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

Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany38 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Acute Malaria

Interventions

M5717 330 mgDRUG

Participants will receive orally 330 mg granules of M5717 in combination with pyronaridine dispersed in water under fasting condition.

M5717 500 mgDRUG

Adolescent participants with weight less than (\<) 45 kilograms (kg) will receive orally 500 mg granules of M5717 in combination with pyronaridine dispersed in water once daily under fasting condition.

M5717 660 mgDRUG

Adult and adolescent participants with weight more than or equal to (\>=) 45 kg will receive orally 660 mg granules of M5717 in combination with pyronaridine dispersed in water once daily under fasting condition.

Eligibility

Sex: ALLMin age: 12 YearsMax age: 55 Years

Medical Language ↔ Plain English

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

Locations (5)

Institut de Recherche en Sciences de la Santé (IRSS)

Nanoro, Burkina Faso

Groupe de Recherche Action en Santé (GRAS)

Ouagadougou, Burkina Faso

Centre de Recherches Médicales de Lambaréné (CERMEL)

Lambaréné, Gabon

Centro de Investigação em saúde de Manhiça/Fundação Manhiça (CISM/FM)

Maputo, Mozambique

Outcomes

Primary Outcomes

Cohort A: Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious TEAEs and Related TEAEs

An adverse event (AE) was defined as any untoward medical occurrence in a participant. TEAEs are defined as AEs which started at or after the administration of study intervention (study treatment) or which started prior to the first administration of study intervention but worsened after the dose intake, until the last scheduled assessment will be regarded as treatment-emergent, but before established rescue antimalarial treatment is administered, if required. A serious TEAE was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. A TEAE was considered to be "related" if a causal relationship between study treatment and the TEAE is at least reasonably possible.

Time frame: Day 1 up to Day 43

Cohort A: Number of Participants With Clinically Significant Change From Baseline in Safety Laboratory Parameters

Number of participants with clinically significant change from baseline in laboratory parameters were reported. Clinical Significance was decided by the investigator. Laboratory investigation included hematology, biochemistry, and coagulation.

Time frame: Day 1 up to Day 29

Cohort A: Number of Participants With Clinically Significant Change From Baseline in 12-lead Electrocardiogram (ECG) Findings

Number of participants with clinically significant change from baseline in ECG parameters were reported. Clinical Significance was decided by the investigator. The 12-lead ECGs were recorded after the participants have rested for at least 5 minutes in supine position. The parameters included heart rate (HR), Respiratory Rate, Pulse Rate, QRS, QT and QTcB calculated by the Bazett formula.

Time frame: Day 1 up to Day 29

Cohort A: Number of Participants With Clinically Significant Change From Baseline in Vital Signs

Number of participants with clinically significant change from baseline in vital signs. Clinical Significance was decided by the investigator. Vital signs included oral body temperature, systolic blood pressure, diastolic blood pressure, and pulse rate.

Data from ClinicalTrials.gov

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Secondary Outcomes

Cohort A and Cohort B0: Area Under Plasma Concentration-Time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of M5717 and Pyronaridine

The AUC from time zero (dosing time) extrapolated to infinity, based on the predicted value for the concentration at tlast, as estimated using the linear regression from lambda z determination. Calculated as AUC0-inf = AUC0-tlast + Clast pred/ lambda z.