Trial Outcomes & Findings for Fexinidazole in Human African Trypanosomiasis Due to T. b. Rhodesiense (NCT NCT03974178)

Last Updated: 2025-01-30

Results Overview

The percentage of patients who died between the first intake of fexinidazole until the End-of-Hospitalization Visit (Day 12-18), considering only deaths possibly related to r-HAT or study treatment as assessed by the Data Safety Monitoring Board (DSMB), was calculated. The World Health Organization(WHO) verbal autopsy questionnaire was used since anatomopathological techniques were not available at the study sites (unless the death occurred at the hospital, in which case the investigator was present). In case of death that was not related to r-HAT nor to the study treatment during the hospitalization, the patient is considered as non-evaluable for efficacy purposes. Any patient who left the hospital without being medically discharged by the site Investigator before the planned End-of-Hospitalization Visit, and for whom no outcome could be retrieved, is also to be considered as non-evaluable.

Recruitment status

COMPLETED

Study phase

PHASE2/PHASE3

Target enrollment

45 participants

Primary outcome timeframe

12 to 18 days after start of treatment

Results posted on

2025-01-30

Participant Flow

The study was conducted at 1 center in Malawi (Rumphi District Hospital) and 1 center in Uganda (Lwala Hospital). 46 participants were screened and signed informed consent. The screening pool was enlarged to other hospitals and centres in Uganda, Rumphi/Mzimba North District (Malawi), and Nkhotakota District (Malawi), from where patients could be referred to Lwala and Rumphi Hospitals for treatment. 45 participants were enrolled between 29 Sep 2019 and 17 Nov 2021.

The pre-treatment period of up to 7 days included screening and treatment of concurrent malaria and soil-transmitted helminthiasis. At the end of this period, all participants were treated with fexinidazole, regardless of the stage of human African trypanosomiasis due to Trypanosoma brucei rhodesiense (r-HAT) and treatment setting.

Participant milestones

Participant milestones
Measure	Patients With Stage 1 r-HAT Patients without trypanosomes in the CSF but with trypanosomes in the blood and/or lymph and CSF WBC ≤5 cells/µL were classified as stage 1. Fexinidazole: Tablets of 600 mg; Participants with a weight between 20 and 34 kg received 1200 mg (2 tablets) for 4 days, then 600 mg (1 tablet) for 6 days (with food); Participants with a weight of 35 kg and above received 1800 mg (3 tablets) for 4 days, then 1200 mg (2 tablets) for 6 days (with food).	Patients With Stage 2 r-HAT Patients with trypanosomes in the CSF (and/or in blood/lymph) and/or CSF WBC \>5 cells/µL were classified as stage 2. Fexinidazole: Tablets of 600 mg; Participants with a weight between 20 and 34 kg received 1200 mg (2 tablets) for 4 days, then 600 mg (1 tablet) for 6 days (with food); Participants with a weight of 35 kg and above received 1800 mg (3 tablets) for 4 days, then 1200 mg (2 tablets) for 6 days (with food).
Overall Study STARTED	10	35
Overall Study COMPLETED	10	34
Overall Study NOT COMPLETED	0	1

Reasons for withdrawal

Reasons for withdrawal
Measure	Patients With Stage 1 r-HAT Patients without trypanosomes in the CSF but with trypanosomes in the blood and/or lymph and CSF WBC ≤5 cells/µL were classified as stage 1. Fexinidazole: Tablets of 600 mg; Participants with a weight between 20 and 34 kg received 1200 mg (2 tablets) for 4 days, then 600 mg (1 tablet) for 6 days (with food); Participants with a weight of 35 kg and above received 1800 mg (3 tablets) for 4 days, then 1200 mg (2 tablets) for 6 days (with food).	Patients With Stage 2 r-HAT Patients with trypanosomes in the CSF (and/or in blood/lymph) and/or CSF WBC \>5 cells/µL were classified as stage 2. Fexinidazole: Tablets of 600 mg; Participants with a weight between 20 and 34 kg received 1200 mg (2 tablets) for 4 days, then 600 mg (1 tablet) for 6 days (with food); Participants with a weight of 35 kg and above received 1800 mg (3 tablets) for 4 days, then 1200 mg (2 tablets) for 6 days (with food).
Overall Study Death	0	1

