Inclusion Criteria:
1. Ability to provide informed consent signed by the study participant or legally authorized representative
2. Adults 18 to 55 years at the time of signing the informed consent form (ICF)
3. Female participants are eligible to participate if they do not qualify as a woman of childbearing potential (WOCBP), as defined in Section 10.4.
4. Male participants who engage in heterosexual intercourse must agree to use protocol specified method(s) of contraception as described in Section 10.4.
5. BMI ≥18 to ≤30 kg/m2
6. Mono-infection with P. falciparum documented by:
* Microscopically confirmed parasite infection using by Giemsa-stained thick film (refer to the laboratory manual for details) consisting of 1000 - 100,000 asexual parasites /µL of blood and
* Documented fever (≥38.0°C oral, rectal or tympanic; ≥37.5°C axillary) or documented history of fever in previous 24 hours
Exclusion Criteria:
1. Presence of severe malaria (as defined by World Health Organization Guidelines for Malaria 16 February 2021).
• Severe falciparum malaria is defined as one or more of the following, occurring in the absence of an identified alternative cause and in the presence of P. falciparum asexual parasitemia.
* Impaired consciousness: A Glasgow coma score \<11 in adults
* Prostration: Generalized weakness so that the person is unable to sit, stand or walk without assistance
* Multiple convulsions: More than 2 episodes within 24 h
* Acidosis: A base deficit of \>8 mEq/L or, if not available, a plasma bicarbonate level of \<15 mmol/L or venous plasma lactate ≥5 mmol/L. Severe acidosis manifests clinically as respiratory distress (rapid, deep, labored breathing).
* Hypoglycemia: Blood or plasma glucose \<2.2 mmol/L (\<40 mg/dL)
* Severe malarial anemia: Hemoglobin concentration ≤7 g/dL or a hematocrit of ≤20% in adults with a parasite count \>10,000/μL
* Renal impairment: Plasma or serum creatinine \>265 μmol/L (3 mg/dL) or blood urea \>20 mmol/L
* Jaundice: Plasma or serum bilirubin \>50 μmol/L (3 mg/dL) with a parasite count \>100,000/ μL
* Pulmonary edema: Radiologically confirmed or oxygen saturation \<92% on room air with a respiratory rate \>30/min, often with chest indrawing and crepitations on auscultation
* Significant bleeding: Including recurrent or prolonged bleeding from the nose, gums or venepuncture sites; hematemesis or melena
* Shock: Compensated shock is defined as capillary refill ≥3 s or temperature gradient on leg (mid to proximal limb), but no hypotension. Decompensated shock is defined as systolic blood pressure \<80 mmHg in adults, with evidence of impaired perfusion (cool peripheries or prolonged capillary refill).
* Hyperparasitemia: P. falciparum parasitemia \>10%
2. Antimalarial treatment (alone or in combination) during the following periods before Screening:
* Piperaquine, mefloquine, naphthoquine or sulfadoxine-pyrimethamine within 6 weeks prior to Screening.
* Amodiaquine, chloroquine within 4 weeks prior to Screening.
* Any artemisinin derivative (artesunate, artemether or dihydroartemisinin), quinine, lumefantrine or any other antimalarial treatment or antibiotic with antimalarial activity (including cotrimoxazole, tetracyclines, quinolones and fluoroquinolones and azithromycin) within 14 days prior to Screening.
* Any herbal products or traditional medicines, within the past 7 days.
3. Previous participation in any malaria vaccine study or received malaria vaccine within 3 months of Screening Visit.
4. Known allergy to any study medication, including allergy to any component of protocol prescribed rescue treatment i.e., country-specific ACT regimen.
5. Any clinically important illness, including but not limited to a history of clinically significant chronic respiratory disease (eg, chronic obstructive pulmonary disease \[COPD\] or asthma), medical/surgical procedure, or trauma within 4 weeks of the first administration of investigational product.
6. Participants participate in another clinical study. There will be a need for washout with 5 half-lives depending on the study treatment or 30 days, whichever is longer.
7. Use of anti-cancer, anti-transplant rejection, or immunomodulatory biological drug or kinase inhibitor (e.g., tocilizumab, sarilumab) or Janus kinase inhibitors (within 30 days of enrollment or 5 times the half-life \[whichever is longer\]).
8. Chronic corticosteroids use equivalent to daily oral prednisone \>10 mg per day (10 mg oral prednisone every other day is allowed).
9. Live (live-attenuated) vaccines are not permitted within 2 weeks prior to study treatment or during the study treatment and safety follow-up periods.
10. Presence of Hepatitis A IgM, Hepatitis B surface antigen, or Hepatitis C antibody.
11. TBL \>1.5 × ULN, ALT \>2 × ULN, or AST \>2 × ULN.
12. Hematocrit \<20%, hemoglobin \<70 g/L (\<7 g/dL), or white blood count \>15,000/μL.
13. Creatinine \>1.5 × ULN.
