Pivotal Study of Fexinidazole for Human African Trypanosomiasis in Stage 2

Brief Title

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

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.
    

Study Phase

Phase 2/Phase 3

Study Type

Interventional


Primary Outcome

success or failure at 18 months FU visit

Secondary Outcome

 Safety endpoint

Condition

Human African Trypanosomiasis (HAT)

Intervention

Fexinidazole

Study Arms / Comparison Groups

 NECT (Nifurtimox Eflornithine Combination Therapy)
Description:  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.

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Drug

Estimated Enrollment

394

Start Date

October 2012

Completion Date

April 26, 2017

Primary Completion Date

November 11, 2016

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
      

Gender

All

Ages

15 Years - N/A

Accepts Healthy Volunteers

No

Contacts

Victor KANDE, MD, , 

Location Countries

Central African Republic

Location Countries

Central African Republic

Administrative Informations


NCT ID

NCT01685827

Organization ID

DNDiFEX004


Responsible Party

Sponsor

Study Sponsor

Drugs for Neglected Diseases


Study Sponsor

Victor KANDE, MD, Principal Investigator, HAT National Control Program in DRC


Verification Date

February 2018