Baseline Characteristics

Fexinidazole in Human African Trypanosomiasis Due to T. b. Rhodesiense

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Patients With Stage 1 r-HAT n=10 Participants Patients with stage 1 r-HAT were patients without trypanosomes in the cerebrospinal fluid (CSF) but with trypanosomes in the blood and/or lymph and CSF white blood cells (WBC) ≤5 cells/µL.	Patients With Stage 2 r-HAT n=35 Participants Patients with stage 2 r-HAT were patients with trypanosomes in the CSF (and/or in blood/lymph) and/or CSF WBC \>5 cells/µL.	Total n=45 Participants Total of all reporting groups
Age, Continuous	33.2 years STANDARD_DEVIATION 18.3 • n=5 Participants	25.2 years STANDARD_DEVIATION 15.2 • n=7 Participants	27.0 years STANDARD_DEVIATION 16.1 • n=5 Participants
Sex: Female, Male Female	1 Participants n=5 Participants	13 Participants n=7 Participants	14 Participants n=5 Participants
Sex: Female, Male Male	9 Participants n=5 Participants	22 Participants n=7 Participants	31 Participants n=5 Participants
Race/Ethnicity, Customized Sub-Saharan African	10 Participants n=5 Participants	35 Participants n=7 Participants	45 Participants n=5 Participants
Region of Enrollment Malawi	9 Participants n=5 Participants	34 Participants n=7 Participants	43 Participants n=5 Participants
Region of Enrollment Uganda	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
r-HAT stage: Stage 1, Stage 2 Stage 1	10 Participants n=5 Participants	0 Participants n=7 Participants	10 Participants n=5 Participants
r-HAT stage: Stage 1, Stage 2 Stage 2	0 Participants n=5 Participants	35 Participants n=7 Participants	35 Participants n=5 Participants
White blood cells (WBC) in cerebrospinal fluid (CSF)	1.7 cells/µL STANDARD_DEVIATION 1.6 • n=5 Participants	79.3 cells/µL STANDARD_DEVIATION 103.2 • n=7 Participants	62.1 cells/µL STANDARD_DEVIATION 96.4 • n=5 Participants

PRIMARY outcome

Timeframe: 12 to 18 days after start of treatment

Population: The analysis is performed in evaluable patients with stage 2 r-HAT. A total of 35 patients with stage 2 r-HAT were enrolled and treated. One patient died during hospitalization, but the death was considered unrelated to r-HAT and/or the study treatment, as evaluated by the Investigator and the DSMB and accepted by the Sponsor. As per protocol, this patient was considered non-evaluable for efficacy purposes. There were 34 patients with stage 2 r-HAT who were evaluable.

Outcome measures

Outcome measures
Measure	Patients With Stage 2 r-HAT n=34 Participants Patients with trypanosomes in the CSF (and/or in blood/lymph) and/or CSF WBC \>5 cells/µL were classified as stage 2. Fexinidazole: Tablets of 600 mg; Participants with a weight between 20 and 34 kg received 1200 mg (2 tablets) for 4 days, then 600 mg (1 tablet) for 6 days (with food); Participants with a weight of 35 kg and above received 1800 mg (3 tablets) for 4 days, then 1200 mg (2 tablets) for 6 days (with food)
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	0 percentage of participants Interval 0.0 to 8.43

SECONDARY outcome

Timeframe: 12 to 18 days after start of treatment

Treatment outcome at end of hospitalization (Day 12-18) is categorized as success or failure. Failure is defined as any of the following: presence of trypanosomes in any body fluid at end of treatment (Day 11), death related to r-HAT or fexinidazole at end of hospitalization according to the DSMB, or absence of clinical improvement leading to the use of rescue medication. Unrelated deaths are neither success nor failure (the patient is considered non-evaluable for efficacy purposes).

