DengueEarly Phase 1DHITNCT05476757
Safety, Virological and Immunological Assessment of Live Attenuated Dengue Serotype 2 rDEN2delta30-7169.
A Early Phase 1 study testing rDEN2Δ30-7169 in people with Dengue, run by Mahidol University at 1 site in Thailand.
Trial summary
Dengue viral infection and dengue hemorrhagic fever (DHF) are important emerging health problems worldwide. Several candidate dengue vaccines are currently in different stages of development but CYD is the only licensed vaccine currently available. Read more about this study
- Who is it for?
- Ages 18 to 30 yearsHealthy volunteers can take part
- Conditions the study is for
- Dengue
- What is being tested?
- rDEN2Δ30-7169
- Type of treatment
- Vaccines
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 5 participants
- Where
- 1 siteThailand
- Study dates
- Aug 2022to Mar 2026
- Phase
- Early Phase 1
- Are there results?
- None posted in the registry
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 18 to 30 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Thai healthy volunteers, aged between 18 to 30 years old and weight is greater than or equal to 45 kg and have Thai language literacy.
- Don't have any history of previous dengue, zika or Japanese encephalitis virus infection
- Have not given blood donation in the past 3 months
- Education: higher than high school
- Display flavivirus immunity profile defined by the standard PRNT 50% (PRNT50) as follows: flavivirus naïve is defined as the PRNT50 titer against
- DENV1 < 1:5
Show all 13Show fewer
- DENV2 < 1:5
- DENV3 < 1:5
- DENV4 < 1:5
- ZIKV < 1:5
- JEV < 1:5
- Willingness to participate in the study as evidenced by signing the informed consent document.
- Female participants of childbearing potential should be agreed to either abstinence or use at least one primary form of contraception from the time of screening for rDEN2Δ30-7169 administration until 1 month after complete course of Dengvaxia® vaccination (Study Day 568).
Who cannot join
- For female participants: Currently pregnant, as determined by positive β-human choriogonadotropin (HCG) test or breast-feeding, and given birth or abortion within 6 months.
- History of previous acute undifferentiated febrile illness leading to hospitalization in the past 3 months
- Behavioral, cognitive, or psychiatric disease that, in the opinion of the investigator, affects the subject's ability to understand and cooperate with the requirements of the study protocol.
- Any significant alcohol or drug abuse in the past 12 months that has caused medical, occupational, or family problems, as indicated by subject history.
- History of a severe allergic reaction or anaphylaxis
- Severe asthma (emergency room visit or hospitalization within the last 6 months).
Show all 20Show fewer
- Any known immunodeficiency syndrome.
- Having any pre-existing medical conditions consist of thrombocytopenia, autoimmune disease and cancer based on history, physical examination, and/or laboratory studies.
- Current use of anticoagulant medications (this includes anti-platelet medication such as aspirin or non-steroidal anti-inflammatory medications).
- Use of corticosteroids (excluding topical or nasal) or immunosuppressive drugs within 28 days prior to or following vaccination. An immunosuppressive dose of corticosteroids is defined as ≥ 10 mg of a prednisone equivalent per day for ≥ 14 days.
- Asplenia
- Receipt of any vaccine within 28 days or a killed vaccine within 14 days prior to receive virus administration, or anticipated receipt of any vaccine during the 28 days following rDEN2∆30-7169 administration.
- Receipt of blood products within the past 6 months, including transfusions or immunoglobulin, or anticipated receipt of any blood products or immunoglobulin during the 28 days following rDEN2∆30-7169 administration.
- Previous receipt of a flavivirus vaccine (licensed or experimental).
- Screening laboratory values of Grade 1 or above (as defined in this protocol) for ANC (<750 /mm3), Platelet (<100,000 /mm3), PT (> 1.25 x ULN), APTT (> 1.66 x ULN), ALT (>2.5 x ULN) and serum creatinine (> 1.3 x ULN OR Increase to >1.3 x participant's baseline)
- Body temperature higher than 37.5 °C
- HIV infection, as indicated by anti-HIV screening assays.
- Hepatitis C virus (HCV) infection, as indicated by anti-HCV screening assays.
- Hepatitis B virus (HBV) infection, as indicated by hepatitis B surface antigen (HBsAg) and/or anti-HBc screening.
- Any other condition that, in the opinion of the investigator, would jeopardize the safety or rights of a subject participating in the trial, or would render the subject unable to comply with the protocol.
Trial locations and contacts
1 site in 1 country.
Thailand1 site
Siriraj Hospital
Bangkok Noi, Bangkok, 10700
Panisadee Avirutnan, M.D., Ph.D., +6624196667-70, panisadee.avi@mahidol.edu
Panisadee Avirutnan, M.D., Ph.D.
About this study
Official title: Safety, Virological and Immunological Assessment of the Controlled Dengue Human Infection Model in Thailand
Dengue viral infection and dengue hemorrhagic fever (DHF) are important emerging health problems worldwide. Several candidate dengue vaccines are currently in different stages of development but CYD is the only licensed vaccine currently available. Although this vaccine can induce neutralizing antibodies against all four DENV serotypes, the vaccine showed enhanced hospitalization in recipients who were dengue-naïve before vaccination. The long-term safety assessment of the vaccine in endemic regions demonstrated that the risk of hospitalization in year 3 of vaccination was higher in the vaccine group especially among recipients under 9 years of age with a relative risk of 1.58 [95% CI, 0.83 to 3.02].
Surrogate animal models are not good models to see whether the vaccine or therapeutic is able to be tested in clinical trials since animals do not develop symptoms of infection as in humans. The ADE phenomenon and the lack of known correlates of protection in animal models are still the major problems and challenges in the development of an effective dengue vaccine and make it difficult to identify candidate vaccines. The efficacy and safety situation of CYD also highlights the requirement of verification of candidate vaccines before performing clinical trials with a large number of participants.
Read more
The controlled human infection model, therefore, has been proposed to pre-evaluate candidate vaccines before moving into larger clinical trials. It has been previously used for several infectious diseases i.e., malaria, norovirus, influenza, cholera, Campylobacter, and Shigella, to accelerate vaccine or therapeutic development. For dengue, two controlled dengue human infection models (DHIM) have been established for vaccine testing and evaluation of therapeutics in a dengue naïve population in the USA. Although it has been proved useful for studies of dengue in naïve individuals, it is necessary to set up DHIM in endemic regions like Thailand as more than 90% of the population has been previously exposed to the virus and, importantly, host immune status prior to the introduction of viruses can influence clinical outcomes and vaccine efficacy. It will also be very challenging in terms of safety concerns since having pre-existing immune responses to natural DENV infection is a risk factor for severe dengue. The establishment of DHIM will not only allow a small-scale demonstration for safety and efficacy of vaccines or therapeutics which can appropriately guide the design of phase III to be more cost-effective but it will also allow the investigation of immune correlates of protection and determination of factors correlated with disease protection and pathogenesis as clinical endpoints can be closely followed up in all participants.
Safety, Virological and Immunological Assessment of the Controlled Dengue Human Infection Model in Thailand (DHIT) is proposed to challenge the live attenuated dengue virus serotype 2, rDEN2Δ30-7169, in 5 flavivirus naïve participants recruited from Bangkok, Thailand, and aims to assess the safety, viremia, NS1 antigenemia profile, and immunogenicity of the challenge virus in the volunteers.
In addition, this DHIT project will vaccinated all 5 participants with Dengvaxia® after inoculation with the challenge virus to reduce the risk of severe disease of dengue in the future. Blood collection will be obtained after each vaccination to assess virological and immunological profiles. Active and passive surveillance will be set up to monitor for dengue infection after vaccination. The overall study period from administration of live attenuated virus until last follow-up visit is 38 months.
