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

NCT ID: NCT05842954

Last Updated: 2025-12-18

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

1720 participants

Study Classification

INTERVENTIONAL

Study Start Date

2024-03-07

Study Completion Date

2025-11-25

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

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.

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

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).

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Uncomplicated Plasmodium Falciparum Malaria

Keywords

Explore important study keywords that can help with search, categorization, and topic discovery.

malaria Plasmodium falciparum KLU156 Coartem artemether lumefantrine ganaplacide

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

SINGLE

Outcome Assessors
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.

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

KLU156

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

Group Type EXPERIMENTAL

KLU156

Intervention Type 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.

Coartem

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

Group Type ACTIVE_COMPARATOR

Coartem

Intervention Type DRUG

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

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

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.

Intervention Type DRUG

Coartem

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

Intervention Type DRUG

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

Inclusion Criteria

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.

Exclusion Criteria

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.
Minimum Eligible Age

2 Months

Maximum Eligible Age

100 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

Meet the organizations funding or collaborating on the study and learn about their roles.

Medicines for Malaria Venture (MMV), EDCTP, WANECAM

UNKNOWN

Sponsor Role collaborator

Novartis Pharmaceuticals

INDUSTRY

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Responsibility Role SPONSOR

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

Novartis Investigative Site

Banfora, , Burkina Faso

Site Status

Novartis Investigative Site

Bobo-Dioulasso, , Burkina Faso

Site Status

Novartis Investigative Site

Nanoro, , Burkina Faso

Site Status

Novartis Investigative Site

Ouagadougou, , Burkina Faso

Site Status

Novartis Investigative Site

Sabou, , Burkina Faso

Site Status

Novartis Investigative Site

Abidjan, , Côte d’Ivoire

Site Status

Novartis Investigative Site

Agboville, , Côte d’Ivoire

Site Status

Novartis Investigative Site

Azaguié, , Côte d’Ivoire

Site Status

Novartis Investigative Site

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

Site Status

Novartis Investigative Site

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

Site Status

Novartis Investigative Site

Lubumbashi, Du Haut Katanga, Democratic Republic of the Congo

Site Status

Novartis Investigative Site

Kenge, Kwango, Democratic Republic of the Congo

Site Status

Novartis Investigative Site

Masi-Manimba, Kwilu, Democratic Republic of the Congo

Site Status

Novartis Investigative Site

Lambaréné, , Gabon

Site Status

Novartis Investigative Site

Libreville, , Gabon

Site Status

Novartis Investigative Site

Kintampo, , Ghana

Site Status

Novartis Investigative Site

Navrango, , Ghana

Site Status

Novartis Investigative Site

Kombewa, , Kenya

Site Status

Novartis Investigative Site

Nairobi, , Kenya

Site Status

Novartis Investigative Site

Siaya, , Kenya

Site Status

Novartis Investigative Site

Sotouba, , Mali

Site Status

Novartis Investigative Site

Niamey, , Niger

Site Status

Novartis Investigative Site

Gicumbi, Northern Province, Rwanda

Site Status

Novartis Investigative Site

Kigali, , Rwanda

Site Status

Novartis Investigative Site

Kigali, , Rwanda

Site Status

Novartis Investigative Site

Rubavu, , Rwanda

Site Status

Novartis Investigative Site

Rusizi, , Rwanda

Site Status

Novartis Investigative Site

Bagamoyo, , Tanzania

Site Status

Novartis Investigative Site

Korogwe Tanga, , Tanzania

Site Status

Novartis Investigative Site

Tanga, , Tanzania

Site Status

Novartis Investigative Site

Tororo, , Uganda

Site Status

Novartis Investigative Site

Nchelenge, Luapula Province, Zambia

Site Status

Novartis Investigative Site

Ndola, , Zambia

Site Status

Countries

Review the countries where the study has at least one active or historical site.

India Burkina Faso Côte d’Ivoire Democratic Republic of the Congo Gabon Ghana Kenya Mali Niger Rwanda Tanzania Uganda Zambia

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

2022-002675-10

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CKLU156A12301

Identifier Type: -

Identifier Source: org_study_id