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.
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 130
- 试验地点
- 26
- 主要终点
- Presence or absence of sustained parasitological clearance using polymerase chain reaction (PCR) results over 6 months - LXE408 28 days versus placebo.
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
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.
入排标准
- 年龄范围
- 18 Years 至 60 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
- •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.
研究组 & 干预措施
Placebo 28 days
Placebo administered by oral route
干预措施: Placebo (Drug)
Benznidazole 60 days
Benznidazole administered by oral route
干预措施: Benznidazole (Drug)
LXE408 28 days
LXE408 administered by oral route
LXE408 14 days and Placebo 14 days
LXE408 administered by oral route, followed by Placebo administered by oral route
干预措施: LXE408 (Drug)
LXE408 14 days and Placebo 14 days
LXE408 administered by oral route, followed by Placebo administered by oral route
干预措施: Placebo (Drug)
结局指标
主要结局
Presence or absence of sustained parasitological clearance using polymerase chain reaction (PCR) results over 6 months - LXE408 28 days versus placebo.
时间窗: At Months 2, 4, and 6
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.
次要结局
- Maximum plasma concentration (Cmax) of LXE408(At Day 1, 7, 14, 28)
- Time to maximum plasma concentration (Tmax) of LXE408(At Day 1, 7, 14, 28)
- 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 seroreversion using conventional serology(At Month 6 and Month 12)
- Occurrence of adverse events resulting in treatment discontinuation(Up to 12 Months)
- Area under the plasma concentration-time curve from time 0 to 8 hours post-dose (AUC0-8)(At Day 1, 7, 14, 28)
- Pre-dose concentration(At Day 14 and Day 28)
- Occurrence and severity of treatment emergent adverse events during the study(Up to 12 Months)
- 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)
- Occurrence of all-cause mortality through end of study visit(Up to 48 Months)