Outcome measures

Outcome measures
Measure	Patients With Stage 2 r-HAT n=34 Participants Patients with trypanosomes in the CSF (and/or in blood/lymph) and/or CSF WBC \>5 cells/µL were classified as stage 2. Fexinidazole: Tablets of 600 mg; Participants with a weight between 20 and 34 kg received 1200 mg (2 tablets) for 4 days, then 600 mg (1 tablet) for 6 days (with food); Participants with a weight of 35 kg and above received 1800 mg (3 tablets) for 4 days, then 1200 mg (2 tablets) for 6 days (with food)
Percentage of Evaluable Patients With Stage 2 r-HAT, Whose Treatment Outcome is a Failure at the End of Hospitalization	0 percentage of participants Interval 0.0 to 8.43

SECONDARY outcome

Timeframe: 12 months after start of treatment

Treatment outcome at test of cure (Month 12) is categorized as success or failure. Failure is defined as any of the following: presence of trypanosomes in any body fluid, death related to r-HAT or fexinidazole according to the DSMB, absence of clinical improvement leading to the use of rescue medication, or WBC count in the CSF \>20 cells/μL which was unlikely due to causes other than HAT. Unrelated deaths are neither success nor failure (the patient is considered non-evaluable for efficacy purposes).

Outcome measures

Outcome measures
Measure	Patients With Stage 2 r-HAT n=34 Participants Patients with trypanosomes in the CSF (and/or in blood/lymph) and/or CSF WBC \>5 cells/µL were classified as stage 2. Fexinidazole: Tablets of 600 mg; Participants with a weight between 20 and 34 kg received 1200 mg (2 tablets) for 4 days, then 600 mg (1 tablet) for 6 days (with food); Participants with a weight of 35 kg and above received 1800 mg (3 tablets) for 4 days, then 1200 mg (2 tablets) for 6 days (with food)
Percentage of Evaluable Patients With Stage 2 r-HAT, Whose Treatment Outcome is a Failure at 12 Months	2.94 percentage of participants Interval 0.15 to 13.21

SECONDARY outcome

Timeframe: 12 to 18 days after start of treatment

Population: The analysis is performed in evaluable patients with stage 1 r-HAT. None of patients with stage 1 r-HAT died from causes related to r-HAT or study treatment; therefore, all 10 patients were evaluable. Because the number of patients with stage 1 r-HAT is very small, no null hypotheses are testable and only descriptive data are provided.

Outcome measures

Outcome measures
Measure	Patients With Stage 2 r-HAT n=10 Participants Patients with trypanosomes in the CSF (and/or in blood/lymph) and/or CSF WBC \>5 cells/µL were classified as stage 2. Fexinidazole: Tablets of 600 mg; Participants with a weight between 20 and 34 kg received 1200 mg (2 tablets) for 4 days, then 600 mg (1 tablet) for 6 days (with food); Participants with a weight of 35 kg and above received 1800 mg (3 tablets) for 4 days, then 1200 mg (2 tablets) for 6 days (with food)
Percentage of Evaluable Patients With Stage 1 r-HAT, Whose Treatment Outcome is a Failure at the End of Hospitalization	0 percentage of participants

SECONDARY outcome

Timeframe: 12 months after start of treatment

Outcome measures

Outcome measures
Measure	Patients With Stage 2 r-HAT n=10 Participants Patients with trypanosomes in the CSF (and/or in blood/lymph) and/or CSF WBC \>5 cells/µL were classified as stage 2. Fexinidazole: Tablets of 600 mg; Participants with a weight between 20 and 34 kg received 1200 mg (2 tablets) for 4 days, then 600 mg (1 tablet) for 6 days (with food); Participants with a weight of 35 kg and above received 1800 mg (3 tablets) for 4 days, then 1200 mg (2 tablets) for 6 days (with food)
Percentage of Evaluable Patients With Stage 1 r-HAT, Whose Treatment Outcome is a Failure at 12 Months	0 percentage of participants

SECONDARY outcome

Timeframe: 12 to 18 days after start of treatment

Population: The analysis is performed in evaluable patients with any r-HAT stage. A total of 45 patients were enrolled and treated. One patient died during hospitalization, but the death was considered unrelated to r-HAT and/or the study treatment, as evaluated by the Investigator and the DSMB and accepted by the Sponsor. As per protocol, this patient was considered non-evaluable for efficacy purposes. There were 44 patients who were evaluable.

The percentage of patients who died between the first intake of fexinidazole until the End-of-Hospitalization Visit (Day 12-18), considering only deaths possibly related to r-HAT or study treatment as assessed by the DSMB, was calculated. The WHO verbal autopsy questionnaire was used since anatomopathological techniques were not available at the study sites (unless the death occurred at the hospital, in which case the investigator was present). In case of death that was not related to r-HAT nor to the study treatment during the hospitalization, the patient is considered as non-evaluable for efficacy purposes. Any patient who left the hospital without being medically discharged by the site Investigator before the planned End-of-Hospitalization Visit, and for whom no outcome could be retrieved, is also to be considered as non-evaluable.

Outcome measures

Outcome measures
Measure	Patients With Stage 2 r-HAT n=44 Participants Patients with trypanosomes in the CSF (and/or in blood/lymph) and/or CSF WBC \>5 cells/µL were classified as stage 2. Fexinidazole: Tablets of 600 mg; Participants with a weight between 20 and 34 kg received 1200 mg (2 tablets) for 4 days, then 600 mg (1 tablet) for 6 days (with food); Participants with a weight of 35 kg and above received 1800 mg (3 tablets) for 4 days, then 1200 mg (2 tablets) for 6 days (with food)
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	0 percentage of participants Interval 0.0 to 6.58

SECONDARY outcome

Timeframe: 12 to 18 days after start of treatment

Outcome measures

Outcome measures
Measure	Patients With Stage 2 r-HAT n=44 Participants Patients with trypanosomes in the CSF (and/or in blood/lymph) and/or CSF WBC \>5 cells/µL were classified as stage 2. Fexinidazole: Tablets of 600 mg; Participants with a weight between 20 and 34 kg received 1200 mg (2 tablets) for 4 days, then 600 mg (1 tablet) for 6 days (with food); Participants with a weight of 35 kg and above received 1800 mg (3 tablets) for 4 days, then 1200 mg (2 tablets) for 6 days (with food)
Percentage of Evaluable Patients With Any r-HAT Stage, Whose Treatment Outcome is a Failure at the End of Hospitalization	0 percentage of participants Interval 0.0 to 6.58

SECONDARY outcome

Timeframe: 12 months after start of treatment

Outcome measures

Outcome measures
Measure	Patients With Stage 2 r-HAT n=44 Participants Patients with trypanosomes in the CSF (and/or in blood/lymph) and/or CSF WBC \>5 cells/µL were classified as stage 2. Fexinidazole: Tablets of 600 mg; Participants with a weight between 20 and 34 kg received 1200 mg (2 tablets) for 4 days, then 600 mg (1 tablet) for 6 days (with food); Participants with a weight of 35 kg and above received 1800 mg (3 tablets) for 4 days, then 1200 mg (2 tablets) for 6 days (with food)
Percentage of Evaluable Patients With Any r-HAT Stage, Whose Treatment Outcome is a Failure at 12 Months	2.27 percentage of participants Interval 0.12 to 10.34

SECONDARY outcome

Timeframe: 12 to 18 days (between Day 1 and Day 12-18)

Population: The analysis is performed in all patients who took at least one dose of fexinidazole (regardless of r-HAT stage).

Treatment-emergent AEs during the observation period were recorded from the first intake of fexinidazole (Day 1) until the End-of-Hospitalization Visit (between Day 12 and Day 18).

Outcome measures

Outcome measures
Measure	Patients With Stage 2 r-HAT n=45 Participants Patients with trypanosomes in the CSF (and/or in blood/lymph) and/or CSF WBC \>5 cells/µL were classified as stage 2. Fexinidazole: Tablets of 600 mg; Participants with a weight between 20 and 34 kg received 1200 mg (2 tablets) for 4 days, then 600 mg (1 tablet) for 6 days (with food); Participants with a weight of 35 kg and above received 1800 mg (3 tablets) for 4 days, then 1200 mg (2 tablets) for 6 days (with food)
Number of Participants With Any AE (Including Abnormal Laboratory or ECG Finding if Considered Clinically Significant) Until the End of Hospitalization	22 Participants

SECONDARY outcome

Timeframe: 12 months (between Day 1 and Month 12)

Population: The analysis is performed in all patients who took at least one dose of fexinidazole (regardless of r-HAT stage).

Treatment-emergent AEs considered as serious were collected from the first intake of fexinidazole (Day 1) until the End-of-Study Visit (Month 12). An AE was considered as serious if resulted in death, was life-threatening, required in-patient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability or incapacity, was a congenital anomaly or birth defect, or was an important medical event.

Outcome measures

Outcome measures
Measure	Patients With Stage 2 r-HAT n=45 Participants Patients with trypanosomes in the CSF (and/or in blood/lymph) and/or CSF WBC \>5 cells/µL were classified as stage 2. Fexinidazole: Tablets of 600 mg; Participants with a weight between 20 and 34 kg received 1200 mg (2 tablets) for 4 days, then 600 mg (1 tablet) for 6 days (with food); Participants with a weight of 35 kg and above received 1800 mg (3 tablets) for 4 days, then 1200 mg (2 tablets) for 6 days (with food)
Number of Participants With Any AE Considered as Serious Until the End of the Follow-up Period	3 Participants

SECONDARY outcome

Timeframe: 12 months (between Day 1 and Month 12)

Population: The analysis is performed in all patients who took at least one dose of fexinidazole (regardless of r-HAT stage).

Treatment-emergent AEs considered as possibly related to fexinidazole were collected from the first intake of fexinidazole (Day 1) until the End-of-Study Visit (Month 12).

Outcome measures

Outcome measures
Measure	Patients With Stage 2 r-HAT n=45 Participants Patients with trypanosomes in the CSF (and/or in blood/lymph) and/or CSF WBC \>5 cells/µL were classified as stage 2. Fexinidazole: Tablets of 600 mg; Participants with a weight between 20 and 34 kg received 1200 mg (2 tablets) for 4 days, then 600 mg (1 tablet) for 6 days (with food); Participants with a weight of 35 kg and above received 1800 mg (3 tablets) for 4 days, then 1200 mg (2 tablets) for 6 days (with food)
Number of Participants With Any AE Considered as Possibly Related to Fexinidazole Until the End of the Follow-up Period	5 Participants