- Conditions
- Dengue
- Being tested
- rDEN2Δ30-7169
- Keywords
- Controlled Human Infection Model, Flavivirus naïve
- Medical subject headings
- Dengue
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
rDEN2Δ30-7169Biological
rDEN2Δ30-7169 will be inoculated at Study Day 0. After 6 months of the inoculation, the participants will be vaccinated with Dengvaxia® until completion of 3 doses with 6-month interval between each dose.
| Study group | Role | What they receive |
|---|---|---|
| Flavivirus naïve | Experimental | Not described Receives: Biological: rDEN2Δ30-7169 |
What is being measured
The primary outcome is the main question the study is designed to answer.
The safety of rDEN2Δ30-7169 in flavivirus naïve participants
Occurrence of local and general adverse events (AEs) and serious adverse events (SAEs)
Measured: 21 Days
Secondary outcomes (11)
The frequency of viremia following administration with rDEN2Δ30-7169 in flavivirus naïve participants
Proportion of number of volunteer with detectable virus genome assessed by nested RT-PCR, real time RT-PCR and virus culture after administration of DENV2Δ30-7169
Measured: 180 Days
The quantity of viral genome following administration with rDEN2Δ30-7169 in flavivirus naïve participants
The quantity of viral genome (copies/mL) assessed by nested RT-PCR, real time RT-PCR and virus culture after administration of DENV2Δ30-7169
Measured: 180 Days
The duration of viremia following administration with rDEN2Δ30-7169 in flavivirus naïve participants
Days of detectable virus genome assessed by nested RT-PCR, real time RT-PCR and virus culture after administration of DENV2Δ30-7169
Measured: 180 Days
The frequency of viremia following administration with rDEN2Δ30-7169 in flavivirus naïve participants
Proportion of number of volunteer with detectable infectious activity assessed by nested RT-PCR, real time RT-PCR and virus culture after administration of DENV2Δ30-7169
Measured: 180 Days
The quantity of infectious activity following administration with rDEN2Δ30-7169 in flavivirus naïve participants
The quantity of infectious activity (FFU/mL) assessed by nested RT-PCR, real time RT-PCR and virus culture after administration of DENV2Δ30-7169
Measured: 180 Days
The duration of infectious activity following administration with rDEN2Δ30-7169 in flavivirus naïve participants
Days of detectable infectious activity assessed by nested RT-PCR, real time RT-PCR and virus culture after administration of DENV2Δ30-7169
Measured: 180 Days
The frequency of NS1 antigenemia following administration with rDEN2Δ30-7169 in flavivirus naïve participants
Proportion of number of volunteer with detectable NS1 antigen after administration of DENV2Δ30-7169
Measured: 180 Days
The quantity of NS1 antigenemia following administration with rDEN2Δ30-7169 in flavivirus naïve participants
The quantity of NS1 antigenemia (ng/mL) after administration of DENV2Δ30-7169
Measured: 180 Days
The duration of NS1 antigenemia following administration with rDEN2Δ30-7169 in flavivirus naïve participants
Days of detectable NS1 antigen after administration of DENV2Δ30-7169
Measured: 180 Days
The immunogenicity of rDEN2Δ30-7169 in Thai flavivirus naïve participants
Levels of neutralizing antibodies (NT50) as measured by PRNT to dengue virus after administration with rDEN2Δ30-7169
Measured: 180 Days
Measurement of levels of anti-dengue virion-IgM/IgG antibodies following administration with rDEN2Δ30-7169 in flavivirus naïve participants
Levels of anti-dengue virion-IgM/IgG antibodies (titer) as measured by ELISA following administration with rDEN2Δ30-7169 in flavivirus naïve participants
Measured: 180 Days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Jul 2022
- Study startAug 2022 (estimated)
- Primary completionJan 2023 (estimated)
- Study completionMar 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for DengueStudies of the same condition, open and under way.
- More trials run by Mahidol UniversityThe sponsor's other registered studies.
