Ignite Creation Date:
2025-12-24 @ 6:51 PM
Ignite Modification Date:
2026-01-01 @ 10:46 AM
Study NCT ID:
NCT05476757
Status:
NOT_YET_RECRUITING
Last Update Posted:
2022-07-27
First Post:
2022-07-11
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Safety, Virological and Immunological Assessment of Live Attenuated Dengue Serotype 2 rDEN2delta30-7169.
Sponsor:
Mahidol University
Organization:
Study Overview
Official Title:
Safety, Virological and Immunological Assessment of the Controlled Dengue Human Infection Model in Thailand
Status:
NOT_YET_RECRUITING
Status Verified Date:
2022-07
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
DHIT
Brief 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. 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.
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.
Detailed Description:
None
Study Oversight
Has Oversight DMC:
True
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?: