Prospective Study of Benznidazole for Chagas' Disease Children With Chronic Indeterminate Chagas Disease
Primary Purpose
Chagas Disease
Status
Active
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Benznidazole
Sponsored by
About this trial
This is an interventional treatment trial for Chagas Disease
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
Sites / Locations
- Hospital de Ninos "Dr. Ricardo Gutierrez"
- Hospital "Luis Carlos Lagomaggiore"
- Hospital Pediatrico "Dr. Humberto Notti"
- Hospital Público Descentralizado Dr. Guillermo Rawson
- Centro de Enfermedad de Chagas y Patologías Regionales
- Antigua Hospital Viedma
- CEADES - Plataforma de Chagas Sucre
- Fundación Salud para el Trópico
- Centro de Atención e Investigación Médica (CAIMED)
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Benznidazole
Arm Description
Benznidazole 100 mg Tablets or Benznidazole 12.5 mg Tablets by mouth, every 12 hours for 60 days
Outcomes
Primary Outcome Measures
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
Secondary Outcome Measures
Serological Cure by Conventional ELISA at different timepoints
Percentage of patients with negative conventional ELISA results as a measure of serological cure
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
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
Serological Cure by three serology tests at different timepoints
Percentage of patients with three negative serology results as a measure of serological cure
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
Cure by qPCR at different timepoints
Consistently negative quantitative polymerase chain reaction (qPCR) results as a surrogate measure of cure
Serological titres reduction at different timepoints
Reduction of conventional and nonconventional serological titres over the period of follow-up
Progression of clinical disease at different timepoints
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
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
Percentage of patients with no evidence of established cardiomyopathy over the period of follow-up and seroconversion to negative by two assay
Full Information
NCT ID
NCT04024163
First Posted
July 14, 2019
Last Updated
August 8, 2023
Sponsor
Insud Pharma
Collaborators
Chemo Research
1. Study Identification
Unique Protocol Identification Number
NCT04024163
Brief Title
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
2. Study Status
Record Verification Date
August 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
September 19, 2019 (Actual)
Primary Completion Date
August 30, 2027 (Anticipated)
Study Completion Date
March 30, 2028 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Insud Pharma
Collaborators
Chemo Research
4. Oversight
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
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Chagas Disease
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Single Group Assignment
Model Description
Historical control-based comparison, single-arm assignment, multicentre study
Masking
None (Open Label)
Allocation
N/A
Enrollment
178 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Benznidazole
Arm Type
Experimental
Arm Description
Benznidazole 100 mg Tablets or Benznidazole 12.5 mg Tablets by mouth, every 12 hours for 60 days
Intervention Type
Drug
Intervention Name(s)
Benznidazole
Other Intervention Name(s)
National Drug Code (NDC) 0642-7464-10, National Drug Code (NDC) 0642-7464-12
Intervention Description
Drug: Benznidazole Tablets 100 mg (functionally scored) or Tablets 12.5 mg
Primary Outcome Measure Information:
Title
Serological Cure by Conventional ELISA
Description
Percentage of patients with negative conventional ELISA results as a measure of serological cure at the end of the 72-month follow up
Time Frame
72-month follow up
Secondary Outcome Measure Information:
Title
Serological Cure by Conventional ELISA at different timepoints
Description
Percentage of patients with negative conventional ELISA results as a measure of serological cure
Time Frame
Day 60 (EOT), and 4, 6, 12, 24, 36, 48, 60, and 72 months of follow-up
Title
Serological Cure by two conventional serology tests at 72 month
Description
