Clinical trial NCT01685827: Pivotal Study of Fexinidazole for Human African Trypanosomiasis in Stage 2
Official 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Human African Trypanosomiasis (HAT)
Sleeping Sickness
Lead sponsor: Drugs for Neglected Diseases
Sponsor class: OTHER
First posted: 2012-09-14
Enrollment: 394
Sex: ALL
Minimum age (years): 15
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Detailed description: 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.

Eligibility criteria: 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

Primary outcomes:
measure: success or failure at 18 months FU visit
timeFrame: 18 months after treatment
Secondary outcomes:
measure: Safety endpoint
timeFrame: 18 days - observation period
measure: Safety endpoint
timeFrame: 24 months
measure: Pharmacokinetics endpoint
timeFrame: from D8 to D12 after first dosing
measure: QT evaluation
timeFrame: D0 - D4 - D10
Other outcomes:
Locations:
city: Batangafo
country: Central African Republic
facility: Batangafo
city: Bagata
country: Congo, The Democratic Republic of the
facility: Bagata Hospital
state: Bandundu
city: Masi Manimba
country: Congo
facility: Masi Manimba Hospital
state: Bandundu - DRC
city: Vanga
country: Congo
facility: Vanga Hospital
state: Bandundu - DRC
city: Mushie
country: Congo
facility: HGR Mushie hospital
state: Bandundu
city: Mbuji Mayi
country: Congo
facility: CRT (Centre de Réference et de Traitement) Dipumba, Dipumba general hospital
state: East Kasai
city: Katanda
country: Congo
facility: HS Katanda hospital
state: Kasaï Oriental
city: Isangi
country: Congo
facility: HGR ISANGI hospital
state: Province Orientale
city: Bandundu
country: Congo
facility: HGR (General Reference Hospital) Bandundu
city: Dingila
country: Congo
facility: Dingila
Study officials:
affiliation: HAT National Control Program in DRC
name: Victor KANDE, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Mesu VKBK, Kalonji WM, Bardonneau C, Mordt OV, Blesson S, Simon F, Delhomme S, Bernhard S, Kuziena W, Lubaki JF, Vuvu SL, Ngima PN, Mbembo HM, Ilunga M, Bonama AK, Heradi JA, Solomo JLL, Mandula G, Badibabi LK, Dama FR, Lukula PK, Tete DN, Lumbala C, Scherrer B, Strub-Wourgaft N, Tarral A. Oral fexinidazole for late-stage African Trypanosoma brucei gambiense trypanosomiasis: a pivotal multicentre, randomised, non-inferiority trial. Lancet. 2018 Jan 13;391(10116):144-154. doi: 10.1016/S0140-6736(17)32758-7. Epub 2017 Nov 4.