A study of efficacy, safety, tolerability of LXE408 in participants with chronic Chagas disease

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.

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.

• Participants with controlled HIV on antiretroviral therapy are eligible to participate if CD4 ≥ 500 at screening

• 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, 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 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