Clinical trial NCT04024163: Prospective Study of Benznidazole for Chagas' Disease Children With Chronic Indeterminate Chagas Disease
Official title: 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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Chagas Disease
Lead sponsor: Insud Pharma
Sponsor class: INDUSTRY
Collaborators: name: Chemo Research
First posted: 2019-07-18
Enrollment: 178
Sex: ALL
Minimum age (years): 2
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Historical control-based comparison, single-arm assignment, multicentre study
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Serological Cure by Conventional ELISA
timeFrame: 72-month follow up
Secondary outcomes:
measure: Serological Cure by Conventional ELISA at different timepoints
timeFrame: Day 60 (EOT), and 4, 6, 12, 24, 36, 48, 60, and 72 months of follow-up
measure: Serological Cure by two conventional serology tests at 72 month
timeFrame: 72 months of follow-up
measure: Serological Cure by two conventional serology tests at 48 months
timeFrame: 48 months of follow-up
measure: Serological Cure by three serology tests at different timepoints
timeFrame: Day 60 (EOT), and 4, 6, 12, 24, 36, 48, 60, and 72 months of follow-up
measure: Serological Cure by Non-Conventional ELISA at different timepoints
timeFrame: Day 60 (EOT), and 4, 6, 12, 24, 36, 48, 60, and 72 months of follow-up
measure: Cure by qPCR at different timepoints
timeFrame: Day 60 (EOT), and 4, 6, 12, 24, 36, 48, 60, and 72 months of follow-up
measure: Serological titres reduction at different timepoints
timeFrame: Day 60 (EOT), and 4, 6, 12, 24, 36, 48, 60, and 72 months of follow-up
measure: Progression of clinical disease at different timepoints
timeFrame: Day 60 (EOT), and 4, 6, 12, 24, 36, 48, 60, and 72 months of follow-up
measure: Progression of clinical disease and serological cure by one assay at different timepoints
timeFrame: 48 and 72 months of follow-up
measure: Progression of clinical disease and serological cure by two assays at different timepoints
timeFrame: 48 and 72 months of follow-up
Other outcomes:
measure: Safety and Tolerability
timeFrame: Day 60 (EOT), and 4, 6, 12, 24, 36, 48, 60, and 72 months of follow-up
measure: Population Pharmacokinetic - blood concentration
timeFrame: pre-dose, day 7 and day 30
measure: Population Pharmacokinetic - area under the curve (AUC)
timeFrame: pre-dose, day 7 and day 30
measure: Population Pharmacokinetic - volume of distribution
timeFrame: pre-dose, day 7 and day 30
measure: Intensive Pharmacokinetic - blood concentrations
timeFrame: Day 1 or day 7
measure: Intensive Pharmacokinetic - area under the curve (AUC)
timeFrame: Day 1 or day 7
Locations:
city: Ciudad Autónoma de Buenos Aires
country: Argentina
facility: Hospital de Ninos "Dr. Ricardo Gutierrez"
city: Mendoza
country: Argentina
facility: Hospital "Luis Carlos Lagomaggiore"
city: Mendoza
country: Argentina
facility: Hospital Pediatrico "Dr. Humberto Notti"
city: San Juan
country: Argentina
facility: Hospital Público Descentralizado Dr. Guillermo Rawson
city: Santiago Del Estero
country: Argentina
facility: Centro de Enfermedad de Chagas y Patologías Regionales
city: Cochabamba
country: Bolivia
facility: Antigua Hospital Viedma
city: Sucre
country: Bolivia
facility: CEADES - Plataforma de Chagas Sucre
city: Santa Marta
country: Colombia
facility: Fundación Salud para el Trópico
city: Yopal
country: Colombia
facility: Centro de Atención e Investigación Médica (CAIMED)
Study officials:
References: