A Study of Efficacy, Safety, Tolerability of LXE408 in Participants With Chronic Chagas Disease.
- Registration Number
- NCT06632600
- Lead Sponsor
- Novartis Pharmaceuticals
- Brief Summary
This study is to investigate the ability of LXE408 to reduce or remove the level of parasites in the blood of people with chronic Chagas disease. Participants must have chronic Chagas disease without severe organ dysfunction.
- Detailed Description
This is 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 CD (chronic Chagas disease) without severe cardiac or gastrointestinal dysfunction compared to placebo and to benznidazole.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 130
- Male or female participants aged ≥ 18 years to ≤ 60 years old
- Confirmed diagnosis of T. cruzi infection
- History that participant has been determined to be in chronic phase of CD
- Written informed consent must be obtained before any assessment is performed, and participants should express understanding of the consent form and the study
- Participants must be considered by the investigator eligible for and able to comply with local prescribing information for benznidazole
- Ability and willingness to communicate well with the investigator/study site and comply with requirements of the study
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Signs (on physical examination) and/or symptoms of CD in the acute phase as determined by the investigator at screening
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History of CD treatment with benznidazole or nifurtimox at any time in the past
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History of and/or current (at screening) symptoms or signs (physical examination findings) of moderate or severe CD-related gastrointestinal disease
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Participants who weigh < 50 kg or >90kg at screening
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At sites conducting the MRI assessments, participants may participate in the overall study, but will be excluded from the MRI assessment if they have contraindications to MRI imaging
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Any clinically significant disease during screening that, in the opinion of the investigator, would put the safety of the participant at risk through participating, or which would affect the efficacy or safety analysis if the disease/condition exacerbated during the study, or would compromise participant compliance or preclude completion of the study
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Documented history or current findings at screening of clinically significant cardiovascular conditions such as, but not limited to: unstable ischemic heart disease; NYHA Class III/IV heart failure (due to Chagas disease or other conditions); arrhythmias
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Known or suspected ongoing, chronic or recurrent viral, bacterial or fungal infectious diseases including but not limited to: Tuberculosis, leishmaniasis, severe malaria, atypical mycobacterial infection, listeriosis, aspergillosis, or endemic mycoses, and/or documented positivity for human immunodeficiency virus (HIV) infection
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History of lymphoproliferative disease or any known malignancy or history of malignancy of any organ system within the past 5 years prior to screening (except for basal cell carcinoma or actinic keratosis that have been treated with no evidence of recurrence in the past 3 months, carcinoma in situ of the cervix or non-invasive malignant colon polyps that have been removed)
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Any surgical or medical condition which might significantly alter the absorption, distribution, metabolism, or excretion of drugs, or which may jeopardize the participant during the study period
- Pancreatic injury or pancreatitis: If any single parameter of amylase or lipase exceeds 1.5x ULN at screening Participants with known recurrent pancreatitis (more than 1 episode in lifetime, from any cause) are excluded
- Liver disease or liver injury as indicated by abnormal liver function tests (LFTs):
Any single parameter of ALT, AST, GGT, alkaline phosphatase must not exceed 1.5x ULN at screening Serum bilirubin must not exceed the ULN at screening elevated serum bilirubin is not excluded if there is a documented history of Gilbert's Syndrome
• History of renal disease as indicated by creatinine level above 1.5x ULN or microalbuminuria or hematuria at screening; Evidence of urinary obstruction, or difficulty in voiding at screening; evidence of congenital renal abnormalities with known effect on renal function; calculated eGFR <60 mL/min (<0.835 mL/s) using the CKD-EPI formula for adults
- Participants with screening hematology parameters outside of the thresholds
- Current use of medications prohibited by the protocol at screening and/or baseline visits, or expected use of any prohibited medication during the study treatment period
- Use of other investigational drugs at the time of study drug dosing
- History of multiple and recurring allergies or allergy to the investigational compound/compound class being used in this study or to benznidazole
- History of drug abuse or unhealthy alcohol use within the 12 months prior to dosing
- Pregnant or nursing (lactating/breast-feeding) women
- 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 5 days after stopping of investigational drug and benznidazole
- Participants who, in the opinion of the investigator, will not be able to comply with study procedures or visits, adhere to dosing schedule, or other otherwise be in compliance with study requirements
Other protocol-defined inclusion/exclusion criteria may apply.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description LXE408 28 days LXE408 LXE408 administered by oral route LXE408 14 days and Placebo 14 days LXE408 LXE408 administered by oral route, followed by Placebo administered by oral route LXE408 14 days and Placebo 14 days Placebo LXE408 administered by oral route, followed by Placebo administered by oral route Placebo 28 days Placebo Placebo administered by oral route Benznidazole 60 days Benznidazole Benznidazole administered by oral route
- Primary Outcome Measures
Name Time Method Presence or absence of sustained parasitological clearance using polymerase chain reaction (PCR) results over 6 months - LXE408 28 days versus placebo. At Months 2, 4, and 6 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.
- Secondary Outcome Measures
Name Time Method Presence or absence of sustained parasitological clearance using polymerase chain reaction (PCR) results over 6 months - LXE408 -14 days versus placebo At Months 2, 4, and 6 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.
Presence or absence of sustained parasitological clearance using polymerase chain reaction (PCR) results over 6 months-LXE408 - 28 days and 14 days versus benznidazone At Months 2, 4, and 6 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.
Presence or absence of parasitological clearance At Day 7, 14 and 28 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. Parasitological clearance is achieved if participant is negative at all 3 visits.
Presence or absence of sustained parasitological clearance over 12 months by PCR testing Up to 12 Months 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 visits.
Time to parasitological clearance based on serial PCR testing Up to 12 Months Time to parasitological clearance based on PCR by treatment will be estimated using the Kaplan-Meier approach.
Presence or absence of seroreversion using conventional serology At Month 6 and Month 12 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.
Occurrence and severity of treatment emergent adverse events during the study Up to 12 Months Incidence and severity of AEs by treatment group, including changes in the vital signs, echocardiogram, electrocardiogram and laboratory results qualifying and reported as AEs.
Occurrence of adverse events resulting in treatment discontinuation Up to 12 Months Incidence of AEs that result in treatment discontinuation.
Occurrence of all-cause mortality through end of study visit Up to 12 Months Incidence of death through the end of study visit.
Maximum plasma concentration (Cmax) of LXE408 At Day 1, 7, 14, 28 Cmax is defined as the maximum (peak) observed concentration following a dose.
Time to maximum plasma concentration (Tmax) of LXE408 At Day 1, 7, 14, 28 Tmax is defined as the time to reach maximum (peak) concentration following a dose.
Area under the plasma concentration-time curve from time 0 to 8 hours post-dose (AUC0-8) At Day 1, 7, 14, 28 AUC0-8 will be calculated by non-compartmental methods based on LXE408 plasma concentration data.
Pre-dose concentration At Day 14 and Day 28 Pre-dose concentration is the observed plasma concentration that is just prior to the beginning of, or at the end of a dosing interval.
Trial Locations
- Locations (1)
Novartis Investigative Site
🇨🇴Floridablanca, Colombia