Phase 3
N=330
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
Chagas Disease
Bottom Line
View on ClinicalTrials.gov: NCT02625974 ↗Enrolled (actual)
330
Serious AEs
2.7%
Results posted
Oct 2019
Primary outcome: Primary: Part 1 - Percentage of Sero-reduction or Sero-conversion (Cured Subjects) — 32.9; 18.9 Percentage of subjects
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 3
- Interventions
- Nifurtimox (Lampit, BAYA2502) (Drug); Placebo (Drug)
- Age
- Pediatric
- Sex
- All
- Sponsor
- Bayer
- Primary completion
- Jul 2018
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Part 1 - Percentage of Sero-reduction or Sero-conversion (Cured Subjects) |
32.9; 18.9 | — |
| PRIMARY Part 2 - Incidence Rate of Seronegative Conversion in Subjects Received at Least One Dose of the 60-day Nifurtimox Treatment Regimen. |
16 | — |
| SECONDARY Part 1 - Nifurtimox Concentration Over Time in Plasma at Visit 2 |
NA; NA; NA; 21.1; 78.2; 49.0 | — |
| SECONDARY Part 1 - Nifurtimox Concentration Over Time in Plasma at Visit 3 |
47.7; 38.3; 82.6; 56.0; 250.6; 232.3 | — |
| SECONDARY Part 1 - Nifurtimox Concentration Over Time in Plasma at Visit 6 |
23.8; 40.8; 71.7; 73.7; 135.0; 172.7 | — |
| SECONDARY Part 1 - Nifurtimox Concentration Over Time in Plasma at Visit 8 |
NA; NA; 92.4; NA; 139.1; NA | — |
| SECONDARY Part 2 - Incidence Rate of Seronegative Conversion in Subjects Who Received at Least One Dose of the 30-day Nifurtimox Treatment Regimen |
8 | — |
| SECONDARY Part 2 - ECG Signs of Established Chagas-related Cardiomyopathy |
0; 0; 189; 90; 8; 8 | — |
| SECONDARY Part 2 - Serological Response of Established Chagas-related Cardiomyopathy |
14; 6; 176; 84; 7; 8 | — |
| SECONDARY Part 1 + Part 2 - Serial Reduction of Optical Density Values Measured by Total Purified Antigen ELISA |
1.47; 1.52; 1.24; 1.30; -0.24; -0.23 | — |
| SECONDARY Part 1 + Part 2 - Serial Reduction of Optical Density Values Measured by Recombinant ELISA |
2.74; 2.73; 2.27; 2.31; -0.47; -0.41 | — |
| SECONDARY Part 1 - Number of Subjects With Clinical Signs/ Symptoms of Chagas Disease at Visit 1 |
2; 0 | — |
| SECONDARY Part 1 - Number of Subjects With Clinical Signs/ Symptoms of Chagas Disease at Visit 3 |
1; 0; 2; 0; 1; 0 | — |
| SECONDARY Part 1 - Number of Subjects With Clinical Signs/ Symptoms of Chagas Disease at Visit 6 |
1; 0; 0; 1 | — |
| SECONDARY Part 1 - Number of Subjects With Clinical Signs/ Symptoms of Chagas Disease at Visit 8 |
1; 0; 1; 0; 1; 0 | — |
| SECONDARY Part 1 - Number of Subjects With Clinical Signs/ Symptoms of Chagas Disease at Visit 9 |
1; 0 | — |
| SECONDARY Part 1 - Number of Subjects With Clinical Signs/ Symptoms of Chagas Disease at Visit 10 |
1; 0 | — |
| SECONDARY Part 1 - Number of Subjects With Clinical Signs/ Symptoms of Chagas Disease at Visit 11 |
3; 3 | — |
| SECONDARY Part 1 - Number of Subjects With Positive Results in Concentration Test for T. Cruzi (for Subjects <8 Months of Age) |
12; 7; 1; 1; 0; 0 | — |
| SECONDARY Part 1 - Number of Subjects With a Positive Serological Response Using Non-conventional Enzyme-linked Immunosorbent Assay-F29 (ELISAF29) Test |
96; 54; 114; 54; 9; 3 | — |
| SECONDARY Part 1 - Number of Subjects With Positive Quantitative Polymerase Chain Reaction (qPCR) Results |
99; 53; 117; 57; 1; 1 | — |
| SECONDARY Part 1 - Number of Subjects With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) |
147; 66; 6; 3 | — |
| SECONDARY Part 2 - Number of Subjects With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) |
0; 0; 0; 0; 0; 0 | — |
| SECONDARY Part 1 - Number of Subjects With Treatment-emergent High Blood Chemistry Abnormalities by Treatment |
3; 2; 49; 21; 11; 3 | — |
| SECONDARY Part 1 - Number of Subjects With Treatment-emergent Low Blood Chemistry Abnormalities by Treatment |
22; 10; 14; 4; 4; 4 | — |
| SECONDARY Part 1 - Number of Subjects With Treatment-emergent High Hematology Abnormalities by Treatment |
19; 8; 15; 3; 21; 9 | — |
| SECONDARY Part 1 - Number of Subjects With Treatment-emergent Low Hematology Abnormalities by Treatment |
30; 17; 23; 17; 15; 9 | — |
| SECONDARY Part 1 - Number of Subjects With Treatment-emergent High Coagulation Abnormalities by Treatment |
38; 23; 9; 10; 21; 13 | — |
| SECONDARY Part 1 - Number of Subjects With Treatment-emergent Low Coagulation Abnormalities by Treatment |
10; 5; 15; 2; 14; 5 | — |
| SECONDARY Part 1 - Number of Subjects With Abnormal Urinalysis Findings Considered as Clinically Significant or Reported as Adverse Events (AEs) |
0; 0 | — |
| SECONDARY Part 1 - Number of Subjects With Abnormal ECG Findings Considered as Clinically Significant by Investigators |
0; 0 | — |
| SECONDARY Part 1 - Mean Changes in Vital Signs (Systolic Blood Pressure) Between the Treatment Groups From Baseline |
1.09; 0.69; -3.75; -5.00; 1.08; -0.50 | — |
| SECONDARY Part 1 - Mean Changes in Vital Signs (Diastolic Blood Pressure) Between the Treatment Groups From Baseline |
1.00; 0.90; -1.25; -1.00; 0.76; 0.26 | — |
| SECONDARY Part 1 - Mean Changes in Vital Signs (Respiratory Rate) Between the Treatment Groups From Baseline |
0.12; 0.47; -1.50; -1.00; -0.05; -0.14 | — |
| SECONDARY Part 1 - Mean Changes in Vital Signs (Heart Rate) Between the Treatment Groups From Baseline |
-1.08; 0.26; -6.75; -0.75; 0.04; -0.51 | — |
| SECONDARY Part 1 - Mean Changes in Vital Signs (Body Temperature) Between the Treatment Groups From Baseline |
0.01; 0.04; -0.35; -0.03; -0.10; 0.04 | — |
Summary
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.
Eligibility Criteria
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)
Data sourced from ClinicalTrials.gov (NCT02625974). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.