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

NCT05842954 | Completed Phase 3 DMC

• 2 other identifiers: CKLU156A123012022-002675-10
• Study Type: interventional
• Target: 1,720
• Locations: 12 countries
• Sites: 33

Brief Summary

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.

Conditions

Uncomplicated Plasmodium Falciparum Malaria

Keywords

malaria; Plasmodium falciparum; KLU156; Coartem; artemether; lumefantrine; ganaplacide

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (12)

• Uncorrected ACPR

  Day 29

• PCR-corrected and uncorrected ACPR

  Days 22 and 43 (i.e., 21 and 42 days post-first dose administration)

• Incidence rate of recrudescence and new infection

  Days 22, 29 and 43

• Fever Clearance Time

  Up to Day 3

• Parasite Clearance Time

  Up to Day 3

Study Arms (2)

KLU156

EXPERIMENTAL

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

Drug: KLU156

Coartem

ACTIVE COMPARATOR

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

Drug: Coartem

Interventions

KLU156 DRUG

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.

KLU156

Coartem DRUG

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

Coartem

Eligibility Criteria

• Age: 2 Months - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female patients ≥ 10 kg of body weight.
• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead
• Medicines for Malaria Venture (MMV), EDCTP, WANECAM: collaborator

Study Sites (33)

Novartis Investigative Site

Banfora, Burkina Faso

Location

Novartis Investigative Site

Bobo-Dioulasso, 01, Burkina Faso

Location

Novartis Investigative Site

Nanoro, BP 18, Burkina Faso

Location

Novartis Investigative Site

Ouagadougou, 11 BP 218, Burkina Faso

Location

Novartis Investigative Site

Sabou, 06 BP 10248, Burkina Faso

Location

Novartis Investigative Site

Abidjan, 13BP972, Côte d’Ivoire

Location

Novartis Investigative Site

Agboville, BP 154, Côte d’Ivoire

Location

Novartis Investigative Site

Azaguié, BP 173, Côte d’Ivoire

Location

Novartis Investigative Site

Kimpese, Bas-Congo Province, Democratic Republic of the Congo

Location

Novartis Investigative Site

Kisantu, Bas-Congo Province, Democratic Republic of the Congo

Location

Novartis Investigative Site

Lubumbashi, Du Haut Katanga, 7010, Democratic Republic of the Congo

Location

Novartis Investigative Site

Kenge, Kwango, Democratic Republic of the Congo

Location

Novartis Investigative Site

Masi-Manimba, Kwilu, Democratic Republic of the Congo

Location

Novartis Investigative Site

Lambaréné, BP 242, Gabon

Location

Novartis Investigative Site

Libreville, BP 1437, Gabon

Location

Novartis Investigative Site

Kintampo, 92037, Ghana

Location

Novartis Investigative Site

Navrango, VWJ6+8WF, Ghana

Location

Novartis Investigative Site

Kombewa, 40102, Kenya

Location

Novartis Investigative Site

Nairobi, 00200, Kenya

Location

Novartis Investigative Site

Siaya, 2300, Kenya

Location

Novartis Investigative Site

Sotouba, Mali

Location

Novartis Investigative Site

Niamey, 8003, Niger

Location

Novartis Investigative Site

Gicumbi, Northern Province, 00114, Rwanda

Location

Novartis Investigative Site

Kigali, 0000, Rwanda

Location

Novartis Investigative Site

Kigali, BP 4560, Rwanda

Location

Novartis Investigative Site

Rubavu, Rwanda

Location

Novartis Investigative Site

Rusizi, Rwanda

Location

Novartis Investigative Site

Bagamoyo, Tanzania

Location

Novartis Investigative Site

Korogwe Tanga, Tanzania

Location

Novartis Investigative Site

Tanga, 5004, Tanzania

Location

Novartis Investigative Site

Tororo, 10102, Uganda

Location

Novartis Investigative Site

Nchelenge, Luapula Province, 70100, Zambia

Location

Novartis Investigative Site

Ndola, 71769, Zambia

Location

MeSH Terms

Conditions

Malaria; Malaria, Falciparum

Interventions

Artemether, Lumefantrine Drug Combination

Condition Hierarchy (Ancestors)

Protozoan Infections; Parasitic Diseases; Infections; Mosquito-Borne Diseases; Vector Borne Diseases

Intervention Hierarchy (Ancestors)

Artemether; Artemisinins; Reactive Oxygen Species; Free Radicals; Inorganic Chemicals; Organic Chemicals; Lumefantrine; Fluorenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Sesquiterpenes; Terpenes; Polycyclic Compounds; Drug Combinations; Pharmaceutical Preparations

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: The Novartis clinical trial team (CTT) will be blinded to the identity of the treatment from the time of randomization until the database lock for the analysis of the Core phase. Prior to unblinding the data of the Core phase (for the Novartis CTT), at least three DMC reviews are planned to minimize risks in this vulnerable patient population: 1. Once the first 200 patients (across both treatment arms) in the Core phase have been dosed and followed up to at least Day 22. 2. Once the first 750 patients (across both treatment arms) in the Core phase have been dosed and followed up to at least Day 22. 3. Additional DMC reviews may be conducted ad-hoc during the study, as deemed necessary. All safety data from the Core phase as well as from the Extension phase that are available at these 2 scheduled timepoints will be included in the DMC reviews. After the database lock of the Core phase, the CTT will be unblinded.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 24, 2023
• First Posted: May 6, 2023
• Study Start: March 7, 2024
• Primary Completion: June 27, 2025
• Study Completion: November 25, 2025
• Last Updated: January 27, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will share

Locations

GA (2); NI (1); ZA (2); KE (3); DE (5); GH (2); CÔ (3); TA (3); BU (5); RW (5); MA (1); UG (1)