Efficacy, Safety and Tolerability of KLU156 in Adults and Children With Uncomplicated P. Falciparum Malaria (KALUMA)

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 Followed by an Extension Phase With Repeated KLU156 Treatment

This study aims 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 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.

Study Overview

• Status: Completed
• Conditions: Uncomplicated Plasmodium Falciparum Malaria
• Intervention / Treatment: Drug: KLU156; Drug: Coartem

Detailed Description

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 up to 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.

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

• Study Type: Interventional
• Enrollment (Actual): 1720
• Phase: Phase 3

Contacts and Locations

Study Locations

• Burkina Faso
  • Banfora, Burkina Faso
    • Novartis Investigative Site
  • Bobo-Dioulasso, Burkina Faso, 01
    • Novartis Investigative Site
  • Nanoro, Burkina Faso, BP 18
    • Novartis Investigative Site
  • Ouagadougou, Burkina Faso, 11 BP 218
    • Novartis Investigative Site
  • Sabou, Burkina Faso, 06 BP 10248
    • Novartis Investigative Site
• Côte d’Ivoire
  • Abidjan, Côte d’Ivoire, 13BP972
    • Novartis Investigative Site
  • Agboville, Côte d’Ivoire, BP 154
    • Novartis Investigative Site
  • Azaguié, Côte d’Ivoire, BP 173
    • Novartis Investigative Site
• Democratic Republic of the Congo
  • Bas-Congo Province
    • Kimpese, Bas-Congo Province, Democratic Republic of the Congo
      • Novartis Investigative Site
    • Kisantu, Bas-Congo Province, Democratic Republic of the Congo
      • Novartis Investigative Site
  • Du Haut Katanga
    • Lubumbashi, Du Haut Katanga, Democratic Republic of the Congo, 7010
      • Novartis Investigative Site
  • Kwango
    • Kenge, Kwango, Democratic Republic of the Congo
      • Novartis Investigative Site
  • Kwilu
    • Masi-Manimba, Kwilu, Democratic Republic of the Congo
      • Novartis Investigative Site
• Gabon
  • Lambaréné, Gabon, BP 242
    • Novartis Investigative Site
  • Libreville, Gabon, BP 1437
    • Novartis Investigative Site
• Ghana
  • Kintampo, Ghana, 92037
    • Novartis Investigative Site
  • Navrango, Ghana, VWJ6+8WF
    • Novartis Investigative Site
• Kenya
  • Kombewa, Kenya, 40102
    • Novartis Investigative Site
  • Nairobi, Kenya, 00200
    • Novartis Investigative Site
  • Siaya, Kenya, 2300
    • Novartis Investigative Site
• Mali
  • Sotouba, Mali
    • Novartis Investigative Site
• Niger
  • Niamey, Niger, 8003
    • Novartis Investigative Site
• Rwanda
  • Kigali, Rwanda, 0000
    • Novartis Investigative Site
  • Kigali, Rwanda, BP 4560
    • Novartis Investigative Site
  • Rubavu, Rwanda
    • Novartis Investigative Site
  • Rusizi, Rwanda
    • Novartis Investigative Site
  • Northern Province
    • Gicumbi, Northern Province, Rwanda, 00114
      • Novartis Investigative Site
• Tanzania
  • Bagamoyo, Tanzania
    • Novartis Investigative Site
  • Korogwe Tanga, Tanzania
    • Novartis Investigative Site
  • Tanga, Tanzania, 5004
    • Novartis Investigative Site
• Uganda
  • Tororo, Uganda, 10102
    • Novartis Investigative Site
• Zambia
  • Ndola, Zambia, 71769
    • Novartis Investigative Site
  • Luapula Province
    • Nchelenge, Luapula Province, Zambia, 70100
      • Novartis Investigative Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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 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
6. 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.

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 require correction, e.g., hypokalemia, hypocalcemia or hypomagnesemia
6. Anemia (hemoglobin level <7 g/dL)
7. 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.

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 is 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.

Other protocol-defined inclusion/exclusion criteria may apply.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: KLU156; KLU156 once daily (QD) for 3 days under fed conditions (light meal).	Drug: 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.
Active Comparator: Coartem; Coartem twice a day (BID) for 3 days under fed conditions.	Drug: Coartem; Oral use. Dosing will be selected based on patient's body weight as per product's label.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
PCR-corrected adequate clinical and parasitological response (ACPR)	To confirm the efficacy of 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) by demonstrating that KLU156 is non-inferior to Coartem (non-inferiority margin = 5%) based on the PCR-corrected ACPR at Day 29. This primary outcome is applicable to non-US submission.	Day 29 (i.e., 28 days post-first dose administration)
Uncorrected ACPR (US NDA submission)	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. This primary outcome is applicable to US New Drug Application (NDA) submission.	Day 29

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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: Gametocyte carriage over time	To assess gametocyte carriage over time by malaria episode in the extension phase	Up to 2 years
Gametocyte Clearance Time	To confirm the efficacy of KLU156 by assessing gametocyte clearance between the two treatment arms	Up to Day 3
Extension phase: PCR-corrected and uncorrected ACPR	To evaluate efficacy 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) 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 ≥ 10 kg of body weight 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

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals
• Collaborators: Medicines for Malaria Venture (MMV), EDCTP, WANECAM

Study record dates

Study Major Dates

• Study Start (Actual): March 7, 2024
• Primary Completion (Actual): June 27, 2025
• Study Completion (Actual): November 25, 2025

Study Registration Dates

• First Submitted: April 24, 2023
• First Submitted That Met QC Criteria: May 3, 2023
• First Posted (Actual): May 6, 2023

Study Record Updates

• Last Update Posted (Actual): January 27, 2026
• Last Update Submitted That Met QC Criteria: January 24, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Keywords: Plasmodium falciparum; malaria; artemether; lumefantrine; Coartem; ganaplacide; KLU156
• Additional Relevant MeSH Terms: Vector Borne Diseases; Mosquito-Borne Diseases; Infections; Protozoan Infections; Parasitic Diseases; Malaria; Malaria, Falciparum; Organic Chemicals; Pharmaceutical Preparations; Hydrocarbons; Hydrocarbons, Cyclic; Terpenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Polycyclic Compounds; Inorganic Chemicals; Drug Combinations; Reactive Oxygen Species; Free Radicals; Artemether; Artemisinins; Lumefantrine; Fluorenes; Sesquiterpenes; Artemether, Lumefantrine Drug Combination
• Other Study ID Numbers: CKLU156A12301; 2022-002675-10 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: 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.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No