check_circleStudy Completed

Chagas Disease

Bayer Identifier:

16027

ClinicalTrials.gov Identifier:

NCT02625974

EudraCT Number:

2022-001504-17

EU CT Number:

Not Available
A study to learn how well nifurtimox works and how safe it is in children aged 0 to 17 years with Chagas’ disease, an inflammatory, infectious disease caused by the parasite Trypanosoma cruzi

Trial purpose

Researchers are looking for a better way to treat children who have an infectious disease caused by the parasite Trypanosoma cruzi (Chagas’ disease).
Chagas’disease is an inflammatory, infectious disease caused by the parasite Trypanosoma cruzi. This parasite is mainly spread by insects called triatomine bug. If Chagas’ disease is left untreated, it can later cause serious heart and digestive problems.
The study treatment nifurtimox has been used for more than 50 years to treat Chagas’ disease. When used early after infection, it kills the parasite. In people who have long-term Chagas’ disease, it’s no longer possible to kill the parasite. However, nifurtimox may help slow the progression of the disease and its most serious complications.
Nifurtimox was developed for use in adults only, but has also been used in children (off-label) for over 40 years. Currently it is available for doctors to give to adults and to children. However, there are not enough data about nifurtimox in children.

The main purpose of this study is to learn how well nifurtimox works in children aged 8 months to less than 18 years with Chagas’ disease. To answer this, the researchers will compare the amount of antibodies against the parasite Trypanosoma cruzi in the serum (fluid from blood without the clotting factors) between children treated with nifurtimox for 60 days with untreated children from the past (control group):
•   12 months and
•   4 years
after the end of treatment.
The data for the control group will come from 2 previous studies conducted in children.

Key Participants Requirements

Sex

Both

Age

NaN - 17 Years
  • Part 1:
    - Male and female pediatric subjects aged 0 days to younger than 18 years
    - Chagas’ disease diagnosed/ confirmed for a) Subjects < 8 months of age at randomization must demonstrate direct observation of Trypanosoma cruzi by concentration test; b) Subjects ≥ 8 months to < 18 years of age at randomization must demonstrate a positive conventional ELISA result for both recombinant ELISA and total purified antigen ELISA
    Part 2:
    - Male and female subjects who were randomized and received at least one dose of their assigned 60- or 30-day regimen of nifurtimox treatment
  • Part 1:
    - Subjects aged 0 to 27 days who, at birth, were pre-term, weighed less than 2500 g, or had a maximum Apgar score < 7 at 5 minutes
    - Known evidence of Chagas’ disease-related cardiomyopathy/ Chagas’ heart disease
    - Known evidence of Chagas’ disease-related gastrointestinal dysfunction (e.g. megaoesophagus, megacolon, or both) or Chagas’ digestive disease
    - Serious manifestations of acute Chagas’ disease, including myocarditis, meningoencephalitis, or pneumonitis
    - Known evidence of Chagas’ disease-related damage to the peripheral nervous system or peripheral neuropathy
    - Clinically significant psychiatric disorder (e.g. moderate to severe depression, severe anxiety, or psychosis) or epilepsy
    - Subjects with contraindications/ warnings to nifurtimox administration, or with conditions that may increase the risk of the undesirable effects of nifurtimox
    - Subjects who have had previous treatment with trypanocidal agents or an accepted indication for antiparasitic therapy (e.g. reactivation of Chagas' infection due to immunosuppression by several diseases or treatment with steroids)
    - Subjects living in housing conditions where there is no active or effective vector control to Trypanosoma cruzi reinfection as determined by Ministry of Health guidelines in each country
    Part 2:
    - Subjects with acute or chronic health conditions or congenital disorders which, in the opinion of the investigator, would make them unsuitable for participation in the clinical study
    - Subjects living in housing conditions where there is no active or effective vector-control to Trypanosoma cruzi reinfection as determined by Ministry of Health guideline of the respective country
    - Subjects with clinical manifestations of Chagas’ disease-related gastrointestinal dysfunction or serious manifestations of acute Chagas’ disease
    - Immuno-compromised subjects (e.g. with human immunodeficiency virus or treated with immunosuppressive drugs)

