Efficacy, Safety, and PK of M5717 in Combination With Pyronaridine as Chemoprevention in Adults and Adolescents With Asymptomatic Plasmodium Falciparum Infection (CAPTURE-2)

Phase 2a Proof-of-Concept, Multicenter, Randomized, Open Label Study to Evaluate the Efficacy, Safety, and Pharmacokinetics of a Single Dose of the Combination M5717-pyronaridine as Chemoprevention in Asymptomatic Adults and Adolescents With Plasmodium Falciparum Malaria Infection (CAPTURE-2)

This study evaluates the efficacy and safety of a single dose of M5717 plus pyronaridine tetraphosphate in clearing current Plasmodium falciparum infection and protecting against recurrent infections in asymptomatic adults and adolescents. The study will also assess the duration of protection provided by different doses of M5717 plus pyronaridine and the additional contribution of M5717 to the duration of protection using external study data.

Study Overview

• Status: Completed
• Conditions: Malaria Infection
• Intervention / Treatment: Drug: M5717 60 mg; Drug: Pyronaridine; Drug: M5717 200 mg; Drug: M5717 660mg; Drug: Atovaquone-Proguanil

• Study Type: Interventional
• Enrollment (Actual): 192
• Phase: Phase 2

Contacts and Locations

Study Locations

• Burkina Faso
  • Ouagadougou, Burkina Faso
    • Groupe de Recherche Action en Santé (GRAS)
• Kenya
  • Kisumu, Kenya
    • Kisumu County Referral Hospital
• The Gambia
  • Banjul, The Gambia
    • MRC Unit The Gambia at LSHTM
• Zambia
  • Ndola, Zambia
    • Ndola Teaching Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Participants with Asymptomatic Plasmodium falciparum Malaria with no Fever or other sign of Acute Uncomplicated Malaria and, with Microscopic confirmation using Giemsa-stained thick film, and a Parasitemia of >= 40 to <= 10,000 Asexual Parasites/Microliter (μL) of Blood.
• Axillary Temperature < 37.0 degree Celcius (ºC) or oral/Tympanic/rectal Temperature< 37.5ºC; without history of fever during the previous 48 hours.
• Have a body weight >= 45 kilogram (kg)
• Participants capable of giving Signed Informed consent which includes Compliance with the requirements and restriction listed in the Informed consent form
• Other Protocol defined Inclusion Criteria could apply

Exclusion Criteria:

• Participants with any disease requiring Chronic Treatment
• Participants with any Preplanned surgery during the study
• Participants with any previous Treatment with pyronaridine as part of a combination therapy during the last 3 months
• Participants with any adequate Hematological, Hepatic, and renal function as defined in the Protocol
• Other protocol defined Exclusion Criteria could apply

