Efficacy and Safety of Acoziborole (SCYX-7158) in Patients With Human African Trypanosomiasis Due to T.b. Gambiense

Success was defined according to an algorithm based on the criteria adapted from the WHO Recommendations of the Informal Consultation on Issues for Clinical Product Development for Human African Trypanosomiasis 2007 (WHO/CDS/NTD/IDM/2007.1). Success was defined as a cure or a probable cure. Failure was defined as a relapse, probable relapse, death, use of rescue medication, loss to follow-up, refusal of all post-treatment lumbar puncture, and, in the absence of lumbar puncture at the Month 18 visit, an unfavorable outcome earlier than Month 18, or signs and symptoms evoking a relapse at Month 18. An estimate of the percentage of participants whose treatment outcome was a success at Month 18 and the 95% Jeffreys confidence interval (CI) of the estimate were provided.

Success was defined according to an algorithm based on the criteria adapted from the WHO Recommendations of the Informal Consultation on Issues for Clinical Product Development for Human African Trypanosomiasis 2007 (WHO/CDS/NTD/IDM/2007.1). Success was defined as a cure or a probable cure. Failure was defined as a relapse, probable relapse, death, use of rescue medication, loss to follow-up, refusal of all post-treatment lumbar puncture, and, in the absence of lumbar puncture at the end of Month 12, an unfavorable outcome earlier than end of Month 12, or signs and symptoms evoking a relapse at end of Month 12. For participants who continued after Month 12, data after Month 12 were considered in the algorithm. An estimate of the percentage of participants whose treatment outcome was a success at Month 12 and the 95% Jeffreys CI of the estimate were provided.

Success was defined according to an algorithm based on to the criteria adapted from the WHO Recommendations of the Informal Consultation on Issues for Clinical Product Development for Human African Trypanosomiasis 2007 (WHO/CDS/NTD/IDM/2007.1). Success was defined as a cure or a probable cure. Failure was defined as a relapse, probable relapse, death, use of rescue medication, loss to follow-up, refusal of all post-treatment lumbar puncture, and, in the absence of lumbar puncture at the end of Month 6, an unfavorable outcome earlier than end of Month 6, or signs and symptoms evoking a relapse at end of Month 6. For participants who continued after Month 6, data after Month 6 were considered in the algorithm. An estimate of the percentage of participants whose treatment outcome was a success at Month 6 and the 95% Jeffreys CI of the estimate were provided.

Success was defined according to an algorithm based on the criteria adapted from the WHO Recommendations of the Informal Consultation on Issues for Clinical Product Development for Human African Trypanosomiasis 2007 (WHO/CDS/NTD/IDM/2007.1). Success was defined as a cure or a probable cure. Failure was defined as a relapse, probable relapse, death, use of rescue medication, loss to follow-up, refusal of all post-treatment lumbar puncture, and, in the absence of lumbar puncture at the end of Month 18, an unfavorable outcome earlier than end of Month 18, or signs and symptoms evoking a relapse at end of Month 18. An estimate of the percentage of participants whose treatment outcome was a success at Month 18 and the 95% Jeffreys CI of the estimate were provided.

Success was defined according to an algorithm based on the criteria adapted from the WHO Recommendations of the Informal Consultation on Issues for Clinical Product Development for Human African Trypanosomiasis 2007 (WHO/CDS/NTD/IDM/2007.1). Success was defined as a cure or a probable cure. Failure was defined as a relapse, probable relapse, death, use of rescue medication, loss to follow-up, refusal of all post-treatment lumbar puncture, and, in the absence of lumbar puncture at the end of Month 12, an unfavorable outcome earlier than end of Month 12, or signs and symptoms evoking a relapse at end of Month 12. For participants who continued after Month 12, data after Month 12 were considered in the algorithm. An estimate of the percentage of participants whose treatment outcome was a success at Month 12 and the 95% Jeffreys CI of the estimate were provided.

Success was defined according to an algorithm based on the criteria adapted from the WHO Recommendations of the Informal Consultation on Issues for Clinical Product Development for Human African Trypanosomiasis 2007 (WHO/CDS/NTD/IDM/2007.1). Success was defined as a cure or a probable cure. Failure was defined as a relapse, probable relapse, death, use of rescue medication, loss to follow-up, refusal of all post-treatment lumbar puncture, and, in the absence of lumbar puncture at the end of Month 6, an unfavorable outcome earlier than end of Month 6, or signs and symptoms evoking a relapse at end of Month 6. For participants who continued after Month 6, data after Month 6 were considered in the algorithm. An estimate of the percentage of participants whose treatment outcome was a success at Month 6 and the 95% Jeffreys CI of the estimate were provided.

Failure was defined as the first objective evidence of proven and definitive (sustainable) failure, defined as death; rescue medication use; trypanosomes in any body fluid at Month 6, 12, or 18; a cerebrospinal fluid (CSF) white blood cell count (WBC) of >50 cells/μL at Month 6 followed by confirmation of failure (defined as CSF WBC >20 cells/μL at Month 12 and/or Month 18 and/or signs and symptoms evoking a relapse at Month 12 and/or Month 18); a CSF WBC >20 cells/μL at Month 12 followed by confirmation of failure (defined as CSF WBC >20 cells/μL at Month 18 and/or signs and symptoms evoking a relapse at Month 18); or a CSF WBC >20 cells/μL at Month 18. This outcome was analyzed using a Kaplan-Meier approach to estimate the cumulative rate of proven and definitive failures. The proven failure-free probability was estimated as an alternative (more liberal) success rate (95% CI) at Month 18 based on the Kaplan-Meier estimate of the rate of participants who were not proven failures

Occurrence of any AEs, during the observation period and until 6 months post-dose (for non-serious AEs) and until 18 months post-dose for SAEs. Analysis of AEs was based on the concept of TEAEs, defined as any AEs occurring on or after the date of study-drug administration or worsening in intensity on or after the date of study-drug administration.

Occurrence of any serious TEAEs during the observation period and until 18 months post-dose.

Participants received a single dose of 960 mg acoziborole on Day 1. Acoziborole in whole blood was assessed pre-dose and 4, 9, 24, 48, 72, 96, and 240 hours after the single administration, (on Days 1, 2, 3, 4, 5, and 11). Data up to 240 hours post dose were considered for this analysis. Descriptive statistics of the AUC0-240h were presented. The activity of acoziborole is more exposure-dependent than concentration-dependent, therefore the exposure (AUC) was used as the main PK data for efficacy purposes.

Participants received a single dose of 960 mg acoziborole on Day 1. Acoziborole in CSF of participants with late-stage HAT was assessed 240 hours after the single administration (on Day 11). Descriptive statistics of the acoziborole concentration were presented.

Participants received a single dose of 960 mg acoziborole on Day 1. Acoziborole in CSF of participants with early- and intermediate-stage HAT was assessed 240 hours after the single administration (on Day 11). Descriptive statistics of the acoziborole concentration were presented.