Phase II Proof of Concept Trial to Determine Efficacy of Fexinidazole in Visceral Leishmaniasis Patients in Sudan
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 发起方
- 入组人数
- 14
- 试验地点
- 1
- 主要终点
- Initial cure
研究概览
简要总结
This study is designed to determine the efficacy of Fexinidazole as an oral treatment in Visceral Leishmanisasis sudanese adults patients.
The results of this proof of concept study will allow to make a decision on whether to proceed with clinical development of Fexinidazole for visceral leishmaniasis.
详细描述
Visceral Leishmaniasis (VL) is a neglected disease and it is fatal if left untreated.
Until recently the first line treatment in East Africa was 30 days of Sodium Stibogluconate which can be cardiotoxic. Since 2010 WHO recommended Sodium Stibogluconate and Paromomycin for 17 days which is a shorter treatment but there remains the toxicity associated with these drugs. The second line treatment is Ambisome given as 6-10 intravenous infusions, whilst this has a better safety profile than other VL regimens it is expensive.
So there is an urgent need for short course oral treatment for VL particularly in the East African region.
Fexinidazole is a 2 substituted 5-nitroimidazole formulated for oral administration. Fexinidazole through its metabolites has demonstrated potent activity againts L. donovani intracellular amastigotes in vitro and in vivo in a visceral leishmaniasis mouse model.
The dose selected for this study (1800 mg/1200 mg for 4/6 days) has been based on the dose selected for a phase II trial on Human African Trypasonomiasis. It is albeit well tolerated and is one dose level below the maximum tolerated dose level established in phase I.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 15 Years 至 60 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients with clinical signs and symptoms of primary VL (fever for at least 2 weeks, splenomegaly) and diagnosis confirmed by visualization of parasites in tissue samples (lymph node, bone marrow) on microscopy.
- •Patients aged between 15 and 60 years (inclusive) who are able to comply with the protocol.
- •Patients for whom written informed consent has been signed by the patients themselves (if aged 18 years and over) or by parents(s) or legal guardian for patients under 18 years of age together with the patients assent.
- •HIV negative status
排除标准
- •Patients who have previously been diagnosed with VL and received anti-leishmanial treatment (ie relapse)
- •Patients with BMI <16 kg/m2
- •Patients with contra-indication (known hypersensitivity) to other imidazoles (e.g. ketaconazole)
- •Patients suffering from a concomitant severe underlying disease (cardiac, renal, hepatic) including hepatitis B, para kala-azar dermal leishmaniasis and tuberculosis
- •Patient with clinically significant ECG findings or QTcF≥ 450 msec in 2 successive ECGs
- •Major surgical intervention 4 weeks prior to enrollment.
- •Patients who are pregnant or lactating.
- •Female patients of child bearing age who do not agree to use an acceptable method of contraception
- •Patients with haemoglobin < 5g/dl.
- •Patients with platelets < 40,000/mm³.
- •Patients with liver function (ALT and AST) tests of more than 2 times the upper limit of the normal range.
- •Patients with serum creatinine above the normal range for age and gender.
- •Patients with serum potassium (K+) above the normal range
- •Patients with Bilirubin more than 1.5 times the upper limit of the normal range
研究组 & 干预措施
Fexinidazole
600mg tablets
3 tablets once a day for 4 days continued by 2 tablets once a day for 6 days
干预措施: Fexinidazole (Drug)
结局指标
主要结局
Initial cure
时间窗: Day 28
Proportion of patients with an abscence of parasites in tissue aspirate and no rescue treatment administered up to and including day 28
次要结局
- Final cure(Day 210)