Efficacy and Safety of Fexinidazole in Children at Least 6 Years Old and Weighing Over 20 kg With Human African Trypanosomiasis (HAT) Due to T.b. Gambiense: a Prospective, Multicentre, Open Study, plug-in to the Pivotal Study
Primary Purpose
Human African Trypanosomiasis (HAT)
Status
Completed
Phase
Phase 2
Locations
Congo, The Democratic Republic of the
Study Type
Interventional
Intervention
fexinidazole
Sponsored by
About this trial
This is an interventional treatment trial for Human African Trypanosomiasis (HAT)
Eligibility Criteria
Inclusion Criteria:
- Informed consent form signed by one of the parents or the child's legal representative
- Child assent to participate in the study collected in the presence of an impartial witness
- Age between 6 and 15 years old
- > 20 Kg bodyweight
- Boy or girl
- Able to ingest at least one complete meal per day (or at least one Plumpy'Nut® sachet)
- Able to swallow 600mg fexinidazole tablets
- Karnofsky index > 50
- Presence of trypanosomes in blood and/or lymph and/or CSF
- Permanent address and ability to comply with follow-up visit schedule
Exclusion Criteria:
- Child refusing to be included in the trial
- Bodyweight < 20 Kg
- Severe malnutrition, defined as having a BMI below 16 (- 2 Z-score of the norm according to WHO 2007 Growth reference data)
- Inability to take oral medication
- Pregnancy or breastfeeding
- Clinically relevant medical condition other than HAT that, in the Investigator's opinion, may jeopardize subject safety or interfere with participation in the study, including but not limited to significant liver or cardiovascular disease, active documented or suspected infection, central nervous system (CNS) trauma or seizure disorders, coma or altered consciousness
- Severely deteriorated general condition, such as cardiovascular shock, respiratory distress, or terminal illness
- Any medical condition (except HAT-specific symptoms) hindering communication with the Investigator as required for the completion of this study
- Any contraindication to imidazole products (known hypersensitivity to imidazoles)
- History of HAT treatment in the past 2 years
- Patients previously enrolled in the study or having already received fexinidazole.
- Expected follow-up difficulties (migrants, refugees, itinerant vendors, etc.).
- Current alcohol or drug abuse
- Clinically significant abnormal laboratory findings, including ASAT and/or ALAT > 2 times ULN // Total bilirubin > 1.5 times ULN // Severe leukopenia (< 2000/mm3) // Potassium (K+) < 3.5 mmol // Any other clinically significant abnormal laboratory value (see details in Investigator Manual)
- Pregnancy confirmed by a positive urine pregnancy test obtained within 24 hours (h) prior to start of study treatment (see Section 5.8.3 Contraception; p36) for girls over 12 years old and over
- ECG abnormalities assessed by a central cardiologist
- QTcF≥ 450 ms, as measured automatically (if first measurement is abnormal, a second assessment will be done at least 10-20 min later, with the patient in resting position).
- Patients not tested for malaria and/or not treated adequately for this infection
- Patients not treated adequately for soil transmitted helminthic diseases
Sites / Locations
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Fexinidazole
Arm Description
Outcomes
Primary Outcome Measures
Outcome (success or failure) at the test of cure (ToC)
Success at 12 months, adapted from the WHO criteria (51), is defined as a cured patient:
Patient alive;
AND no evidence of trypanosomes in any body fluid;
AND WBC ≤20/µL in CSF.
Secondary Outcome Measures
Full Information
NCT ID
NCT02184689
First Posted
June 19, 2014
Last Updated
June 23, 2020
Sponsor
Drugs for Neglected Diseases
1. Study Identification
Unique Protocol Identification Number
NCT02184689
Brief Title
Efficacy and Safety of Fexinidazole in Children at Least 6 Years Old and Weighing Over 20 kg With Human African Trypanosomiasis (HAT) Due to T.b. Gambiense: a Prospective, Multicentre, Open Study, plug-in to the Pivotal Study
Official Title
Efficacy and Safety of Fexinidazole in Children at Least 6 Years Old and Weighing Over 20 kg With Human African Trypanosomiasis (HAT) Due to T.b. Gambiense: a Prospective, Multicentre, Open Study, plug-in to the Pivotal Study
Study Type
Interventional
2. Study Status
Record Verification Date
June 2020
Overall Recruitment Status
Completed
Study Start Date
May 3, 2014 (Actual)
Primary Completion Date
December 14, 2016 (Actual)
Study Completion Date
June 27, 2017 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Drugs for Neglected Diseases
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The aim of the study is to assess the efficacy and safety of an oral regimen of fexinidazole (once daily for 10 days) in the treatment of stage 1 and stage 2 T.b. gambiense sleeping sickness in children at least 6 years old and over 20 kg bodyweight.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Human African Trypanosomiasis (HAT)
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2, Phase 3
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
125 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Fexinidazole
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
fexinidazole
Primary Outcome Measure Information:
Title
Outcome (success or failure) at the test of cure (ToC)
Description
Success at 12 months, adapted from the WHO criteria (51), is defined as a cured patient:
Patient alive;
AND no evidence of trypanosomes in any body fluid;
AND WBC ≤20/µL in CSF.
Time Frame
12 months after the end of treatment
10. Eligibility
Sex
All
Minimum Age & Unit of Time
6 Years
Maximum Age & Unit of Time
14 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Informed consent form signed by one of the parents or the child's legal representative
Child assent to participate in the study collected in the presence of an impartial witness
Age between 6 and 15 years old
> 20 Kg bodyweight
Boy or girl
Able to ingest at least one complete meal per day (or at least one Plumpy'Nut® sachet)
Able to swallow 600mg fexinidazole tablets
Karnofsky index > 50
Presence of trypanosomes in blood and/or lymph and/or CSF
Permanent address and ability to comply with follow-up visit schedule
Exclusion Criteria:
Child refusing to be included in the trial
Bodyweight < 20 Kg
Severe malnutrition, defined as having a BMI below 16 (- 2 Z-score of the norm according to WHO 2007 Growth reference data)
Inability to take oral medication
Pregnancy or breastfeeding
Clinically relevant medical condition other than HAT that, in the Investigator's opinion, may jeopardize subject safety or interfere with participation in the study, including but not limited to significant liver or cardiovascular disease, active documented or suspected infection, central nervous system (CNS) trauma or seizure disorders, coma or altered consciousness
Severely deteriorated general condition, such as cardiovascular shock, respiratory distress, or terminal illness
Any medical condition (except HAT-specific symptoms) hindering communication with the Investigator as required for the completion of this study
Any contraindication to imidazole products (known hypersensitivity to imidazoles)
History of HAT treatment in the past 2 years
Patients previously enrolled in the study or having already received fexinidazole.
Expected follow-up difficulties (migrants, refugees, itinerant vendors, etc.).
Current alcohol or drug abuse
Clinically significant abnormal laboratory findings, including ASAT and/or ALAT > 2 times ULN // Total bilirubin > 1.5 times ULN // Severe leukopenia (< 2000/mm3) // Potassium (K+) < 3.5 mmol // Any other clinically significant abnormal laboratory value (see details in Investigator Manual)
Pregnancy confirmed by a positive urine pregnancy test obtained within 24 hours (h) prior to start of study treatment (see Section 5.8.3 Contraception; p36) for girls over 12 years old and over
ECG abnormalities assessed by a central cardiologist
QTcF≥ 450 ms, as measured automatically (if first measurement is abnormal, a second assessment will be done at least 10-20 min later, with the patient in resting position).
Patients not tested for malaria and/or not treated adequately for this infection
Patients not treated adequately for soil transmitted helminthic diseases
Facility Information:
City
Kinshasa
Country
Congo, The Democratic Republic of the
12. IPD Sharing Statement
Citations:
PubMed Identifier
36179736
Citation
Kande Betu Kumesu V, Mutombo Kalonji W, Bardonneau C, Valverde Mordt O, Ngolo Tete D, Blesson S, Simon F, Delhomme S, Bernhard S, Nganzobo Ngima P, Mahenzi Mbembo H, Fina Lubaki JP, Lumeya Vuvu S, Kuziena Mindele W, Ilunga Wa Kyhi M, Mandula Mokenge G, Kaninda Badibabi L, Kasongo Bonama A, Kavunga Lukula P, Lumbala C, Scherrer B, Strub-Wourgaft N, Tarral A. Safety and efficacy of oral fexinidazole in children with gambiense human African trypanosomiasis: a multicentre, single-arm, open-label, phase 2-3 trial. Lancet Glob Health. 2022 Nov;10(11):e1665-e1674. doi: 10.1016/S2214-109X(22)00338-2. Epub 2022 Sep 27.
Results Reference
derived
Learn more about this trial
Efficacy and Safety of Fexinidazole in Children at Least 6 Years Old and Weighing Over 20 kg With Human African Trypanosomiasis (HAT) Due to T.b. Gambiense: a Prospective, Multicentre, Open Study, plug-in to the Pivotal Study
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