A Study of Efficacy, Safety, Tolerability of LXE408 in Participants With Chronic Chagas Disease.

NCT06632600 | Recruiting Phase 2 FDA Drug

• 1 other identifier: CLXE408B12201
• Study Type: interventional
• Target: 130
• Locations: 4 countries
• Sites: 19

Brief Summary

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.

Conditions

Chagas Disease

Keywords

LXE408; Chronic Chagas disease; Chronic indeterminate Chagas disease; Chronic Chagas disease without severe organ dysfunction; CICD; Chronic CD; Trypanosoma cruzi

Outcome Measures

Primary Outcomes (1)

• Presence 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.

  At Months 2, 4, and 6

Secondary Outcomes (13)

• 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

• 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

• Presence or absence of early parasitological clearance

  At Day 7, 14 and 28

• Presence or absence of sustained parasitological clearance over 12 months by PCR testing

  12 Months

• Time to parasitological clearance based on serial PCR testing

  12 Months

Study Arms (4)

LXE408 28 days

EXPERIMENTAL

LXE408 administered by oral route

Drug: LXE408

LXE408 14 days and Placebo 14 days

EXPERIMENTAL

LXE408 administered by oral route, followed by Placebo administered by oral route

Drug: LXE408; Drug: Placebo

Placebo 28 days

PLACEBO COMPARATOR

Placebo administered by oral route

Drug: Placebo

Benznidazole 60 days

ACTIVE COMPARATOR

Benznidazole administered by oral route

Drug: Benznidazole

Interventions

LXE408 DRUG

LXE408 administered by oral route

LXE408 14 days and Placebo 14 days; LXE408 28 days

Placebo DRUG

Placebo administered by oral route

LXE408 14 days and Placebo 14 days; Placebo 28 days

Benznidazole DRUG

Benznidazole administered by oral route (administered as standard of care)

Benznidazole 60 days

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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 \<60 mL/min (\<0.835 mL/s) using the CKD-EPI formula for adults

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (19)

Olive View UCLA Educ and Res Ins

Sylmar, California, 91342, United States

RECRUITING

University of Florida Shands

Gainesville, Florida, 32610-0486, United States

RECRUITING

Boston Medical Center

Boston, Massachusetts, 02118, United States

RECRUITING

Baylor College of Medicine

Houston, Texas, 77030-3411, United States

RECRUITING

Novartis Investigative Site

CABA, Buenos Aires, 1407, Argentina

RECRUITING

Novartis Investigative Site

CABA, Buenos Aires, C1221ADC, Argentina

RECRUITING

Novartis Investigative Site

Corrientes, W3400CDS, Argentina

RECRUITING

Novartis Investigative Site

Córdoba, X5016KEH, Argentina

RECRUITING

Novartis Investigative Site

Formosa, P3600KGC, Argentina

RECRUITING

Novartis Investigative Site

Montes Claros, Minas Gerais, 39401-001, Brazil

RECRUITING

Novartis Investigative Site

Recife, Pernambuco, 50100-060, Brazil

RECRUITING

Novartis Investigative Site

Rio de Janeiro, Rio de Janeiro, 21040-360, Brazil

RECRUITING

Novartis Investigative Site

São Caetano do Sul, São Paulo, 09521-160, Brazil

RECRUITING

Novartis Investigative Site

Barranquilla, Atlántico, 080005, Colombia

RECRUITING

Novartis Investigative Site

Yopal, Casanare Department, 850009, Colombia

RECRUITING

Novartis Investigative Site

Bogotá, 110131, Colombia

RECRUITING

Novartis Investigative Site

Bogotá, 111411, Colombia

RECRUITING

Novartis Investigative Site

Floridablanca, 681017, Colombia

RECRUITING

Novartis Investigative Site

San Gil, 684031, Colombia

RECRUITING

MeSH Terms

Conditions

Chagas Disease

Interventions

LXE408; benzonidazole

Condition Hierarchy (Ancestors)

Trypanosomiasis; Euglenozoa Infections; Protozoan Infections; Parasitic Diseases; Infections; Vector Borne Diseases

Central Study Contacts

Novartis Pharmaceuticals

CONTACT

1-888-669-6682; novartis.email@novartis.com

Novartis Pharmaceuticals

CONTACT

+41613241111

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: The benznidazole arm is open-label. For the LXE and placebo arms: Participants, investigator, staff, and persons performing the assessments will remain blinded to the identity of the treatment from the time of randomization until 12 month database lock for blinded arms. The sponsor clinical trial team (CTT) will be blinded until the primary endpoint analysis (when all participants complete 6 month visit) and may become unblinded as needed at any other interim analysis.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 7, 2024
• First Posted: October 9, 2024
• Study Start: April 28, 2025
• Primary Completion (Estimated): March 22, 2027
• Study Completion (Estimated): September 21, 2030
• Last Updated: March 30, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share

Locations

AR (5); US (4); BR (4); CO (6)