-inoculation to Day 10 for uninfected participants or Day 14 for infected participants
Duration of DENV viraemia measured using viral culture
Time frame: Day 1 post-inoculation to Day 10 for uninfected participants or Day 14 for infected participants
Incubation period of DENV in serum samples measured using viral culture
Time frame: Day 1 post-inoculation to Day 10 for uninfected participants or Day 14 for infected participants
Peak viral load in serum samples measured using quantitative NS1 antigen
Time frame: Day 1 post-inoculation to Day 10 for uninfected participants or Day 14 for infected participants
Duration of DENV viraemia measured using quantitative NS1 antigen
Time frame: Day 1 post-inoculation to Day 10 for uninfected participants or Day 14 for infected participants
Incubation period of DENV in serum samples measured using quantitative NS1 antigen
Time frame: Day 1 post-inoculation to Day 10 for uninfected participants or Day 14 for infected participants
Severity of DENV-induced symptoms during quarantine period
Time frame: Day 1 post-viral challenge to Day 10.
Incidence of DENV illness
Time frame: Day of inoculation (Day 0) to Day 14
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Oct 2026.
- Background: PubMed 15642976Blaney JE Jr, Hanson CT, Firestone CY, Hanley KA, Murphy BR, Whitehead SS. Genetically modified, live attenuated dengue virus type 3 vaccine candidates. Am J Trop Med Hyg. 2004 Dec;71(6):811-21.
- BackgroundPierce 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: PubMed 37971871Pierce KK, Durbin AP, Walsh MR, Carmolli M, Sabundayo BP, Dickson DM, Diehl SA, Whitehead SS, Kirkpatrick BD. TV005 dengue vaccine protects against dengue serotypes 2 and 3 in two controlled human infection studies. J Clin Invest. 2024 Feb 1;134(3):e173328. doi: 10.1172/JCI173328.
- Individual participant dataSharing planned: No. All study findings and documents will be regarded as confidential. The investigators and other study personnel must not disclose such information without prior written approval from the PI. Participant confidentiality will be strictly maintained to the extent possible under the law and local hospital policy. Identifiable information will be removed from any published data.
Related trials for Dengue
RecruitingPhase 1
Phase 1 Challenge Study Using rDEN2delta30-7169 to Evaluate Host-Pathogen Interactions in Primary, Homotypic, and Heterotypic Dengue Virus Infection
Healthy Volunteers, Dengue
RecruitingPhase 2/3
Emetine for Viral Outbreaks (a.k.a. EVOLVE Antiviral Initiative)
Dengue
RecruitingPhase 2
Adaptive Dengue Antiviral Platform Trial
Dengue, Antiviral Drugs
RecruitingObservational study
Immune Responses to Dengue and Sepsis
Dengue, Sepsis
Active, not recruitingPhase 3
A Study to Evaluate V181 Dengue Vaccine in Healthy Participants 2 to 17 Years of Age (V181-005/MOBILIZE-1)
Healthy
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Barnaby E Young, MB BChir, PhD principal investigator
National Centre for Infectious Diseases (NCID)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing GMP-produced rDEN3delta30 virus in people with Dengue, run by Tan Tock Seng Hospital at 1 site in Singapore.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 26 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 16 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Singapore. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence of unsolicited Adverse Events (AEs) [Safety] (time frame: From day of viral challenge (Day 0) to Day 28 follow-up visit). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT07412483, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Oct 2026.