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Efficacy and Safety of Fexinidazole in Patients With Stage 1 or Early Stage 2 Human African Trypanosomiasis (HAT) Due to T.b. Gambiense: a Prospective, Multicentre, Open-label Cohort Study, plug-in to the Pivotal Study

Primary Purpose

Human African Trypanosomiasis (HAT)

Status

Completed

Phase

Phase 2

Locations

Congo, The Democratic Republic of the

Study Type

Interventional

Intervention

Fexinidazole

About this trial

This is an interventional treatment trial for Human African Trypanosomiasis (HAT)

Eligibility Criteria

15 Years - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Signed informed consent
15 years old or more
Male or female
Ability to ingest at least one complete meal per day (or at least one Plumpy'Nut® sachet)
Karnofsky index > 50
Presence of trypanosomes in blood or lymph
Absence of trypanosomes in CSF
Permanent address and ability to comply with the follow-up visit schedule
Patient agreeing to be hospitalized to receive the treatment

Exclusion Criteria:

Severely malnutrition, defined as BMI < 16.
Inability to take oral medication.
Pregnancy or breastfeeding (a urine pregnancy test will be performed in all women of childbearing age within 24 h prior to treatment).
Clinically relevant medical condition other than HAT that, in the Investigator's opinion, may jeopardize patient safety or interfere with participation in the study, including but not limited to significant liver or cardiovascular disease, documented or suspected active infection (including AIDS), CNS trauma or seizure disorders, coma or altered consciousness.
Severely deteriorated general condition, e.g. cardiovascular shock, respiratory distress syndrome, or terminal illness.
Any medical condition (except HAT specific symptoms) hindering communication with the Investigator as required for the completion of this study.
Any contraindication to imidazole products (known hypersensitivity to imidazoles).
History of HAT treatment in the past 2 years.
Patients previously enrolled in the study or having already received fexinidazole.
Expected follow-up difficulties (migrants, refugees, itinerant vendors, etc.).
Current alcohol or drug abuse.
Clinically significant abnormal laboratory value, such as:
Alanine aminotransferase (ALAT) and/or aspartate aminotransferase (ASAT) > 2 times ULN
Total bilirubin (TBIL) > 1.5 times ULN
Severe leukopenia (< 2000/mm3)
Potassium (K+) < 3.5 mmol/L
Any clinically significant abnormal value (see details in Investigator Manual)
Pregnancy confirmed by a positive urine pregnancy test obtained within 24 h prior to start of study treatment (see Section 5.8.3 Contraception; p35) QTcF ≥ 450 ms as measured automatically (if the first measurement is abnormal, a second assessment will be done at least 10-20 min later, with the patient in resting position)
Patients not tested for malaria and/or not treated adequately for this infection
Patients not treated adequately for soil-transmitted helminthic diseases

Sites / Locations

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Fexinidazole

Arm Description

Outcomes

Primary Outcome Measures

Outcome (success or failure) at the test of cure (ToC) visit 12 months after the end of treatment (EOT).

Secondary Outcome Measures

Success or failure at each visit between the End of treatment and 18 months visit.

Full Information

NCT ID

NCT02169557

First Posted

May 15, 2014

Last Updated

June 23, 2020

Sponsor

Drugs for Neglected Diseases

1. Study Identification

Unique Protocol Identification Number

NCT02169557

Brief Title

Efficacy and Safety of Fexinidazole in Patients With Stage 1 or Early Stage 2 Human African Trypanosomiasis (HAT) Due to T.b. Gambiense: a Prospective, Multicentre, Open-label Cohort Study, plug-in to the Pivotal Study

Official Title

Study Type

Interventional

2. Study Status

Record Verification Date

June 2020

Overall Recruitment Status

Completed

Study Start Date

April 30, 2014 (Actual)

Primary Completion Date

October 9, 2016 (Actual)

Study Completion Date

April 25, 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Drugs for Neglected Diseases

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

The purpose of this study is to demonstrate the treatment success of fexinidazole, at one year follow-up visit, in HAT stage 1 and early stage 2 patients.

