Clinical Research Directory

A Study to Assess the Efficacy, Safety and Pharmacokinetics of EYU688 in Patients With Dengue Fever

The purpose of this study is to characterize the effect on dengue viral load, fever clearance time as well as on clinical signs and symptoms with the treatment of EYU688 compared with placebo in patients with dengue fever.

Trial to Evaluate the Immunogenicity and Safety of the Co-administration of Live Attenuated Dengue and Chikungunya Vaccines Compared to Separate Administration in Adults Aged 18 to 59 Years.

This randomized, controlled, double blind trial aims at assessing the safety and immunogenicity profiles of the co-administered Live Attenuated Dengue and Chikungunya vaccines comparatively to the isolated administration, in the adult population aged 18 to 59 years without prior exposure to either arbovirus.

Butantan-DV Vaccine in Elderly Populations (DEN-04-IB)

This is a randomized, double-blind (60 -79 years) and open-label (40-59 years), three-arm parallel Phase 3b, multicenter study to evaluate the safety and non-inferiority of the humoral immune response of the Butantan Dengue vaccine (Dengue 1,2,3,4 (attenuated)) in participants aged 60 -79 years (elderly) compared to participants aged 40 to 59 years (adults), with or without previous dengue and healthy based on clinical examination.

A Controlled Human Infection Model of Dengue

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. 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. Characterise the clinical, haematological and virological response following controlled inoculation of the attenuated DEN3 challenge agent. 3. Conduct deep immunophenotyping to understand the cellular, humoral and innate immune response to dengue infection. 4. Explore the longitudinal immune response in the 3 years after challenge, including following subsequent dengue vaccination.

Risk Assessment of Community Spread of Multiple Endemic Infectious Diseases in a One Health Perspective

RACSMEI addresses the high burden of infectious diseases in low- and middle-income countries, including Cambodia, where limited surveillance and laboratory capacity often obscure etiologies and transmission dynamics. This knowledge gap hinders the design of effective prevention and control strategies. RACSMEI will improve understanding across multiple pathogens using a multidisciplinary One Health approach. We will answer key questions on burden, ecology, transmission and population immune status to inform targeted and culturally appropriate interventions. The project combines a nationally representative One Health survey, social-science methods, and multiplex, diverse diagnostics to efficiently test for 57 priority pathogens, including zoonotic and vector-borne agents, vaccine-preventable and elimination-targeted diseases, enteric, respiratory, and environmentally transmitted pathogens and selected neglected tropical diseases and parasites relevant to Cambodia. Mathematical modelling will reconstruct and forecast transmission dynamics and assess the potential impact of future public-health strategies. By integrating intersectoral data and innovative methods, RACSMEI will generate actionable evidence for public-health authorities, support precision One Health interventions, and help reduce disease burden in affected communities. The project also aims to ensure the transferability of methods and insights to other countries facing similar challenges.

Anakinra in Dengue With Hyperinflammation ( AnaDen )

This study aims to evaluate the effect of anakinra in dengue patients with hyperinflammation as compared to placebo Primary Objective: To evaluate the efficacy of Anakinra in moderate-severe dengue patients with hyperinflammation. Secondary Objectives: * To assess the safety of anakinra therapy in dengue with hyperinflammation * To assess the effect of anakinra therapy in patients with dengue on physiological, clinical and virological parameters * To assess the immunomodulation effects of anakinra in dengue * Immune cell signatures in dengue with and without anakinra * To assess difference in gene expression between treatment group compared to non-treatment population

Emetine for Viral Outbreaks (a.k.a. EVOLVE Antiviral Initiative)

The goal of this study is to evaluate the efficacy and safety of emetine administered orally for symptomatic patients aged 18-65 years infected with the dengue virus. The main questions it aims to answer are: 1. Does emetine reduce 28-day mortality or progression to severe dengue (severe plasma leakage, severe bleeding, or severe organ involvement)? 2. What are the safety outcomes of emetine, including serious adverse events and toxicities? Participants will be asked to: 1. Take either 6mg emetine, 12mg emetine, or a placebo pill for 7 consecutive days as part of the treatment regimen. 2. Have blood samples taken for at least 5 days to monitor viral load, inflammatory markers, and safety parameters. 3. Be monitored by healthcare staff for daily vital signs and symptoms for clinical assessments for 28 days.

Dengue - Sample Collection Study Pakistan

The objective of this study is to collect well-characterized serum and plasma specimens from confirmed dengue positive and dengue negative subjects to support dengue diagnostic products development.

Risk Factors for Hospitalization and Transfusion Criteria in Patients With Dengue Virus Infection

This 3-year prospective observational study aims to identify clinical and laboratory risk factors associated with hospitalization in patients with confirmed dengue virus infection. It also seeks to analyze real-world transfusion practices and their outcomes. The study will be conducted in a second-level hospital in northern Mexico and will follow patients from emergency department entry to clinical resolution or hospital discharge.

Evaluation of T-cell Responses After Vaccination With the Attenuated Tetravalent Dengue Vaccine (Takeda).

Dengue is one of the most epidemiologically and clinically relevant arboviral diseases, affecting half of the global population. This disease is caused by one of the four serotypes of the dengue virus (DENV1-4), belonging to the flavivirus family transmitted to humans by Aedes aegypti and Aedes albopictus mosquitoes. Dengue is not endemic in Europe, and recorded cases are almost exclusively imported by individuals who have recently visited endemic areas. In Italy, several imported cases are recorded every year, although in the past summer season of 2023, numerous autochthonous cases of dengue were observed, with a particular incidence in Rome and Lazio. In 75-80% of cases the first infection is asymptomatic or paucisymptomatic, while in 20-25% of cases flu-like symptoms may appear, in more severe cases, dengue hemorrhagic fever may occur. Individuals who are infected for the first time are protected for life from that particular serotype that caused the infection. However, Individuals who are infected for the second time with a different serotype are at greater risk of severe dengue.To reduce the risk of dengue epidemics, the most effective method is a systematic and continuous mosquito control. Although the use of an effective vaccine remains a primary prevention measure that should be integrated into the healthcare system. The recent vaccine developed, TAK-003, is an innovative live attenuated vaccine based on serotype 2 (DENV-2), which uses recombinant technology to ensure immunization against all four virus serotypes. However, it showed the highest efficacy against DENV-2, both in seropositive and seronegative people. To date, there is partial knowledge of the dynamics between viral and host factors that influence the development of disease caused by DENV. In this infections it has been observed that T lymphocytes play a crucial role in dealing with viral pathogens with both harmful and beneficial effects. A debate still persists as whether memory T lymphocytes play solely a protective role in secondary DENV infections or may instead have the potential to contribute to immunopathological mechanisms leading to severe forms of dengue. Our study aims are to investigate the responses of T lymphocytes against DENV, identifying reliable and meaningful markers of protection. This will be achieved by analyzing the response of T lymphocytes to DENV1-4 serotype epitopes in subjects who will be vaccinated with the attenuated tetravalent dengue TAK003.

Immune Responses to Dengue and Sepsis

The goal of this research study is to help the investigators better understand serious dengue disease. The investigators will collect clinical information and up to four blood samples from participants with dengue, sepsis, or healthy people. The investigators will perform multiple analyses on the blood samples and compare results between dengue patients and those with sepsis and healthy people.

Effectiveness Evaluation of the "Mosquito-Free Campus" Initiative on Dengue Fever Prevention and Control: A Cluster Randomized Controlled Trial

The goal of this cluster randomized controlled trial is to evaluate the effect of health education interventions on the score of the knowledge, attitudes, and practices (KAP) of dengue in in primary and middle school students in the city of Guangzhou and Foshan in China. Individuals aged 6 to 15 years who are in grades 1-9 in primary schools in Guangzhou and Foshan will be enrolled. 20 primary schools will be randomly selected, with half designated as intervention group schools and the remaining half as control group schools. The intervention group will receive a health education intervention focused on dengue prevention every semester for 6 months, while the control group will continue with their routine school health education for 6 months. Researchers will compare the differences in the score of the KAP of dengue between the intervention and control groups after 6 months to see if health education can improve knowledge, attitudes and practices of dengue among primary and middle school students.

Efficacy of Montelukast in Preventing Transaminase Elevation in Adult Dengue Patients

The goal of this clinical trial is to learn if drug montelukast works to treat dengue in adults. It will also learn about the safety of drug montelukast . The main questions it aims to answer are: Does drug montelukast lower the incidence of liver enzyme elevations in participants ? What medical problems do participants have when taking drug montelukast ?

Safety, Virological and Immunological Assessment of the Controlled Dengue Human Infection Model in Dengue-Immune Participants in Thailand (DHIT-Immune)

rDEN2Δ30-7169 is a dengue challenge strain that previously reports its viremia induction effect in participants with minimal symptoms in US flavivirus naïve participants. Moreover, preliminary result of five Thai dengue naïve participants from previous project (registered number NCT05476757) demonstrated 100% viremia status without severe adverse event after 60 days post-virus challenge. However, result from previous project may not fully represent the clinical manifestation and immunological responses of major population of endemic areas, where most people in endemic area have dengue immune status. Therefore, this controlled human infection model protocol proposes to challenge the attenuated virus in 12 dengue-immune participants recruited from Bangkok metropolitan area, Thailand. We aim to assess the safety, viremia, NS1 antigenemia profile, and immunogenicity of the challenge virus in the dengue immune participants. After finish safety assessment, all participants will be vaccinated with a full course of dengue vaccines to prevent recurrent dengue infection. Immunological responses after vaccination will be also evaluated the vaccine efficacy. Our expected outcomes are all participants present viremia profiles after virus challenge without serious adverse events (SAE). The exploratory profiles include assesment of immune profiles and parameters comparison with the other dengue challenge study.

Impact of IIT-SIT on Dengue Clusters

This randomized controlled trial aims to evaluate the efficacy of Wolbachia-infected male mosquitoes combined with sterile insect technique (IIT-SIT) to mitigate active dengue transmission in Singapore.

Dengue Vaccine Strategy in Children Aged 9 to 17 Years in the French Caribbean

Dengue fever, an arbovirus transmitted by the Aedes mosquito, is a public health problem in all tropical and subtropical regions of the world. There is currently no antiviral treatment and vector control has shown its limits. The 2018 European marketing authorization of the tetravalent chimeric yellow fever / dengue vaccine (Dengvaxia®) is a major step forward in the fight against the disease. Dengvaxia® is indicated for the prevention of dengue due to serotypes DENV 1-4 in subjects aged 9 to 45 years with a history of infection with the dengue virus and living in endemic areas (seroprevalence of at least 70% in the target population). Dengue seroprevalence data in the French Caribbean territories of Martinique and Guadeloupe dates back to 2011 and concerns only adult blood donors aged 18 to 70 years. To date, no data exists for individuals aged 9 to 17 years in the region. In order to implement an optimal vaccine introduction strategy for these territories, the main aim of the DengueSEA study is to estimate the seroprevalence of the Dengue viruses (DENV 1-4) in 9-17 year olds giving a blood sample as part of care in hospital departments of the French Caribbean islands of Martinique and Guadeloupe.

Improving Disease Prevention Strategies by Integrating Socio-spatial Characterization of Human Mobility

In contrast to the trend expected based on existing prediction models, dengue incidence was historically low during the pandemic mobility restrictions of 2020-2021 in most dengue endemic countries. This highlights that current transmission models do not correctly take human mobility into account. Within a pilot-study in Cienfuegos, South-Central Cuba, we will characterise the epidemiological spread and distribution of dengue outbreaks (2012-2025) in districts repeatedly involved in previous dengue outbreaks as initiating, case-concentrating or transmission sustaining areas. This will be linked with fine-grained mobility data and socio-spatial characterizations of commuting flows and population hubs where people are concentrated during day-time (time when transmission happens). This information, together with entomological and environmental risk-data, will be used to i) improve the accuracy of mathematical dengue models, ii) better understand the transmission process and iii) inform and improve the design of disease control strategies. The project will contribute to much-needed evidence-based guidance for public health actors on improved prevention strategies of epidemics dispersion and where and when to implement control measures.

