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

Официальное название

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.

Обзор

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.

Подробное описание

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.

Вмешательства

• Препарат LXE408
  LXE408 administered by oral route
• Препарат Placebo
  Placebo administered by oral route
• Препарат Benznidazole
  Benznidazole administered by oral route (administered as standard of care)

Первичные конечные точки

• Presence or absence of sustained parasitological clearance using polymerase chain reaction (PCR) results over 6 months - LXE408 28 days versus placebo. [Срок оценки: At Months 2, 4, and 6]

Вторичные конечные точки (12)

• Presence or absence of sustained parasitological clearance using polymerase chain reaction (PCR) results over 6 months - LXE408 -14 days versus placebo [Срок оценки: 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 [Срок оценки: At Months 2, 4, and 6]
• Presence or absence of early parasitological clearance [Срок оценки: At Day 7, 14 and 28]
• Presence or absence of sustained parasitological clearance over 12 months by PCR testing [Срок оценки: 12 Months]
• Time to parasitological clearance based on serial PCR testing [Срок оценки: 12 Months]
• Presence or absence of seroreversion using conventional serology [Срок оценки: At Month 6 and Month 12]
• Occurrence and severity of treatment emergent adverse events during the study [Срок оценки: Up to 12 Months]
• Occurrence of adverse events resulting in treatment discontinuation [Срок оценки: Up to 12 Months]
• Occurrence of all-cause mortality through end of study visit [Срок оценки: Up to 48 Months]
• Maximum plasma concentration (Cmax) of LXE408 [Срок оценки: At Day 1, 7, 14, 28]
• Time to maximum plasma concentration (Tmax) of LXE408 [Срок оценки: At Day 1, 7, 14, 28]
• Area under the plasma concentration-time curve from time 0 to 8 hours post-dose (AUC0-8) [Срок оценки: At Day 1, 7, 14, 28]

Критерии участия

Критерии включения

• 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

Критерии исключения

• 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

• 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

Other protocol-defined inclusion/exclusion criteria may apply.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Четверное слепое

Основная цель

Лечение

Центры проведения

Аргентина · 6 центров

• Novartis Investigative Site — CABA
• Novartis Investigative Site — CABA
• Novartis Investigative Site — Córdoba
• Novartis Investigative Site — Caba
• Novartis Investigative Site — Corrientes
• Novartis Investigative Site — Formosa

Колумбия · 6 центров

• Novartis Investigative Site — Barranquilla
• Novartis Investigative Site — Yopal
• Novartis Investigative Site — Bogotá
• Novartis Investigative Site — Bogotá
• Novartis Investigative Site — Floridablanca
• Novartis Investigative Site — San Gil

США · 4 центра

• Olive View UCLA Educ and Res Ins — Sylmar
• University of Florida Shands — Gainesville
• Boston Medical Center — Boston
• Baylor College of Medicine — Houston

Бразилия · 4 центра

• Novartis Investigative Site — Montes Claros
• Novartis Investigative Site — Recife
• Novartis Investigative Site — Rio de Janeiro
• Novartis Investigative Site — São Caetano do Sul

Идентификаторы

NCT: NCT06632600 · CLXE408B12201

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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