Efficacy, Safety and Tolerability of KLU156 in Adults and Children ≥ 5 kg Body Weight With Uncomplicated P. Falciparum Malaria

Key Inclusion criteria (Core phase)

1. Male or female patients ≥ 5 kg of body weight and ≥ 2 months of age

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.