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

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.

Time frame: 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.

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).

Time frame: 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.

Time frame: 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 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).

Time frame: 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).

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.

Time frame: 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.

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).

Time frame: 12 months 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.

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).

Time frame: 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.

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).

Time frame: 12 months 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.

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).

Time frame: 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.

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).

Time frame: 12 months 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.

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).

Time frame: 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.