Phase IIa Proof of Concept Study of M5717-Pyronaridine in Adults and Adolescents With Acute Uncomplicated Plasmodium Falciparum Malaria (CAPTURE 1)
Acute Malaria
About this trial
This is an interventional treatment trial for Acute Malaria focused on measuring M5717, Plasmodium mutants, Acute Malaria, Pyronaridine, Plasmodium falciparum, Polymerase chain reaction, Adequate Clinical and Parasitological Response, Plasmodium eukaryotic translation Elongation Factor 2
Eligibility Criteria
Inclusion Criteria: Participants with microscopic confirmation of acute uncomplicated Plasmodium falciparum using Giemsa-stained thick and thin film P. falciparum parasitemia of 1,000 to 50,000 asexual parasites/microliter of blood in Part A and P. falciparum parasitemia of >1,000 to <= 150,000 asexual parasites/microliter of blood in Part B Axillary temperature >= 37.5 degree Celsius or tympanic temperature >= 38.0 degree Celsius (use as per Coronavirus disease 2019 (COVID-19) protocols at the site [only at Screening]), or history of fever during the previous 24 hours (at least documented verbally) The Investigator confirms that each participant agrees to use appropriate contraception and barriers, if applicable Capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the Informed Consent Form (ICF) and this protocol Other protocol defined inclusion criteria could apply Exclusion Criteria: Mixed Plasmodium infections as per thin film microscopy results Signs and symptoms of severe malaria according to World Health Organisation (WHO) 2021 criteria (WHO 2021) Known liver abnormalities, liver cirrhosis (compensated or decompensated), known active or history of hepatitis B or C (testing not required), underlying hepatic injury or known severe liver disease, known gallbladder or bile duct disease, acute or chronic pancreatitis, or severe malnutrition Known history or evidence of clinically significant disorders such as, cardiovascular, respiratory (including active tuberculosis), hepatic, renal, gastrointestinal, immunological [including known Human Immunodeficiency Virus-Acquired Immunodeficiency Syndrome (HIV-AIDS)], neurological (including auditory), endocrine, infectious, malignancy, psychiatric, history of convulsions, or other abnormality (including head trauma) Previous treatment with pyronaridine as part of a combination therapy during the last 3 months Prior antimalarial therapy or antibiotics with antimalarial activity within a minimum of their 5 plasma half-lives (or within 4 weeks of Screening if half-life is unknown) Participants taking medications prohibited by the protocol Other protocol defined exclusion criteria could apply
Sites / Locations
- Institut de Recherche en Sciences de la Santé (IRSS)
- Groupe de Recherche Action en Santé (GRAS)
- Centre de Recherches Médicales de Lambaréné (CERMEL)
- Centro de Investigação em saúde de Manhiça/Fundação Manhiça (CISM/FM)
- Infectious Diseases Research Collaboration (IDRC)Recruiting
Arms of the Study
Arm 1
Arm 2
Arm 3
Experimental
Experimental
Active Comparator
Part A: Safety Run-in Cohort M5717+Pyronaridine
Part B: Dose escalation cohort; M5717+Pyronaridine
Pyronaridine-artesunate
M5717 and pyronaridine once daily in a single day treatment regimen at low dose of 330 milligrams (mg) and 360 mg respectively.
After completion of Part A, if dose will be considered safe and well tolerated, the Internal Data Monitoring Committee (IDMC) will have the option to recommend dose adjustments. M5717 and pyronaridine once daily will be administered in an escalated dose in a single day or 2-day treatment regimen.
Pyronaridine-artesunate (Pyramax) once daily in a 3-day treatment regimen.