Pivotal Study of Fexinidazole for Human African Trypanosomiasis in Stage 2

NCT01685827 | Completed Phase 2 DMC

• 1 other identifier: DNDiFEX004
• Study Type: interventional
• Target: 394
• Locations: 3 countries
• Sites: 10

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.

Conditions

Human African Trypanosomiasis (HAT); Sleeping Sickness

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (4)

• Safety endpoint

  18 days - observation period

• Safety endpoint

  24 months

• Pharmacokinetics endpoint

  from D8 to D12 after first dosing

• QT evaluation

  D0 - D4 - D10

Study Arms (2)

NECT (Nifurtimox Eflornithine Combination Therapy)

ACTIVE COMPARATOR

* 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.

Drug: Nifurtimox; Drug: Eflornithine

Fexinidazole

EXPERIMENTAL

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.

Drug: Fexinidazole

Interventions

Fexinidazole DRUG

Fexinidazole

Nifurtimox DRUG

Also known as: Lampit

NECT (Nifurtimox Eflornithine Combination Therapy)

Eflornithine DRUG

Also known as: Ornidyl

NECT (Nifurtimox Eflornithine Combination Therapy)

Eligibility Criteria

• Age: 15 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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).

Sponsors & Collaborators

• Drugs for Neglected Diseases: lead

Study Sites (10)

Batangafo

Batangafo, Central African Republic

Location

Bagata Hospital

Bagata, Bandundu, Democratic Republic of the Congo

Location

Masi Manimba Hospital

Masi Manimba, Bandundu - DRC, Republic of the Congo

Location

Vanga Hospital

Vanga, Bandundu - DRC, Republic of the Congo

Location

HGR (General Reference Hospital) Bandundu

Bandundu, Bandundu, Republic of the Congo

Location

HGR Mushie hospital

Mushie, Bandundu, Republic of the Congo

Location

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

Mbuji Mayi, East Kasai, Republic of the Congo

Location

HS Katanda hospital

Katanda, Kasaï Oriental, Republic of the Congo

Location

HGR ISANGI hospital

Isangi, Province Orientale, Republic of the Congo

Location

Dingila

Dingila, Republic of the Congo

Location

Related Publications (1)

• 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.

  PMID: 29113731 DERIVED

Related Links

• Sponsor Website

MeSH Terms

Conditions

Trypanosomiasis, African

Interventions

fexinidazole; Nifurtimox; Eflornithine

Condition Hierarchy (Ancestors)

Trypanosomiasis; Euglenozoa Infections; Protozoan Infections; Parasitic Diseases; Infections; Vector Borne Diseases

Intervention Hierarchy (Ancestors)

Nitrofurans; Nitro Compounds; Organic Chemicals; Thiazines; Sulfur Compounds; Furans; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Ornithine; Amino Acids, Basic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Diamino

Study Officials

• Victor KANDE, MD

  HAT National Control Program in DRC

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 12, 2012
• First Posted: September 14, 2012
• Study Start: October 1, 2012
• Primary Completion: November 11, 2016
• Study Completion: April 26, 2017
• Last Updated: February 20, 2018

Record last verified: 2018-02

Locations

DE (1); RE (8); CE (1)