Fexinidazole in Human African Trypanosomiasis Due to T.b. Gambiense at Any Stage

An Open-label Study Assessing Effectiveness, Safety and Compliance With Fexinidazole in Patients With Human African Trypanosomiasis Due to T.b. Gambiense at Any Stage

This study evaluates the effectiveness of fexinidazole administered to patients with human African trypanosomiasis due to T. b. gambiense (g-HAT) at all stages of the disease. The aim of the present study is to provide additional information on the effectiveness and safety of fexinidazole and to assess its use under conditions as close as possible to those in real life, both in patients treated on an out-patient basis and in the hospital setting, depending on clinical status.

Participants will receive fexinidazole oral treatment for 10 days. Regular blood draws and lumbar punctures will be performed over 18 months to confirm the cure of the disease. Other assessments will include the recording of adverse events, signs and symptoms of the disease, laboratory tests, vital signs, electrocardiograms. Treatment compliance, feasibility, and packaging acceptability will be thoroughly assessed in the participants receiving treatment at home. Those participants will complete questionnaires to check that instructions for fexinidazole administration are clear enough and followed correctly.

See attached protocol.

Inclusion Criteria:

• Male or female patient, including breastfeeding or pregnant women in the second or third trimester.
• ≥ 6 years of age.
• ≥ 20 kg body weight.
• Signed Informed Consent Form and Assent Form for patients less than 18 years of age
• Trypanosomes detected in any body fluid.
• Physically able to ingest at least one solid meal per day.
• Able to take oral medication.
• Karnofsky Performance Status > 40%.
• Able to comply with the schedule of follow-up visits and with the study constraints.
• Easily reachable during the out-patient follow-up period.
• Willing to undergo lumbar punctures.

Exclusion Criteria:

• Active clinically relevant medical conditions other than HAT that, in the Investigator's opinion, could jeopardize patient safety or interfere with participation in the study, including but not limited to significant liver or cardiovascular diseases, human immunodeficiency virus (HIV) infection, central nervous system (CNS) trauma or seizure disorders, coma or altered consciousness not related to HAT.
• Severe renal or hepatic impairment defined as:

elevated creatinine at > 3 times the upper limit of normal (ULN); elevated alanine aminotranferase (ALT), aspartate aminotransferase (AST), or bilirubin at > 3 ULN

• Severely deteriorated general condition, such as cardiovascular shock, respiratory distress or terminal illness.
• Any condition (except symptoms of HAT) that compromises ability to communicate with the Investigator as required for completion of the study.
• Any contraindication to imidazole products (known hypersensitivity to imidazoles).
• Treatment for HAT within 2 years prior to inclusion.
• Prior enrolment in the study or prior intake of fexinidazole.
• Foreseeable difficulty in complying with the schedule of follow-up visits (migrants, refugees, itinerant traders, etc.).

Temporary Non-inclusion Criteria:

• Recovery period after antimalarial treatment and/or treatment of helminthiasis (at least 3 days).
• Uncontrolled diabetes or hypertension or any patients requiring clinical stabilization; wait until appropriate treatment to control the disease has been initiated.
• First trimester of pregnancy.
• Traumatic lumbar puncture at Screening i.e. red blood cells visible in cerebrospinal fluid (CSF); wait for 48 hours before repeating lumbar puncture.

Eligibility Criteria for Out-patient Treatment

• Accepting to be treated on an out-patient basis;
• Karnofsky Performance Status > 50%;
• Good understanding of the method of administration of fexinidazole by the patient and/or caregiver* (checked using a questionnaire at the time of dispensing fexinidazole);
• Residing close to the investigational center, i.e. approximately one hour by road and/or boat, during the treatment period**;
• Easily reachable during the treatment period;
• No medical or psychiatric contraindications for treatment as out-patient;
• No pregnancy or breastfeeding;
• No neurological symptoms.