Clinical trial NCT03025789: Fexinidazole in Human African Trypanosomiasis Due to T.b. Gambiense at Any Stage
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Trypanosomiasis, African
Sleeping Sickness
Trypanosomiasis; Gambian
Keywords: T.b gambiense
HAT
outpatients
Lead sponsor: Drugs for Neglected Diseases
Sponsor class: OTHER
Collaborators: name: Sanofi
First posted: 2017-01-20
Enrollment: 174
Sex: ALL
Minimum age (years): 6
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: See attached protocol.

Eligibility criteria: 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.

Primary outcomes:
measure: Percentage of Participants Whose Treatment Outcome at Month 18 is a Success
timeFrame: Between the first intake of fexinidazole (Day 1) and the end of the follow-up period (18 months)
Secondary outcomes:
measure: Percentage of Participants Whose Treatment Outcome at Month 12 is a Success
timeFrame: Between the first intake of fexinidazole (Day 1) and the end of the follow-up period (18 months)
measure: Number of Participants With Any Grade ≥ 3 Treatment-emergent Adverse Events (AEs) Including Laboratory and Hematological Abnormalities (if Considered Clinically Significant)
timeFrame: Between the first intake of fexinidazole (Day 1) and the end of the observation period, or the end of the follow-up period (18 months) for non-serious AEs assessed as related to fexinidazole
measure: Number of Participants With Any Treatment-emergent Serious Adverse Event (SAE)
timeFrame: Between the first intake of fexinidazole (Day 1) and the end of the follow-up period (18 months)
measure: Number of Participants With Any Temporary or Permanent Treatment Discontinuation (Inpatient or Outpatient) for Reasons Related to Safety
timeFrame: Between the first intake (Day 1) and last intake of fexinidazole (Day 10, or Day 11 if re-administration occurred)
measure: Number of Participants With Any Hospitalization for Reasons Related to Safety (Outpatients Only)
timeFrame: Between the first intake (Day 1) and last intake of fexinidazole (Day 10, or Day 11 if re-administration occurred)
measure: Number of Participants With Any Permanent Treatment Discontinuation (Inpatient or Outpatient) for Reasons Related to Safety
timeFrame: Between the first intake (Day 1) and last intake of fexinidazole (Day 10, or Day 11 if re-administration occurred)
measure: Number of Outpatients Who Were Compliant With the Full Course of the 10-day Treatment
timeFrame: Between the first intake (Day 1) and last intake of fexinidazole (Day 10, or Day 11 if re-administration occurred)
measure: Number of Outpatients Who Were Compliant With the 10-day Treatment Posology, Including Taking the Correct Number of Tablets During the 2 Phases of Treatment and Taking Tablets All at Once Every Day, With Food and Without Any Interruption of Treatment
timeFrame: End-of-treatment visit (Day 11)
measure: Feasibility of Self-management of Treatment Intake in Outpatients: Occurrence of Temporary Treatment Discontinuation
timeFrame: End-of-treatment visit (Day 11)
measure: Feasibility of Self-management of Treatment Intake in Outpatients: Occurrence of Permanent Treatment Discontinuation
timeFrame: End-of-treatment visit (Day 11)
measure: Feasibility of Self-management of Treatment Intake in Outpatients: Delayed Treatment Start
timeFrame: End-of-treatment visit (Day 11)
measure: Feasibility of Self-management of Treatment Intake in Outpatients: Hospitalization During the Treatment Period Due to Non-compliance
timeFrame: End-of-treatment visit (Day 11)
measure: Acceptability of Packaging in Outpatients: Full Understanding of Instructions Concerning Dosing Regimen
timeFrame: Before treatment (Day 0)
measure: Acceptability of Packaging in Outpatients: Help Requested to Follow the Treatment
timeFrame: End-of-treatment visit (Day 11)
measure: Acceptability of Packaging in Outpatients: Instructions Found Helpful
timeFrame: End-of-treatment visit (Day 11)
measure: Whole Blood Concentration of Fexinidazole From Dry Blood Spot, Measured 24 Hours After the Last Dose of Fexinidazole
timeFrame: End-of-treatment visit (Day 11, 24 hours after last treatment administration)
measure: Whole Blood Concentration of Fexinidazole Metabolite M1 From Dry Blood Spot, Measured 24 Hours After the Last Dose of Fexinidazole
timeFrame: End-of-treatment visit (Day 11, 24 hours after last treatment administration)
measure: Whole Blood Concentration of Fexinidazole Metabolite M2 From Dry Blood Spot, Measured 24 Hours After the Last Dose of Fexinidazole
timeFrame: End-of-treatment visit (Day 11, 24 hours after last treatment administration)
Other outcomes:
Locations:
city: Mbuji-Mayi
country: Congo, The Democratic Republic of the
facility: Dipumba Hospital
state: Kasaï Oriental Province
city: Bagata
country: Congo, The Democratic Republic of the
facility: Bagata Hospital
state: Kwilu Province
city: Bandundu
country: Congo, The Democratic Republic of the
facility: Bandundu Hospital
state: Kwilu Province
city: Masi Manimba
country: Congo, The Democratic Republic of the
facility: Masi Manimba Hospital
state: Kwilu Province
city: Nkara
country: Congo, The Democratic Republic of the
facility: Nkara Secondary Hospital
state: Kwilu Province
city: Mushie
country: Congo, The Democratic Republic of the
facility: Mushie Hospital
state: Maï Ndombe Province
city: Kinshasa
country: Congo, The Democratic Republic of the
facility: Roi Baudouin Hospital
city: Dubreka
country: Guinea
facility: Dubreka Hospital
Study officials:
affiliation: Ministry of Health, Kinshasa, The Democratic Republic of the Congo
name: Victor Kande Betu Kumeso, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: National HAT Control Programme, Conakry, Guinea
name: Mamadou Camara, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: National HAT Control Programme, Kinshasa, The Democratic Republic of the Congo
name: Médard Ilunga Wa Kyhi, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: National HAT Control Programme, Kinshasa, The Democratic Republic of the Congo
name: Digas Ngolo Tete, MPH
role: PRINCIPAL_INVESTIGATOR
References:
citation: WHO. Human African trypanosomiasis: update of the methodological framework for clinical trials: report of the first meeting of the Development of New Tools subgroup, Geneva, 24 September 2014. World Health Organization 2015. WHO/HTM/NTD/IDM/2015.5