Chagas Disease
Conditions
Brief summary
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.
Interventions
DRUGBenznidazole
Drug: Benznidazole Tablets 100 mg (functionally scored) or Tablets 12.5 mg
Sponsors
Chemo Research
Insud Pharma
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Historical control-based comparison, single-arm assignment, multicentre study
Eligibility
Sex/Gender
ALL
Age
2 Years to 18 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Serological Cure by Conventional ELISA | 72-month follow up | Percentage of patients with negative conventional ELISA results as a measure of serological cure at the end of the 72-month follow up |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Serological Cure by two conventional serology tests at 48 months | 48 months of follow-up | Percentage of patients with two negative conventional serology results as a measure of serological cure |
| Serological Cure by Non-Conventional ELISA at different timepoints | Day 60 (EOT), and 4, 6, 12, 24, 36, 48, 60, and 72 months of follow-up | Percentage of patients with negative non-conventional ELISA (F29) results as a measure of serological cure |
| Cure by qPCR at different timepoints | Day 60 (EOT), and 4, 6, 12, 24, 36, 48, 60, and 72 months of follow-up | Consistently negative quantitative polymerase chain reaction (qPCR) results as a surrogate measure of cure |
| Serological titres reduction at different timepoints | Day 60 (EOT), and 4, 6, 12, 24, 36, 48, 60, and 72 months of follow-up | Reduction of conventional and nonconventional serological titres over the period of follow-up |
| Progression of clinical disease at different timepoints | Day 60 (EOT), and 4, 6, 12, 24, 36, 48, 60, and 72 months of follow-up | Percentage of patients with progression to clinical disease over the period of follow-up |
| Progression of clinical disease and serological cure by one assay at different timepoints | 48 and 72 months of follow-up | Percentage of patients with no evidence of established cardiomyopathy over the period of follow-up and seroconversion to negative by one assay |
| Progression of clinical disease and serological cure by two assays at different timepoints | 48 and 72 months of follow-up | Percentage of patients with no evidence of established cardiomyopathy over the period of follow-up and seroconversion to negative by two assay |
| Serological Cure by Conventional ELISA at different timepoints | Day 60 (EOT), and 4, 6, 12, 24, 36, 48, 60, and 72 months of follow-up | Percentage of patients with negative conventional ELISA results as a measure of serological cure |
| Serological Cure by two conventional serology tests at 72 month | 72 months of follow-up | Percentage of patients with two negative conventional serology results as a measure of serological cure |
| Serological Cure by three serology tests at different timepoints | Day 60 (EOT), and 4, 6, 12, 24, 36, 48, 60, and 72 months of follow-up | Percentage of patients with three negative serology results as a measure of serological cure |
Other
| Measure | Time frame | Description |
|---|---|---|
| Population Pharmacokinetic - area under the curve (AUC) | pre-dose, day 7 and day 30 | Benznidazole area under the curve (AUC) |
| Population Pharmacokinetic - volume of distribution | pre-dose, day 7 and day 30 | Benznidazole volume of distribution |
| Intensive Pharmacokinetic - blood concentrations | Day 1 or day 7 | Benznidazole blood concentrations |
| Intensive Pharmacokinetic - area under the curve (AUC) | Day 1 or day 7 | Benznidazole area under the curve (AUC) |
| Safety and Tolerability | Day 60 (EOT), and 4, 6, 12, 24, 36, 48, 60, and 72 months of follow-up | Rate and severity of adverse events (AEs) |
| Population Pharmacokinetic - blood concentration | pre-dose, day 7 and day 30 | Benznidazole blood concentrations |
Countries
Argentina, Bolivia, Colombia
Outcome results
None listed