Platform Study to Evaluate the Efficacy and Safety of Anti-malarial Agents in Participants With Uncomplicated Plasmodium Falciparum Malaria

The Cohort A1 of this Platfom study (NCT05750628) is an open-label, randomized, multi-arm monotherapy part evaluating a single oral administration of an anti-malarial agent (INE963) at 3 parallel dose levels followed by optional adaptive sequential dose level(s).

Inclusion criteria

• Male and female patients ≥18 years of age at screening.
• Patients must have acute uncomplicated P. falciparum malaria mono infection at screening confirmed by a parasite count between 5,000 to 150,000 asexual parasite count/μl of blood for P. falciparum
• Patients must weigh between 40 kg and 90 kg.
• Axillary temperature ≥ 37.5ºC or oral/tympanic/rectal temperature ≥ 38.0ºC; or history of fever during the previous 24 hours.

Exclusion criteria

• Patients with signs and symptoms of severe/complicated malaria at screening or mixed Plasmodium infection (i.e., infection with more than one malaria species) at screening
• Moderate to severe anemia, chronic hemoglobinopathy (Hemoglobin level < 8 g/dL), or known chronic underlying disease such as sickle cell disease at screening
• Known clinically significant liver disease (e.g., chronic hepatitis, liver cirrhosis (compensated or decompensated), history of hepatitis B or C, hepatitis A or B vaccination in the last 3 months, known gallbladder or bile duct disease, acute or chronic pancreatitis. Clinical or laboratory evidence of any of the following at screening:

• AST/ALT > 3 x the upper limit of normal range (ULN), regardless of the level of total bilirubin
• AST/ALT > 1.5 and ≤ 2 x ULN and total bilirubin is > ULN
• Total bilirubin > 2 x ULN, regardless of the level of AST/ALT
• Any known/suspected immunosuppressive or immunodeficient condition, including human immunodeficiency virus (HIV) infection at screening.
• Pregnant or nursing (lactating) women, women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using methods of effective contraception, and sexually active patients not willing to practice effective contraception.
• History or current diagnosis of ECG abnormalities indicating significant risk of safety for patients participating in the study such as:

• Concomitant clinically significant cardiac arrhythmias, e.g., sustained ventricular tachycardia, and clinically significant second or third degree AV block without a pacemaker
• History of familial long QT syndrome or known family history of Torsades de Pointe.
• Resting heart rate (physical exam or 12 lead ECG) < 50 bpm

Other protocol-defined inclusion/exclusion criteria may apply.