Trial summary

Enrollment Goal
330
Trial Dates
January 2016 - August 2021
Phase
Phase 3
Could I Receive a placebo
Yes
Products
Lampit (Nifurtimox, BAYA2502)
Accepts Healthy Volunteer
No

Where to participate

StatusInstitutionLocation
Completed
Buenos Aires, C1425EFD, Argentina
Withdrawn
Córdoba, X50000JDR, Argentina
Completed
Rosario, 2000, Argentina
Completed
Santiago del Estero, 4202, Argentina
Completed
Buenos Aires, C1270AAN, Argentina
Completed
Mendoza, 5535, Argentina
Completed
Mendoza, 5500, Argentina
Completed
La Plata, 1900, Argentina
Withdrawn
Buenos Aires, 1063, Argentina
Completed
Buenos Aires, C1425AGP, Argentina
Withdrawn
La Plata, 1900, Argentina
Completed
Yopal, Colombia
Completed
Santa Marta, Colombia
Completed
Floridablabca, 681011, Colombia
Completed
Cochabamba, Bolivia,plurinational State Of
Completed
Tarija, Bolivia,plurinational State Of
Withdrawn
Buenos Aires, C1246ABQ, Argentina
Withdrawn
Berazategui, 1884, Argentina
Completed
Salta, A4400ESE, Argentina
Completed
San Salvador de Jujuy, 4600, Argentina
Withdrawn
Buenos Aires, C1408INH, Argentina
Completed
Punata, Bolivia,plurinational State Of
Completed
Salta, 4400, Argentina
Completed
Buenos Aires, 1281, Argentina
Completed
Formosa, P3600HZL, Argentina
Completed
Tucuman, 4000, Argentina
Completed
Soledad, Colombia
Completed
Posadas, Argentina
Completed
San Juan, 5400, Argentina
Completed
La Rioja, Argentina
Completed
Corrientes, W3400CBI, Argentina

Primary Outcome

  • Part 1 - Percentage of sero-reduction or sero-conversion (cured subjects)
    Cure is defined as sero-reduction (in subjects ≥8 months to <18 years of age at randomization) or sero-conversion (in all subjects). Sero-reduction is defined as a ≥20% reduction in optical density [OD]) measured by two conventional ELISA serology tests and sero-conversion is defined as negative Immunoglobulin G (IgG) concentration measured by two conventional ELISA serology tests. Subjects who have missing conventional serology results at the 12 month time point were treated as failures (ie, no cure). For the primary objective in the study, superiority over placebo was confirmed if the lower limit of the 95% Confidence Interval (CI) for the nifurtimox (60-day regimen) cure rate is greater than 16%, the larger of the upper limits of the 95% CIs for historical placebo control.
    date_rangeTime Frame:
    At 12 months post-treatment
  • Part 2 - Incidence rate of seronegative conversion in subjects received at least one dose of the 60-day nifurtimox treatment regimen.
    Seronegative conversion measured by two types of assay (recombinant ELISA and indirect hemagglutination assay [IHA]) in subjects who were randomized and received at least one dose of the 60-day nifurtimox treatment regimen compared to an external control group of historical placebo patients with Chagas’ disease. Incidence rate is the number of new cases of seronegative conversion over the study period (i.e., 4 years after end of nifurtimox treatment) divided by the person-time at risk. It was modelled using a Poisson distribution with a 2-sided 95% exact CI. Number of participants with events were reported.
    date_rangeTime Frame:
    Subjects participating in Part 2 were followed up for another 3 years, for a total follow-up period of 4 years after end of nifurtimox treatment in Part 1

Secondary Outcome

  • Part 1 - Nifurtimox concentration over time in plasma at Visit 2
    Measured in sub-population.
    date_rangeTime Frame:
    At Visit 2 (Day 1): Pre-dose and Post-dose at 5-10 minutes, 10-120 minutes, 2-4 hours, and 4-8 hours
  • Part 1 - Nifurtimox concentration over time in plasma at Visit 3
    Measured in sub-population.
    date_rangeTime Frame:
    At Visit 3 (Day 7): Pre-dose and Post-dose at 5-10 minutes, 10-120 minutes, 2-4 hours, and 4-8 hours
  • Part 1 - Nifurtimox concentration over time in plasma at Visit 6
    The evaluation was based on clinical examinations. Measured in sub-population.
    date_rangeTime Frame:
    At Visit 6 (Day 30): Pre-dose and Post-dose at 5-10 minutes, 10-120 minutes, 2-4 hours, and 4-8 hours
  • Part 1 - Nifurtimox concentration over time in plasma at Visit 8
    Measured in sub-population.
    date_rangeTime Frame:
    At Visit 8 (Day 60): Pre-dose and Post-dose at 5-10 minutes, 10-120 minutes, 2-4 hours, and 4-8 hours
  • Part 2 - Incidence rate of seronegative conversion in subjects who received at least one dose of the 30-day nifurtimox treatment regimen
    Seronegative conversion measured by two types of assay (recombinant ELISA and indirect hemagglutination assay [IHA]) in subjects who were randomized and received at least one dose of the 30-day nifurtimox treatment regimen. Incidence rate is the number of new cases of seronegative conversion over the study period (i.e., 4 years after end of nifurtimox treatment) divided by the person-time at risk. It was modelled using a Poisson distribution with a 2-sided 95% exact CI. Number of participants with events were reported.
    date_rangeTime Frame:
    Subjects participating in Part 2 were followed up for another 3 years, for a total follow-up period of 4 years after end of nifurtimox treatment in Part 1
  • Part 2 - ECG signs of established Chagas-related cardiomyopathy
    Summary of subjects by evidence of established Chagas-related cardiomyopathy as measured by electrocardiogram (ECG). Evidence of established Chagas-related cardiomyopathy: Total
    date_rangeTime Frame:
    Subjects participating in Part 2 were followed up for another 3 years, for a total follow-up period of 4 years after end of nifurtimox treatment in Part 1
    enhanced_encryption
    Safety Issue:
    No
  • Part 2 - Serological response of established Chagas-related cardiomyopathy
    Summary of subjects by evidence of established Chagas-related cardiomyopathy as measured by Serological response. Evidence of established Chagas-related cardiomyopathy: Total
    date_rangeTime Frame:
    Subjects participating in Part 2 were followed up for another 3 years, for a total follow-up period of 4 years after end of nifurtimox treatment in Part 1
    enhanced_encryption
    Safety Issue:
    No
  • Part 1 + Part 2 - Serial reduction of optical density values measured by Total Purified Antigen ELISA
    Summary and change from baseline of optical density values measured by total purified antigen ELISA. Optical density is the measure of absorbance, and is defined as the ratio of the intensity of light falling upon a material and the intensity transmitted.
    date_rangeTime Frame:
    Baseline and Subjects participating in Part 2 were followed up for another 3 years, for a total follow-up period of 4 years after end of nifurtimox treatment in Part 1
  • Part 1 + Part 2 - Serial reduction of optical density values measured by Recombinant ELISA
    Summary and change from baseline of optical density values measured by recombinant ELISA. Optical density is the measure of absorbance, and is defined as the ratio of the intensity of light falling upon a material and the intensity transmitted.
    date_rangeTime Frame:
    Baseline and Subjects participating in Part 2 were followed up for another 3 years, for a total follow-up period of 4 years after end of nifurtimox treatment in Part 1
  • Part 1 - Number of subjects with Clinical signs/ symptoms of Chagas disease at Visit 1
    The evaluation was based on clinical examinations.
    date_rangeTime Frame:
    At Visit 1 (before treatment started)
  • Part 1 - Number of subjects with Clinical signs/ symptoms of Chagas disease at Visit 3
    The evaluation was based on clinical examinations.
    date_rangeTime Frame:
    Up to 7 days (Visit 3)
