An Open-label Study Assessing Effectiveness, Safety and Compliance With Fexinidazole in Patients With Human African Trypanosomiasis Due to T.b. Gambiense at Any Stage
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 174
- 试验地点
- 8
- 主要终点
- Percentage of Participants Whose Treatment Outcome at Month 18 is a Success
研究概览
简要总结
This study evaluates the effectiveness of fexinidazole administered to patients with human African trypanosomiasis due to T. b. gambiense (g-HAT) at all stages of the disease. The aim of the present study is to provide additional information on the effectiveness and safety of fexinidazole and to assess its use under conditions as close as possible to those in real life, both in patients treated on an out-patient basis and in the hospital setting, depending on clinical status.
Participants will receive fexinidazole oral treatment for 10 days. Regular blood draws and lumbar punctures will be performed over 18 months to confirm the cure of the disease. Other assessments will include the recording of adverse events, signs and symptoms of the disease, laboratory tests, vital signs, electrocardiograms. Treatment compliance, feasibility, and packaging acceptability will be thoroughly assessed in the participants receiving treatment at home. Those participants will complete questionnaires to check that instructions for fexinidazole administration are clear enough and followed correctly.
详细描述
See attached protocol.
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
- 6 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, including breastfeeding or pregnant women in the second or third trimester.
- •≥ 6 years of age.
- •≥ 20 kg body weight.
- •Signed Informed Consent Form and Assent Form for patients less than 18 years of age
- •Trypanosomes detected in any body fluid.
- •Physically able to ingest at least one solid meal per day.
- •Able to take oral medication.
- •Karnofsky Performance Status > 40%.
- •Able to comply with the schedule of follow-up visits and with the study constraints.
- •Easily reachable during the out-patient follow-up period.
- •Willing to undergo lumbar punctures.
排除标准
- •Active clinically relevant medical conditions other than HAT that, in the Investigator's opinion, could jeopardize patient safety or interfere with participation in the study, including but not limited to significant liver or cardiovascular diseases, human immunodeficiency virus (HIV) infection, central nervous system (CNS) trauma or seizure disorders, coma or altered consciousness not related to HAT.
- •Severe renal or hepatic impairment defined as:
- •elevated creatinine at > 3 times the upper limit of normal (ULN); elevated alanine aminotranferase (ALT), aspartate aminotransferase (AST), or bilirubin at > 3 ULN
- •Severely deteriorated general condition, such as cardiovascular shock, respiratory distress or terminal illness.
- •Any condition (except symptoms of HAT) that compromises ability to communicate with the Investigator as required for completion of the study.
- •Any contraindication to imidazole products (known hypersensitivity to imidazoles).
- •Treatment for HAT within 2 years prior to inclusion.
- •Prior enrolment in the study or prior intake of fexinidazole.
- •Foreseeable difficulty in complying with the schedule of follow-up visits (migrants, refugees, itinerant traders, etc.).
- •Temporary Non-inclusion Criteria:
- •Recovery period after antimalarial treatment and/or treatment of helminthiasis (at least 3 days).
- •Uncontrolled diabetes or hypertension or any patients requiring clinical stabilization; wait until appropriate treatment to control the disease has been initiated.
- •First trimester of pregnancy.
- •Traumatic lumbar puncture at Screening i.e. red blood cells visible in cerebrospinal fluid (CSF); wait for 48 hours before repeating lumbar puncture.
- •Eligibility Criteria for Out-patient Treatment
- •Accepting to be treated on an out-patient basis;
- •Karnofsky Performance Status > 50%;
- •Good understanding of the method of administration of fexinidazole by the patient and/or caregiver* (checked using a questionnaire at the time of dispensing fexinidazole);
- •Residing close to the investigational center, i.e. approximately one hour by road and/or boat, during the treatment period**;
- •Easily reachable during the treatment period;
- •No medical or psychiatric contraindications for treatment as out-patient;
- •No pregnancy or breastfeeding;
- •No neurological symptoms.
