Parallel Group, Double-blind, Randomized Study Assessing the Efficacy, Safety and Pharmacokinetic Profiles of Ferroquine Associated With Artesunate and a Single-blind Dose Level of Ferroquine Alone in a 3-day Treatment of Uncomplicated Malaria Due to Plasmodium Falciparum in an Immune Symptomatic African Adult and Pediatric Population.
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 发起方
- Sanofi
- 入组人数
- 440
- 试验地点
- 10
- 主要终点
- Recrudescent infections at D28 in the groups with ferroquine associated with artesunate. Recrudescence is defined as the recurrence of the same original strain of Plasmodium falciparum regardless of clinical symptoms
研究概览
简要总结
Primary objective: To assess the Day 28 efficacy defined as the percentage of patients with no parasitic recrudescence, of 3 treatment groups - 3 dose levels of ferroquine associated with artesunate - for a 3-day treatment.
Secondary objectives:
- To assess the efficacy of ferroquine at one dose level alone for a 3-day treatment.
- To assess the clinical safety of 4 treatment groups - 3 dose levels of ferroquine associated with artesunate and one dose level of ferroquine alone.
- To assess pharmacokinetics parameters of ferroquine and its metabolites along sparse sampling schedules.
详细描述
The overall study duration is 64 days, consisting of a screening period (less or equal 1 day), of a 3-day treatment period during which the patient is hospitalized for a maximum of 60 hours, and a follow-up period of 61 days.
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
- Double (Participant, Investigator)
入排标准
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •3 cohorts enrolled in sequence with data interim review by Data Monitoring Committee (DMC) between cohort 1-2 and cohort 2-3
- •Cohort 1 : Adults > 50 kg or Adolescents >30 kg and age > or = 14 years
- •Cohort 2 : Children with body weight [30 kg- 15 kg[
- •Cohort 3 : Children with body weight [15 kg-10 kg]
- •Age related Body Mass Index (BMI)> or = 5 th percentile.
- •Presence of body temperature > or = 37.5°C or history of fever in the last 24 hours.
- •Monoinfection with Plasmodium falciparum with parasitemia from 1,000/microL to 200,000/microL.
- •Signed Informed Consent Form by the patient (if the patient is > or = age defining majority) or by the parents or legal guardian of minor patients (<18 years of age or < other age locally defining majority). In addition, participants with capacity for writing will sign off on an Assent Form. Patients with no capacity for writing will have the Assent Form read. In that case, an impartial witness will certify the document was read to the child.
排除标准
- •Presence of HBs antigen and of anti-HCV antibodies
- •Laboratory parameters with clinical significant abnormalities and/or reaching critical values : Hemoglobin (< 7g/dl), hematocrit, red blood cell count, white blood cell, reticulocytes, platelets, glucose, creatinine, aspartate transferase (AST), alanine transferase (ALT > 3 ULN), alkaline phosphatase, total bilirubine > 1.5 ULN.
- •History or presence of any clinically significant disease or symptoms which might confound the interpretation of the safety and efficacy information.
- •Splenectomized patients.
- •Presence of criteria for complicated malaria
- •Patients unable to drink
- •Breastfeeding patients.
- •Permanent vomiting.
- •Female participants with child bearing potential not willing to use an effective contraceptive(s) method(s) for the duration of the study (e.g. implants, oral contraceptives, some intra-uterine devices or a double barrier method). The need for an efficient method will be reminded to the patient and the patient's legal guardian(s) by the investigator.
- •Previous treatment within 5 times the elimination half-life or within the last 14 days, whichever the longest :
- •with any anti-malaria agents i.e., quinine, chloroquine, amodiaquine, mefloquine, halofantrine, sufladoxine-pyrimethamine, doxycycline-pyrimethamine, primaquine, artemether, atovaquone, proguanil, lumefantrine,
- •with an other investigational drug
- •with 2D6 main substrates
- •Past or concomitant participation in a study with an anti-malaria vaccine.
- •Measles vaccine injection within the last 15 days.
研究组 & 干预措施
Ferroquine high dose + artesunate
Ferroquine at 6 mg/kg/d OD and artesunate 4mg/kg/d OD for 3 days + ferroquine placebo capsules to maintain the blind between treatment groups.
干预措施: Ferroquine (SSR97193) (Drug)
Ferroquine high dose + artesunate
Ferroquine at 6 mg/kg/d OD and artesunate 4mg/kg/d OD for 3 days + ferroquine placebo capsules to maintain the blind between treatment groups.
干预措施: Placebo (Drug)
Ferroquine high dose + artesunate
Ferroquine at 6 mg/kg/d OD and artesunate 4mg/kg/d OD for 3 days + ferroquine placebo capsules to maintain the blind between treatment groups.
干预措施: artesunate (Drug)
Ferroquine medium dose + artesunate
Ferroquine at 4 mg/kg/d OD and artesunate 4mg/kg/d OD for 3 days + ferroquine placebo capsules to maintain the blind between treatment groups.
干预措施: Ferroquine (SSR97193) (Drug)
Ferroquine medium dose + artesunate
Ferroquine at 4 mg/kg/d OD and artesunate 4mg/kg/d OD for 3 days + ferroquine placebo capsules to maintain the blind between treatment groups.
干预措施: Placebo (Drug)
Ferroquine medium dose + artesunate
Ferroquine at 4 mg/kg/d OD and artesunate 4mg/kg/d OD for 3 days + ferroquine placebo capsules to maintain the blind between treatment groups.
干预措施: artesunate (Drug)
Ferroquine low dose + artesunate
Ferroquine at 2 mg/kg/d OD and artesunate 4mg/kg/d OD for 3 days + ferroquine placebo capsules to maintain the blind between treatment groups.
干预措施: Ferroquine (SSR97193) (Drug)
Ferroquine low dose + artesunate
Ferroquine at 2 mg/kg/d OD and artesunate 4mg/kg/d OD for 3 days + ferroquine placebo capsules to maintain the blind between treatment groups.
干预措施: Placebo (Drug)
Ferroquine low dose + artesunate
Ferroquine at 2 mg/kg/d OD and artesunate 4mg/kg/d OD for 3 days + ferroquine placebo capsules to maintain the blind between treatment groups.
干预措施: artesunate (Drug)
Ferroquine alone at medium dose
Ferroquine at 4 mg/kg/d OD alone for 3 days + ferroquine placebo capsules to maintain the blind between treatment groups.
干预措施: Ferroquine (SSR97193) (Drug)
Ferroquine alone at medium dose
Ferroquine at 4 mg/kg/d OD alone for 3 days + ferroquine placebo capsules to maintain the blind between treatment groups.
干预措施: Placebo (Drug)
结局指标
主要结局
Recrudescent infections at D28 in the groups with ferroquine associated with artesunate. Recrudescence is defined as the recurrence of the same original strain of Plasmodium falciparum regardless of clinical symptoms
时间窗: 4 weeks
次要结局
- Fever Clearance Time (Median)(up to 63 days)
- Cure rate at Day 28(4 weeks)
- Parasite Clearance Time (Median).(up to 63 days)
- Recrudescent infections at Day 28 in the ferroquine group in monotherapy(4 weeks)
- Recrudescent infections at Day 63(9 weeks)
- Adequate Clinical and Parasitological Response (ACPR) at D28(4 weeks)