Prospective Study of Benznidazole for Chagas' Disease Children With Chronic Indeterminate Chagas Disease

Study Overview
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Brief Summary
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This study evaluate the efficacy and safety of benznidazole in the treatment of chronic indeterminate Chagas disease in children. All subjects will receive benznidazole and results will be compared to historically to a placebo arm.

Official Title
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Prospective, Single-arm, Multicentre Study, Using a Historical Control, to Evaluate the Efficacy/Safety and Population Pharmacokinetics of Benznidazole in Children With Chronic Indeterminate Chagas Disease

Conditions
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Chagas Disease

Intervention / Treatment
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* Drug: Benznidazole


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age between 2 years and 18 years (age limits inclusive) Diagnosis of Trypanosoma cruzi (T. cruzi) infection by conventional serology based on positive ELISA and at least 1 other positive conventional serology test (recombinant ELISA or IIF) Written informed consent by parent/legal representative and informed assent from patients if >7 years old when applicable (as requirements may vary by country and by site) Females of childbearing potential (ie, female patients who have experienced menarche) and male patients must agree to use highly effective contraception if sexually active from the time of signing of the informed consent/assent form until ≥5 days after the last dose of study treatment Exclusion Criteria: Pregnant or intending to become pregnant during treatment and within 5 days after the last dose of study treatment Patient presenting any other acute or chronic health conditions, which in the opinion of the Principal Investigator (PI), may interfere with the pharmacokinetic (PK), efficacy, and/or safety evaluation of the study treatment Signs and/or symptoms of acute Chagas Disease Known history of hypersensitivity or serious adverse reactions to nitroimidazoles History of Chagas Disease treatment with Benznidazole (BZN) or nifurtimox Immunocompromised (clinical history compatible with human immunodeficiency virus (HIV) infection, primary immunodeficiency, or prolonged treatment with corticosteroids or other immunosuppressive drugs) Abnormal laboratory test values (as per protocol-specified ranges) at Screening for the following parameters: total white blood cell (WBC) count, platelet count, alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin, and creatinine Abnormal ECG (as per protocol-specified ranges) and/or any Chagas disease associated findings Any condition that prevents the patient from taking oral medication Patient is known to or suspected of not being able to comply with the study protocol and the use of the investigational medicinal product (IMP) Evidence or history of alcohol or drug abuse (within the last 12 months) Any planned procedure that may interfere with highly effective contraception during treatment and within 5 days after the last dose of study treatment Employee of the Investigator or trial centre, or family member of the employees or the Investigator Any condition that, in the opinion of the Investigator, may jeopardise the trial conduct according to the protocol

Ages Eligible for Study
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Minimum Age: 2 Years
Maximum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: Historical control-based comparison, single-arm assignment, multicentre study
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Benznidazole<br>Benznidazole 100 mg Tablets or Benznidazole 12.5 mg Tablets by mouth, every 12 hours for 60 days | Drug: Benznidazole<br>* Drug: Benznidazole Tablets 100 mg (functionally scored) or Tablets 12.5 mg<br>* Other names: National Drug Code (NDC) 0642-7464-12;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Serological Cure by Conventional ELISA | Percentage of patients with negative conventional ELISA results as a measure of serological cure at the end of the 72-month follow up | 72-month follow up | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Serological Cure by Conventional ELISA at different timepoints | Percentage of patients with negative conventional ELISA results as a measure of serological cure | Day 60 (EOT), and 4, 6, 12, 24, 36, 48, 60, and 72 months of follow-up | 
| Serological Cure by two conventional serology tests at 72 month | Percentage of patients with two negative conventional serology results as a measure of serological cure | 72 months of follow-up | 
| Serological Cure by two conventional serology tests at 48 months | Percentage of patients with two negative conventional serology results as a measure of serological cure | 48 months of follow-up | 
| Serological Cure by three serology tests at different timepoints | Percentage of patients with three negative serology results as a measure of serological cure | Day 60 (EOT), and 4, 6, 12, 24, 36, 48, 60, and 72 months of follow-up | 
| Serological Cure by Non-Conventional ELISA at different timepoints | Percentage of patients with negative non-conventional ELISA (F29) results as a measure of serological cure | Day 60 (EOT), and 4, 6, 12, 24, 36, 48, 60, and 72 months of follow-up | 
| Cure by qPCR at different timepoints | Consistently negative quantitative polymerase chain reaction (qPCR) results as a surrogate measure of cure | Day 60 (EOT), and 4, 6, 12, 24, 36, 48, 60, and 72 months of follow-up | 
| Serological titres reduction at different timepoints | Reduction of conventional and nonconventional serological titres over the period of follow-up | Day 60 (EOT), and 4, 6, 12, 24, 36, 48, 60, and 72 months of follow-up | 
| Progression of clinical disease at different timepoints | Percentage of patients with progression to clinical disease over the period of follow-up | Day 60 (EOT), and 4, 6, 12, 24, 36, 48, 60, and 72 months of follow-up | 
| Progression of clinical disease and serological cure by one assay at different timepoints | Percentage of patients with no evidence of established cardiomyopathy over the period of follow-up and seroconversion to negative by one assay | 48 and 72 months of follow-up | 
| Progression of clinical disease and serological cure by two assays at different timepoints | Percentage of patients with no evidence of established cardiomyopathy over the period of follow-up and seroconversion to negative by two assay | 48 and 72 months of follow-up |