研究组 & 干预措施
Inpatients
Participants received fexinidazole orally for 10 days as inpatients (at the hospital)
干预措施: Fexinidazole (Drug)
Outpatients
Participants received fexinidazole orally for 10 days as outpatients (at home)
干预措施: Fexinidazole (Drug)
结局指标
主要结局
Percentage of Participants Whose Treatment Outcome at Month 18 is a Success
时间窗: Between the first intake of fexinidazole (Day 1) and the end of the follow-up period (18 months)
Treatment outcome at Month 18 is categorized as success or failure. Success is defined as a cure, according to the criteria adapted from the World Health Organization (WHO) update of the methodological framework for clinical trials in Sept 2014 (WHO/HTM/NTD/IDM/2015.5). Failure is 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. Success rate at Month 18 is defined as the percentage of participants (regardless of g-HAT stage) whose treatment outcome is a success at Month 18. An estimate of the success rate at Month 18 and the 95% exact Clopper-Pearson confidence interval (CI) of the estimate are provided.
次要结局
- Percentage of Participants Whose Treatment Outcome at Month 12 is a Success(Between the first intake of fexinidazole (Day 1) and the end of the follow-up period (18 months))
- Number of Participants With Any Grade ≥ 3 Treatment-emergent Adverse Events (AEs) Including Laboratory and Hematological Abnormalities (if Considered Clinically Significant)(Between the first intake of fexinidazole (Day 1) and the end of the observation period, or the end of the follow-up period (18 months) for non-serious AEs assessed as related to fexinidazole)
- Number of Participants With Any Treatment-emergent Serious Adverse Event (SAE)(Between the first intake of fexinidazole (Day 1) and the end of the follow-up period (18 months))
- Number of Participants With Any Temporary or Permanent Treatment Discontinuation (Inpatient or Outpatient) for Reasons Related to Safety(Between the first intake (Day 1) and last intake of fexinidazole (Day 10, or Day 11 if re-administration occurred))
- Number of Participants With Any Hospitalization for Reasons Related to Safety (Outpatients Only)(Between the first intake (Day 1) and last intake of fexinidazole (Day 10, or Day 11 if re-administration occurred))
- Number of Participants With Any Permanent Treatment Discontinuation (Inpatient or Outpatient) for Reasons Related to Safety(Between the first intake (Day 1) and last intake of fexinidazole (Day 10, or Day 11 if re-administration occurred))
- Number of Outpatients Who Were Compliant With the Full Course of the 10-day Treatment(Between the first intake (Day 1) and last intake of fexinidazole (Day 10, or Day 11 if re-administration occurred))
- Number of Outpatients Who Were Compliant With the 10-day Treatment Posology, Including Taking the Correct Number of Tablets During the 2 Phases of Treatment and Taking Tablets All at Once Every Day, With Food and Without Any Interruption of Treatment(End-of-treatment visit (Day 11))
- Feasibility of Self-management of Treatment Intake in Outpatients: Occurrence of Temporary Treatment Discontinuation(End-of-treatment visit (Day 11))
- Feasibility of Self-management of Treatment Intake in Outpatients: Occurrence of Permanent Treatment Discontinuation(End-of-treatment visit (Day 11))
- Feasibility of Self-management of Treatment Intake in Outpatients: Delayed Treatment Start(End-of-treatment visit (Day 11))
- Feasibility of Self-management of Treatment Intake in Outpatients: Hospitalization During the Treatment Period Due to Non-compliance(End-of-treatment visit (Day 11))
- Acceptability of Packaging in Outpatients: Full Understanding of Instructions Concerning Dosing Regimen(Before treatment (Day 0))
- Acceptability of Packaging in Outpatients: Help Requested to Follow the Treatment(End-of-treatment visit (Day 11))
- Acceptability of Packaging in Outpatients: Instructions Found Helpful(End-of-treatment visit (Day 11))
- Whole Blood Concentration of Fexinidazole From Dry Blood Spot, Measured 24 Hours After the Last Dose of Fexinidazole(End-of-treatment visit (Day 11, 24 hours after last treatment administration))
- Whole Blood Concentration of Fexinidazole Metabolite M1 From Dry Blood Spot, Measured 24 Hours After the Last Dose of Fexinidazole(End-of-treatment visit (Day 11, 24 hours after last treatment administration))
- Whole Blood Concentration of Fexinidazole Metabolite M2 From Dry Blood Spot, Measured 24 Hours After the Last Dose of Fexinidazole(End-of-treatment visit (Day 11, 24 hours after last treatment administration))