Adverse Events

Patients With Stage 1 r-HAT

Serious events: 0 serious events

Other events: 6 other events

Deaths: 0 deaths

Patients With Stage 2 r-HAT

Serious events: 3 serious events

Other events: 16 other events

Deaths: 1 deaths

Serious adverse events

Serious adverse events
Measure	Patients With Stage 1 r-HAT n=10 participants at risk Patients with stage 1 r-HAT were patients without trypanosomes in the cerebrospinal fluid (CSF) but with trypanosomes in the blood and/or lymph and CSF white blood cells (WBC) ≤5 cells/µL.	Patients With Stage 2 r-HAT n=35 participants at risk Patients with stage 2 r-HAT were patients with trypanosomes in the CSF (and/or in blood/lymph) and/or CSF WBC \>5 cells/µL.
Renal and urinary disorders Acute kidney injury	0.00% 0/10 • Non-serious treatment-emergent adverse events (AEs) were recorded from the first intake of fexinidazole (Day 1) until the End-of-Hospitalization Visit (Day 12-18). Treatment-emergent AEs considered as serious or related to fexinidazole treatment were collected from the first intake of fexinidazole (Day 1) until the End-of-Study Visit (Month 12). The population of analysis includes all patients who received at least one dose of fexinidazole. Adverse events were classified as serious according to the standard definition. In addition, in this study, alanine aminotransferase or aspartate aminotransferase levels higher than 3 times the upper limit of normal associated with total bilirubin levels higher than 2 times the upper limit of normal were considered as serious AEs (SAEs). Furthermore, any suspected transmission of an infectious agent via a medicinal product was also considered as an SAE.	2.9% 1/35 • Number of events 1 • Non-serious treatment-emergent adverse events (AEs) were recorded from the first intake of fexinidazole (Day 1) until the End-of-Hospitalization Visit (Day 12-18). Treatment-emergent AEs considered as serious or related to fexinidazole treatment were collected from the first intake of fexinidazole (Day 1) until the End-of-Study Visit (Month 12). The population of analysis includes all patients who received at least one dose of fexinidazole. Adverse events were classified as serious according to the standard definition. In addition, in this study, alanine aminotransferase or aspartate aminotransferase levels higher than 3 times the upper limit of normal associated with total bilirubin levels higher than 2 times the upper limit of normal were considered as serious AEs (SAEs). Furthermore, any suspected transmission of an infectious agent via a medicinal product was also considered as an SAE.
Infections and infestations Pneumonia	0.00% 0/10 • Non-serious treatment-emergent adverse events (AEs) were recorded from the first intake of fexinidazole (Day 1) until the End-of-Hospitalization Visit (Day 12-18). Treatment-emergent AEs considered as serious or related to fexinidazole treatment were collected from the first intake of fexinidazole (Day 1) until the End-of-Study Visit (Month 12). The population of analysis includes all patients who received at least one dose of fexinidazole. Adverse events were classified as serious according to the standard definition. In addition, in this study, alanine aminotransferase or aspartate aminotransferase levels higher than 3 times the upper limit of normal associated with total bilirubin levels higher than 2 times the upper limit of normal were considered as serious AEs (SAEs). Furthermore, any suspected transmission of an infectious agent via a medicinal product was also considered as an SAE.	2.9% 1/35 • Number of events 1 • Non-serious treatment-emergent adverse events (AEs) were recorded from the first intake of fexinidazole (Day 1) until the End-of-Hospitalization Visit (Day 12-18). Treatment-emergent AEs considered as serious or related to fexinidazole treatment were collected from the first intake of fexinidazole (Day 1) until the End-of-Study Visit (Month 12). The population of analysis includes all patients who received at least one dose of fexinidazole. Adverse events were classified as serious according to the standard definition. In addition, in this study, alanine aminotransferase or aspartate aminotransferase levels higher than 3 times the upper limit of normal associated with total bilirubin levels higher than 2 times the upper limit of normal were considered as serious AEs (SAEs). Furthermore, any suspected transmission of an infectious agent via a medicinal product was also considered as an SAE.
Infections and infestations Urinary tract infection	0.00% 0/10 • Non-serious treatment-emergent adverse events (AEs) were recorded from the first intake of fexinidazole (Day 1) until the End-of-Hospitalization Visit (Day 12-18). Treatment-emergent AEs considered as serious or related to fexinidazole treatment were collected from the first intake of fexinidazole (Day 1) until the End-of-Study Visit (Month 12). The population of analysis includes all patients who received at least one dose of fexinidazole. Adverse events were classified as serious according to the standard definition. In addition, in this study, alanine aminotransferase or aspartate aminotransferase levels higher than 3 times the upper limit of normal associated with total bilirubin levels higher than 2 times the upper limit of normal were considered as serious AEs (SAEs). Furthermore, any suspected transmission of an infectious agent via a medicinal product was also considered as an SAE.	2.9% 1/35 • Number of events 1 • Non-serious treatment-emergent adverse events (AEs) were recorded from the first intake of fexinidazole (Day 1) until the End-of-Hospitalization Visit (Day 12-18). Treatment-emergent AEs considered as serious or related to fexinidazole treatment were collected from the first intake of fexinidazole (Day 1) until the End-of-Study Visit (Month 12). The population of analysis includes all patients who received at least one dose of fexinidazole. Adverse events were classified as serious according to the standard definition. In addition, in this study, alanine aminotransferase or aspartate aminotransferase levels higher than 3 times the upper limit of normal associated with total bilirubin levels higher than 2 times the upper limit of normal were considered as serious AEs (SAEs). Furthermore, any suspected transmission of an infectious agent via a medicinal product was also considered as an SAE.

Other adverse events

Additional Information

Dr. Olaf Valverde Mordt

Drugs for Neglected Diseases initiative (DNDi)

Phone: +41229069239/+41795431713

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The sponsor authorizes publications by a single site provided that multicentric results are published beforehand and that any communication is submitted to sponsor for review at least 28 days ahead of the expected date of publication. Upon sponsor request, any confidential information will have to be removed from the communication before publishing.
Publication restrictions are in place

Restriction type: OTHER