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

Primary Purpose

Dengue

Status
Not yet recruiting
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
EYU688
Placebo
Sponsored by
Novartis Pharmaceuticals
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Dengue focused on measuring Dengue, EYU688

Eligibility Criteria

18 Years - 60 Years (Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm Type

    Experimental

    Placebo Comparator

    Arm Label

    EYU688

    Placebo

    Arm Description

    EYU688 administered by oral route

    Matching placebo

    Outcomes

    Primary Outcome Measures

    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.

    Secondary Outcome Measures

    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.
    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
    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
    Changes of viral load over time
    Efficacy assessment will allow to assess the viremia kinetic from treatment start to Day15
    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.
    Incidence and severity of Serious Adverse Events (SAEs)
    Incidence and severity of SAEs by treatment group
    Change of white blood cell count over time from baseline
    Assessment of safety and tolerability of EYU688
    Change of platelet count over time
    Assessment of safety and tolerability of EYU688
    Change of hematocrit level and percentage increase from baseline over time
    Assessment of safety and tolerability of EYU688
    Change of AST, ALT levels over time
    Assessment of safety and tolerability of EYU688
    No warning signs by day 7 of fever onset
    Assessment of the dengue fever clinical evolution under EYU688
    Diagnosis of severe dengue fever
    Assessment of the dengue fever clinical evolution under EYU688
    Diagnosis of dengue hemorrhagic fever (DHF)
    Assessment of the dengue fever clinical evolution under EYU688
    Plasma leakage
    Assessment of the dengue fever clinical evolution under EYU688
    Requiring fluid infusion
    Assessment of the dengue fever clinical evolution under EYU688
    Time from fever onset to clinical recovery
    Assessment of the dengue fever clinical evolution under EYU688
    PK parameter (Cmax)
    Pharmacokinetic assessment of EYU688 in dengue fever patients
    PK parameter (Tmax)
    Pharmacokinetic assessment of EYU688 in dengue fever patients
    PK parameter (partial AUCs)
    Pharmacokinetic assessment of EYU688 in dengue fever patients
    PK concentrations following multiple doses
    Pharmacokinetic assessment of EYU688 in dengue fever patients

    Full Information

    First Posted
    August 17, 2023
    Last Updated
    October 9, 2023
    Sponsor
    Novartis Pharmaceuticals
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    1. Study Identification

    Unique Protocol Identification Number
    NCT06006559
    Brief Title
    A Study to Assess the Efficacy, Safety and Pharmacokinetics of EYU688 in Patients With Dengue Fever
    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
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    October 2023
    Overall Recruitment Status
    Not yet recruiting
    Study Start Date
    November 10, 2023 (Anticipated)
    Primary Completion Date
    October 25, 2024 (Anticipated)
    Study Completion Date
    November 27, 2024 (Anticipated)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    Novartis Pharmaceuticals

    4. Oversight

    Studies a U.S. FDA-regulated Drug Product
    No
    Studies a U.S. FDA-regulated Device Product
    No
    Data Monitoring Committee
    No

    5. Study Description

    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]).

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Dengue
    Keywords
    Dengue, EYU688

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 2
    Interventional Study Model
    Parallel Assignment
    Masking
    ParticipantCare ProviderInvestigatorOutcomes Assessor
    Allocation
    Randomized
    Enrollment
    108 (Anticipated)

    8. Arms, Groups, and Interventions

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

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Maximum Age & Unit of Time
    60 Years
    Accepts Healthy Volunteers
    No
    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.
    Central Contact Person:
    First Name & Middle Initial & Last Name or Official Title & Degree
    Novartis Pharmaceuticals
    Phone
    +41613241111
    Email
    novartis.email@novartis.com
    First Name & Middle Initial & Last Name or Official Title & Degree
    Novartis Pharmaceuticals

    12. IPD Sharing Statement

    Plan to Share IPD
    Yes
    IPD Sharing Plan Description
    Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com.

    Learn more about this trial

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

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