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

Human African Trypanosomiasis (HAT) Clinical Trial

Official 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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02169557
• Other study ID #: DNDiHATFEX005
• Status: Completed
• Phase: Phase 2/Phase 3
• Start date: April 30, 2014
• Est. completion date: April 25, 2017

Study information

• Verified date: June 2020
• Source: Drugs for Neglected Diseases
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 230
• Est. completion date: April 25, 2017
• Est. primary completion date: October 9, 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 15 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Human African Trypanosomiasis (HAT)
• Trypanosomiasis
• Trypanosomiasis, African

Intervention

Drug:
• Fexinidazole

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Drugs for Neglected Diseases

Country where clinical trial is conducted

Congo, The Democratic Republic of the, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Safety	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).	From signature of informed consent to 18 months Follow up visit
Primary	Outcome (success or failure) at the test of cure (ToC) visit 12 months after the end of treatment (EOT).		12 months after end of treatment (day 11)
Secondary	Success or failure at each visit between the End of treatment and 18 months visit.		End of treatment (day 11) to last follow-up visit (18 months)