Efficacy and Safety of Fexinidazole in Patients With Human African Trypanosomiasis (HAT) Due to Trypanosoma Brucei Rhodesiense: a Multicentre, Open-label Clinical Trial
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 45
- 试验地点
- 2
- 主要终点
- Percentage of Evaluable Patients With Stage 2 r-HAT Who Died by the End of Hospitalization, Considering Only Deaths Possibly Related to r-HAT or Fexinidazole
研究概览
简要总结
The ultimate goal of this study is to show that fexinidazole offers an alternative over the existing treatments of Human African trypanosomiasis due to Trypanosoma brucei rhodesiense (r-HAT): melarsoprol in patients with stage 2 r-HAT and suramin in patients with stage 1 r-HAT. The main questions it aims to answer are:
- Is the short-term fatality rate and failure rate associated with fexinidazole lower than those of melarsoprol in patients with stage 2 r-HAT?
- Is the long-term failure rate associated with fexinidazole lower than that of melarsoprol in patients with stage 2 r-HAT?
- Can fexinidazole in patients with stage 1 r-HAT replace the treatment with suramin?
- Is fexinidazole treatment safe in patient with r-HAT, regardless of stage?
Participants will receive fexinidazole oral treatment for 10 days. Regular blood draws and lumbar punctures will be performed over 12 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.
详细描述
Nowadays, the only treatment available for the stage 2 of HAT due to t.b rhodesiense is melarsoprol, a very toxic drug.
The primary objective of this trial is to evaluate fexinidazole as an alternative treatment over melarsoprol in patients with stage 2 of HAT disease due to t.b rhodesiense in a Phase II/III cohort trial with 34 stage 2 patients. All stages of the disease will be recruited but the recruitment will stop once 34 evaluable stage-2 patients have reached the end of treatment.
The trial will be a multicentre, non-randomized, clinical trial in patients with r-HAT.
Subjects will be recruited among the patients reporting to Lwala Hospital (Uganda) and Rumphi District Hospital (Malawi). If feasible, r-HAT patients from other hospitals and centres in Kaberamaido/Dokolo Districts (Uganda) and Rumphi/Mzimba North District (Malawi) and well as Zambia bordering areas, will be referred to Lwala and Rumphi Hospitals, respectively, for treatment.
Fexinidazole is an oral treatment which has to be taken every day for 10 days. In case of lack of efficacy (e.g. disease relapse) the patients will be switched to the standart treatment that is part of the National Control Program in each country (melarsoprol for stage-2 patients and suramin for stage-1 patients)
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
- •Signed Informed Consent Form (plus assent for children)
- •≥ 6 years old
- •≥ 20 kg body weight
- •Ability to ingest at least one complete meal per day (or at least one Plumpy'Nut® sachet)
- •Karnofsky index ≥ 40
- •Parasitological confirmation of T. b. rhodesiense infection
- •Having a permanent address or being traceable by others and willing and able to comply with follow-up visit schedule
- •Agreement to be hospitalised for a minimum of 13 days and to receive the study treatment
排除标准
- •Active clinically relevant medical conditions other than HAT that may jeopardize subject safety or at the investigator discretion may interfere with participation in the study.
- •Compromised general health or severely deteriorated general condition, such as severe malnutrition, cardiovascular shock, respiratory distress, or terminal illness
- •Patients with severe hepatic impairment (e.g.: clinical signs of cirrhosis or jaundice)
- •Known hypersensitivity to fexinidazole, to any nitroimidazole drugs (e.g. metronidazole, tinidazole), or to any of the excipients
- •Patients previously enrolled in the study or having already received fexinidazole
研究组 & 干预措施
Patients with stage 1 r-HAT
Patients with stage 1 r-HAT were patients without trypanosomes in the cerebrospinal fluid (CSF) but with trypanosomes in the blood and/or lymph and CSF white blood cells (WBC) ≤5 cells/µL. Patients were to receive fexinidazole orally for 10 days.
干预措施: Fexinidazole (Drug)
Patients with stage 2 r-HAT
Patients with stage 2 r-HAT were patients with trypanosomes in the CSF (and/or in blood/lymph) and/or CSF WBC >5 cells/µL. Patients were to receive fexinidazole orally for 10 days.
干预措施: Fexinidazole (Drug)
结局指标
主要结局
Percentage of Evaluable Patients With Stage 2 r-HAT Who Died by the End of Hospitalization, Considering Only Deaths Possibly Related to r-HAT or Fexinidazole
时间窗: 12 to 18 days after start of treatment
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.
次要结局
- Percentage of Evaluable Patients With Stage 2 r-HAT, Whose Treatment Outcome is a Failure at the End of Hospitalization(12 to 18 days after start of treatment)
- Number of Participants With Any AE (Including Abnormal Laboratory or ECG Finding if Considered Clinically Significant) Until the End of Hospitalization(12 to 18 days (between Day 1 and Day 12-18))
- Percentage of Evaluable Patients With Stage 2 r-HAT, Whose Treatment Outcome is a Failure at 12 Months(12 months after start of treatment)
- Percentage of Evaluable Patients With Stage 1 r-HAT, Whose Treatment Outcome is a Failure at the End of Hospitalization(12 to 18 days after start of treatment)
- Percentage of Evaluable Patients With Stage 1 r-HAT, Whose Treatment Outcome is a Failure at 12 Months(12 months after start of treatment)
- Percentage of Evaluable Patients With Any r-HAT Stage Who Died by the End of Hospitalization, Considering Only Deaths Possibly Related to r-HAT or Fexinidazole(12 to 18 days after start of treatment)
- Number of Participants With Any AE Considered as Serious Until the End of the Follow-up Period(12 months (between Day 1 and Month 12))
- Number of Participants With Any AE Considered as Possibly Related to Fexinidazole Until the End of the Follow-up Period(12 months (between Day 1 and Month 12))
- Percentage of Evaluable Patients With Any r-HAT Stage, Whose Treatment Outcome is a Failure at the End of Hospitalization(12 to 18 days after start of treatment)
- Percentage of Evaluable Patients With Any r-HAT Stage, Whose Treatment Outcome is a Failure at 12 Months(12 months after start of treatment)