Efficacy and Safety Study of Acoziborole (SCYX-7158) in Patients With Human African Trypanosomiasis (HAT) Due to Trypanosoma Brucei Gambiense: a Multicentre, Open-label, Prospective Study
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 208
- 试验地点
- 12
- 主要终点
- Percentage of Participants With Late-stage HAT Whose Treatment Outcome Was a Success at Month 18 According to Adapted World Health Organization (WHO) Criteria
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 15 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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
研究组 & 干预措施
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.
干预措施: Acoziborole (Drug)
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.
干预措施: Acoziborole (Drug)
结局指标
主要结局
Percentage of Participants With Late-stage HAT Whose Treatment Outcome Was a Success at Month 18 According to Adapted World Health Organization (WHO) Criteria
时间窗: 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.
次要结局
- 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)
- 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)
- 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)
- 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)
- 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)
- 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)
- 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)
- Number of Participants With Serious TEAEs(From the single dose acoziborole administration 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)
- Mean Acoziborole Concentration in CSF After 240 Hours in Participants With Late-stage HAT(240 hours post-dose)
- Mean Acoziborole Concentration in CSF After 240 Hours in Participants With Early- and Intermediate-stage HAT(240 hours post-dose)