- 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
- Early Phase 1
- Primary purpose
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- 5 flavivirus naïve participants
- Masking
- None (open label)
- Enrolment
- 5 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Mahidol University
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05476757
- Sponsor's protocol ID
- 022/2565(IRB1)
- Acronym
- DHIT
- Status last verified
- Jul 2022
- First submitted
- 11 Jul 2022
- Last updated
- 27 Jul 2022
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 27 Jul 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Safety, Virological and Immunological Assessment of the Controlled Dengue Human Infection Model in Thailand
- ClinicalTrials.gov ID
- NCT05476757
- Acronym / sponsor ID
- DHIT / 022/2565(IRB1)
- Conditions
- Dengue
- Keywords
- Controlled Human Infection Model, Flavivirus naïve
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 5 participants (estimated)
- Lead sponsor
- Mahidol UniversityUniversity, hospital or other
- Study start
- Aug 2022 (estimated)
- Primary completion
- Jan 2023 (estimated)
- Study completion
- Mar 2026 (estimated)
- First posted
- 27 Jul 2022 (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.
Dengue viral infection and dengue hemorrhagic fever (DHF) are important emerging health problems worldwide. Several candidate dengue vaccines are currently in different stages of development but CYD is the only licensed vaccine currently available. Although this vaccine can induce neutralizing antibodies against all four DENV serotypes, the vaccine showed enhanced hospitalization in recipients who were dengue-naïve before vaccination. The long-term safety assessment of the vaccine in endemic regions demonstrated that the risk of hospitalization in year 3 of vaccination was higher in the vaccine group especially among recipients under 9 years of age with a relative risk of 1.58 [95% CI, 0.83 to 3.02].
Surrogate animal models are not good models to see whether the vaccine or therapeutic is able to be tested in clinical trials since animals do not develop symptoms of infection as in humans. The ADE phenomenon and the lack of known correlates of protection in animal models are still the major problems and challenges in the development of an effective dengue vaccine and make it difficult to identify candidate vaccines. The efficacy and safety situation of CYD also highlights the requirement of verification of candidate vaccines before performing clinical trials with a large number of participants.
The controlled human infection model, therefore, has been proposed to pre-evaluate candidate vaccines before moving into larger clinical trials. It has been previously used for several infectious diseases i.e., malaria, norovirus, influenza, cholera, Campylobacter, and Shigella, to accelerate vaccine or therapeutic development. For dengue, two controlled dengue human infection models (DHIM) have been established for vaccine testing and evaluation of therapeutics in a dengue naïve population in the USA. Although it has been proved useful for studies of dengue in naïve individuals, it is necessary to set up DHIM in endemic regions like Thailand as more than 90% of the population has been previously exposed to the virus and, importantly, host immune status prior to the introduction of viruses can influence clinical outcomes and vaccine efficacy. It will also be very challenging in terms of safety concerns since having pre-existing immune responses to natural DENV infection is a risk factor for severe dengue. The establishment of DHIM will not only allow a small-scale demonstration for safety and efficacy of vaccines or therapeutics which can appropriately guide the design of phase III to be more cost-effective but it will also allow the investigation of immune correlates of protection and determination of factors correlated with disease protection and pathogenesis as clinical endpoints can be closely followed up in all participants.
Safety, Virological and Immunological Assessment of the Controlled Dengue Human Infection Model in Thailand (DHIT) is proposed to challenge the live attenuated dengue virus serotype 2, rDEN2Δ30-7169, in 5 flavivirus naïve participants recruited from Bangkok, Thailand, and aims to assess the safety, viremia, NS1 antigenemia profile, and immunogenicity of the challenge virus in the volunteers.
In addition, this DHIT project will vaccinated all 5 participants with Dengvaxia® after inoculation with the challenge virus to reduce the risk of severe disease of dengue in the future. Blood collection will be obtained after each vaccination to assess virological and immunological profiles. Active and passive surveillance will be set up to monitor for dengue infection after vaccination. The overall study period from administration of live attenuated virus until last follow-up visit is 38 months.
