Trial Condition(s):
Chagas disease
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
Bayer Identifier:
16027
ClinicalTrials.gov Identifier:
EudraCT Number:
EU CT Number:
Not Available
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.
Inclusion Criteria
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
Exclusion Criteria
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
Trial Dates
Phase
Could I receive a placebo?
Products
Accepts Healthy Volunteers
Where to Participate
| Locations | |
|---|---|
Locations Investigative Site Buenos Aires, Argentina, C1425EFD | Contact Us: E-mail: [email protected] Phone: (+)1-888-84 22937 |
Locations Investigative Site Rosario, Argentina, 2000 | Contact Us: E-mail: [email protected] Phone: (+)1-888-84 22937 |
Locations Investigative Site Santiago del Estero, Argentina, 4202 | Contact Us: E-mail: [email protected] Phone: (+)1-888-84 22937 |
Locations Investigative Site Buenos Aires, Argentina, C1270AAN | Contact Us: E-mail: [email protected] Phone: (+)1-888-84 22937 |
Locations Investigative Site Mendoza, Argentina, 5535 | Contact Us: E-mail: [email protected] Phone: (+)1-888-84 22937 |
Locations Investigative Site Mendoza, Argentina, 5500 | Contact Us: E-mail: [email protected] Phone: (+)1-888-84 22937 |
Locations Investigative Site La Plata, Argentina, 1900 | Contact Us: E-mail: [email protected] Phone: (+)1-888-84 22937 |
Locations Investigative Site Buenos Aires, Argentina, C1425AGP | Contact Us: E-mail: [email protected] Phone: (+)1-888-84 22937 |
Locations Investigative Site Yopal, Colombia, 0 | Contact Us: E-mail: [email protected] Phone: (+)1-888-84 22937 |
Locations Investigative Site Santa Marta, Colombia, 0 | Contact Us: E-mail: [email protected] Phone: (+)1-888-84 22937 |
Locations Investigative Site Floridablabca, Colombia, 681011 | Contact Us: E-mail: [email protected] Phone: (+)1-888-84 22937 |
Locations Investigative Site Cochabamba, Bolivia | Contact Us: E-mail: [email protected] Phone: (+)1-888-84 22937 |
Locations Investigative Site Tarija, Bolivia | Contact Us: E-mail: [email protected] Phone: (+)1-888-84 22937 |
Locations Investigative Site Salta, Argentina, A4400ESE | Contact Us: E-mail: [email protected] Phone: (+)1-888-84 22937 |
Locations Investigative Site San Salvador de Jujuy, Argentina, 4600 | Contact Us: E-mail: [email protected] Phone: (+)1-888-84 22937 |
Locations Investigative Site Punata, Bolivia | Contact Us: E-mail: [email protected] Phone: (+)1-888-84 22937 |
Locations Investigative Site Salta, Argentina, 4400 | Contact Us: E-mail: [email protected] Phone: (+)1-888-84 22937 |
Locations Investigative Site Buenos Aires, Argentina, 1281 | Contact Us: E-mail: [email protected] Phone: (+)1-888-84 22937 |
Locations Investigative Site Formosa, Argentina, P3600HZL | Contact Us: E-mail: [email protected] Phone: (+)1-888-84 22937 |
Locations Investigative Site Tucuman, Argentina, 4000 | Contact Us: E-mail: [email protected] Phone: (+)1-888-84 22937 |
Locations Investigative Site Soledad, Colombia | Contact Us: E-mail: [email protected] Phone: (+)1-888-84 22937 |
Locations Investigative Site Posadas, Argentina | Contact Us: E-mail: [email protected] Phone: (+)1-888-84 22937 |
Locations Investigative Site San Juan, Argentina, 5400 | Contact Us: E-mail: [email protected] Phone: (+)1-888-84 22937 |
Locations Investigative Site La Rioja, Argentina | Contact Us: E-mail: [email protected] Phone: (+)1-888-84 22937 |
Locations Investigative Site Corrientes, Argentina, W3400CBI | Contact Us: E-mail: [email protected] Phone: (+)1-888-84 22937 |
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
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.Timeframe: 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.Timeframe: 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 2Measured in sub-population.Timeframe: 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 3Measured in sub-population.Timeframe: 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 6The evaluation was based on clinical examinations. Measured in sub-population.Timeframe: 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 8Measured in sub-population.Timeframe: 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 regimenSeronegative 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.Timeframe: 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 cardiomyopathySummary of subjects by evidence of established Chagas-related cardiomyopathy as measured by electrocardiogram (ECG). Evidence of established Chagas-related cardiomyopathy: TotalTimeframe: 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 - Serological response of established Chagas-related cardiomyopathySummary of subjects by evidence of established Chagas-related cardiomyopathy as measured by Serological response. Evidence of established Chagas-related cardiomyopathy: TotalTimeframe: 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 Total Purified Antigen ELISASummary 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.Timeframe: 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 ELISASummary 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.Timeframe: 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 1The evaluation was based on clinical examinations.Timeframe: At Visit 1 (before treatment started)
- Part 1 - Number of subjects with Clinical signs/ symptoms of Chagas disease at Visit 3The evaluation was based on clinical examinations.Timeframe: Up to 7 days (Visit 3)
- Part 1 - Number of subjects with Clinical signs/ symptoms of Chagas disease at Visit 6The evaluation was based on clinical examinations.Timeframe: Up to 30 days (Visit 6)
- Part 1 - Number of subjects with Clinical signs/ symptoms of Chagas disease at Visit 8The evaluation was based on clinical examinations.Timeframe: Up to 60 days (Visit 8; end of treatment)
- Part 1 - Number of subjects with Clinical signs/ symptoms of Chagas disease at Visit 9The evaluation was based on clinical examinations.Timeframe: Up to 90 days (Visit 9 post-treatment)
- Part 1 - Number of subjects with Clinical signs/ symptoms of Chagas disease at Visit 10The evaluation was based on clinical examinations.Timeframe: Up to 240 days (Visit 10 post-treatment)
- Part 1 - Number of subjects with Clinical signs/ symptoms of Chagas disease at Visit 11The evaluation was based on clinical examinations.Timeframe: 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)Timeframe: 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) testThe non-conventional ELISA-F29 test is considered an early marker of treatment efficacy in chronic Chagas disease.Timeframe: Up to 420 days (Visit 11 post-treatment)
- Part 1 - Number of subjects with positive quantitative polymerase chain reaction (qPCR) resultsThe 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) resultsTimeframe: 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 drugTimeframe: 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.Timeframe: 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 treatmentThe 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.Timeframe: Up to 420 days (Visit 11 post-treatment)
- Part 1 - Number of subjects with treatment-emergent low blood chemistry abnormalities by treatmentThe 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.Timeframe: Up to 420 days (Visit 11 post-treatment)
- Part 1 - Number of subjects with treatment-emergent high hematology abnormalities by treatmentThe 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.Timeframe: Up to 420 days (Visit 11 post-treatment)
- Part 1 - Number of subjects with treatment-emergent low hematology abnormalities by treatmentThe 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.Timeframe: Up to 420 days (Visit 11 post-treatment)
- Part 1 - Number of subjects with treatment-emergent high coagulation abnormalities by treatmentThe 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.Timeframe: Up to 420 days (Visit 11 post-treatment)
- Part 1 - Number of subjects with treatment-emergent low coagulation abnormalities by treatmentThe 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.Timeframe: 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.Timeframe: Up to 420 days (Visit 11 post-treatment)
- Part 1 - Number of subjects with abnormal ECG findings considered as clinically significant by investigatorsClinical significance of abnormal ECG was based on the judgement of the investigatorTimeframe: Up to 420 days (Visit 11 post-treatment)
- Part 1 - Mean changes in vital signs (Systolic Blood Pressure) between the treatment groups from baselineSystolic Blood PressureTimeframe: 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 baselineDiastolic Blood PressureTimeframe: Baseline and up to 420 days (Visit 11 post-treatment)
- Part 1 - Mean changes in vital signs (Respiratory Rate) between the treatment groups from baselineRespiratory RateTimeframe: Baseline and up to 420 days (Visit 11 post-treatment)
- Part 1 - Mean changes in vital signs (Heart Rate) between the treatment groups from baselineHeart RateTimeframe: Baseline and up to 420 days (Visit 11 post-treatment)
- Part 1 - Mean changes in vital signs (Body Temperature) between the treatment groups from baselineTemperatureTimeframe: Baseline and up to 420 days (Visit 11 post-treatment)
Additional Information
Copyright © Bayer
Powered by
