Pivotal Study of Fexinidazole for Human African Trypanosomiasis in Stage 2
Pivotal Study of Fexinidazole for Human African Trypanosomiasis in Stage 2
This clinical trial is designed to prove the efficacy and safety of Fexinidazole as an oral
 treatment for human african trypanosomiasis in advanced stage. The Fexinidazole is compared
 to reference treatment NECT. The trial will try to demonstrate that Fexinidazole is not
 inferior to NECT treatment.
Human African Trypanosomiasis (HAT) is a life-threatening and neglected disease.

 Few treatment options are currently available for stage 2 (meningo-encephalitic stage) HAT,
 with NECT being the most commonly used one since 2010. Though NECT represents a significant
 improvement over current therapies, it is still far from ideal given the environment in which
 HAT patients live (remote, poor areas with little health infrastructure, if any, and
 difficult logistics). There is an urgent need for less toxic and more easily manageable
 compounds to treat this fatal disease.

 Fexinidazole is a 2-5-nitroimidazole, formulated for oral administration, which has been
 shown to possess in vitro and in vivo activity against both T. b. rhodesiense and T. b.
 gambiense parasites.

 Predicted CSF concentrations reached target levels after repeated dosing. Its efficacy and
 safety must now be tested in patients with stage 2 HAT.
Inclusion Criteria:

 -  15 years old or more

 -  Male or female

 -  Able to ingest at least one complete meal per day (or at least one Plumpy'Nut® sachet)

 -  Karnofsky index>50 (see Appendix 2 - Karnofsky Scale; p81)

 -  Parasitologically confirmed late-stage African trypanosomiasis infection with T. b.
 gambiense in the blood and/or lymph and/or CSF, attested by mobile team report (with
 detail of exams performed and values of WBC measured in CSF) or done at the study
 centre. If parasitologically negative in CSF, WBC >20/µl detected in the CSF to
 document stage 2 infection.

 -  Having a permanent address and able to comply with follow-up visit schedule

 -  Signed Informed Consent Form

 Exclusion Criteria:

 -  Severely malnourished patients, defined as having a BMI < 16.

 -  Patients unable to take oral medication.*

 -  Pregnancy or lactation

 -  Active clinically relevant medical conditions 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, CNS trauma or seizure disorders, coma or altered consciousness.

 -  Severely deteriorated general condition, such as cardiovascular shock, respiratory
 distress, or terminal illness.

 -  Any condition which compromises ability to communicate with the Investigator as
 required for the completion of this study.

 -  Any contraindication to imidazole products (known hypersensitivity to imidazoles) and
 NECT (known hypersensitivity to eflornithine).

 -  Patients previously treated for HAT.

 -  Patients previously enrolled in the study.

 -  Follow-up expectable difficulties (migrants, refugees, traders, etc.).

 -  History of alcohol abuse or any drug addiction.

 -  Clinically significant abnormal laboratory value

 -  Pregnancy

 -  Unstable ECG abnormalities

 -  QTcF≥ 450 msec in resting position (confirmed by 2 measurement).

 -  Patients not tested for malaria and/or treated adequately for this infection

 -  Patients not treated adequately for soil transmitted helminthic diseases