This study is to investigate the ability of LXE408 to clear or reduce the level of parasites in the blood of people with chronic Chagas disease. Participants must have chronic Chagas disease without severe organ dysfunction.
This is an interventional, phase 2, PoC (Proof of Concept) randomized, participant- and investigator-blinded, controlled, parallel group study, with 4 treatment arms. The purpose of this study is to assess the efficacy (anti-parasitological activity), safety, PK (pharmacokinetics), and PD (pharmacodynamics) of LXE408 in participants with CICD (chronic indeterminate Chagas disease) and chronic Chagas disease without severe cardiac or gastrointestinal dysfunction compared to placebo and to benznidazole.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
130
LXE408 administered by oral route
Placebo administered by oral route
Benznidazole administered by oral route (administered as standard of care)
Olive View UCLA Educ and Res Ins
Sylmar, California, United States
RECRUITINGPresence or absence of sustained parasitological clearance using polymerase chain reaction (PCR) results over 6 months - LXE408 28 days versus placebo.
The parasitological load will be measured using polymerase chain reaction (PCR) at 2 months, 4 months, and at 6 months. At each timepoint, multiple samples are evaluated. The participant will be considered negative at a visit if the parasite is not detectable in all samples at a visit and positive if the parasite level is detectable in at least one sample. Sustained parasitological clearance is achieved if participant is negative at all 3 visits.
Time frame: At Months 2, 4, and 6
Presence or absence of sustained parasitological clearance using polymerase chain reaction (PCR) results over 6 months - LXE408 -14 days versus placebo
The parasitological load will be measured using polymerase chain reaction (PCR) at 2 months, 4 months, and at 6 months. At each timepoint, multiple samples are evaluated. The participant will be considered negative at a visit if the parasite is not detectable in all samples at a visit and positive if the parasite level is detectable in at least one sample. Sustained parasitological clearance is achieved if participant is negative at all 3 visits.
Time frame: At Months 2, 4, and 6
Presence or absence of sustained parasitological clearance using polymerase chain reaction (PCR) results over 6 months-LXE408 - 28 days and 14 days versus benznidazone
The parasitological load will be measured using polymerase chain reaction (PCR) at 2 months, 4 months, and at 6 months. At each timepoint, multiple samples are evaluated. The participant will be considered negative at a visit if the parasite is not detectable in all samples at a visit and positive if the parasite level is detectable in at least one sample. Sustained parasitological clearance is achieved if participant is negative at all 3 visits.
Time frame: At Months 2, 4, and 6
Presence or absence of early parasitological clearance
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
University of Florida Shands
Gainesville, Florida, United States
RECRUITINGBoston Medical Center
Boston, Massachusetts, United States
RECRUITINGBaylor College of Medicine
Houston, Texas, United States
RECRUITINGNovartis Investigative Site
CABA, Buenos Aires, Argentina
RECRUITINGNovartis Investigative Site
CABA, Buenos Aires, Argentina
RECRUITINGNovartis Investigative Site
Corrientes, Argentina
RECRUITINGNovartis Investigative Site
Córdoba, Argentina
RECRUITINGNovartis Investigative Site
Formosa, Argentina
RECRUITINGNovartis Investigative Site
Montes Claros, Minas Gerais, Brazil
RECRUITING...and 8 more locations
The parasitological load will be measured using polymerase chain reaction (PCR). The participant will be considered negative at a visit if the parasite is not detectable in all samples at a visit and positive if the parasite level is detectable in at least one sample.
Time frame: At Day 7, 14 and 28
Presence or absence of sustained parasitological clearance over 12 months by PCR testing
The parasitological load will be measured using polymerase chain reaction (PCR). The participant will be considered negative at a visit if the parasite is not detectable in all samples at a visit and positive if the parasite level is detectable in at least one sample. Sustained parasitological clearance is achieved if participant is negative at all subsequent visits.
Time frame: 12 Months
Time to parasitological clearance based on serial PCR testing
Time to parasitological clearance based on PCR by treatment will be estimated using the Kaplan-Meier approach.
Time frame: 12 Months
Presence or absence of seroreversion using conventional serology
Seroreversion as measured by conventional serology will be evaluated at 6 and 12-month study visits. Seroreversion is determined by the proportion of participants achieving serology changes from positive at baseline to negative at each time point.
Time frame: At Month 6 and Month 12
Occurrence and severity of treatment emergent adverse events during the study
Incidence and severity of AEs by treatment group, including changes in the vital signs, electrocardiogram and laboratory results qualifying and reported as AEs.
Time frame: Up to 12 Months
Occurrence of adverse events resulting in treatment discontinuation
Incidence of AEs that result in treatment discontinuation.
Time frame: Up to 12 Months
Occurrence of all-cause mortality through end of study visit
Incidence of death through the end of study visit.
Time frame: Up to 48 Months
Maximum plasma concentration (Cmax) of LXE408
Cmax is defined as the maximum (peak) observed concentration following a dose.
Time frame: At Day 1, 7, 14, 28
Time to maximum plasma concentration (Tmax) of LXE408
Tmax is defined as the time to reach maximum (peak) concentration following a dose.
Time frame: At Day 1, 7, 14, 28
Area under the plasma concentration-time curve from time 0 to 8 hours post-dose (AUC0-8)
AUC0-8 will be calculated by non-compartmental methods based on LXE408 plasma concentration data.
Time frame: At Day 1, 7, 14, 28
Pre-dose concentration
Pre-dose concentration is the observed plasma concentration that is just prior to the beginning of, or at the end of a dosing interval.
Time frame: At Day 14 and Day 28