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

Chagas Disease Clinical Trial

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04024163
• Other study ID #: LPRI747-301
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: September 19, 2019
• Est. completion date: March 30, 2028

Study information

• Verified date: August 2023
• Source: Insud Pharma
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 178
• Est. completion date: March 30, 2028
• Est. primary completion date: August 30, 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 2 Years to 18 Years

Eligibility

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

Related Conditions & MeSH terms

• Chagas Disease

Intervention

Drug:
• Benznidazole
Drug: Benznidazole Tablets 100 mg (functionally scored) or Tablets 12.5 mg

Locations

Country	Name	City	State
Argentina	Hospital de Ninos "Dr. Ricardo Gutierrez"	Ciudad Autónoma de Buenos Aires
Argentina	Hospital "Luis Carlos Lagomaggiore"	Mendoza
Argentina	Hospital Pediatrico "Dr. Humberto Notti"	Mendoza
Argentina	Hospital Público Descentralizado Dr. Guillermo Rawson	San Juan
Argentina	Centro de Enfermedad de Chagas y Patologías Regionales	Santiago Del Estero
Bolivia	Antigua Hospital Viedma	Cochabamba
Bolivia	CEADES - Plataforma de Chagas Sucre	Sucre
Colombia	Fundación Salud para el Trópico	Santa Marta
Colombia	Centro de Atención e Investigación Médica (CAIMED)	Yopal

Sponsors (2)

Lead Sponsor	Collaborator
Insud Pharma	Chemo Research

Countries where clinical trial is conducted

Argentina,  Bolivia,  Colombia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Safety and Tolerability	Rate and severity of adverse events (AEs)	Day 60 (EOT), and 4, 6, 12, 24, 36, 48, 60, and 72 months of follow-up
Other	Population Pharmacokinetic - blood concentration	Benznidazole blood concentrations	pre-dose, day 7 and day 30
Other	Population Pharmacokinetic - area under the curve (AUC)	Benznidazole area under the curve (AUC)	pre-dose, day 7 and day 30
Other	Population Pharmacokinetic - volume of distribution	Benznidazole volume of distribution	pre-dose, day 7 and day 30
Other	Intensive Pharmacokinetic - blood concentrations	Benznidazole blood concentrations	Day 1 or day 7
Other	Intensive Pharmacokinetic - area under the curve (AUC)	Benznidazole area under the curve (AUC)	Day 1 or day 7
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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