Clinical trial NCT06632600: A Study of Efficacy, Safety, Tolerability of LXE408 in Participants With Chronic Chagas Disease.
Official title: A Randomized, Participant- and Investigator-blinded, Controlled, Parallel Group Study to Assess the Efficacy, Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of LXE408 in Participants With Chronic Chagas Disease Without Severe Organ Dysfunction.
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Chagas Disease
Keywords: LXE408
Chronic Chagas disease
Chronic indeterminate Chagas disease
Chronic Chagas disease without severe organ dysfunction
CICD
Chronic CD
Trypanosoma cruzi
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2024-10-09
Enrollment: 130
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: 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.

Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* Signs (on physical examination) and/or symptoms of CD in the acute phase as determined by the investigator at screening
* History of CD treatment with benznidazole or nifurtimox at any time in the past
* History of and/or current (at screening) symptoms or signs (physical examination findings) of moderate or severe CD-related gastrointestinal disease
* Participants who weigh \< 50 kg or \>90kg at screening
* 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
* 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
* 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
* 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
* 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)
* 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.

Primary outcomes:
measure: Presence or absence of sustained parasitological clearance using polymerase chain reaction (PCR) results over 6 months - LXE408 28 days versus placebo.
timeFrame: At Months 2, 4, and 6
Secondary outcomes:
measure: Presence or absence of sustained parasitological clearance using polymerase chain reaction (PCR) results over 6 months - LXE408 -14 days versus placebo
timeFrame: At Months 2, 4, and 6
measure: Presence or absence of sustained parasitological clearance using polymerase chain reaction (PCR) results over 6 months-LXE408 - 28 days and 14 days versus benznidazone
timeFrame: At Months 2, 4, and 6
measure: Presence or absence of parasitological clearance
timeFrame: At Day 7, 14 and 28
measure: Presence or absence of sustained parasitological clearance over 12 months by PCR testing
timeFrame: Up to 12 Months
measure: Time to parasitological clearance based on serial PCR testing
timeFrame: Up to 12 Months
measure: Presence or absence of seroreversion using conventional serology
timeFrame: At Month 6 and Month 12
measure: Occurrence and severity of treatment emergent adverse events during the study
timeFrame: Up to 12 Months
measure: Occurrence of adverse events resulting in treatment discontinuation
timeFrame: Up to 12 Months
measure: Occurrence of all-cause mortality through end of study visit
timeFrame: Up to 12 Months
measure: Maximum plasma concentration (Cmax) of LXE408
timeFrame: At Day 1, 7, 14, 28
measure: Time to maximum plasma concentration (Tmax) of LXE408
timeFrame: At Day 1, 7, 14, 28
measure: Area under the plasma concentration-time curve from time 0 to 8 hours post-dose (AUC0-8)
timeFrame: At Day 1, 7, 14, 28
measure: Pre-dose concentration
timeFrame: At Day 14 and Day 28
Other outcomes:
Locations:
city: Caba
country: Argentina
facility: Novartis Investigative Site
state: Buenos Aires
city: Corrientes
country: Argentina
facility: Novartis Investigative Site
city: Barranquilla
country: Colombia
facility: Novartis Investigative Site
state: Atlantico
city: Yopal
country: Colombia
facility: Novartis Investigative Site
state: Casanare
city: Floridablanca
country: Colombia
facility: Novartis Investigative Site
city: San Gil
country: Colombia
facility: Novartis Investigative Site
Study officials:
References: