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合併症のない熱帯熱マラリア原虫の成人および体重5kg以上の子供におけるKLU156の有効性、安全性および忍容性 (KALUMA)

2026年10月30日 更新者：Novartis Pharmaceuticals

体重5kg以上の成人および小児における合併症のない熱帯熱マラリア原虫の治療において、KLU156の有効性、安全性および忍容性をCoartem®と比較する無作為化非盲検多施設試験

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.

調査の概要

状態

完了

条件

介入・治療

詳細な説明

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.

研究の種類

介入

入学 (実際)

1720

段階

  • フェーズ 3

連絡先と場所

このセクションには、調査を実施する担当者の連絡先の詳細と、この調査が実施されている場所に関する情報が記載されています。

研究場所

  • ウガンダ
      • Tororo、ウガンダ、10102
        • Novartis Investigative Site
  • ガボン
      • Lambaréné、ガボン、BP 242
        • Novartis Investigative Site
      • Libreville、ガボン、BP 1437
        • Novartis Investigative Site
  • ガーナ
      • Kintampo、ガーナ、92037
        • Novartis Investigative Site
      • Navrango、ガーナ、VWJ6+8WF
        • Novartis Investigative Site
  • ケニア
      • Kombewa、ケニア、40102
        • Novartis Investigative Site
      • Nairobi、ケニア、00200
        • Novartis Investigative Site
      • Siaya、ケニア、2300
        • Novartis Investigative Site
  • コンゴ民主共和国
    • Bas-Congo Province
      • Kimpese、Bas-Congo Province、コンゴ民主共和国
        • Novartis Investigative Site
      • Kisantu、Bas-Congo Province、コンゴ民主共和国
        • Novartis Investigative Site
    • Du Haut Katanga
      • Lubumbashi、Du Haut Katanga、コンゴ民主共和国、7010
        • Novartis Investigative Site
    • Kwango
      • Kenge、Kwango、コンゴ民主共和国
        • Novartis Investigative Site
    • Kwilu
      • Masi-Manimba、Kwilu、コンゴ民主共和国
        • Novartis Investigative Site
  • コートジボワール
      • Abidjan、コートジボワール、13 BP 972
        • Novartis Investigative Site
      • Agboville、コートジボワール
        • Novartis Investigative Site
      • Azaguié、コートジボワール
        • Novartis Investigative Site
  • ザンビア
      • Ndola、ザンビア、71769
        • Novartis Investigative Site
    • Luapula Province
      • Nchelenge、Luapula Province、ザンビア、70100
        • Novartis Investigative Site
  • タンザニア
      • Bagamoyo、タンザニア、78373
        • Novartis Investigative Site
      • Korogwe Tanga、タンザニア、9653
        • Novartis Investigative Site
      • Tanga、タンザニア、5004
        • Novartis Investigative Site
  • ニジェール
      • Niamey、ニジェール、8003
        • Novartis Investigative Site
  • ブルキナファソ
      • Banfora、ブルキナファソ
        • Novartis Investigative Site
      • Bobo-Dioulasso、ブルキナファソ
        • Novartis Investigative Site
      • Nanoro、ブルキナファソ、BP 18
        • Novartis Investigative Site
      • Ouagadougou、ブルキナファソ
        • Novartis Investigative Site
      • Sabou、ブルキナファソ
        • Novartis Investigative Site
  • マリ
      • Sotouba、マリ
        • Novartis Investigative Site
  • ルワンダ
      • Kigali、ルワンダ
        • Novartis Investigative Site
      • Rubavu、ルワンダ
        • Novartis Investigative Site
      • Rusizi、ルワンダ
        • Novartis Investigative Site
    • Northern Province
      • Gicumbi、Northern Province、ルワンダ
        • Novartis Investigative Site

参加基準

研究者は、適格基準と呼ばれる特定の説明に適合する人を探します。これらの基準のいくつかの例は、人の一般的な健康状態または以前の治療です。

適格基準

就学可能な年齢

2ヶ月～100年 (子、大人、高齢者)

健康ボランティアの受け入れ

いいえ

受講資格のある性別

全て

説明

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.

研究計画

このセクションでは、研究がどのように設計され、研究が何を測定しているかなど、研究計画の詳細を提供します。

研究はどのように設計されていますか？

デザインの詳細

  • 主な目的：処理
  • 割り当て：ランダム化
  • 介入モデル：並列代入
  • マスキング：独身

武器と介入

参加者グループ / アーム
介入・治療
実験的：KLU156

KLU156 once daily (QD) for 3 days under fed conditions (light meal).
薬：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.
アクティブコンパレータ：Coartem

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

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

KLU156 once daily (QD) for 3 days under fed conditions (light meal).
薬：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.
アクティブコンパレータ：Coartem (Participants with <10 kg Body Weight)

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

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

この研究は何を測定していますか？

主要な結果の測定

結果測定
メジャーの説明
時間枠
Core Phase: PCR-corrected Adequate Clinical and Parasitological Response (ACPR) at Day 29
時間枠：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
時間枠：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

二次結果の測定

結果測定
メジャーの説明
時間枠
Core Phase: PCR-corrected ACPR at Days 22 and 43
時間枠：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
時間枠：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
時間枠：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
時間枠：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
時間枠：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
時間枠：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
時間枠：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
時間枠：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
時間枠：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
時間枠：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
時間枠：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
時間枠：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
時間枠：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
時間枠：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
時間枠：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
時間枠：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

協力者と研究者

ここでは、この調査に関係する人々や組織を見つけることができます。

スポンサー

Novartis Pharmaceuticals

協力者

Medicines for Malaria Venture (MMV), EDCTP, WANECAM

研究記録日

これらの日付は、ClinicalTrials.gov への研究記録と要約結果の提出の進捗状況を追跡します。研究記録と報告された結果は、国立医学図書館 (NLM) によって審査され、公開 Web サイトに掲載される前に、特定の品質管理基準を満たしていることが確認されます。

主要日程の研究

研究開始 (実際)

2024年3月7日

一次修了 (実際)

2025年6月27日

研究の完了 (実際)

2025年11月25日

試験登録日

最初に提出

2023年4月24日

QC基準を満たした最初の提出物

2023年5月3日

最初の投稿 (実際)

2023年5月6日

学習記録の更新

投稿された最後の更新 (実際)

2026年11月4日

QC基準を満たした最後の更新が送信されました

2026年10月30日

最終確認日

2026年10月1日

詳しくは

本研究に関する用語

キーワード

追加の関連 MeSH 用語

その他の研究ID番号

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

個々の参加者データ (IPD) の計画

個々の参加者データ (IPD) を共有する予定はありますか?

はい

IPD プランの説明

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.

医薬品およびデバイス情報、研究文書

米国FDA規制医薬品の研究

いいえ

米国FDA規制機器製品の研究

いいえ

この情報は、Web サイト clinicaltrials.gov から変更なしで直接取得したものです。研究の詳細を変更、削除、または更新するリクエストがある場合は、register@clinicaltrials.gov。 までご連絡ください。 clinicaltrials.gov に変更が加えられるとすぐに、ウェブサイトでも自動的に更新されます。

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