A Multi-part, Multi-center PLATform Study to Assess the Efficacy, Safety, Tolerability and Pharmacokinetics of Anti-malarial Agents Administered as Monotherapy and/or Combination Therapy IN Patients With Uncomplicated Plasmodium Falciparum Malaria
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 327
- 试验地点
- 1
- 主要终点
- Part A: parasite clearance time (PCT)
研究概览
简要总结
Platform study to evaluate the efficacy and safety of anti-malarial agents in patients with uncomplicated Plasmodium falciparum malaria
详细描述
The purpose of this platform study is to evaluate the parasiticidal effect and potential for cure with different anti-malarial agents administered as monotherapy and/or in combination therapy with other anti-malarial agents in adults, adolescents, and children with uncomplicated Plasmodium falciparum malaria. Additionally, the safety, tolerability, and pharmacokinetics of these anti-malarial agents will be evaluated for dose selection for future studies.
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
盲法说明
This study is open-label, but certain members of the CTT will be blinded to the treatment information
入排标准
- 年龄范围
- 2 Years 至 100 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male and female patients ≥18 years of age for Part A, ≥12 years of age for Part B and 2 to <12 years of age for Part C at screening.
- •Patients must have acute uncomplicated P. falciparum malaria mono infection at screening confirmed by a parasite count between 5,000 to 150,000 asexual parasite count/μl of blood for P. falciparum for Part A and between 1,000 to 150,000 asexual parasite count/μl of blood for Parts B and C.
- •Patients in Part A must weigh between 40 kg and 90 kg. Patients in Part B must weigh between 35 kg and 90 kg at screening. Patients in Part C must weigh at least 10 kg at screening.
- •Axillary temperature ≥ 37.5ºC or oral/tympanic/rectal temperature ≥ 38.0ºC; or history of fever during the previous 24 hours.
排除标准
- •Patients with signs and symptoms of severe/complicated malaria at screening or mixed Plasmodium infection (i.e., infection with more than one malaria species) at screening
- •Moderate to severe anemia, chronic hemoglobinopathy (Hemoglobin level < 8 g/dL), or known chronic underlying disease such as sickle cell disease at screening
- •Known clinically significant liver disease (e.g., chronic hepatitis, liver cirrhosis (compensated or decompensated), history of hepatitis B or C, hepatitis A or B vaccination in the last 3 months, known gallbladder or bile duct disease, acute or chronic pancreatitis. Clinical or laboratory evidence of any of the following at screening:
- •AST/ALT > 3 x the upper limit of normal range (ULN), regardless of the level of total bilirubin
- •AST/ALT > 1.5 and ≤ 2 x ULN and total bilirubin is > ULN
- •Total bilirubin > 2 x ULN, regardless of the level of AST/ALT
- •Any known/suspected immunosuppressive or immunodeficient condition, including human immunodeficiency virus (HIV) infection at screening.
- •Pregnant or nursing (lactating) women, women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using methods of effective contraception, and sexually active patients not willing to practice effective contraception.
- •History or current diagnosis of ECG abnormalities indicating significant risk of safety for patients participating in the study such as:
- •Concomitant clinically significant cardiac arrhythmias, e.g., sustained ventricular tachycardia, and clinically significant second or third degree AV block without a pacemaker
- •History of familial long QT syndrome or known family history of Torsades de Pointe.
- •Resting heart rate (physical exam or 12 lead ECG) < 50 bpm
- •Other protocol-defined inclusion/exclusion criteria may apply.
研究组 & 干预措施
Cohort A1: Dose Level 3 INE963
Cohort A1: Dose Level 3 INE963
干预措施: INE963 (Drug)
Cohort B1: Cipargamin + INE963
Cohort B1: Cipargamin + INE963
干预措施: KAE609 (Cipargamin) (Drug)
Cohort B1: SoC (Coartem)
Cohort B1: SoC (Coartem)
干预措施: SoC (Coartem) (Drug)
Cohort B2: Cipargamin + KLU156
Cohort B2: Cipargamin + KLU156
干预措施: KAE609 (Cipargamin) (Drug)
Cohort B2: Cipargamin + KLU156
Cohort B2: Cipargamin + KLU156
干预措施: KLU156 (Drug)
Cohort B2: SoC (Coartem)
Cohort B2: SoC (Coartem)
干预措施: SoC (Coartem) (Drug)
Cohort C2: Cipargamin + KLU156
Cohort C2: Cipargamin + KLU156
干预措施: KAE609 (Cipargamin) (Drug)
Cohort C2: Cipargamin + KLU156
Cohort C2: Cipargamin + KLU156
干预措施: KLU156 (Drug)
Cohort C2: SoC (Coartem)
Cohort C2: SoC (Coartem)
干预措施: SoC (Coartem) (Drug)
Cohort A1: Dose Level 4 INE963
Cohort A1: Dose level 4 INE963
干预措施: INE963 (Drug)
Cohort A1: Dose Level 1 INE963
Cohort A1: Dose Level 1 INE963
干预措施: INE963 (Drug)
Cohort A1: Dose Level 2 INE963
Cohort A1: Dose Level 2 INE963
干预措施: INE963 (Drug)
结局指标
主要结局
Part A: parasite clearance time (PCT)
时间窗: up to Day 7
Part A: To assess the parasite clearance time (PCT) of oral doses of an anti-malarial agent administered as monotherapy in patients with uncomplicated P. falciparum malaria. PCT is defined as the time from the first positive blood slide at inclusion to the time of the first negative slide followed by two consecutive slides.
Part B and C: polymerase chain reaction (PCR) corrected adequate clinical and parasitological response (ACPR)
时间窗: Day 29
Part B and C: To assess the 28-day cure rate of an anti malarial agent administered orally as combination therapy versus the standard of care (SoC) in patients with uncomplicated P. falciparum malaria. ACPR is defined as the absence of parasitemia on Study Day 29 irrespective of axillary temperature, without previously meeting any of the criteria of Early Treatment Failure (ETF) or Late Clinical Failure (LCF) or Late Parasitological Failure (LPF).
次要结局
- Part A: PCR-corrected and uncorrected ACPR(Day 29)
- Parts B and C: PCT(up to Day 7)
- Parts B and C: PCR-uncorrected ACPR(Day 29)
- Area under the concentration-time curve from time zero to the last measurable concentration sampling time (AUClast) of the anti-malarial agents (wherever possible)(Day 22)
- Area under the concentration-time curve from time zero to infinity (AUCinf) of the anti-malarial agents (wherever possible)(Day 22)
- Maximum observed concentration (Cmax) of the anti-malarial agents(Day 22)
- Time to reach maximum observed concentration (Tmax)(Day 22)
- Elimination half-life (T1/2) of the anti-malarial agents (wherever possible)(Day 22)
- Total body clearance (CL/F) of the anti-malarial agents (wherever possible)(Day 22)
- Apparent volume of distribution (V/F) of the anti-malarial agents (wherever possible)(Day 22)
- Incidence and severity of Adverse Events (AEs) and Serious Adverse Events (SAEs)(Day 43)