Gambiense Trypanosomiasis, Sleeping Sickness, Trypanosomiasis, African
Conditions
Brief summary
The goal of this study is to assess efficacy and safety of acoziborole in adult participants with Trypanosoma brucei gambiense (T.b. gambiense) HAT, either early- or intermediate-stage HAT (first arm) or late-stage HAT (second arm). Participants will receive 3 tablets of 320 mg as a single oral dose of acoziborole in the fasting state on Day 1. Participants will stay in the hospital for observation for 15 days. In total, participants will be followed for 18 months.
Interventions
DRUGAcoziborole
Acoziborole 3 x 320 mg tablets (fasted state)
Sponsors
Bill and Melinda Gates Foundation
Drugs for Neglected Diseases
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
15 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Male or female patient * 15 years of age or older * Signed informed consent form (as well as assent from illiterate and under-age patients, and those unable to give consent) * Karnofsky Performance Status above 50 * Able to ingest oral tablets * Having a permanent address or being traceable by other persons * Able to comply with the schedule of follow-up visits and requirements of the study * Agreement to be hospitalised in order to receive treatment * For patients with late-stage HAT: * Confirmation of g-HAT by detection of the parasite in the blood and/or the lymph and/or the CSF, at the investigational centre * If trypanosomes are found in the blood or lymph, but not in the CSF, the CSF WBC, measured at the investigational centre, must be above 20/μL for the patient to be included in the cohort of patients with late-stage HAT * For patients with early- or intermediate-stage HAT: * Confirmation of g-HAT by detection of the parasite in the blood and/or the lymph, at the investigational centre * Absence of parasites in the CSF * The CSF WBC, measured at the investigational centre, must be between 6 and 20/μL for the patient to be included in the cohort of patients with intermediate-stage HAT and equal to or below 5/μL for the patient to be included in the cohort of patients with early-stage HAT.
Exclusion criteria
* Severe malnourishment, defined as body-mass index (BMI) below 16 * Pregnancy or breastfeeding (for women of child-bearing potential, confirmed pregnancy on a urine pregnancy test performed within 24 hours prior to administration of acoziborole) * Clinically significant medical condition that could, in the opinion of the Investigator, jeopardise the patient's safety or interfere with participation in the study, including, but not limited to significant liver or cardiovascular disease, suspected or proven active infection, central nervous system trauma or seizure disorder, coma or consciousness disturbances * Severely deteriorated health status, e.g. due to cardiovascular shock, respiratory distress syndrome or end-stage disease * Previously treated for HAT (except prior treatment with pentamidine) * Prior enrolment in the study * Foreseeable difficulty complying with follow-up, including migrant worker, refugee status, itinerant trader etc. * Current alcohol abuse or drug addiction * Not tested for malaria and/or not having received appropriate treatment for malaria * Not having received appropriate treatment for soil-transmitted helminthiasis * Clinically significant abnormal laboratory values including aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) more than 2 times the upper limit of normal (ULN), total bilirubin more than 1.5 ULN, severe leukopenia at less than 2000/mm\^3, Potassium below 3.5 mmol/L, any other clinically significant abnormal laboratory value
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Late-stage HAT Whose Treatment Outcome Was a Success at Month 18 According to Adapted World Health Organization (WHO) Criteria | 18 months post-dose | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Late-stage HAT Whose Treatment Outcome Was a Success at Month 6 According to Adapted WHO Criteria | 6 months post-dose | 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. |
| Percentage of Participants With Early- and Intermediate-stage HAT Whose Treatment Outcome Was a Success at Month 18 According to Adapted WHO Criteria | 18 months post-dose | 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. |
| Percentage of Participants With Early- and Intermediate-stage HAT Whose Treatment Outcome Was a Success at Month 12 According to Adapted WHO Criteria | 12 months post-dose | 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. |
| Percentage of Participants With Early- and Intermediate-stage HAT Whose Treatment Outcome Was a Success at Month 6 According to Adapted WHO Criteria | 6 months post-dose | 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. |
| Estimated Percentage of Participants With Late-stage HAT Whose Treatment Outcome Was Not a Proven Failure at Month 18, Based on the Kaplan-Meier Analysis of Time to Proven and Definitive Failure | 18 months post-dose | 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 |
| Percentage of Participants With Late-stage HAT Whose Treatment Outcome Was a Success at Month 12 According to Adapted WHO Criteria | 12 months post-dose | 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. |
| Number of Participants With Serious TEAEs | From the single dose acoziborole administration until 18 months post-dose | Occurrence of any serious TEAEs during the observation period and until 18 months post-dose. |
| Acoziborole Area Under the Curve From Time Zero to 240 Hours Post Dose (AUC0-240h) in Whole Blood Considering Concentration-time Data up to 240 Hours After a Single Administration | Pre-dose and 4, 9, 24, 48, 72, 96, and 240 hours 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. |
| Mean Acoziborole Concentration in CSF After 240 Hours in Participants With Late-stage HAT | 240 hours post-dose | 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. |
| Mean Acoziborole Concentration in CSF After 240 Hours in Participants With Early- and Intermediate-stage HAT | 240 hours post-dose | 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. |
| Number of Participants With Treatment-emergent Adverse Events (TEAEs) | From the single dose acoziborole administration until 6 months post-dose for non-serious AEs and 18 months post-dose for serious AEs | 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. |
Countries
Democratic Republic of the Congo, Guinea
Participant flow
Recruitment details
The study was conducted at Human African Trypanosomiasis (HAT) treatment centers in the Democratic Republic of Congo and Guinea. A total of 260 HAT-positive participants signed informed consent and 208 participants (167 with late- and 41 with early- and intermediate-stage HAT) were included in the study and treated. 52 participants were not included, mainly due to exclusion criteria met and/or inclusion criteria not met. Participants were enrolled between 11 October 2016 and 25 March 2019.
Pre-assignment details
The pre-treatment period of up to 15 days included pre-screening, screening, and treatment of concurrent malaria/soil-transmitted helminthiasis. At the end of this period, all participants (regardless of HAT-stage) were treated with acoziborole.
Participants by arm
| Arm | Count |
|---|---|
| Late-stage HAT Participants with confirmation of HAT by detection of the parasite in the blood and/or lymph and/or cerebrospinal fluid (CSF) at the investigational center. If testing for parasites in CSF was negative, the CSF white blood cell count, measured at the investigational center, had to be above 20 cells/µL for classification as late-stage HAT. Participants received 960 mg acoziborole as a single oral dose.
Acoziborole: Acoziborole 960 mg as a single oral dose (3 x 320 mg tablets; fasted state) | 167 |
| Early- and Intermediate-stage HAT Participants with confirmation of HAT by detection of the parasite in the blood and/or lymph at the investigational center. Parasites had to be absent from the CSF. The CSF white blood cell count, measured at the investigational center, had to be between 6 and 20 cells/µL for classification as intermediate stage HAT and equal to or below 5 cells/µL for classification as early-stage HAT. Participants received 960 mg acoziborole as a single oral dose.
Acoziborole: Acoziborole 960 mg as a single oral dose (3 x 320 mg tablets; fasted state) | 41 |
| Total | 208 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 4 | 0 |
| Overall Study | Lack of Efficacy | 2 | 0 |
| Overall Study | Lost to Follow-up | 1 | 0 |
Baseline characteristics
| Characteristic | Late-stage HAT | Early- and Intermediate-stage HAT | Total |
|---|---|---|---|
| Age, Continuous | 32.4 years STANDARD_DEVIATION 11.2 | 40.9 years STANDARD_DEVIATION 15 | 34.0 years STANDARD_DEVIATION 12.4 |
| Race/Ethnicity, Customized Sub-Saharan African | 167 Participants | 41 Participants | 208 Participants |
| Region of Enrollment Congo, The Democratic Republic of the | 140 participants | 34 participants | 174 participants |
| Region of Enrollment Guinea | 27 participants | 7 participants | 34 participants |
| Sex: Female, Male Female | 65 Participants | 26 Participants | 91 Participants |
| Sex: Female, Male Male | 102 Participants | 15 Participants | 117 Participants |
| White blood cells (WBC) in cerebrospinal fluid (CSF) | 398.8 cells/µL STANDARD_DEVIATION 438.4 | 7.8 cells/µL STANDARD_DEVIATION 5.3 | 321.3 cells/µL STANDARD_DEVIATION 422.3 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 4 / 167 | 0 / 41 |
| other Total, other adverse events | 127 / 167 | 27 / 41 |
| serious Total, serious adverse events | 18 / 167 | 3 / 41 |
Outcome results
Primary
Percentage of Participants With Late-stage HAT Whose Treatment Outcome Was a Success at Month 18 According to Adapted World Health Organization (WHO) Criteria
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.
