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 Participants With Uncomplicated Plasmodium Falciparum Malaria
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 60
- 试验地点
- 3
- 主要终点
- Polymerase Chain Reaction (PCR) Corrected Adequate Clinical and Parasitological Response (ACPR)
研究概览
简要总结
This was Cohort B2 of the Platform study (NCT05750628) to evaluate the efficacy and safety of Cipargamin + KLU156 in participants with uncomplicated Plasmodium falciparum malaria.
详细描述
The Cohort B2 of this Platfom study (NCT05750628) was the open-label, randomized, two-arm combination therapy evaluating a single oral dose of up to three anti-malarial agents as a loose combination vs. standard of care (SoC), Coartem in adult and adolescent participants.
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 was open-label, but Core Clinical Team is blinded to treatment information.
入排标准
- 年龄范围
- 12 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 ≥12 years of age at screening.
- •Patients must have acute uncomplicated P. falciparum malaria mono infection at screening confirmed by a parasite count between 1,000 to 150,000 asexual parasite count/μl of blood for P. falciparum.
- •Patients must weigh between 35 kg and 90 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 B2: KLU156 400/480 mg + KAE609 75 mg
KLU156 [(400 mg KAF156, 480 mg Lumefantrine (LUM)-solid dispersion formulation (SDF)] + KAE609 75 mg was administered orally with light meal as a single dose.
干预措施: KAE609 (Drug)
Cohort B2: SoC (Artemether 80 mg + lumefantrine 480 mg)
Artemether 80 mg + lumefantrine 480 mg was administered twice a day for 3 days with a standard meal or drink rich in fat within 30 min of dosing, as per label.
干预措施: SoC (Coartem) (Drug)
Cohort B2: KLU156 400/480 mg + KAE609 75 mg
KLU156 [(400 mg KAF156, 480 mg Lumefantrine (LUM)-solid dispersion formulation (SDF)] + KAE609 75 mg was administered orally with light meal as a single dose.
干预措施: KLU156 (Drug)
结局指标
主要结局
Polymerase Chain Reaction (PCR) Corrected Adequate Clinical and Parasitological Response (ACPR)
时间窗: Day 29
ACPR is defined as absence of parasitaemia (PS) on Study Day 29 regardless of axillary temperature, in patients who have not previously met any of the criteria of Early Treatment Failure (ETF), Late Clinical Failure (LCF), or Late Parasitological Failure (LPF). A patient was considered as PCR-corrected ACPR at Day 29 when the patient did not meet any of the criteria of ETF (up to Day 4), LCF (Day 5 to Day 29), or LPF (Day 8 to Day 29), and was absence of PS on Day 29, unless the presence of PS detected after 7 days (Day 8 or later) was due to reinfection. The presence of PS after 7 days of treatment initiation was considered as a reinfection only when the PS had cleared before Day 8, and none of the parasite strain(s) detected on or after Day 8 matched with the parasite strain at baseline.
次要结局
- Parasite Clearance Time (PCT)(up to Day 7)
- PCR Uncorrected Adequate Clinical and Parasitological Response (ACPR)(Day 29)
- Maximum Observed Plasma Concentration (Cmax)(Pre-dose, 1, 2, 4, 6, 8, 12, 24, and 48 hours post dose.)
- Time to Reach Maximum Observed Plasma Concentration (Tmax)(Pre-dose, 1, 2, 4, 6, 8, 12, 24, and 48 hours post dose.)
- Area Under Plasma Concentration-time Curve From Time 0 to 24 Hours (AUC0-24h)(Pre-dose, 1, 2, 4, 6, 8, 12, and 24 hours post dose.)
- Area Under Plasma Concentration-time Curve From Time 0 to 48 Hours (AUC0-48h)(Pre-dose, 1, 2, 4, 6, 8, 12, 24, and 48 hours post dose.)
- Area Under Plasma Concentration-time Curve (AUClast)(Pre-dose, 1, 2, 4, 6, 8, 12, 24, 48, 72 and 168 hours post dose.)
- Area Under Plasma Concentration-time Curve (AUC[0-inf])(Pre-dose, 1, 2, 4, 6, 8, 12, 24, 48, 72 and 168 hours post dose.)
- Terminal Elimination Half-life (T1/2)(Pre-dose, 1, 2, 4, 6, 8, 12, 24, 48, 72 and 168 hours post dose.)
- Apparent Clearance (CL/F)(Pre-dose, 1, 2, 4, 6, 8, 12, 24, and 48 hours post dose.)
- Apparent Volume of Distribution During Terminal Elimination Phase (Vz/F)(Pre-dose, 1, 2, 4, 6, 8, 12, 24, and 48 hours post dose.)