Study design
- Primary purpose
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- 5 flavivirus naïve participants
| Arm | Type | Receives |
|---|---|---|
| Flavivirus naïve | Experimental | Biological: rDEN2Δ30-7169 |
Who may qualify
- Ages
- 18 to 30 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (13 listed)
- Thai healthy volunteers, aged between 18 to 30 years old and weight is greater than or equal to 45 kg and have Thai language literacy.
- Don't have any history of previous dengue, zika or Japanese encephalitis virus infection
- Have not given blood donation in the past 3 months
- Education: higher than high school
- Display flavivirus immunity profile defined by the standard PRNT 50% (PRNT50) as follows: flavivirus naïve is defined as the PRNT50 titer against
Key exclusion criteria (20 listed)
- For female participants: Currently pregnant, as determined by positive β-human choriogonadotropin (HCG) test or breast-feeding, and given birth or abortion within 6 months.
- History of previous acute undifferentiated febrile illness leading to hospitalization in the past 3 months
- Behavioral, cognitive, or psychiatric disease that, in the opinion of the investigator, affects the subject's ability to understand and cooperate with the requirements of the study protocol.
- Any significant alcohol or drug abuse in the past 12 months that has caused medical, occupational, or family problems, as indicated by subject history.
- History of a severe allergic reaction or anaphylaxis
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 |
|---|---|---|
| rDEN2Δ30-7169rDEN2Δ30-7169 will be inoculated at Study Day 0. After 6 months of the inoculation, the participants will be vaccinated with Dengvaxia® until completion of 3 doses with 6-month interval between each dose. | Biological | Flavivirus naïve |
Primary outcome
The safety of rDEN2Δ30-7169 in flavivirus naïve participants
Time frame: 21 Days
Occurrence of local and general adverse events (AEs) and serious adverse events (SAEs)
11 secondary outcomes
The frequency of viremia following administration with rDEN2Δ30-7169 in flavivirus naïve participants
Time frame: 180 Days
The quantity of viral genome following administration with rDEN2Δ30-7169 in flavivirus naïve participants
Time frame: 180 Days
The duration of viremia following administration with rDEN2Δ30-7169 in flavivirus naïve participants
Time frame: 180 Days
The frequency of viremia following administration with rDEN2Δ30-7169 in flavivirus naïve participants
Time frame: 180 Days
The quantity of infectious activity following administration with rDEN2Δ30-7169 in flavivirus naïve participants
Time frame: 180 Days
The duration of infectious activity following administration with rDEN2Δ30-7169 in flavivirus naïve participants
Time frame: 180 Days
The frequency of NS1 antigenemia following administration with rDEN2Δ30-7169 in flavivirus naïve participants
Time frame: 180 Days
The quantity of NS1 antigenemia following administration with rDEN2Δ30-7169 in flavivirus naïve participants
Time frame: 180 Days
The duration of NS1 antigenemia following administration with rDEN2Δ30-7169 in flavivirus naïve participants
Time frame: 180 Days
The immunogenicity of rDEN2Δ30-7169 in Thai flavivirus naïve participants
Time frame: 180 Days
Measurement of levels of anti-dengue virion-IgM/IgG antibodies following administration with rDEN2Δ30-7169 in flavivirus naïve participants
Time frame: 180 Days
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Jul 2022.
Related trials for Dengue
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
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
Active, not recruiting
A Controlled Human Infection Model of Dengue
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
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.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing rDEN2Δ30-7169 in people with Dengue, run by Mahidol University at 1 site in Thailand.
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 13 inclusion and 20 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: status not confirmed, as of the sponsor's last update on 27 Jul 2022. 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 Thailand. 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.
What does this phase mean?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Panisadee Avirutnan, M.D., Ph.D. (+6624196667-70, panisadee.avi@mahidol.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The safety of rDEN2Δ30-7169 in flavivirus naïve participants (time frame: 21 Days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 27 Jul 2022.