Time frame: 18 months post-dose
Population: The modified intention-to-treat (mITT) set included all participants who received at least 1 tablet of acoziborole, excluding participants who fled the region due to armed conflict or natural disaster or due to force majeure and for whom no failure was detected early\* and no data were available at Month 12 and Month 18.\*\* \* Parasite, need for rescue medication, death, or more than 50 WBC/μL in CSF at Month 6.~\*\* Due to armed conflict, natural disaster, or force majeure affecting the site.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Late-stage HAT | Percentage of Participants With Late-stage HAT Whose Treatment Outcome Was a Success at Month 18 According to Adapted World Health Organization (WHO) Criteria | 95.2 percentage of participants |
Secondary
Acoziborole Area Under the Curve From Time Zero to 240 Hours Post Dose (AUC0-240h) in Whole Blood Considering Concentration-time Data up to 240 Hours After a Single Administration
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.
Time frame: Pre-dose and 4, 9, 24, 48, 72, 96, and 240 hours post-dose
Population: The pharmacokinetic (PK) analysis set included participants who received an oral dose of 960 mg acoziborole, as far as the information about time and amount was available, and for whom at least one blood sample for PK was available.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Late-stage HAT | Acoziborole Area Under the Curve From Time Zero to 240 Hours Post Dose (AUC0-240h) in Whole Blood Considering Concentration-time Data up to 240 Hours After a Single Administration | 2217617.78 h*ng/mL | Standard Deviation 647696.87 |
| Early- and Intermediate-stage HAT | Acoziborole Area Under the Curve From Time Zero to 240 Hours Post Dose (AUC0-240h) in Whole Blood Considering Concentration-time Data up to 240 Hours After a Single Administration | 2051104.88 h*ng/mL | Standard Deviation 485620.67 |
| Any Stage HAT | Acoziborole Area Under the Curve From Time Zero to 240 Hours Post Dose (AUC0-240h) in Whole Blood Considering Concentration-time Data up to 240 Hours After a Single Administration | 2184795.53 h*ng/mL | Standard Deviation 621610.31 |
Secondary
Estimated Percentage of Participants With Late-stage HAT Whose Treatment Outcome Was Not a Proven Failure at Month 18, Based on the Kaplan-Meier Analysis of Time to Proven and Definitive Failure
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
Time frame: 18 months post-dose
Population: The modified intention-to-treat (mITT) set included all participants who received at least 1 tablet of acoziborole, excluding participants who fled the region due to armed conflict or natural disaster or due to force majeure and for whom no failure was detected early\* and no data were available at Month 12 and Month 18.\*\* \* Parasite, need for rescue medication, death, or more than 50 WBC/μL in CSF at Month 6.~\*\* Due to armed conflict, natural disaster, or force majeure affecting the site.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Late-stage HAT | Estimated Percentage of Participants With Late-stage HAT Whose Treatment Outcome Was Not a Proven Failure at Month 18, Based on the Kaplan-Meier Analysis of Time to Proven and Definitive Failure | 96.0 percentage of participants |
Secondary
Mean Acoziborole Concentration in CSF After 240 Hours in Participants With Early- and Intermediate-stage HAT
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.
Time frame: 240 hours post-dose
Population: The PK analysis set included participants who received an oral dose of 960 mg acoziborole, as far as the information about time and amount was available, and for whom at least one blood sample for PK was available.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Late-stage HAT | Mean Acoziborole Concentration in CSF After 240 Hours in Participants With Early- and Intermediate-stage HAT | 81.4 ng/mL | Standard Deviation 48.5 |
Secondary
Mean Acoziborole Concentration in CSF After 240 Hours in Participants With Late-stage HAT
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.
Time frame: 240 hours post-dose
Population: The PK analysis set included participants who received an oral dose of 960 mg acoziborole, as far as the information about time and amount was available, and for whom at least one blood sample for PK was available.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Late-stage HAT | Mean Acoziborole Concentration in CSF After 240 Hours in Participants With Late-stage HAT | 100.8 ng/mL | Standard Deviation 63.968 |
Secondary
Number of Participants With Serious TEAEs
Occurrence of any serious TEAEs during the observation period and until 18 months post-dose.
Time frame: From the single dose acoziborole administration until 18 months post-dose
Population: The Treated set included all participants who received at least one tablet of acoziborole.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Late-stage HAT | Number of Participants With Serious TEAEs | 18 Participants |
| Early- and Intermediate-stage HAT | Number of Participants With Serious TEAEs | 3 Participants |
| Any Stage HAT | Number of Participants With Serious TEAEs | 21 Participants |
Secondary
Number of Participants With Treatment-emergent Adverse Events (TEAEs)
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.
Time frame: From the single dose acoziborole administration until 6 months post-dose for non-serious AEs and 18 months post-dose for serious AEs
Population: The Treated set included all participants who received at least one tablet of acoziborole.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Late-stage HAT | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | 127 Participants |
| Early- and Intermediate-stage HAT | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | 28 Participants |
| Any Stage HAT | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | 155 Participants |
Secondary
Percentage of Participants With Early- and Intermediate-stage HAT Whose Treatment Outcome Was a Success at Month 12 According to Adapted WHO Criteria
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.
Time frame: 12 months post-dose
Population: The modified intention-to-treat (mITT) set included all participants who received at least 1 tablet of acoziborole, excluding participants who fled the region due to armed conflict or natural disaster or due to force majeure and for whom no failure was detected early\* and no data were available at Month 12 and Month 18.\*\* \* Parasite, need for rescue medication, death, or more than 50 WBC/μL in CSF at Month 6.~\*\* Due to armed conflict, natural disaster, or force majeure affecting the site.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Late-stage HAT | Percentage of Participants With Early- and Intermediate-stage HAT Whose Treatment Outcome Was a Success at Month 12 According to Adapted WHO Criteria | 100.0 percentage of participants |
Secondary
Percentage of Participants With Early- and Intermediate-stage HAT Whose Treatment Outcome Was a Success at Month 18 According to Adapted WHO Criteria
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.
Time frame: 18 months post-dose
Population: The modified intention-to-treat (mITT) set included all participants who received at least 1 tablet of acoziborole, excluding participants who fled the region due to armed conflict or natural disaster or due to force majeure and for whom no failure was detected early\* and no data were available at Month 12 and Month 18.\*\* \* Parasite, need for rescue medication, death, or more than 50 WBC/μL in CSF at Month 6.~\*\* Due to armed conflict, natural disaster, or force majeure affecting the site.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Late-stage HAT | Percentage of Participants With Early- and Intermediate-stage HAT Whose Treatment Outcome Was a Success at Month 18 According to Adapted WHO Criteria | 100.0 percentage of participants |
Secondary
Percentage of Participants With Early- and Intermediate-stage HAT Whose Treatment Outcome Was a Success at Month 6 According to Adapted WHO Criteria
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.
Time frame: 6 months post-dose
Population: The modified intention-to-treat (mITT) set included all participants who received at least 1 tablet of acoziborole, excluding participants who fled the region due to armed conflict or natural disaster or due to force majeure and for whom no failure was detected early\* and no data were available at Month 12 and Month 18.\*\* \* Parasite, need for rescue medication, death, or more than 50 WBC/μL in CSF at Month 6.~\*\* Due to armed conflict, natural disaster, or force majeure affecting the site.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Late-stage HAT | Percentage of Participants With Early- and Intermediate-stage HAT Whose Treatment Outcome Was a Success at Month 6 According to Adapted WHO Criteria | 100.0 percentage of participants |
Secondary
Percentage of Participants With Late-stage HAT Whose Treatment Outcome Was a Success at Month 12 According to Adapted WHO Criteria
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.
Time frame: 12 months post-dose
Population: The modified intention-to-treat (mITT) set included all participants who received at least 1 tablet of acoziborole, excluding participants who fled the region due to armed conflict or natural disaster or due to force majeure and for whom no failure was detected early\* and no data were available at Month 12 and Month 18.\*\* \* Parasite, need for rescue medication, death, or more than 50 WBC/μL in CSF at Month 6.~\*\* Due to armed conflict, natural disaster, or force majeure affecting the site.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Late-stage HAT | Percentage of Participants With Late-stage HAT Whose Treatment Outcome Was a Success at Month 12 According to Adapted WHO Criteria | 95.8 percentage of participants |
Secondary
Percentage of Participants With Late-stage HAT Whose Treatment Outcome Was a Success at Month 6 According to Adapted WHO Criteria
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.
Time frame: 6 months post-dose
Population: The modified intention-to-treat (mITT) set included all participants who received at least 1 tablet of acoziborole, excluding participants who fled the region due to armed conflict or natural disaster or due to force majeure and for whom no failure was detected early\* and no data were available at Month 12 and Month 18.\*\* \* Parasite, need for rescue medication, death, or more than 50 WBC/μL in CSF at Month 6.~\*\* Due to armed conflict, natural disaster, or force majeure affecting the site.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Late-stage HAT | Percentage of Participants With Late-stage HAT Whose Treatment Outcome Was a Success at Month 6 According to Adapted WHO Criteria | 94.6 percentage of participants |