The study will evaluate the safety and efficacy of a new antimalarial drug GSK3772701 (a pyrrolidinamide), using different doses and treatment durations, in adult participants with uncomplicated Plasmodium (P.) falciparum malaria.

Inclusion Criteria:

• Male and female patients aged 18 to 65 years.

• Presence of malaria due to mono-infection with P. falciparum confirmed by:

  • Fever, as defined by axillary temperature >=37.5°C or oral/tympanic temperature >=38°C and,
  • Microscopically confirmed P. falciparum malaria parasite mono-infection,
  • A parasite count between 2,000 to 60,000 asexual parasite count/µL of blood for P. falciparum.

• Have a BMI between >=18 and <=30 kg/m2.

• Able to swallow oral medication.

• Signed informed consent, acknowledging understanding and willingness to comply with the requirements of the study. If the patient is unable to write, thumb print consent, signed by an impartial witness is permitted according to local ethical considerations.

• Contraceptive use by women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.

• A female participant is eligible to participate if she is not pregnant or breastfeeding, and one of the following conditions applies:

  • Is a woman of non-childbearing potential (WONCBP) or
  • Is a woman of childbearing potential (WOCBP) and using an acceptable contraceptive method, from Study Day 1, and during the study intervention period (40 +/-3 days).

Exclusion Criteria:

• Patients with signs and symptoms of severe/complicated malaria according to the WHO 2024 Criteria.
• Mixed Plasmodium infection, i.e., infection with more than one malaria (plasmodium) species (by microscopy; participant to be withdrawn from study treatment if PCR subsequently indicates presence of mixed infection).
• Abnormal values: QTcF >450 msec or QTcF >480 msec for patients with bundle branch block.
• Any clinically significant ECG abnormalities at Screening unrelated to malaria (including but not limited to, second degree AV block (Mobitz Type 2), complete heart block, ST changes, atrial fibrillation, atrial flutter, supraventricular tachycardia, ventricular tachycardia, prolonged QT interval.
• History of malignancy (or current malignancy) of any organ system (other than localized carcinoma of the skin), treated or untreated, within the past 5 years, regardless of whether there is evidence of local recurrence or metastases.
• Creatinine >=2 x ULN.
• Significant illness within two weeks prior to screening.
• Positive HIV antibody test at screening, or history of HIV infection based on past positive test result, clinical record or current treatment.
• Severe vomiting, defined as more than 3 times in the 24 hours before screening or inability to tolerate oral treatment.
• Severe diarrhoea defined as more than 3 watery stools per day in the 24 hours before screening.
• Known history or evidence (based on clinical examination or investigation) of uncontrolled active cardiovascular disease (including hypertension), respiratory disease (including active tuberculosis even if treatment is ongoing), liver cirrhosis or liver disease (based on prior investigation, clinical signs and/or interpretation of liver enzymes), other active hepatic, renal, gastrointestinal, immunological, neurological, endocrine, infectious, or psychiatric disease.
• Anaemia (Hb <=8.0g/dl) or known clinically important chronic underlying haematological disease such as sickle cell disease at screening.
• Significant chronic medical conditions which in the opinion of the investigator preclude enrolment into the study.
• Have received any antimalarial treatment in the preceding 6 weeks (see Section 6.10), as determined by history or medical record.
• Prior enrolment in this study and receipt of treatment with GSK3772701.
• Use of other investigational drugs at the time of enrolment, or within 6 weeks, or 5 half-lives prior to enrolment into this study, whichever is longer; or longer if required by local regulations, and for any other limitation of participation in an investigational trial based on local regulations.
• History of hypersensitivity to the study drug or drug formulation and capsule (Hypromellose (hydroxypropyl methylcellulose)) constituents.
• History of drug or alcohol abuse within 3 months prior to dosing, or clinical evidence of such abuse.
• Participants who in the opinion of the Investigator are unsuitable for participation in the study or cannot be enrolled due to logistical reasons.
• ALT >2.0 x ULN.
• Total bilirubin >1.5 x ULN; Participants with Gilbert's syndrome can be included with total bilirubin >1.5xULN as long as direct bilirubin is <=1.5xULN.
• Current or chronic history of liver disease or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
• Presence of hepatitis B surface antigen (HBsAg) at screening or within 3 months prior to first dose of study intervention.
• Positive hepatitis C antibody test result at screening or within 3 months prior to first dose of study intervention.

Note: Participants with positive hepatitis C antibody due to prior resolved disease can be enrolled, only if a confirmatory negative Hepatitis C RNA test is obtained.

• Positive hepatitis C RNA test result at screening or within 3 months prior to first dose of study intervention.

Note: Test is optional and participants with negative Hepatitis C antibody test are not required to also undergo Hepatitis C RNA testing.

GSK will assess requests from qualified researchers for anonymized individual patient-level data and related study documents. Data sharing is subject to certain criteria, conditions, and exceptions. For further information, refer to https://www.gsk-studyregister.com/About\_GSK\_Patient\_Level\_Data\_Sharing\_Final\_13July2023.pdf.

Anonymized IPD will be made available within 6 months of publication of primary, key secondary and safety results for studies in product with approved indication(s) or asset(s) with development terminated across all indications.

Anonymized IPD is shared with researchers whose proposals are approved by an Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months, but an extension may be granted, when justified, for up to 6 months.

Open-label