Adaptive Dengue Antiviral Platform Trial

This is a randomized, open-label adaptive platform trial aiming to screen the antiviral effectiveness of the experimental drug(s) in early dengue infection * Primary objectives: * To determine the antiviral effectiveness of the experimental drug(s) in early dengue infection * To assess the safety and tolerability of the experimental drug(s) in dengue patients * Secondary objective: * To assess the effect of the experimental drug(s) in dengue patients on physiological, clinical and virological parameters

Dengue Controlled Human Infection Model in Dhaka, Bangladesh

The primary objective is to determine, among dengue-naïve adults in an endemic population, the protective efficacy of TetraVax-DV TV005 vaccine against dengue infection induced by a live recombinant attenuated rDEN2∆30-7169 attenuated virus strain administered 6, 12, or 24 months after vaccination. Secondary objectives are: 1. Determine the durability of protection of TetraVax-DV TV005. 2. Evaluate the safety of TetraVax-DV TV005 in dengue-naïve volunteers in a dengue endemic population. 3. Evaluate the safety of the rDEN2∆30-7169 attenuated virus strain in a dengue endemic population.

Virological and Immunological Determinants of Arbovirus Infection in New Caledonia

Arboviruses, diseases transmitted to humans by the bite of an insect vector, are a major public health problem, particularly in tropical and sub-tropical countries. In New Caledonia, dengue epidemics are recurrent and may be associated with the co-circulation of other arboviruses such as Zika or chikungunya. The virological determinants which condition the occurrence of these epidemics may be linked to an increased vectorial competence of the vector mosquito Aedes aegypti for a particular viral isolate. In fact, the Aedes aegypti mosquito is infected by making a blood meal on a person infected with an arbovirus. The virus infects its digestive tract, then spreads throughout the mosquito's body until it reaches its salivary glands. The virus is then present in the saliva and will be injected into the human host during a new blood meal. Some viral variants are best transmitted by Aedes aegypti. In general, the study of this vectorial competence is carried out by experiments in the laboratory during which an artificial blood meal composed of mammalian blood (human, rabbit, etc.) is mixed with a viral stock. Carrying out deported blood meals during which blood collected from patients infected with an arbovirus is used to gorge mosquitoes makes it possible to place oneself in experimental conditions as close as possible to the natural cycle of transmission of arboviruses. In the human host, cells of the myeloid lineage present in the peripheral blood constitute preferred targets of replication for arboviruses. At the same time, the peripheral blood cells of patients are activated in response to infection and secrete many soluble factors released into the blood of patients. The study of blood samples from patients infected with arboviruses is therefore of prime importance for understanding both the replicative mechanisms of arboviruses but also the immune response they induce.

Genetic Evolution of Arboviruses in New Caledonia Between 1995 and 2024 and Impact of Wolbachia

Arboviruses, diseases transmitted to humans by the bite of an insect vector, are a major public health problem, especially in tropical and sub-tropical countries. A promising strategy aimed at blocking the circulation of arboviruses is to release Aedes aegypti mosquitoes carrying the endosymbiotic bacterium Wolbachia. In 2019, the Wolbachia strategy was implemented in Nouméa as part of the World Mosquito Program. This intervention will modify the epidemiological profile of arboviruses in New Caledonia. Epidemiological surveillance of arboviruses requires molecular characterization of the virus contained in the serum obtained from the blood collected from patients. This molecular characterization by RNA isolation techniques, RT-qPCR monitoring and sequencing allows the construction of phylogenetic trees. In the context of the implementation of the World Mosquito Program in Nouméa, the investigators plan to follow the molecular evolution of arboviruses, over the period preceding the releases of mosquitoes carrying Wolbachia (from 1995 to 2019) then over a period of 5 years. following the releases. At the same time, the virus can be isolated by cell culture techniques and in vitro infections, allowing its study in vitro in cells or in vivo in mosquitoes. This study allows us to measure the impact of the Wolbachia strategy on the evolution of the virus's ability to replicate in cells in the presence of Wolbachia and to be transmitted by the mosquito.

Study of Dengue in Patients With Autoimmune Diseases During the Epidemics of 2020 and 2021 in Reunion Island

It is not known whether there is a different clinical profile of dengue in patients with immune system dysfunction. Preliminary data and previous literature suggest that autoimmune diseases, and in particular their treatment, may favour the evolution to severe forms of dengue. Our research hypothesis is that the clinico-biological presentation of dengue might be different in case of autoimmune disease, either on the side of overactivation (autoimmune and auto inflammatory diseases without treatment) or immunodepression (autoimmune and auto inflammatory diseases under immunosuppressive treatment).