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임상시험 NCT05842954 (KALUMA)은(는) 비복잡성 열대열 말라리아에 대해 진행중, 모집종료 상태입니다. 모든 세부 정보를 보려면 임상시험 레이더 카드 뷰와 AI 발견 도구를 확인하거나 여기에서 무엇이든 물어보세요. | ||
노바티스Efficacy, Safety and Tolerability of KLU156 in Adults and Children ≥ 5 kg Body Weight With Uncomplicated P. Falciparum Malaria (KALUMA)
In the Extension phase, the safety, tolerability and efficacy of repeated treatment with KLU156 will be assessed for a maximum of two years in patients who did not experience early treatment failure (ETF), who did not experience any study treatment-related SAE (Serious Adverse Event) previously and who gave informed consent to participate in the Extension phase.
The purpose of this study is to confirm the efficacy, safety and tolerability of KLU156 in patients with uncomplicated P. falciparum malaria (with or without other Plasmodium spp. co-infection) by demonstrating that KLU156 is non-inferior to Coartem.
- The study duration will be 43 days (Core phase) plus 24 months (Extension phase).
- The treatment duration will be 3 days for each malaria episode.
- The visit frequency will be Days 1-3 (hospitalized) and 5 follow-up visits (Days 4, 8, 22, 29 and 43) in the Core phase and Days 1-3 (hospitalized) and 3 follow-up visits (Days 4, 8 and 29) in the Extension phase.
A Randomized, Open-label, Multicenter Study to Compare Efficacy, Safety and Tolerability of KLU156 With Coartem® in the Treatment of Uncomplicated Plasmodium Falciparum Malaria in Adults and Children ≥ 5 kg Body Weight Followed by an Extension Phase With Repeated KLU156 Treatment
- KALUMA
- CKLU156A12301
- 2022-002675-10 (EudraCT 번호)
Plasmodium falciparum
KLU156
Coartem
artemether
lumefantrine
ganaplacide
| 참가자 그룹/시험군 | 개입/치료 |
|---|---|
실험적KLU156 KLU156 once daily (QD) for 3 days under fed conditions (light meal). | KLU156 Oral use. KLU156 (400/480 mg) is the dose for patients with a bodyweight ≥ 35kg. Patients \< 35kg will take a fraction of the dose according to weight group as defined in the protocol. |
활성 대조군Coartem Coartem twice a day (BID) for 3 days under fed conditions. | Coartem Oral use. Dosing will be selected based on patient's body weight as per product's label. |
| 결과변수 | 측정값 설명 | 시간 범위 |
|---|---|---|
PCR-corrected adequate clinical and parasitological response (ACPR) | To confirm the efficacy of KLU156 in adults and children ≥ 5 kg body weight and ≥ 2 months of age suffering from uncomplicated malaria caused by P. falciparum (with or without other Plasmodium spp. co-infection) by demonstrating that KLU156 is non-inferior to Coartem (non-inferiority margin = 5%) based on the PCR-corrected ACPR at Day 29. | Day 29 (i.e., 28 days post-first dose administration) |
| 결과변수 | 측정값 설명 | 시간 범위 |
|---|---|---|
PCR-corrected and uncorrected ACPR | To confirm the efficacy of KLU156 by assessing uncorrected and PCR-corrected ACPR at additional time points | Days 22 and 43 (i.e., 21 and 42 days post-first dose administration) |
Uncorrected ACPR | To further confirm the efficacy of KLU156 by demonstrating non-inferiority of KLU156 to Coartem (NI margin 7.5%) based on the uncorrected ACPR at Day 29 | Day 29 |
Incidence and severity of Adverse Events (AEs) and Serious Adverse Events (SAEs) | Incidence and severity of AEs and SAEs by treatment group, including changes in vital signs, electrocardiograms (ECGs), and laboratory results qualifying and reported as AEs. | Day 43 |
Fever Clearance Time | To confirm the efficacy of KLU156 by assessing fever clearance between the two treatment arms | Up to Day 3 |
Parasite Clearance Time | To assess parasite clearance time between the two treatment arms | Up to Day 3 |
Incidence rate of recrudescence and new infection | Proportion of patients with recrudescence and new infections between the two treatment arms | Days 22, 29 and 43 |
Proportion of patients with parasitemia | For the parasitemia assessment, blood sampling can be done by means of a finger prick except when the timing for parasitology assessments coincides with time for clinical laboratory tests, in which case, blood sample can be taken from the venous blood collected for clinical laboratory analyses. | 12, 24, 48 and 72 hours after treatment |
