Clinical trial NCT06006559: 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
Overall status: RECRUITING
Phase: PHASE2
Conditions: Dengue
Keywords: Dengue
EYU688
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2023-08-23
Enrollment: 108
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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 \[cohort 2\]).

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 4 days 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.

Primary outcomes:
measure: Viremia reduction (viral load reduction (VLR) on log scale) at 48 hours post treatment start
timeFrame: From predose to 48 hours post treatment start
Secondary outcomes:
measure: Time from fever onset to start of the first 48 hours period during which the oral temperature remained below 37.5℃
timeFrame: From fever onset to Day 15
measure: Time from fever onset to the first of two consecutive negative viremia by PCR
timeFrame: From fever onset to Day 15
measure: Area under the log-transformed viremia curve (AUC) from the first dose to Day 15
timeFrame: From fever onset to Day 15
measure: Changes of viral load over time
timeFrame: From baseline to Day 15
measure: Incidence and severity of Adverse Events (AEs)
timeFrame: From inclusion to Day 15
measure: Incidence and severity of Serious Adverse Events (SAEs)
timeFrame: From inclusion to Day 35
measure: Change of white blood cell count over time from baseline
timeFrame: From baseline to Day 15
measure: Change of platelet count over time
timeFrame: From baseline to Day 15
measure: Change of hematocrit level and percentage increase from baseline over time
timeFrame: From baseline to Day 15
measure: Change of AST, ALT levels over time
timeFrame: From baseline to Day 15
measure: No warning signs by day 7 of fever onset
timeFrame: From inclusion to Day 15
measure: Diagnosis of severe dengue fever
timeFrame: From inclusion to Day 15
measure: Diagnosis of dengue hemorrhagic fever (DHF)
timeFrame: From inclusion to Day 15
measure: Plasma leakage
timeFrame: From inclusion to Day 15
measure: Requiring fluid infusion
timeFrame: From inclusion to Day 15
measure: Time from fever onset to clinical recovery
timeFrame: From fever onset to Day 15
measure: PK parameter (Cmax)
timeFrame: From Day 1 to Day 6
measure: PK parameter (Tmax)
timeFrame: From Day 1 to Day 6
measure: PK parameter (partial AUCs)
timeFrame: From Day 1 to Day 6
measure: PK concentrations following multiple doses
timeFrame: From Day 1 to Day 6
Other outcomes:
Locations:
city: Manaus
country: Brazil
facility: Novartis Investigative Site
state: AM
city: Brasilia
country: Brazil
facility: Novartis Investigative Site
state: DF
city: Sorocaba
country: Brazil
facility: Novartis Investigative Site
state: SP
city: Sao Jose do Rio Preto
country: Brazil
facility: Novartis Investigative Site
city: Mumbai
country: India
facility: Novartis Investigative Site
state: Maharashtra
city: Pune
country: India
facility: Novartis Investigative Site
state: Maharashtra
city: Jaipur
country: India
facility: Novartis Investigative Site
state: Rajasthan
city: Chennai
country: India
facility: Novartis Investigative Site
state: Tamilnadu
city: Kuantan
country: Malaysia
facility: Novartis Investigative Site
state: Pahang
city: Ipoh
country: Malaysia
facility: Novartis Investigative Site
state: Perak
city: Seberang Jaya
country: Malaysia
facility: Novartis Investigative Site
state: Pulau Pinang
city: Miri
country: Malaysia
facility: Novartis Investigative Site
state: Sarawak
city: Singapore
country: Singapore
facility: Novartis Investigative Site
city: Singapore
country: Singapore
facility: Novartis Investigative Site
city: Hanoi
country: Vietnam
facility: Novartis Investigative Site
city: Ho Chi Minh
country: Vietnam
facility: Novartis Investigative Site
Study officials:
References: