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

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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Chagas Disease
• Intervention / Treatment: Drug: Benznidazole

• Study Type: Interventional
• Enrollment (Actual): 178
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Enrico Colli, MD; Phone Number: 0034-913-021-560; Email: enrico.colli@exeltis.com

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 years to 18 years (Child, Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Benznidazole; Benznidazole 100 mg Tablets or Benznidazole 12.5 mg Tablets by mouth, every 12 hours for 60 days	Drug: Benznidazole; Drug: Benznidazole Tablets 100 mg (functionally scored) or Tablets 12.5 mg; Other Names: National Drug Code (NDC) 0642-7464-10; National Drug Code (NDC) 0642-7464-12

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
Population Pharmacokinetic - blood concentration	Benznidazole blood concentrations	pre-dose, day 7 and day 30
Population Pharmacokinetic - area under the curve (AUC)	Benznidazole area under the curve (AUC)	pre-dose, day 7 and day 30
Population Pharmacokinetic - volume of distribution	Benznidazole volume of distribution	pre-dose, day 7 and day 30
Intensive Pharmacokinetic - blood concentrations	Benznidazole blood concentrations	Day 1 or day 7
Intensive Pharmacokinetic - area under the curve (AUC)	Benznidazole area under the curve (AUC)	Day 1 or day 7

Collaborators and Investigators

• Sponsor: Insud Pharma
• Collaborators: Chemo Research

Study record dates

Study Major Dates

• Study Start (Actual): September 19, 2019
• Primary Completion (Estimated): August 30, 2027
• Study Completion (Estimated): March 30, 2028

Study Registration Dates

• First Submitted: July 14, 2019
• First Submitted That Met QC Criteria: July 16, 2019
• First Posted (Actual): July 18, 2019

Study Record Updates

• Last Update Posted (Actual): August 14, 2023
• Last Update Submitted That Met QC Criteria: August 8, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infections; Vector Borne Diseases; Parasitic Diseases; Protozoan Infections; Trypanosomiasis; Euglenozoa Infections; Chagas Disease; Physiological Effects of Drugs; Anti-Infective Agents; Immunosuppressive Agents; Immunologic Factors; Antiprotozoal Agents; Antiparasitic Agents; Trypanocidal Agents; Benzonidazole
• Other Study ID Numbers: LPRI747-301

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes