Please select the eligibility criteria that correspond to the clinical trial below.
Title: Efficacy and Safety of Fexinidazole Compared to Nifurtimox-Eflornithine Combination Therapy (NECT) in Patients With Late-stage Human African Trypanosomiasis (HAT) Due to T.b. Gambiense: Pivotal, Non-inferiority, Multicentre, Randomised, Open-label Study
Brief Summary: 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.


Options:
A: 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
B: Inclusion Criteria:

* confirmed second-stage T.b. gambiense infection : presence of the parasite in blood, lymph node fluid or CSF and \>20 white blood cells/µL in CSF. In presence of blood in the CSF, lumbar puncture must be done again or the patient cannot be included in the study (see 10.9.1).
* and of age 15 years or older.
* and resident in __________ (each site will define boundaries or maximum distance)
* and written informed consent of the patient or of a legally acceptable representative if the patient is a minor (\<18 years for both genders in Uganda and Angola, \<18 years for males and \<16 years for females in the Democratic Republic of Congo) or unable to communicate.

Exclusion Criteria:

* pregnant woman (systematic testing of women of childbearing potential)
* treated for late-stage HAT during the last 36 months. Patients previously treated for first-stage (pentamidine) can be included.
* unlikely to have access to the treatment centre or be accessible at their place of residence for 18 months after treatment
* unable to take oral medication
* suffering from conditions other than second stage HAT that seriously limit the chances of survival over 18 months time
* Severe anemia (Hb\< 5g/dl)
* Severe underlying diseases upon admission (e.g. Active tuberculosis and/or being treated for TB; Bacterial or cryptococcal meningitis; Stages 3 or 4 HIV/AIDS according to the WHO clinical definition) (WHO, 1986).
* Severe renal failure based on clinical examination combined with biochemistry if available: creatinine clearance \<20mL/min
* Severe hepatic failure based on clinical examination combined with biochemistry if available: total bilirubin \>50 µmol/L, ALAT/GPT \>70 UI/L, unless these laboratory values are determined by the investigator as likely due to conditions other than hepatic failure.
C: Inclusion Criteria:

* Signed informed consent
* 15 years old or more
* Male or female
* Ability to ingest at least one complete meal per day (or at least one Plumpy'Nut® sachet)
* Karnofsky index \> 50
* Presence of trypanosomes in blood or lymph
* Absence of trypanosomes in CSF
* Permanent address and ability to comply with the follow-up visit schedule
* Patient agreeing to be hospitalized to receive the treatment

Exclusion Criteria:

* Severely malnutrition, defined as BMI \< 16.
* Inability to take oral medication.
* Pregnancy or breastfeeding (a urine pregnancy test will be performed in all women of childbearing age within 24 h prior to treatment).
* Clinically relevant medical condition other than HAT that, in the Investigator's opinion, may jeopardize patient safety or interfere with participation in the study, including but not limited to significant liver or cardiovascular disease, documented or suspected active infection (including AIDS), CNS trauma or seizure disorders, coma or altered consciousness.
* Severely deteriorated general condition, e.g. cardiovascular shock, respiratory distress syndrome, 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 value, such as:
* Alanine aminotransferase (ALAT) and/or aspartate aminotransferase (ASAT) \> 2 times ULN
* Total bilirubin (TBIL) \> 1.5 times ULN
* Severe leukopenia (\< 2000/mm3)
* Potassium (K+) \< 3.5 mmol/L
* Any clinically significant abnormal value (see details in Investigator Manual)
* Pregnancy confirmed by a positive urine pregnancy test obtained within 24 h prior to start of study treatment (see Section 5.8.3 Contraception; p35) QTcF ≥ 450 ms as measured automatically (if the 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
D: Inclusion Criteria:

All patients diagnosed as stage 2 HAT according to the diagnostic protocols in use at the treatment center (generally, if presence of parasites in blood, lymph node fluid or CSF and an elevated white blood cell count in the CSF, but this can vary from center to center) will be included if a written Informed Consent is given by the patient or a legally acceptable representative if the patient is a minor or unable to communicate.

* Pregnancy and breastfeeding women: On a case by case basis according to the guidelines of the National HAT Control Programme or the NGO, the Investigator will decide to treat the patient or to defer the treatment. In case of inclusion, the mother-child pairs or the children of lactating mothers will be closely monitored during treatment and follow up.
* Children under 2 years of age: On a case by case basis, the Investigator will decide to treat an infant with NECT or an alternative treatment (preferably eflornithine). In case of inclusion, these infants will be closely monitored during treatment and follow up like all children less than 12 years of age.

Exclusion Criteria:

* Unable to take oral medication, and impossibility to use a nasogastric tube.
* Treatment failure after nifurtimox-eflornithine treatment.
* Any other condition or reason for which the Investigator (or the responsible treating staff member) judges that another or no HAT treatment is warranted.

Answer: A