An Open Label, Phase III, Randomized Controlled, Multicentre Non-Inferiority Trial to Compare Efficacy and Safety of Miltefosine and Paromomycin With SSG and PM Combination for Treatment of Primary Visceral Leishmaniasis (VL) Patients in Eastern Africa
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 439
- 试验地点
- 7
- 主要终点
- Definitive Cure
研究概览
简要总结
This is an open label, Phase III, randomized, controlled, parallel arm multicentre non-inferiority clinical trial to compare the efficacy and safety of two combination regimens of Miltefosine and Paromomycin with the standard SSG-PM for the treatment of primary adult and children VL patients in Eastern Africa.
详细描述
The 2 treatment regimens to be tested are:
- Arm 1: Paromomycin 20 mg/kg/d IM for 14 days combined with oral miltefosine allometric dosing for 14 days
- Arm 2: Paromomycin 20 mg/kg/d IM for 14 days combined with oral miltefosine allometric dosing for 28 days (recruitment in this arm was discontinued under protocol v4.0 dated 22 Jul 2019)
The reference arm is the current standard treatment for VL:
• Arm 3: Sodium Stibogluconate 20 mg/kg/day IM/IV combined with Paromomycin 15 mg/kg/day IM for 17 days
The target population will be VL patients from 4 to 50 years old in order to cover both paediatric and adult population.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 4 Years 至 50 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 VL and confirmatory parasitological microscopic diagnosis
- •Patients aged 4 to < 50 years who are able to comply with the study protocol.
- •Patients for whom written informed consent has been obtained (if aged 18 years and over) or signed by parents(s) or legal guardian for patients under 18 years of age. In the case of minors, assent from the children also needs to be obtained as per each country regulatory requirements
排除标准
- •Patients who are relapse cases
- •Patients with Para-Kala azar dermal leishmaniasis grade 3
- •Patients who have received any anti-leishmanial drugs in the last 6 months
- •Patients with severe malnutrition (for children aged <5 years: weight-for-height WHO reference curves by sex, z score <-3; for children patients 5-18 years: BMI-for-age WHO reference curves by sex, z score < -3; for adults >18 years: BMI < 16)*
- •Patients with positive HIV diagnosis
- •Patients with previous history of hypersensitivity reaction or known drug class allergy to any of the study treatments
- •Patients with previous history of cardiac arrhythmia or with a clinically significant abnormal ECG
- •Patients suffering from a concomitant severe infection such as TB, schistosomiasis or any other serious underlying disease (e.g. cardiac, renal, hepatic) or chronic condition which would preclude evaluation of the patient's response to study medication
- •Pregnant or lactating women
- •Female patients of child bearing age who do not accept to have a pregnancy test done at screening and/or who do not agree to use contraception from treatment period until 5 months after the end of treatment (see section 15.2)
- •Patients with haemoglobin < 5g/dl
- •Patients with signs of severe VL according to Investigator's judgement, requiring an indication for AmBisome therapy based on the clinical manifestations (such as jaundice, bleeding, edema) and clinically significant abnormalities in the following laboratory parameters: haemoglobin, WBC, platelets, liver enzymes (ALT and AST), total bilirubin and creatinine
- •Patients with pre-existing hearing loss based on audiometry at baseline
- •Patients who cannot comply with the planned scheduled visits and procedures of the study protocol
- •Note: for Ethiopia only: Patients with severe malnutrition (for patients 4-18 years: MUAC cut-off based on MUAC-for-height reference table; for patients > 18 years: MUAC < 170 mm)
研究组 & 干预措施
Arm 1 - MF/PM 14d
Paromomycin 20 mg/kg/d IM for 14 days combined with oral miltefosine allometric dosing for 14 days
干预措施: Miltefosine (Drug)
Arm 1 - MF/PM 14d
Paromomycin 20 mg/kg/d IM for 14 days combined with oral miltefosine allometric dosing for 14 days
干预措施: Paromomycin (Drug)
Arm 2 - MF 28d/PM 14d
Paromomycin 20 mg/kg/d IM for 14 days combined with oral miltefosine allometric dosing for 28 days
干预措施: Miltefosine (Drug)
Arm 2 - MF 28d/PM 14d
Paromomycin 20 mg/kg/d IM for 14 days combined with oral miltefosine allometric dosing for 28 days
干预措施: Paromomycin (Drug)
Arm 3 - SSG/PM 17d
Sodium Stibogluconate 20 mg/kg/day IM/IV combined with Paromomycin 15 mg/kg/day IM for 17 days
干预措施: Paromomycin (Drug)
Arm 3 - SSG/PM 17d
Sodium Stibogluconate 20 mg/kg/day IM/IV combined with Paromomycin 15 mg/kg/day IM for 17 days
干预措施: Sodium stibogluconate (Drug)
结局指标
主要结局
Definitive Cure
时间窗: 6 months follow-up (Day 210)
Cure at 6 months follow up defined as absence of clinical signs and symptoms of VL at D210 and no requirement for rescue treatment during the trial (e.g. no relapse or initial treatment failure).
次要结局
- Incidence of Treatment-Emergent Adverse Events(From Screening to day 210)
- Pharmacodynamics(From baseline until day 210, and at any suspicion of relapse during the trial.)
- Compliance to miltefosine treatment in an outpatient setting(Day 15 to day 28 miltefosine treatment)
- Initial cure at day 28(Initial cure: day 28; Probable cure: day 56)
- Pharmacokinetics of paromomycin and miltefosine(During treatment, at 1 month (day 56) and 6 months (day 210) follow-up)