Percentage of patients with two negative conventional serology results as a measure of serological cure
Time Frame
72 months of follow-up
Title
Serological Cure by two conventional serology tests at 48 months
Description
Percentage of patients with two negative conventional serology results as a measure of serological cure
Time Frame
48 months of follow-up
Title
Serological Cure by three serology tests at different timepoints
Description
Percentage of patients with three negative serology results as a measure of serological cure
Time Frame
Day 60 (EOT), and 4, 6, 12, 24, 36, 48, 60, and 72 months of follow-up
Title
Serological Cure by Non-Conventional ELISA at different timepoints
Description
Percentage of patients with negative non-conventional ELISA (F29) results as a measure of serological cure
Time Frame
Day 60 (EOT), and 4, 6, 12, 24, 36, 48, 60, and 72 months of follow-up
Title
Cure by qPCR at different timepoints
Description
Consistently negative quantitative polymerase chain reaction (qPCR) results as a surrogate measure of cure
Time Frame
Day 60 (EOT), and 4, 6, 12, 24, 36, 48, 60, and 72 months of follow-up
Title
Serological titres reduction at different timepoints
Description
Reduction of conventional and nonconventional serological titres over the period of follow-up
Time Frame
Day 60 (EOT), and 4, 6, 12, 24, 36, 48, 60, and 72 months of follow-up
Title
Progression of clinical disease at different timepoints
Description
Percentage of patients with progression to clinical disease over the period of follow-up
Time Frame
Day 60 (EOT), and 4, 6, 12, 24, 36, 48, 60, and 72 months of follow-up
Title
Progression of clinical disease and serological cure by one assay at different timepoints
Description
Percentage of patients with no evidence of established cardiomyopathy over the period of follow-up and seroconversion to negative by one assay
Time Frame
48 and 72 months of follow-up
Title
Progression of clinical disease and serological cure by two assays at different timepoints
Description
Percentage of patients with no evidence of established cardiomyopathy over the period of follow-up and seroconversion to negative by two assay
Time Frame
48 and 72 months of follow-up
Other Pre-specified Outcome Measures:
Title
Safety and Tolerability
Description
Rate and severity of adverse events (AEs)
Time Frame
Day 60 (EOT), and 4, 6, 12, 24, 36, 48, 60, and 72 months of follow-up
Title
Population Pharmacokinetic - blood concentration
Description
Benznidazole blood concentrations
Time Frame
pre-dose, day 7 and day 30
Title
Population Pharmacokinetic - area under the curve (AUC)
Description
Benznidazole area under the curve (AUC)
Time Frame
pre-dose, day 7 and day 30
Title
Population Pharmacokinetic - volume of distribution
Description
Benznidazole volume of distribution
Time Frame
pre-dose, day 7 and day 30
Title
Intensive Pharmacokinetic - blood concentrations
Description
Benznidazole blood concentrations
Time Frame
Day 1 or day 7
Title
Intensive Pharmacokinetic - area under the curve (AUC)
Description
Benznidazole area under the curve (AUC)
Time Frame
Day 1 or day 7
10. Eligibility
Sex
All
Minimum Age & Unit of Time
2 Years
Maximum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Facility Information:
Facility Name
Hospital de Ninos "Dr. Ricardo Gutierrez"
City
Ciudad Autónoma de Buenos Aires
Country
Argentina
Facility Name
Hospital "Luis Carlos Lagomaggiore"
City
Mendoza
Country
Argentina
Facility Name
Hospital Pediatrico "Dr. Humberto Notti"
City
Mendoza
Country
Argentina
Facility Name
Hospital Público Descentralizado Dr. Guillermo Rawson
City
San Juan
Country
Argentina
Facility Name
Centro de Enfermedad de Chagas y Patologías Regionales
City
Santiago Del Estero
Country
Argentina
Facility Name
Antigua Hospital Viedma
City
Cochabamba
Country
Bolivia
Facility Name
CEADES - Plataforma de Chagas Sucre
City
Sucre
Country
Bolivia
Facility Name
Fundación Salud para el Trópico
City
Santa Marta
Country
Colombia
Facility Name
Centro de Atención e Investigación Médica (CAIMED)
City
Yopal
Country
Colombia
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Prospective Study of Benznidazole for Chagas' Disease Children With Chronic Indeterminate Chagas Disease
We'll reach out to this number within 24 hrs