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Prospective Study of a Pediatric Nifurtimox Formulation for Chagas' Disease (CHICO)

This study is currently recruiting participants. (see Contacts and Locations)
Verified November 2016 by Bayer
Sponsor:
Information provided by (Responsible Party):
Bayer
ClinicalTrials.gov Identifier:
NCT02625974
First received: December 7, 2015
Last updated: November 1, 2016
Last verified: November 2016
  Purpose
This study was designed to develop a better understanding of the efficacy, safety/tolerability, and pharmacokinetics (PK) (absorption, distribution, metabolism, and elimination) of nifurtimox in children with a diagnosis of Chagas' disease (Trypanosoma cruzi infection) using pediatric formulations.

Condition Intervention Phase
Chagas Disease
Drug: Nifurtimox (BAYA2502)
Drug: Nifurtimox (BAYA2502) followed by Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Bayer:

Primary Outcome Measures:
  • Superiority of nifurtimox to historical untreated control in children: Sero-conversion for subjects ≤ 8 months of age at randomization [ Time Frame: 360 days from end of treatment [EOT] ] [ Designated as safety issue: No ]
    Sero-conversion: defined as negative antibody concentration to Trypanosoma cruzi Binary variables: CURE (negative ELISA result) / NO CURE (positive ELISA result)

  • Superiorty of nifurtimox to historical untreated control in children: Sero-reduction for subjects ≥ 8 months to <18 years of age [ Time Frame: 360 days from end of treatment [EOT] ] [ Designated as safety issue: No ]
    Sero-reduction:defined as Recombinant ELISA (enzyme-linked immune sorbent assay) serology tests based upon a target of ≥ 20% decrease in antibody concentration to Trypanosoma cruzi Binary variables: CURE (20% or more reduction in antibody) / NO CURE ( less than 20% reduction in antibody)


Secondary Outcome Measures:
  • Comparability of a 60-day regimen of nifurtimox to historical active control (benznidazole) as sero-reduction or sero-conversion [ Time Frame: up to 420 days (Visit 11) post-treatment ] [ Designated as safety issue: No ]
    Binary variables : CURE (negative ELISA result or ≥ 20% reduction in antibody concentration) / NO CURE (positive ELISA result or less than 20% reduction in antibody).

  • Comparability of a 30-day regimen of nifurtimox to a 60-day regimen of nifurtimox as sero-reduction or sero-conversion and to qualitative polymerase chain reaction (qPCR) [ Time Frame: up to 420 days (Visit 11) post-treatment ] [ Designated as safety issue: No ]
    Binary variables :CURE (negative ELISA result , ≥20% reduction in antibody concentration, or non-reactive PCR test) / NO CURE (positive ELISA result , less than 20% reduction in antibody, or , reactive PCR test).

  • Relationship of conventional serology (as sero-reduction or sero-conversion) to qPCR using frequencies of matches and mismatches to assess agreement [ Time Frame: up to 420 days (Visit 11) post-treatment ] [ Designated as safety issue: No ]
    Comparison of CURE / NO CURE results for ELISA tests and PCR tests.

  • Relationship of non-conventional serology to conventional serology [ Time Frame: up to 420 days (Visit 11) post-treatment ] [ Designated as safety issue: No ]
    Compare CURE / NO CURE results for non-conventional ELISA and conventional ELISA tests.

  • Safety/tolerability profile of nifurtimox by assessing the number of participants with Adverse Event as a measure of safety and tolerability [ Time Frame: up to 420 days (Visit 11) post-treatment ] [ Designated as safety issue: Yes ]
  • Safety/tolerability profile of nifurtimox by laboratory parameters [ Time Frame: up to 420 days (Visit 11) post-treatment ] [ Designated as safety issue: Yes ]
    Hematology Blood chemistry Urinalysis

  • Safety/tolerability profile of nifurtimox by electrocardiogram (ECG) monitoring [ Time Frame: up to 420 days (Visit 11) post-treatment ] [ Designated as safety issue: Yes ]
  • Safety/tolerability profile of nifurtimox by laboratory parameters vital sign measurements [ Time Frame: up to 420 days (Visit 11) post-treatment ] [ Designated as safety issue: Yes ]
    Blood pressure Heart rate Respiratory rate Temperature

  • Safety/tolerability profile of nifurtimox by physical examinations [ Time Frame: up to 420 days (Visit 11) post-treatment ] [ Designated as safety issue: Yes ]
    Neurological examinations

  • Pharmacokinetics - Plasma concentration time courses in children: maximum concentration (Cmax) of nifurtimox, after first dose and at steady state [ Time Frame: up to 60 days (Visit 8) ] [ Designated as safety issue: No ]
  • Pharmacokinetics - Plasma concentration time courses in children: time to maximum plasma concentration (Tmax) of nifurtimox, after first dose and at steady state [ Time Frame: up to 60 days (Visit 8) ] [ Designated as safety issue: No ]
  • Pharmacokinetics - Plasma concentration time courses in children: Area under the curve (AUC), regarding plasma nifurtimox concentration-time curve after first dose and at steady state [ Time Frame: up to 60 days (Visit 8) ] [ Designated as safety issue: No ]
  • Pharmacokinetics - Plasma concentration time courses in children: Half-life (t1/2) of nifurtimox, after first dose and at steady state [ Time Frame: up to 60 days (Visit 8) ] [ Designated as safety issue: No ]

Estimated Enrollment: 390
Study Start Date: January 2016
Estimated Study Completion Date: November 2018
Estimated Primary Completion Date: November 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Nifurtimox 60 days / Arm 1
Nifurtimox tablets administered three times daily for 60 days (Days 1 - 60, active nifurtimox treatment)
Drug: Nifurtimox (BAYA2502)

For pediatric subjects with body weight ≤ 40 kg: maximum dosage15 mg/kg/day in three divided doses For pediatric subjects with body weight > 40 kg: 8 - 10 mg/kg/day in three divided doses.

60 days of nifurtimox treatment

Placebo Comparator: Nifurtimox 30 days / Arm 2
Nifurtimox tablets administered three times daily for 30 days, followed by nifurtimox placebo administered three times daily for 30 days (Days 1 - 30, active nifurtimox treatment; Days 31 - 60, placebo)
Drug: Nifurtimox (BAYA2502) followed by Placebo

For pediatric subjects with body weight ≤ 40 kg: maximum dosage15 mg/kg/day in three divided doses For pediatric subjects with body weight > 40 kg: 8 - 10 mg/kg/day in three divided doses.

30 days of nifurtimox treatment followed by 30 days of placebo


  Eligibility

Ages Eligible for Study:   up to 17 Years   (Child)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Male and female pediatric subjects aged 0 days to younger than 18 years
  • Chagas' disease diagnosed/confirmed by:
  • Subjects < 8 months of age at randomization must demonstrate direct observation of Trypanosoma cruzi by concentration test
  • Subjects ≥ 8 months to < 18 years of age at randomization must demonstrate a positive conventional ELISA result for both of the following tests to confirm diagnosis:
  • Recombinant ELISA
  • Total purified antigen ELISA
  • Females of childbearing potential (i.e., female subjects who have experienced menarche) and male subjects must agree to use adequate contraception if sexually active from the time of signing the informed consent/assent form until 3 months after the last study drug administration.

Exclusion Criteria:

  • Subjects aged 0 to 27 days who, at birth, were pre-term (i.e., gestational age less than 37 weeks), weighed less than 2500 g, or had a maximum Apgar score <7 at 5 minutes
  • Subjects with any of the following conditions that is associated with Chagas' disease, such as:
  • 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
  • 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, including:
  • Hypersensitivity to nifurtimox or any hydantoin, or to any of the excipients
  • Suspected or known porphyria
  • Severe renal impairment
  • Severe hepatic impairment
  • History of brain injury, predisposition to seizures or epilepsy, psychiatric disease, or serious behavioral alteration
  • 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 T. cruzi reinfection as determined by Ministry of Health guidelines in each country
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02625974

Contacts
Contact: Bayer Clinical Trials Contact clinical-trials-contact@bayer.com

Locations
Argentina
Terminated
Berazategui, Buenos Aires, Argentina, 1884
Not yet recruiting
La Plata, Buenos Aires, Argentina, 1900
Not yet recruiting
Buenos Aires, Ciudad Auton. de Buenos Aires, Argentina, 1281
Not yet recruiting
Buenos Aires, Ciudad Auton. de Buenos Aires, Argentina, C1408INH
Recruiting
Buenos Aires, Ciudad Auton. de Buenos Aires, Argentina, C1425AGP
Recruiting
Buenos Aires, Ciudad Auton. de Buenos Aires, Argentina, C1425EFD
Recruiting
San Salvador de Jujuy, Jujuy, Argentina, 4600
Not yet recruiting
Posadas, Misiones, Argentina
Maternidad Martín-CEMAR Terminated
Rosario, Santa Fe, Argentina, 2000
Recruiting
Rosario, Santa Fe, Argentina, 2000
Hospital Pediátrico Juan Pablo II Terminated
Corrientes, Argentina, 3400
Not yet recruiting
Córdoba, Argentina, X50000JDR
Recruiting
Formosa, Argentina, P3600HZL
Recruiting
Mendoza, Argentina, 5500
Recruiting
Salta, Argentina, 4400
Not yet recruiting
San Juan, Argentina, 5400
Recruiting
Santiago del Estero, Argentina, 4202
Recruiting
Tucuman, Argentina, 4000
Bolivia
Hospital Manuel Asencio Recruiting
Punata, Cochabamba, Bolivia
Recruiting
Cochabamba, Bolivia
Recruiting
Tarija, Bolivia
Colombia
Not yet recruiting
Barranquilla, Atlántico, Colombia
Recruiting
Yopal, Casanare, Colombia, 0
Not yet recruiting
Santa Marta, Magdalena, Colombia, 0
Recruiting
Floridablanca-Bucaramanga, Santander, Colombia
Sponsors and Collaborators
Bayer
Investigators
Study Director: Bayer Study Director Bayer
  More Information

Additional Information:
Responsible Party: Bayer
ClinicalTrials.gov Identifier: NCT02625974     History of Changes
Other Study ID Numbers: 16027 
Study First Received: December 7, 2015
Last Updated: November 1, 2016
Health Authority: Argentina: Administración Nacional de Medicamentos, Alimentos y Tecnología Médica
Colombia: Instituto Nacional de Vigilancia de Medicamentos y Alimentos
Bolivia: Unidad de Medicamentos y Acreditación de Laboratorios
United States: Food and Drug Administration

Additional relevant MeSH terms:
Chagas Disease
Trypanosomiasis
Euglenozoa Infections
Protozoan Infections
Parasitic Diseases
Nifurtimox
Trypanocidal Agents
Antiprotozoal Agents
Antiparasitic Agents
Anti-Infective Agents

ClinicalTrials.gov processed this record on December 05, 2016