An Open Label, Randomized, Parallel Arm Clinical Trial of Two Regimens to Assess the Safety and Efficacy for Treatment of Post Kala-azar Dermal Leishmaniasis (PKDL) Patients in Sudan
试验速览
- 阶段
- 2 期
- 发起方
- 入组人数
- 110
- 试验地点
- 1
- 主要终点
- Definitive Cure
研究概览
简要总结
This is an open label, randomized non comparative phase II clinical trial conducted on parallel groups, to assess the safety and efficacy of the combination of Paromomycin (20 mg/kg/d) IM for 14 days and Miltefosine (allometric dosing) oral for 42 days, and a combination of AmBisome® (20 mg/kg total dose) IV over 7 days and Miltefosine oral for 28 days (allometric dosing) for the treatment of PKDL patients in Sudan.
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
- 6 Years 至 60 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Confirmed PKDL case by clinical presentation and demonstration of parasites by microscopy in a skin smear or by PCR, with documented stable or progressive disease for at least 6 months or grade 3 PKDL
- •Male or Female patients aged 6 to 60 years
- •Written voluntarily informed consent is obtained from the patient, or his guardian if the patient is < 18 years old. In the case of minors aged >12 to <18, assent from the children is also needed in addition to the guardian's consent.
排除标准
- •Patients who had prior treatment of PKDL within the last 1 year
- •Pregnant and lactating women and women of childbearing age (12 to 55 years) who do not accept to have a pregnancy test and who do not agree to use contraception during treatment period and for 5 months after the end of treatment.
- •Patients with signs and symptoms of severe diseases: defined as suffering from a concomitant severe infection such as TB or any other serious known underlying disease (cardiac, renal, hepatic),
- •Severe malnutrition defined by BMI for age WHO reference curves for gender, Z score < -3 for subjects 6 to < 19 years; BMI < 16 for subjects > 19 years old
- •Patients with haemoglobin < 5g/dL
- •Patients with known skin disease
- •Patients with abnormal liver function (ALT and AST) tests of more than three times the normal range.
- •Patients with total bilirubin levels >1.5 times the upper normal range
- •Patients with serum creatinine above the upper limit of normal range
- •Patients with serum potassium < 3.5 mmol/L
- •Patients with pre-existing clinical hearing loss based on audiometry at baseline
- •Patients with a positive HIV test as applicable
- •Patients / guardian not willing to participate
- •Patients with history of allergy or hypersensitivity to the relevant study drug
- •Patients on immunomodulators therapy
研究组 & 干预措施
Arm 1: Paromomycin + Miltefosine
Paromomycin 20 mg/kg/d IM for 14 days combined with Miltefosine allometric BID PO dosing for 42 days
干预措施: Paromomycin (Drug)
Arm 1: Paromomycin + Miltefosine
Paromomycin 20 mg/kg/d IM for 14 days combined with Miltefosine allometric BID PO dosing for 42 days
干预措施: Miltefosine (Drug)
Arm 2: Ambisome + Miltefosine
AmBisome® 5mg/kg/d IV infusion at D1, D3, D5 and D7 (20 mg/kg total dose) combined with Miltefosine allometric BID PO dosing for 28 days
干预措施: Ambisome (Drug)
Arm 2: Ambisome + Miltefosine
AmBisome® 5mg/kg/d IV infusion at D1, D3, D5 and D7 (20 mg/kg total dose) combined with Miltefosine allometric BID PO dosing for 28 days
干预措施: Miltefosine (Drug)
结局指标
主要结局
Definitive Cure
时间窗: 12 months follow-up assessment
definitive cure at 12 months after treatment onset, defined as clinical cure (100% lesions resolution) and no additional PKDL treatment between end of therapy and 12 months follow-up assessment.
Incidence of treatment-emergent adverse events
时间窗: from start of treatment to 12 month follow-up
Frequency of SAE from start of treatment to 12 months follow-up Frequency and severity of all adverse events Frequency and severity of adverse events that lead to treatment discontinuation
次要结局
- Pharmacokinetics of Amphotericin B (MF + Ambisome arm only)(Amphotericin B concentration will be measured in the skin at day 7 and day 28. Amphotericin B concentration in the blood will be measured at day 1 and day 7.)
- Immune Response(At screening, at day 42 (end of treatment) and at 6 month follow-up)
- Pharmacokinetics of Miltefosine(Miltefosine concentration in the skin will be measured at day 14 and day 42 for MF+PM arm and at day 7 and day 28 for Ambisome+MF arm. Miltefosine concentration in the blood will be measured at day 1, day 7, day 14, day 28, day 42 and 3 month)
- Parasite quantification in blood and skin(At screening, day 42 (end of treatment), 3 month follow-up, 6 month follow-up and 12 month follow-up.)
- Pharmacokinetics of Paromomycin (MF + Paromomycin arm only)(Paromomycin concentration will be measured in the skin at day 14 and day 42. Paromomycin concentration in the blood will be measured at day 1 and day 14.)