Clinical trial NCT03974178: Fexinidazole in Human African Trypanosomiasis Due to T. b. Rhodesiense
Official title: Efficacy and Safety of Fexinidazole in Patients With Human African Trypanosomiasis (HAT) Due to Trypanosoma Brucei Rhodesiense: a Multicentre, Open-label Clinical Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Trypanosomiasis, African
Sleeping Sickness
Trypanosoma Brucei Rhodesiense; Infection
Keywords: Trypanosoma Brucei (T. b.) rhodesiense
HAT
Neglected Tropical Disease
Lead sponsor: Drugs for Neglected Diseases
Sponsor class: OTHER
Collaborators: name: European and Developing Countries Clinical Trials Partnership (EDCTP)
First posted: 2019-06-04
Enrollment: 45
Sex: ALL
Minimum age (years): 6
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The ultimate goal of this study is to show that fexinidazole offers an alternative over the existing treatments of Human African trypanosomiasis due to Trypanosoma brucei rhodesiense (r-HAT): melarsoprol in patients with stage 2 r-HAT and suramin in patients with stage 1 r-HAT. The main questions it aims to answer are:

* Is the short-term fatality rate and failure rate associated with fexinidazole lower than those of melarsoprol in patients with stage 2 r-HAT?
* Is the long-term failure rate associated with fexinidazole lower than that of melarsoprol in patients with stage 2 r-HAT?
* Can fexinidazole in patients with stage 1 r-HAT replace the treatment with suramin?
* Is fexinidazole treatment safe in patient with r-HAT, regardless of stage?

Participants will receive fexinidazole oral treatment for 10 days. Regular blood draws and lumbar punctures will be performed over 12 months to confirm the cure of the disease. Other assessments will include the recording of adverse events, signs and symptoms of the disease, laboratory tests, vital signs, electrocardiograms.


Eligibility criteria: Inclusion Criteria:

* Signed Informed Consent Form (plus assent for children)
* ≥ 6 years old
* ≥ 20 kg body weight
* Ability to ingest at least one complete meal per day (or at least one Plumpy'Nut® sachet)
* Karnofsky index ≥ 40
* Parasitological confirmation of T. b. rhodesiense infection
* Having a permanent address or being traceable by others and willing and able to comply with follow-up visit schedule
* Agreement to be hospitalised for a minimum of 13 days and to receive the study treatment

Exclusion Criteria:

* Active clinically relevant medical conditions other than HAT that may jeopardize subject safety or at the investigator discretion may interfere with participation in the study.
* Compromised general health or severely deteriorated general condition, such as severe malnutrition, cardiovascular shock, respiratory distress, or terminal illness
* Patients with severe hepatic impairment (e.g.: clinical signs of cirrhosis or jaundice)
* Known hypersensitivity to fexinidazole, to any nitroimidazole drugs (e.g. metronidazole, tinidazole), or to any of the excipients
* Patients previously enrolled in the study or having already received fexinidazole

Primary outcomes:
measure: Percentage of Evaluable Patients With Stage 2 r-HAT Who Died by the End of Hospitalization, Considering Only Deaths Possibly Related to r-HAT or Fexinidazole
timeFrame: 12 to 18 days after start of treatment
Secondary outcomes:
measure: Percentage of Evaluable Patients With Stage 2 r-HAT, Whose Treatment Outcome is a Failure at the End of Hospitalization
timeFrame: 12 to 18 days after start of treatment
measure: Percentage of Evaluable Patients With Stage 2 r-HAT, Whose Treatment Outcome is a Failure at 12 Months
timeFrame: 12 months after start of treatment
measure: Percentage of Evaluable Patients With Stage 1 r-HAT, Whose Treatment Outcome is a Failure at the End of Hospitalization
timeFrame: 12 to 18 days after start of treatment
measure: Percentage of Evaluable Patients With Stage 1 r-HAT, Whose Treatment Outcome is a Failure at 12 Months
timeFrame: 12 months after start of treatment
measure: Percentage of Evaluable Patients With Any r-HAT Stage Who Died by the End of Hospitalization, Considering Only Deaths Possibly Related to r-HAT or Fexinidazole
timeFrame: 12 to 18 days after start of treatment
measure: Percentage of Evaluable Patients With Any r-HAT Stage, Whose Treatment Outcome is a Failure at the End of Hospitalization
timeFrame: 12 to 18 days after start of treatment
measure: Percentage of Evaluable Patients With Any r-HAT Stage, Whose Treatment Outcome is a Failure at 12 Months
timeFrame: 12 months after start of treatment
measure: Number of Participants With Any AE (Including Abnormal Laboratory or ECG Finding if Considered Clinically Significant) Until the End of Hospitalization
timeFrame: 12 to 18 days (between Day 1 and Day 12-18)
measure: Number of Participants With Any AE Considered as Serious Until the End of the Follow-up Period
timeFrame: 12 months (between Day 1 and Month 12)
measure: Number of Participants With Any AE Considered as Possibly Related to Fexinidazole Until the End of the Follow-up Period
timeFrame: 12 months (between Day 1 and Month 12)
Other outcomes:
Locations:
city: Rumphi
country: Malawi
facility: Rumphi District Hospital
city: Lwala
country: Uganda
facility: Lwala Hospital
state: Kadeberamaido
Study officials:
affiliation: Makerere University
name: Enock Matovu, Prof
role: PRINCIPAL_INVESTIGATOR
References: