Resumen

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.

Descripción detallada

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.

Elegibilidad

Edad mínima: 18 YearsEdad máxima: 60 YearsSexo: ALL

Criterios de inclusión

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

Criterios de exclusión

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
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):
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
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 benznidazole in the blinded arms is prohibited until unblinding occurs after all participants complete Month 12.
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

Ubicaciones

Novartis Investigative Site

CABA, Buenos Aires, Argentina

RECRUITING

Novartis Investigative Site

CABA, Buenos Aires, Argentina

RECRUITING

Novartis Investigative Site

Corrientes, Argentina

RECRUITING

Novartis Investigative Site

Córdoba, Argentina

RECRUITING

Novartis Investigative Site

Formosa, Argentina

RECRUITING

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.

Resumen

Descripción detallada

Elegibilidad

Criterios de inclusión

Criterios de exclusión

Intervenciones

LXE408

Placebo

Benznidazole

Ubicaciones

Novartis Investigative Site

Novartis Investigative Site

Novartis Investigative Site

Novartis Investigative Site

Novartis Investigative Site

Patrocinadores

Contactos

Novartis Pharmaceuticals

Novartis Pharmaceuticals