Gametocytemia | Disappearance or development of gametocytemia in patients with or without gametocytemia at baseline (pre-first dose administration), respectively | From baseline up to Day 43 |
Extension phase: PCR-corrected and uncorrected ACPR | To evaluate efficacy over repeated treatment with KLU156 in adults and children ≥ 5 kg body weight and ≥ 2 months of age suffering from uncomplicated malaria caused by P. falciparum (with or without other Plasmodium spp. co-infection) for a maximum of 2 years | Day 29 of malaria episode |
Extension phase: KLU156-related AE/SAE incidence and severity by malaria episode | To assess the safety and tolerability over repeated treatment with KLU156 in adults and children ≥ 5 kg body weight and ≥ 2 months of age suffering from uncomplicated malaria caused by P. falciparum (with or without other Plasmodium spp. co-infection) for a maximum of 2 years | Up to 2 years |
Extension phase: Gametocyte carriage over time | To assess gametocyte carriage over time by malaria episode in the extension phase | Up to 2 years |
- Male or female patients ≥ 5 kg of body weight and ≥ 2 months of age
- Microscopically confirmed diagnosis of uncomplicated P. falciparum malaria with an asexual P. falciparum parasitemia ≥ 1,000 and ≤ 200,000 parasites/µL at the time of pre-screening with or without other Plasmodium spp. co-infection.
- Axillary temperature ≥ 37.5 ºC or oral temperature ≥ 38.0 ºC or tympanic/rectal temperature ≥ 38.5 ºC; or history of fever during the previous 24 hours (at least documented verbally)
- Negative pregnancy test for patients of childbearing potential
- Signed informed consent must be obtained before any assessment is performed; for minors, signed informed consent must be obtained from parent/legal guardian. If the parent/legal guardian is unable to read and write, then a witnessed consent according to local ethical standards is permitted. Patients who are capable of providing assent, must provide it along with parent/legal guardian consent or as per local ethical standards
- The patient and/or their parent/legal guardian is able to understand and comply with protocol requirements, instructions and protocol-stated restrictions and is likely to complete the study as planned.
Signs and symptoms of severe malaria according to WHO 2015 (World Health Organization)
Concurrent febrile illnesses (e.g., typhoid fever, known or suspected dengue fever, known COVID19)
Severe malnutrition. For patients ≥ 12 years: body mass index (BMI) < 16.0. For children < 12 years: less than 70% of median normalized WHO reference weight or very low mid-upper arm circumference (MUAC < 115 mm)
Repeated vomiting (defined as > 3 times in the 24 hours prior to start of screening) or severe diarrhea (defined as > 3 watery stools in the 24 hours prior to start of screening)
Clinically relevant abnormalities of electrolyte balance which require correction, e.g., hypokalemia, hypocalcemia or hypomagnesemia
Anemia (hemoglobin level <7 g/dL)
Any surgical or medical condition which might significantly alter the absorption, distribution, metabolism, or excretion of drugs (e.g., Human immunodeficiency virus (HIV) patients on antiretroviral therapy (ART) or tuberculosis (TB) patients on treatment), or which may jeopardize the patient in case of participation in the study.
Any of the following:
- Aspartate Aminotransferase/ Alanine Aminotransferase (AST/ALT) > 3 x the upper limit of normal (ULN), regardless of the level of total bilirubin
- Total bilirubin > 3 x ULN
- Resting QT interval corrected by Fridericia's formula (QTcF) > 450 ms at screening
Prior antimalarial therapy or antibiotics with antimalarial activity within minimum of their five plasma half-lives (or within 4 weeks of screening if half-life is unknown)
History or family history of long QT syndrome or sudden cardiac death, or any other clinical condition known to prolong the QTc interval, such as history of symptomatic cardiac arrhythmias, clinically relevant bradycardia or severe heart disease
Pregnant or nursing (lactating) patients.
Other protocol-defined inclusion/exclusion criteria may apply.
MMV, EDCTP, WANECAMBas-Congo Province
Du Haut Katanga
Kwango
Kwilu
Odisha
Northern Province
Luapula Province