Pivotal Study of Fexinidazole for Human African Trypanosomiasis in Stage 2

Sleeping Sickness Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01685827
• Other study ID #: DNDiFEX004
• Status: Completed
• Phase: Phase 2/Phase 3
• First received: September 12, 2012
• Last updated: February 17, 2018
• Start date: October 2012
• Est. completion date: April 26, 2017

Study information

• Verified date: February 2018
• Source: Drugs for Neglected Diseases
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 394
• Est. completion date: April 26, 2017
• Est. primary completion date: November 11, 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 15 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Human African Trypanosomiasis (HAT)
• Sleeping Sickness
• Trypanosomiasis
• Trypanosomiasis, African

Intervention

Drug:
• Fexinidazole

• Nifurtimox

• Eflornithine

Locations

Country	Name	City	State
Central African Republic	Batangafo	Batangafo
Congo	HGR (General Reference Hospital) Bandundu	Bandundu
Congo	Dingila	Dingila
Congo	HGR ISANGI hospital	Isangi	Province Orientale
Congo	HS Katanda hospital	Katanda	Kasaï Oriental
Congo	Masi Manimba Hospital	Masi Manimba	Bandundu - DRC
Congo	CRT (Centre de Réference et de Traitement) Dipumba, Dipumba general hospital	Mbuji Mayi	East Kasai
Congo	HGR Mushie hospital	Mushie	Bandundu
Congo	Vanga Hospital	Vanga	Bandundu - DRC
Congo, The Democratic Republic of the	Bagata Hospital	Bagata	Bandundu

Sponsors (1)

Lead Sponsor	Collaborator
Drugs for Neglected Diseases

Countries where clinical trial is conducted

Central African Republic,  Congo,  Congo, The Democratic Republic of the, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	success or failure at 18 months FU visit	The primary endpoint is the outcome (success or failure) at the test of cure (ToC) visit 18 months after the end of treatment (EOT) adapted from WHO criteria.; Success at 18 months is: Either cure: patient alive,; AND with no evidence of trypanosomes in any body fluid,; AND 20 or less WBC/µl CSF; Or Probable cure: Patient with no parasitological evidence of relapse in blood and lymph; AND who refuses lumbar puncture OR whose CSF sample is haemorrhagic without trypanosomes; AND whose clinical condition is satisfactory (without clinical symptom or signs) OR whose clinical status is unlikely to be due to HAT	18 months after treatment
Secondary	Safety endpoint	Occurrence of any grade (all grades combined) adverse events during the observation period (D1-18) including: any worsening of clinical symptoms listed in the inclusion checklist of symptoms and signs,; laboratory abnormalities of grade = 2; Occurrence of grade = 3 adverse events during the observation period; Occurrence of drug-related adverse events (grade = 3 and any grade) during the observation period	18 days - observation period
Secondary	Safety endpoint	Occurrence of any serious adverse events from first drug intake to the end of follow-up period (18 months), and from M18 to M24.	24 months
Secondary	Pharmacokinetics endpoint	Whole blood and CSF concentrations of fexinidazole, M1, M2 and PK parameters derived from a model of population PK data.	from D8 to D12 after first dosing
Secondary	QT evaluation	recording of triplicates ECG	D0 - D4 - D10

External Links

•   Sponsor Website