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Эффективность, безопасность и переносимость KLU156 у взрослых и детей с массой тела ≥ 5 кг при неосложненной малярии, вызванной P. falciparum (KALUMA)

30 октября 2026 г. обновлено: Novartis Pharmaceuticals

Рандомизированное открытое многоцентровое исследование для сравнения эффективности, безопасности и переносимости KLU156 с Coartem® при лечении неосложненной малярии Plasmodium falciparum у взрослых и детей с массой тела ≥ 5 кг с последующей фазой продления с повторным лечением KLU156

This study aimed to confirm the efficacy, safety and tolerability of KLU156, a fixed dose combination of ganaplacide (KAF156) and a solid dispersion formulation of lumefantrine (lumefantrine-SDF), when administered once daily for three days in adults and children ≥ 10 kg of body weight suffering from uncomplicated P. falciparum malaria (with or without other Plasmodium spp. co-infection).

In the extension phase, the safety, tolerability and efficacy of repeated treatment with KLU156 was assessed for a maximum of approximately 18 months 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.

Обзор исследования

Статус

Завершенный

Условия

Вмешательство/лечение

Подробное описание

The purpose of this study was 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 total study duration was up to approximately 20 months.
  • The treatment duration was 3 days for each malaria episode.
  • The visit frequency was 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.

This study had two different primary outcomes depending on the submission (US New Drug Application (NDA) or non-US submissions).

Protocol amendment 01 increased the minimum body weight requirement for study participation from ≥ 5 kg to ≥ 10 kg and revised the statistical analysis plan to exclude patients < 10 kg from the main analyses.

Тип исследования

Интервенционный

Регистрация (Действительный)

1720

Фаза

  • Фаза 3

Контакты и местонахождение

В этом разделе приведены контактные данные лиц, проводящих исследование, и информация о том, где проводится это исследование.

Места учебы

  • Берег Слоновой Кости
      • Abidjan, Берег Слоновой Кости, 13 BP 972
        • Novartis Investigative Site
      • Agboville, Берег Слоновой Кости
        • Novartis Investigative Site
      • Azaguié, Берег Слоновой Кости
        • Novartis Investigative Site
  • Буркина-Фасо
      • Banfora, Буркина-Фасо
        • Novartis Investigative Site
      • Bobo-Dioulasso, Буркина-Фасо
        • Novartis Investigative Site
      • Nanoro, Буркина-Фасо, BP 18
        • Novartis Investigative Site
      • Ouagadougou, Буркина-Фасо
        • Novartis Investigative Site
      • Sabou, Буркина-Фасо
        • Novartis Investigative Site
  • Габон
      • Lambaréné, Габон, BP 242
        • Novartis Investigative Site
      • Libreville, Габон, BP 1437
        • Novartis Investigative Site
  • Гана
      • Kintampo, Гана, 92037
        • Novartis Investigative Site
      • Navrango, Гана, VWJ6+8WF
        • Novartis Investigative Site
  • Демократическая Республика Конго
    • Bas-Congo Province
      • Kimpese, Bas-Congo Province, Демократическая Республика Конго
        • Novartis Investigative Site
      • Kisantu, Bas-Congo Province, Демократическая Республика Конго
        • Novartis Investigative Site
    • Du Haut Katanga
      • Lubumbashi, Du Haut Katanga, Демократическая Республика Конго, 7010
        • Novartis Investigative Site
    • Kwango
      • Kenge, Kwango, Демократическая Республика Конго
        • Novartis Investigative Site
    • Kwilu
      • Masi-Manimba, Kwilu, Демократическая Республика Конго
        • Novartis Investigative Site
  • Замбия
      • Ndola, Замбия, 71769
        • Novartis Investigative Site
    • Luapula Province
      • Nchelenge, Luapula Province, Замбия, 70100
        • Novartis Investigative Site
  • Кения
      • Kombewa, Кения, 40102
        • Novartis Investigative Site
      • Nairobi, Кения, 00200
        • Novartis Investigative Site
      • Siaya, Кения, 2300
        • Novartis Investigative Site
  • Мали
      • Sotouba, Мали
        • Novartis Investigative Site
  • Нигер
      • Niamey, Нигер, 8003
        • Novartis Investigative Site
  • Руанда
      • Kigali, Руанда
        • Novartis Investigative Site
      • Rubavu, Руанда
        • Novartis Investigative Site
      • Rusizi, Руанда
        • Novartis Investigative Site
    • Northern Province
      • Gicumbi, Northern Province, Руанда
        • Novartis Investigative Site
  • Танзания
      • Bagamoyo, Танзания, 78373
        • Novartis Investigative Site
      • Korogwe Tanga, Танзания, 9653
        • Novartis Investigative Site
      • Tanga, Танзания, 5004
        • Novartis Investigative Site
  • Уганда
      • Tororo, Уганда, 10102
        • Novartis Investigative Site

Критерии участия

Исследователи ищут людей, которые соответствуют определенному описанию, называемому критериям приемлемости. Некоторыми примерами этих критериев являются общее состояние здоровья человека или предшествующее лечение.

Критерии приемлемости

Возраст, подходящий для обучения

От 2 месяца до 100 лет (Ребенок, Взрослый, Пожилой взрослый)

Принимает здоровых добровольцев

Нет

Полы, имеющие право на обучение

Все

Описание

Key Inclusion criteria (Core phase)

  1. Male or female patients ≥ 10 kg of body weight.
  2. 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.
  3. 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)
  4. Negative pregnancy test for patients of childbearing potential
  5. Signed informed consent was obtained before any assessment is performed; for minors, signed informed consent was obtained from parent/legal guardian. If the parent/legal guardian was unable to read and write, then a witnessed consent according to local ethical standards was permitted. Patients who were capable of providing assent, must have provided it along with parent/legal guardian consent or as per local ethical standards
  6. The patient and/or their parent/legal guardian was able to understand and comply with protocol requirements, instructions and protocol-stated restrictions and was likely to complete the study as planned.

Key Exclusion criteria (Core phase)

  1. Signs and symptoms of severe malaria according to WHO 2015 (World Health Organization)

  2. Concurrent febrile illnesses (e.g., typhoid fever, known or suspected dengue fever, known COVID19)

  3. 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)

  4. 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)

  5. Clinically relevant abnormalities of electrolyte balance which required correction, e.g., hypokalemia, hypocalcemia or hypomagnesemia

  6. Anemia (hemoglobin level <7 g/dL)

  7. Any surgical or medical condition which might have significantly altered 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 have jeopardized the patient in case of participation in the study.

  8. 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

  9. 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 was unknown)

  10. 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

  11. Pregnant or nursing (lactating) patients.

Учебный план

В этом разделе представлена ​​подробная информация о плане исследования, в том числе о том, как планируется исследование и что оно измеряет.

Как устроено исследование?

Детали дизайна

  • Основная цель: Уход
  • Распределение: Рандомизированный
  • Интервенционная модель: Параллельное назначение
  • Маскировка: Одинокий

Оружие и интервенции

Группа участников / Армия
Вмешательство/лечение
Экспериментальный: KLU156

KLU156 once daily (QD) for 3 days under fed conditions (light meal).
Лекарство: KLU156

Oral use. KLU156 (400/480 mg) was the dose for patients with a bodyweight ≥ 35kg. Patients < 35kg took a fraction of the dose according to weight group as defined in the protocol.
Активный компаратор: Coartem

Coartem twice a day (BID) for 3 days under fed conditions.
Лекарство: Coartem

Oral use. Dosing was selected based on patient's body weight as per product's label.
Экспериментальный: KLU156 (Participants with <10 kg Body Weight)

KLU156 once daily (QD) for 3 days under fed conditions (light meal).
Лекарство: KLU156

Oral use. KLU156 (400/480 mg) was the dose for patients with a bodyweight ≥ 35kg. Patients < 35kg took a fraction of the dose according to weight group as defined in the protocol.
Активный компаратор: Coartem (Participants with <10 kg Body Weight)

Coartem twice a day (BID) for 3 days under fed conditions.
Лекарство: Coartem

Oral use. Dosing was selected based on patient's body weight as per product's label.

Что измеряет исследование?

Первичные показатели результатов

Мера результата
Мера Описание
Временное ограничение
Core Phase: PCR-corrected Adequate Clinical and Parasitological Response (ACPR) at Day 29
Временное ограничение: Day 29 (i.e., 28 days post-first dose administration)

PCR-corrected Adequate Clinical and Parasitological Response (ACPR) at Day 29 is defined as the percentage of participants who are clinically well and have no recrudescence (reappearance of the original malaria infection) by 29 days after treatment, with PCR genotyping used to distinguish new infections from recrudescence. This primary outcome was applicable to the non-US submission.
Day 29 (i.e., 28 days post-first dose administration)
Core Phase: Uncorrected ACPR (US NDA Submission) at Day 29
Временное ограничение: Day 29

Uncorrected ACPR at Day 29 is defined as the percentage of participants who are clinically well and have no malaria parasite reappearance detected by Day 29 after treatment, without using parasite genotyping to distinguish new infections from recrudescence of the original infection. This primary outcome was applicable to US New Drug Application (NDA) submission.
Day 29

Вторичные показатели результатов

Мера результата
Мера Описание
Временное ограничение
Core Phase: PCR-corrected ACPR at Days 22 and 43
Временное ограничение: Days 22 and 43 (i.e., 21 and 42 days post-first dose administration)

To confirm the efficacy of KLU156 by assessing PCR-corrected ACPR at additional time points.
Days 22 and 43 (i.e., 21 and 42 days post-first dose administration)
Core Phase: Uncorrected ACPR at Days 22 and 43
Временное ограничение: Days 22 and 43 (i.e., 21 and 42 days post-first dose administration)

To confirm the efficacy of KLU156 by assessing uncorrected ACPR at additional time points.
Days 22 and 43 (i.e., 21 and 42 days post-first dose administration)
Core Phase: Percentage of Participants With Recrudescence
Временное ограничение: Days 22, 29 and 43

Recrudescence is defined as appearance of asexual parasites after clearance of initial infection with a genotype identical to that of parasites present at baseline. Recrudescence had to be confirmed by PCR analysis.
Days 22, 29 and 43
Core Phase: Percentage of Participants With New Infection
Временное ограничение: Days 22, 29 and 43

New infection is defined as appearance of asexual parasites after clearance of initial infection with a genotype different from those parasites present at baseline. New infection had to be confirmed by PCR analysis.
Days 22, 29 and 43
Core Phase: Fever Clearance Time
Временное ограничение: Up to Day 3

Fever clearance time is defined as time from the first dose until the first time the axillary body temperature decreased below and remained below 37.5°C axillary or 38.0°C oral/tympanic/rectal for at least a further 24 hours.
Up to Day 3
Core Phase: Parasite Clearance Time
Временное ограничение: Up to Day 3

Parasite clearance time is defined as time from the first dose until the first total and continued disappearance of asexual parasite forms which remained at least a further 48 hours.
Up to Day 3
Core Phase: Gametocyte Clearance Time
Временное ограничение: Up to Day 3

To confirm the efficacy of KLU156 by assessing gametocyte clearance between the two treatment arms
Up to Day 3
Core Phase: Percentage of Participants With Parasitemia
Временное ограничение: 12, 24, 48 and 72 hours after treatment

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
Core Phase: Clearance of Gametocytes in Participants With Gametocytemia at Baseline
Временное ограничение: From baseline up to Day 43

Assessed by microscopy. Baseline was pre-first dose administration.
From baseline up to Day 43
Core Phase: Percentage of Participants With Treatment-emergent Adverse Events (TEAEs) and AEs of Grade 3 Severity or Higher
Временное ограничение: Day 43

Incidence and severity of TEAEs by treatment group, including changes in vital signs, electrocardiograms (ECGs), and laboratory results qualifying and reported as AEs. Severity was graded according to the Common Terminology Criteria for Adverse Events (CTCAE): Grade 1 (Mild), Grade 2 (Moderate), Grade 3 (Severe), Grade 4 (Life-threatening), and Grade 5 (Death).
Day 43
Core Phase: Percentage of Participants With Treatment-emergent Serious Adverse Events (SAEs), Graded by Severity
Временное ограничение: Day 43

Incidence and severity of treatment-emergent SAEs by treatment group, including changes in vital signs, electrocardiograms (ECGs), and laboratory results qualifying and reported as AEs. Severity was graded according to the Common Terminology Criteria for Adverse Events (CTCAE): Grade 1 (Mild), Grade 2 (Moderate), Grade 3 (Severe), Grade 4 (Life-threatening), and Grade 5 (Death).
Day 43
Extension Phase: PCR-corrected ACPR
Временное ограничение: Up to Day 29 for each KLU156 treatment episode