Detailed Description

Primary Objective -To demonstrate that the success rate of fexinidazole at one year follow-up in stage 1 and early stage 2 patients is greater than 80%. An 80 % success rate is considered as unacceptable. Secondary Objectives To verify whether the success rate of fexinidazole treatment depends on the stage of the disease (stage 1 versus early stage 2); and, if the difference between the 2 stages is significant, to show that the success rate is greater than 80% and compatible with the historical success rate of NECT in early stage 2 patients and with the historical success rate of pentamidine in stage 1 patients. To verify whether the success rate of fexinidazole treatment depends on the number of WBCs in CSF before treatment initiation. To assess changes in the success rate over time. To evaluate the safety of fexinidazole and determine whether its safety profile is comparable to the historical safety profile of pentamidine.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Human African Trypanosomiasis (HAT)

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2, Phase 3

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

230 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Fexinidazole

Arm Type

Experimental

Intervention Type

Drug

Intervention Name(s)

Fexinidazole

Primary Outcome Measure Information:

Title

Outcome (success or failure) at the test of cure (ToC) visit 12 months after the end of treatment (EOT).

Time Frame

12 months after end of treatment (day 11)

Secondary Outcome Measure Information:

Title

Success or failure at each visit between the End of treatment and 18 months visit.

Time Frame

End of treatment (day 11) to last follow-up visit (18 months)

Other Pre-specified Outcome Measures:

Title

Safety

Description

Occurrence of any grade AEs (all grades combined) during the observation period. Occurrence of drug-related AEs (Grade ≥ 3 and any grade) during the observation period. Occurrence of any serious adverse events (SAE) from first drug intake to the end of follow up period (M18).

Time Frame

From signature of informed consent to 18 months Follow up visit

10. Eligibility

Sex

All

Minimum Age & Unit of Time

15 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Signed informed consent 15 years old or more Male or female Ability to ingest at least one complete meal per day (or at least one Plumpy'Nut® sachet) Karnofsky index > 50 Presence of trypanosomes in blood or lymph Absence of trypanosomes in CSF Permanent address and ability to comply with the follow-up visit schedule Patient agreeing to be hospitalized to receive the treatment Exclusion Criteria: Severely malnutrition, defined as BMI < 16. Inability to take oral medication. Pregnancy or breastfeeding (a urine pregnancy test will be performed in all women of childbearing age within 24 h prior to treatment). Clinically relevant medical condition other than HAT that, in the Investigator's opinion, may jeopardize patient safety or interfere with participation in the study, including but not limited to significant liver or cardiovascular disease, documented or suspected active infection (including AIDS), CNS trauma or seizure disorders, coma or altered consciousness. Severely deteriorated general condition, e.g. cardiovascular shock, respiratory distress syndrome, or terminal illness. Any medical condition (except HAT specific symptoms) hindering communication with the Investigator as required for the completion of this study. Any contraindication to imidazole products (known hypersensitivity to imidazoles). History of HAT treatment in the past 2 years. Patients previously enrolled in the study or having already received fexinidazole. Expected follow-up difficulties (migrants, refugees, itinerant vendors, etc.). Current alcohol or drug abuse. Clinically significant abnormal laboratory value, such as: Alanine aminotransferase (ALAT) and/or aspartate aminotransferase (ASAT) > 2 times ULN Total bilirubin (TBIL) > 1.5 times ULN Severe leukopenia (< 2000/mm3) Potassium (K+) < 3.5 mmol/L Any clinically significant abnormal value (see details in Investigator Manual) Pregnancy confirmed by a positive urine pregnancy test obtained within 24 h prior to start of study treatment (see Section 5.8.3 Contraception; p35) QTcF ≥ 450 ms as measured automatically (if the first measurement is abnormal, a second assessment will be done at least 10-20 min later, with the patient in resting position) Patients not tested for malaria and/or not treated adequately for this infection Patients not treated adequately for soil-transmitted helminthic diseases

Facility Information:

City

Kinshasa

Country

Congo, The Democratic Republic of the

12. IPD Sharing Statement

Citations:

PubMed Identifier

34143998

Citation

Kande Betu Ku Mesu V, Mutombo Kalonji W, Bardonneau C, Valverde Mordt O, Ngolo Tete D, Blesson S, Simon F, Delhomme S, Bernhard S, Mahenzi Mbembo H, Mpia Moke C, Lumeya Vuvu S, Mudji E'kitiak J, Akwaso Masa F, Mukendi Ilunga M, Mpoyi Muamba Nzambi D, Mayala Malu T, Kapongo Tshilumbwa S, Botalema Bolengi F, Nkieri Matsho M, Lumbala C, Scherrer B, Strub-Wourgaft N, Tarral A. Oral fexinidazole for stage 1 or early stage 2 African Trypanosoma brucei gambiense trypanosomiasis: a prospective, multicentre, open-label, cohort study. Lancet Glob Health. 2021 Jul;9(7):e999-e1008. doi: 10.1016/S2214-109X(21)00208-4.

Results Reference

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