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

Study Overview
=================
Brief Summary
-----------------
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.

Detailed Description
-----------------
This is a randomized, participant- and investigator- blinded, placebo-controlled study to investigate the efficacy and safety of EYU688 administered orally in patients with dengue fever. Due to the different PK sampling schedules applied, the study consists of two cohorts run in parallel (intensive PK [cohort 1] and sparse PK sampling [cohort 2]).

Official Title
-----------------
A Randomized, Participant- and Investigator-blinded, Placebo-controlled, Parallel Group Study to Assess the Efficacy, Safety and Pharmacokinetics of EYU688 in Patients With Dengue Fever

Conditions
-----------------
Dengue

Intervention / Treatment
-----------------
* Drug: EYU688
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Male or female, 18 - 60 years old (inclusive). History or presence of fever (≥ 38°C). At least one of the following criteria indicating dengue infection: Nausea or vomiting. Presence of rash, aches or pains including headache, muscle or joint pain. Onset of fever ≤ 48 hours prior to treatment start. Positive test on dengue fever. Exclusion Criteria: Participants with any of abnormalities of clinical laboratory parameters. Usage of any anticoagulant drugs. Current significant medical conditions or illness that the investigator considers should exclude the participants, especially those that require continuation of other medications likely to have an interaction with the study drug. Pregnant or nursing (lactating) women. Clinical signs and symptoms for severe dengue according to Dengue Guideline (WHO 2009) at screening. Participants with any of the following abnormalities of clinical laboratory parameters at screening: Hemoglobin <12.0 g/dL in males; <11.0 g/dL in females Hematocrit >52 % in males; >46 % in females Absolute neutrophil count <1500/μL Platelet count <80,000/mm3 Creatinine >165 μmol/L in males; >130 μmol/L in females Serum creatine kinase > 600 U/L ALT, AST levels more than 1.5X upper limit of normal (ULN) Total bilirubin >24 μmol/L Usage of PPIs (proton pump inhibitor) which could affect absorption of EYU688 due to stomach pH value increase up to 48 hours prior to screening. Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using highly effective methods of contraception during dosing and for five half-lives or 4 days whichever is longer after stopping of investigational drug. History or long-QT syndrome, or clinically significant ECG abnormalities, or any of the following ECG abnormalities at screening: QTcF > 450 msec (males) QTcF > 460 msec (females) Other protocol-defined inclusion/exclusion criteria may apply.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: EYU688<br>EYU688 administered by oral route | Drug: EYU688<br>* EYU688 administered by oral route<br>|
| Placebo Comparator: Placebo<br>Matching placebo | Drug: Placebo<br>* Matching placebo administered orally as capsules<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Viremia reduction (viral load reduction (VLR) on log scale) at 48 hours post treatment start | Efficacy assessment of EYU688. It will allow to quantify the viremia reduction at 48 hours post treatment start from baseline. | From predose to 48 hours post treatment start | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time from fever onset to start of the first 48 hours period during which the oral temperature remained below 37.5℃ | Efficacy assessment of EYU688. It will allow to assess the time needed between fever onset and defervescence. | From fever onset to Day 15 | 
| Time from fever onset to the first of two consecutive negative viremia by PCR | Efficacy assessment will allow to assess the viremia kinetic from treatment start to Day15 | From fever onset to Day 15 | 
| Area under the log-transformed viremia curve (AUC) from the first dose to Day 15 | Efficacy assessment will allow to assess the viremia kinetic from treatment start to Day 15 | From fever onset to Day 15 | 
| Changes of viral load over time | Efficacy assessment will allow to assess the viremia kinetic from treatment start to Day15 | From baseline to Day 15 | 
| Incidence and severity of Adverse Events (AEs) | Incidence and severity of AEs by treatment group, including changes in vital signs, electrocardiograms (ECGs) and laboratory results qualifying and reported as AEs. | From inclusion to Day 15 | 
| Incidence and severity of Serious Adverse Events (SAEs) | Incidence and severity of SAEs by treatment group | From inclusion to Day 35 | 
| Change of white blood cell count over time from baseline | Assessment of safety and tolerability of EYU688 | From baseline to Day 15 | 
| Change of platelet count over time | Assessment of safety and tolerability of EYU688 | From baseline to Day 15 | 
| Change of hematocrit level and percentage increase from baseline over time | Assessment of safety and tolerability of EYU688 | From baseline to Day 15 | 
| Change of AST, ALT levels over time | Assessment of safety and tolerability of EYU688 | From baseline to Day 15 | 
| No warning signs by day 7 of fever onset | Assessment of the dengue fever clinical evolution under EYU688 | From inclusion to Day 15 | 
| Diagnosis of severe dengue fever | Assessment of the dengue fever clinical evolution under EYU688 | From inclusion to Day 15 | 
| Diagnosis of dengue hemorrhagic fever (DHF) | Assessment of the dengue fever clinical evolution under EYU688 | From inclusion to Day 15 | 
| Plasma leakage | Assessment of the dengue fever clinical evolution under EYU688 | From inclusion to Day 15 | 
| Requiring fluid infusion | Assessment of the dengue fever clinical evolution under EYU688 | From inclusion to Day 15 | 
| Time from fever onset to clinical recovery | Assessment of the dengue fever clinical evolution under EYU688 | From fever onset to Day 15 | 
| PK parameter (Cmax) | Pharmacokinetic assessment of EYU688 in dengue fever patients | From Day 1 to Day 6 | 
| PK parameter (Tmax) | Pharmacokinetic assessment of EYU688 in dengue fever patients | From Day 1 to Day 6 | 
| PK parameter (partial AUCs) | Pharmacokinetic assessment of EYU688 in dengue fever patients | From Day 1 to Day 6 | 
| PK concentrations following multiple doses | Pharmacokinetic assessment of EYU688 in dengue fever patients | From Day 1 to Day 6 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Dengue, EYU688