Fexinidazole in Human African Trypanosomiasis Due to T.b. Gambiense at Any Stage

Sponsor

Drugs for Neglected Diseases (Other)

Overall Status

Completed

CT.gov ID

NCT03025789

Collaborator

Sanofi (Industry)

174

Enrollment

Locations

Arm

50.5

Actual Duration (Months)

21.8

Patients Per Site

0.4

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This study evaluates the effectiveness of fexinidazole administered to patients with g-HAT at all stages of the disease. The aim of the present study is to provide additional information on the effectiveness and safety of fexinidazole and to assess its use under conditions as close as possible to those in real life, both in patients treated on an out-patient basis and in the hospital setting, depending on clinical status

Condition or Disease	Intervention/Treatment	Phase
Trypanosomiasis, African Sleeping Sickness Trypanosomiasis; Gambian	Drug: Fexinidazole	Phase 3

Study Design

Study Type:

Interventional

Actual Enrollment :

174 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

An Open-label Study Assessing Effectiveness, Safety and Compliance With Fexinidazole in Patients With Human African Trypanosomiasis Due to T.b. Gambiense at Any Stage

Actual Study Start Date :

Nov 17, 2016

Actual Primary Completion Date :

Feb 1, 2021

Actual Study Completion Date :

Feb 1, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Open label arm children and adults to receive fexinidazole either as inpatients or outpatients.	Drug: Fexinidazole Tablets of 600 mg Patients with a weight between 20 and 34kg: 1200mg for 4 days, then 600mg for 6 days Patients with a weight of 35kg and above: 1800mg for 4 days, then 1200mg for 6 days

Arm

Intervention/Treatment

Experimental: Open label arm

children and adults to receive fexinidazole either as inpatients or outpatients.

Drug: Fexinidazole

Tablets of 600 mg Patients with a weight between 20 and 34kg: 1200mg for 4 days, then 600mg for 6 days Patients with a weight of 35kg and above: 1800mg for 4 days, then 1200mg for 6 days

Outcome Measures

Primary Outcome Measures

Outcome (success or failure) [18 months follow up]
Success is defined as a cure, according to the criteria adapted from the WHO
Outcome (success or failure) [12 month follow up]
Success is defined as a cure, according to the criteria adapted from the WHO

Secondary Outcome Measures

Occurrence of grade ≥ 3 adverse events (AEs) including laboratory and haematological abnormalities [between the first intake of fexinidazole and the end of the observation period or the follow-up period (18 months) for non-serious AEs assessed as related to fexinidazole]
AE severity will be graded according to the National Cancer Institute (NCI) Common Toxicity Criteria for AEs (CTCAE), Version 4.03 (13) and, for certain laboratory parameters, modified CTCAE will be used
Occurrence of any serious adverse event (SAE) [between the first intake of fexinidazole and the end of the follow-up period (18 months)]
Pharmacokinetic measure to assess patient compliance [at Day 11]
Presence of fexinidazole and/or its main metabolites in the blood for PK analyses
Outpatients compliance [at Day 11]
Number of tablets left over and patient's responses to the questionnaire
Outpatients compliance [at Day 11]
Patient's responses to the questionnaire
Feasibility of self-management of treatment intake in outpatients [Day 11]
based on interview and left over tablets at D11
questionnaire on acceptability of packaging for outpatients only [day 0 and day 11]
questionnaire to be completed by patients and caregivers
Whole blood concentration of fexinidazole and its metabolites from dry blood spot of inpatients [day8, day9, day10, 3hour after treatment administration, Day10, 7h15 after treatment administration, Day10, 24h after treatment administration, Day10, 48h after treatment administration]
measured by HPLC/MS/MS Bioanalytical method in all patients treated in hospital

Eligibility Criteria

Criteria

Ages Eligible for Study:

6 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Male or female patient, including breastfeeding or pregnant women in the second or third trimester.
≥ 6 years of age.
≥ 20 kg body weight.
Signed Informed Consent Form and Assent Form for patients less than 18 years of age
Trypanosomes detected in any body fluid.
Physically able to ingest at least one solid meal per day.
Able to take oral medication.
Karnofsky Performance Status > 40%.
Able to comply with the schedule of follow-up visits and with the study constraints.
Easily reachable during the out-patient follow-up period.
Willing to undergo lumbar punctures.

Exclusion Criteria:

Active clinically relevant medical conditions other than HAT that, in the Investigator's opinion, could jeopardise patient safety or interfere with participation in the study, including but not limited to significant liver or cardiovascular diseases, HIV infection, CNS trauma or seizure disorders, coma or altered consciousness not related to HAT.
Severe renal or hepatic impairment defined as:

elevated creatinine at > 3 times the upper limit of normal (ULN) elevated ALT, AST or bilirubin at > 3 ULN

Severely deteriorated general condition, such as cardiovascular shock, respiratory distress or terminal illness.
Any condition (except symptoms of HAT) that compromises ability to communicate with the Investigator as required for completion of the study.
Any contraindication to imidazole products (known hypersensitivity to imidazoles).
Treatment for HAT within 2 years prior to inclusion.
Prior enrolment in the study or prior intake of fexinidazole.
Foreseeable difficulty in complying with the schedule of follow-up visits (migrants, refugees, itinerant traders, etc.).

Temporary Non-inclusion Criteria:

Recovery period after antimalarial treatment and/or treatment of helminthiasis (at least 3 days).
Uncontrolled diabetes or hypertension or any patients requiring clinical stabilisation; wait until appropriate treatment to control the disease has been initiated.
First trimester of pregnancy.
Traumatic lumbar puncture at Screening i.e. red blood cells visible in CSF; wait for 48 hours before repeating lumbar puncture.

Eligibility Criteria for Out-patient Treatment

Accepting to be treated on an out-patient basis;
Karnofsky Performance Status > 50%;
Good understanding of the method of administration of fexinidazole by the patient and/or caregiver* (checked using a questionnaire at the time of dispensing fexinidazole);
Residing close to the investigational centre, i.e. approximately one hour by road and/or boat, during the treatment period**;
Easily reachable during the treatment period;
No medical or psychiatric contraindications for treatment as out-patient;
No pregnancy or breastfeeding;
No neurological symptoms.

Contacts and Locations

Locations

	Site	City	State	Country
1	Hôpital de Dipumba	Mbuji-Mayi	Kasaï Oriental	Congo, The Democratic Republic of the
2	Hopital General de réference	Bagata		Congo, The Democratic Republic of the
3	Hopital Général de réference	Bandundu		Congo, The Democratic Republic of the
4	Hôpital Général de Référence Roi Baudouin	Kinshasa		Congo, The Democratic Republic of the
5	Hopital Genral de Reference Masi MAnimba	Masi-Manimba		Congo, The Democratic Republic of the
6	Hopital General de réference	Mushie		Congo, The Democratic Republic of the
7	HGR Nkara	Nkara		Congo, The Democratic Republic of the
8	Hopital de Dubreka	Dubreka		Guinea