  • Part 1 - Number of subjects with Clinical signs/ symptoms of Chagas disease at Visit 6
    The evaluation was based on clinical examinations.
    date_rangeTime Frame:
    Up to 30 days (Visit 6)
    enhanced_encryption
    Safety Issue:
    No
  • Part 1 - Number of subjects with Clinical signs/ symptoms of Chagas disease at Visit 8
    The evaluation was based on clinical examinations.
    date_rangeTime Frame:
    Up to 60 days (Visit 8; end of treatment)
  • Part 1 - Number of subjects with Clinical signs/ symptoms of Chagas disease at Visit 9
    The evaluation was based on clinical examinations.
    date_rangeTime Frame:
    Up to 90 days (Visit 9 post-treatment)
  • Part 1 - Number of subjects with Clinical signs/ symptoms of Chagas disease at Visit 10
    The evaluation was based on clinical examinations.
    date_rangeTime Frame:
    Up to 240 days (Visit 10 post-treatment)
  • Part 1 - Number of subjects with Clinical signs/ symptoms of Chagas disease at Visit 11
    The evaluation was based on clinical examinations.
    date_rangeTime Frame:
    Up to 420 days (Visit 11 post-treatment)
  • Part 1 - Number of subjects with positive results in concentration test for T. cruzi (for subjects <8 months of age)
    date_rangeTime Frame:
    Up to 90 days (Visit 9 post-treatment)
  • Part 1 - Number of subjects with a positive serological response using non-conventional enzyme-linked immunosorbent assay-F29 (ELISAF29) test
    The non-conventional ELISA-F29 test is considered an early marker of treatment efficacy in chronic Chagas disease.
    date_rangeTime Frame:
    Up to 420 days (Visit 11 post-treatment)
  • Part 1 - Number of subjects with positive quantitative polymerase chain reaction (qPCR) results
    The qPCR is molecular technique, considered a tool to diagnose acute and congenital Chagas disease, as well as a marker to measure treatment failure when demonstrating positive (detectable) results
    date_rangeTime Frame:
    Up to 420 days (Visit 11 post-treatment)
  • Part 1 - Number of Subjects With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs)
    TEAEs comprised events which first occurred or worsened at or after first application of study drug during the course of the study up to and including 7 days after last application of study drug
    date_rangeTime Frame:
    up to 7 days after last application of study drug
  • Part 2 - Number of Subjects With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs)
    TEAEs comprised events which first occurred or worsened at study start up to end of study in part 2. In Part 2, only AEs considered at least possibly related to nifurtimox (administered in part 1) and those caused by protocol-related procedures were reported.
    date_rangeTime Frame:
    Subjects participating in Part 2 were followed up for another 3 years, for a total follow-up period of 4 years after end of nifurtimox treatment in Part 1
  • Part 1 - Number of subjects with treatment-emergent high blood chemistry abnormalities by treatment
    The Number Analyzed represents the number of subjects at baseline with a normal or lower than normal laboratory assessment who also had at least one valid laboratory value after start of treatment. The number of subjects represents subjects with at least one high laboratory assessment after start of treatment who had a normal or lower than normal laboratory assessment at baseline.
    date_rangeTime Frame:
    Up to 420 days (Visit 11 post-treatment)
  • Part 1 - Number of subjects with treatment-emergent low blood chemistry abnormalities by treatment
    The number analyzed represents the number of subjects at baseline with a normal or higher than normal laboratory assessment who also had at least one valid laboratory value after start of treatment. The number of subjects represents subjects with at least one low laboratory assessment after start of treatment who had a normal or higher than normal laboratory assessment at baseline.
    date_rangeTime Frame:
    Up to 420 days (Visit 11 post-treatment)
  • Part 1 - Number of subjects with treatment-emergent high hematology abnormalities by treatment
    The number analyzed represents the number of subjects at baseline with a normal or lower than normal laboratory assessment who also had at least one valid laboratory value after start of treatment. Subjects with missing or high abnormal values at baseline are not included in the number analyzed. The number of subjects represents subjects with at least one high laboratory assessment after start of treatment who had a normal or lower than normal laboratory assessment at baseline.
