Pivotal Study of Fexinidazole for Human African Trypanosomiasis in Stage 2

NCT ID: NCT01685827

Last Updated: 2018-02-20

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 394 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-10-31
• Study Completion Date: 2017-04-26

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.

Conditions

Human African Trypanosomiasis (HAT); Sleeping Sickness

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

NECT (Nifurtimox Eflornithine Combination Therapy)

• Nifurtimox tablets will be given orally three times a day, at the daily dose of 15 mg/kg/day, for 10 days.
• Eflornithine (400 mg/kg/day) will be given twice daily for 7 days, as a 2-hour IV infusion.

Group Type: ACTIVE_COMPARATOR

Nifurtimox

Intervention Type: DRUG

Eflornithine

Intervention Type: DRUG

Fexinidazole

Fexinidazole, 600 mg tablets given by oral route, after the main daily meal (within 30 minutes from the start of the meal), at the daily dose of:

• 1 800 mg (3 tablets) once a day for 4 days,
• Followed by 1 200 mg (2 tablets) once a day for 6 days. Total duration of treatment will be 10 days.

Group Type: EXPERIMENTAL

Fexinidazole

Intervention Type: DRUG

Interventions

Fexinidazole

Intervention Type: DRUG

Nifurtimox

Intervention Type: DRUG

Eflornithine

Intervention Type: DRUG

Other Intervention Names

Lampit; Ornidyl

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

• Minimum Eligible Age: 15 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Drugs for Neglected Diseases

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Victor KANDE, MD

Role: PRINCIPAL_INVESTIGATOR

HAT National Control Program in DRC

Locations

Batangafo

Batangafo, , Central African Republic

Bagata Hospital

Bagata, Bandundu, Democratic Republic of the Congo

Masi Manimba Hospital

Masi Manimba, Bandundu - DRC, Republic of the Congo

Vanga Hospital

Vanga, Bandundu - DRC, Republic of the Congo

HGR (General Reference Hospital) Bandundu

Bandundu, Bandundu, Republic of the Congo

HGR Mushie hospital

Mushie, Bandundu, Republic of the Congo

CRT (Centre de Réference et de Traitement) Dipumba, Dipumba general hospital

Mbuji Mayi, East Kasai, Republic of the Congo

HS Katanda hospital

Katanda, Kasaï Oriental, Republic of the Congo

HGR ISANGI hospital

Isangi, Province Orientale, Republic of the Congo

Dingila

Dingila, , Republic of the Congo

Countries

Central African Republic; Democratic Republic of the Congo; Republic of the Congo

References

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.

Reference Type: DERIVED

PMID: 29113731 (View on PubMed)

Related Links

http://www.dndi.org

Sponsor Website

Other Identifiers

DNDiFEX004

Identifier Type: -

Identifier Source: org_study_id