Phase IIa Proof of Concept Study of M5717-Pyronaridine in Adults and Adolescents With Acute Uncomplicated Plasmodium Falciparum Malaria (CAPTURE 1)

Merck KGaA (EMD Serono)

Status and phase: Completed; Phase 2

Conditions: Acute Malaria

Treatments: Drug: Pyronaridine 540 mg; Drug: M5717 330 mg; Drug: M5717 500 mg; Drug: Pyronaridine 360 mg; Drug: M5717 660 mg; Drug: Pyronaridine 720 mg

Study type: Interventional

Funder types: Industry

Identifiers

NCT05689047

MS201618_0033

Details and patient eligibility

About

The purpose of this study was to evaluate the safety, efficacy, and pharmacokinetic of the combination M5717 plus pyronaridine in participants with acute uncomplicated Plasmodium falciparum malaria.

Enrollment: 38 patients

Sex: All

Ages: 12 to 55 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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38 participants in 2 patient groups

Part A: Safety Run-in Cohort M5717+Pyronaridine

Experimental group

Description:

M5717 and pyronaridine once daily in a single day treatment regimen at low dose of 330 milligrams (mg) and 360 mg respectively.

Treatment:

Drug: Pyronaridine 360 mg

Drug: M5717 330 mg

Drug: Pyronaridine 360 mg

Part B: Dose escalation cohort; M5717+Pyronaridine

Experimental group

Description:

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.

Treatment:

Drug: Pyronaridine 720 mg

Drug: M5717 660 mg

Drug: Pyronaridine 360 mg

Drug: M5717 500 mg

Drug: Pyronaridine 540 mg

Drug: Pyronaridine 360 mg