To evaluate PCR-corrected ACPR over repeated treatment with KLU156 in adults and children ≥ 10 kg of body weight suffering from uncomplicated malaria caused by P. falciparum (with or without other Plasmodium spp. co-infection). Patients were instructed to return to the study site whenever symptoms suggestive of malaria occurred. At each suspected malaria episode, eligibility for KLU156 treatment was reassessed, including confirmation of malaria diagnosis.
Up to Day 29 for each KLU156 treatment episode
Extension Phase: Uncorrected ACPR
Временное ограничение: Up to Day 29 for each KLU156 treatment episode

To evaluate uncorrected ACPR over repeated treatment with KLU156 in adults and children ≥ 10 kg of body weight suffering from uncomplicated malaria caused by P. falciparum (with or without other Plasmodium spp. co-infection).
Up to Day 29 for each KLU156 treatment episode
Extension Phase: Percentage of Participants With KLU156-related AEs by Malaria Episode
Временное ограничение: Up to approximately 18 months

To assess the safety and tolerability over repeated treatment with KLU156 in adults and children ≥ 10 kg of body weight suffering from uncomplicated malaria caused by P. falciparum (with or without other Plasmodium spp. co-infection).
Up to approximately 18 months
Extension Phase: Percentage of Participants With SAEs by Severity and Malaria Episode
Временное ограничение: Up to approximately 18 months

To assess the safety and tolerability over repeated treatment with KLU156 in adults and children ≥ 10 kg of body weight suffering from uncomplicated malaria caused by P. falciparum (with or without other Plasmodium spp. co-infection).
Up to approximately 18 months
Extension Phase: Gametocyte Carriage Over Time
Временное ограничение: Up to Day 29 for each KLU156 treatment episode

To assess gametocyte carriage over time by malaria episode in the extension phase
Up to Day 29 for each KLU156 treatment episode

Соавторы и исследователи

Здесь вы найдете людей и организации, участвующие в этом исследовании.

Спонсор

Novartis Pharmaceuticals

Соавторы

Medicines for Malaria Venture (MMV), EDCTP, WANECAM

Даты записи исследования

Эти даты отслеживают ход отправки отчетов об исследованиях и сводных результатов на сайт ClinicalTrials.gov. Записи исследований и сообщаемые результаты проверяются Национальной медицинской библиотекой (NLM), чтобы убедиться, что они соответствуют определенным стандартам контроля качества, прежде чем публиковать их на общедоступном веб-сайте.

Изучение основных дат

Начало исследования (Действительный)

7 марта 2024 г.

Первичное завершение (Действительный)

27 июня 2025 г.

Завершение исследования (Действительный)

25 ноября 2025 г.

Даты регистрации исследования

Первый отправленный

24 апреля 2023 г.

Впервые представлено, что соответствует критериям контроля качества

3 мая 2023 г.

Первый опубликованный (Действительный)

6 мая 2023 г.

Обновления учебных записей

Последнее опубликованное обновление (Действительный)

4 ноября 2026 г.

Последнее отправленное обновление, отвечающее критериям контроля качества

30 октября 2026 г.

Последняя проверка

1 октября 2026 г.

Дополнительная информация

Термины, связанные с этим исследованием

Ключевые слова

Дополнительные соответствующие термины MeSH

Другие идентификационные номера исследования

  • CKLU156A12301
  • 2022-002675-10 (Номер EudraCT)

Планирование данных отдельных участников (IPD)

Планируете делиться данными об отдельных участниках (IPD)?

ДА

Описание плана IPD

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com.

Информация о лекарствах и устройствах, исследовательские документы

Изучает лекарственный продукт, регулируемый FDA США.

Нет

Изучает продукт устройства, регулируемый Управлением по санитарному надзору за качеством пищевых продуктов и медикаментов США.

Нет

Эта информация была получена непосредственно с веб-сайта clinicaltrials.gov без каких-либо изменений. Если у вас есть запросы на изменение, удаление или обновление сведений об исследовании, обращайтесь по адресу register@clinicaltrials.gov. Как только изменение будет реализовано на clinicaltrials.gov, оно будет автоматически обновлено и на нашем веб-сайте. .

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