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

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.

Study Overview

• Status: Completed
• Conditions: Human African Trypanosomiasis (HAT)
• Intervention / Treatment: Drug: fexinidazole

• Study Type: Interventional
• Enrollment (Actual): 125
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• Congo, The Democratic Republic of the
  • Kinshasa, Congo, The Democratic Republic of the

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 years to 14 years (CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Fexinidazole	Drug: fexinidazole

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	12 months after the end of treatment

Collaborators and Investigators

• Sponsor: Drugs for Neglected Diseases

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): May 3, 2014
• Primary Completion (Actual): December 14, 2016
• Study Completion (Actual): June 27, 2017

Study Registration Dates

• First Submitted: June 19, 2014
• First Submitted That Met QC Criteria: July 8, 2014
• First Posted (Estimate): July 9, 2014

Study Record Updates

• Last Update Posted (Actual): June 24, 2020
• Last Update Submitted That Met QC Criteria: June 23, 2020
• Last Verified: June 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infections; Vector Borne Diseases; Parasitic Diseases; Protozoan Infections; Euglenozoa Infections; Trypanosomiasis; Trypanosomiasis, African
• Other Study ID Numbers: DNDiHATFEX006