    date_rangeTime Frame:
    Up to 420 days (Visit 11 post-treatment)
  • Part 1 - Number of subjects with treatment-emergent low hematology abnormalities by treatment
    The number analyzed represents the number of subjects at baseline with a normal or lower than normal laboratory assessment who also had at least one valid laboratory value after start of treatment. Subjects with missing or low abnormal values at baseline are not included in the number analyzed. The number of subjects represents subjects with at least one low laboratory assessment after start of treatment who had a normal or higher than normal laboratory assessment at baseline.
    date_rangeTime Frame:
    Up to 420 days (Visit 11 post-treatment)
  • Part 1 - Number of subjects with treatment-emergent high coagulation abnormalities by treatment
    The Number Analyzed represents the number of subjects at baseline with a normal or lower than normal laboratory assessment who also had at least one valid laboratory value after start of treatment. The number of subjects represents subjects with at least one high laboratory assessment after start of treatment who had a normal or lower than normal laboratory assessment at baseline.
    date_rangeTime Frame:
    Up to 420 days (Visit 11 post-treatment)
  • Part 1 - Number of subjects with treatment-emergent low coagulation abnormalities by treatment
    The number analyzed represents the number of subjects at baseline with a normal or higher than normal laboratory assessment who also had at least one valid laboratory value after start of treatment. The number of subjects represents subjects with at least one low laboratory assessment after start of treatment who had a normal or higher than normal laboratory assessment at baseline.
    date_rangeTime Frame:
    Up to 420 days (Visit 11 post-treatment)
  • Part 1 - Number of subjects with abnormal Urinalysis findings considered as clinically significant or reported as Adverse Events (AEs)
    Urinalysis was performed and the following parameters evaluated: bilirubin, blood (red blood cells, white blood cells), chorionic gonadotropin β, glucose, ketones, leukocytes, nitrite, pH, protein, specific gravity, and urobilinogen.
    date_rangeTime Frame:
    Up to 420 days (Visit 11 post-treatment)
  • Part 1 - Number of subjects with abnormal ECG findings considered as clinically significant by investigators
    Clinical significance of abnormal ECG was based on the judgement of the investigator
    date_rangeTime Frame:
    Up to 420 days (Visit 11 post-treatment)
  • Part 1 - Mean changes in vital signs (Systolic Blood Pressure) between the treatment groups from baseline
    Systolic Blood Pressure
    date_rangeTime Frame:
    Baseline and up to 420 days (Visit 11 post-treatment)
  • Part 1 - Mean changes in vital signs (Diastolic Blood Pressure) between the treatment groups from baseline
    Diastolic Blood Pressure
    date_rangeTime Frame:
    Baseline and up to 420 days (Visit 11 post-treatment)
  • Part 1 - Mean changes in vital signs (Respiratory Rate) between the treatment groups from baseline
    Respiratory Rate
    date_rangeTime Frame:
    Baseline and up to 420 days (Visit 11 post-treatment)
  • Part 1 - Mean changes in vital signs (Heart Rate) between the treatment groups from baseline
    Heart Rate
    date_rangeTime Frame:
    Baseline and up to 420 days (Visit 11 post-treatment)
  • Part 1 - Mean changes in vital signs (Body Temperature) between the treatment groups from baseline
    Temperature
    date_rangeTime Frame:
    Baseline and up to 420 days (Visit 11 post-treatment)

Trial design

Prospective, historically controlled study to evaluate the efficacy and safety of a new pediatric formulation of nifurtimox in children aged 0 to 17 years with Chagas’ disease
Trial Type
Interventional
Intervention Type
Drug
Trial Purpose
Treatment
Allocation
Randomized
Blinding
Double Blind
Assignment
Parallel Assignment
Trial Arms
2

Additional Information

Click here to find information about studies related to Bayer Healthcare products conducted in EuropeClick here to find results for studies related to Bayer products.