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1: M5717 (60 mg) + Pyronaridine; Participants received single oral dose of M5717 60 milligram (mg) plus pyronaridine tetraphosphate (pyronaridine) 720 mg (Participants >= 65 kilogram [kg]) or pyronaridine 540 mg (Participants >= 45 to < 65 kg) once daily in a single day treatment regimen.	Drug: M5717 60 mg; Participants received single oral dose (Capsules) of 60 mg M5717 on Day 1 under fasting condition; Drug: Pyronaridine; Participants received Pyronaridine tablets orally single dose of 720 (Participants >= 65 kg) and 540 mg (Participants >= 45 to < 65 kg) on Study Day 1 under fasting condition; Other Names: Pyronaridine tetraphosphate
Experimental: Cohort 2: M5717 (200 mg) + Pyronaridine; Participants received single oral dose of M5717 200 mg plus pyronaridine 720 mg (Participants >= 65 kg) or pyronaridine 540 mg (Participants >= 45 to < 65 kg) once daily in a single day treatment regimen.	Drug: Pyronaridine; Participants received Pyronaridine tablets orally single dose of 720 (Participants >= 65 kg) and 540 mg (Participants >= 45 to < 65 kg) on Study Day 1 under fasting condition; Other Names: Pyronaridine tetraphosphate; Drug: M5717 200 mg; Participants received single oral dose (Capsules) of 200 mg M5717 on Day 1 under fasting condition
Experimental: Cohort 3: M5717 (660 mg)+ Pyronaridine; Participants received single oral dose of M5717 660 mg plus pyronaridine 720 mg (Participants >= 65 kg) or pyronaridine 540 mg (Participants >= 45 to < 65 kg) once daily in a single day treatment regimen.	Drug: Pyronaridine; Participants received Pyronaridine tablets orally single dose of 720 (Participants >= 65 kg) and 540 mg (Participants >= 45 to < 65 kg) on Study Day 1 under fasting condition; Other Names: Pyronaridine tetraphosphate; Drug: M5717 660mg; Participants received single oral dose (Capsules) of 660 mg M5717 on Day 1 under fasting condition
Experimental: Cohort 4: Atovaquone-proguanil; Participants received orally 3 doses of Malarone (fixed-dose combination of atovaquone-proguanil) once daily in a 3-day treatment regimen.	Drug: Atovaquone-Proguanil; Participants received Atovaquone-Proguanil tablets 1000/400 mg once daily in a 3-day treatment regimen.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to Parasitemia Since Negative Blood Smear After Treatment	The time (in days) to first recorded parasitemia (parasite count >0) since the first negative blood smear (parasite count of 0) after treatment (followed at least by 1 subsequent visit with a negative blood film), i.e. the time without a positive blood smear. Median time and 95% CI was estimated using the Kaplan Meier method for each cohort.	From treatment Day 1 up to End of observation period Day 64 (Week 10)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Parasitemia (Positive Blood Smear)	Percentage of participants with a positive blood smear (parasitemia) was reported. Parasitemia is the presence of parasites in blood (parasite count >0).	From treatment Day 1 up to End of observation period Day 64 (Week 10)
Percentage of Participants With Polymerase Chain Reaction (PCR)-Adjusted Parasitemia (Due to New Infections)	Percentage of participants with polymerase chain reaction (PCR)-adjusted Parasitemia (Thick Smear/Microscopy, after Adjustment for Parasitemia due to new Infections as determined by Genotyping using PCR Techniques) was reported.	From treatment Day 1 up to End of observation period Day 64 (Week 10)
Percentage of Participants With PCR-adjusted Parasitemia (Due to Recrudescence)	Percentage of participants with polymerase chain reaction (PCR)-adjusted Parasitemia (Thick Smear/Microscopy, after Adjustment for Parasitemia due to Recrudescence as determined by Genotyping using PCR Techniques) was reported.	From treatment Day 1 up to End of observation period Day 64 (Week 10)
Parasite Clearance Time	Parasite clearance time defined as time from dosing to the first negative (no parasites) blood film (microscopy). Median parasite clearance time was estimated by Kaplan-Meier method	Time from dosing to the first negative (no parasites) blood film (microscopy) , assessed up to 12 weeks
Number of Participants With Treatment-Emergent Adverse Events (TEAE), Serious TEAEs and Treatment Related TEAEs	An adverse event (AE) was defined as any untoward medical occurrence in a participant administered with study drug which does not necessarily had a causal relationship with the treatment. An AE was any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with use of a medicinal product, whether or not considered related to the medicinal product. A serious adverse event (SAE) 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. TEAE was defined as AEs starting or worsening after the first intake of the study drug. TEAEs included both serious TEAEs and non-serious TEAEs. Treatment-related TEAEs: reasonably related to study intervention.	Up to End of Study (approximately 12 Weeks)
Area Under the Blood Concentration-Time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of M5717 and Pyronaridine	AUC0-inf was calculated by combining AUC0-t and AUCextra. AUC extra represents an extrapolated value obtained by Clast/ λz, where Clast is the calculated blood concentration at the last sampling time point at which the measured blood concentration is at or above the Lower Limit of quantification (LLQ) and λz is the apparent terminal rate constant determined by log-linear regression analysis of the measured blood concentrations of the terminal log-linear phase.	Predose, 1, 2, 4, 6, 8, and 12 hours on Day 1 and 24 hours on Day 2
Area Under the Blood Concentration-Time Curve From Time Zero to 24 Hours Post-dose (AUC 0-24) of M5717 and Pyronaridine	AUC from time zero to 24 hours post dose, calculated using the mixed log linear trapezoidal rule (linear up, log down) using the nominal dosing interval.	Predose, 1, 2, 4, 6, 8, and 12 hours on Day 1 and 24 hours on Day 2
Area Under the Blood Concentration-Time Curve From Time Zero to the Last Sampling Time (AUC 0-tlast) of M5717 and Pyronaridine	Area under the blood concentration vs time curve from time zero to the last sampling time t at which the concentration was at or above the lower limit of quantification (LLQQ). AUC0-t was to be calculated according to the mixed log-linear trapezoidal rule.	Predose, 1, 2, 4, 6, 8, and 12 hours on Day 1 and 24 hours on Day 2
Apparent Total Body Clearance From Blood (CL/f) of M5717 and Pyronaridine	Clearance of a drug was a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Apparent body clearance of the drug from blood, CL= Dose/AUC0-inf.	Predose, 1, 2, 4, 6, 8, and 12 hours on Day 1 and 24 hours on Day 2
Maximum Observed Blood Concentration (Cmax) of M5717 and Pyronaridine	Cmax was obtained directly from the concentration versus time curve.	Predose, 1, 2, 4, 6, 8, and 12 hours on Day 1 and 24 hours on Day 2
Apparent Terminal Half-life (t1/2) of M5717 and Pyronaridine	Terminal half-life is the time measured for the concentration to decrease by one half. Terminal half-life calculated by natural log 2 divided by lambda z.	Predose, 1, 2, 4, 6, 8, and 12 hours on Day 1 and 24 hours on Day 2
Time to Reach the Maximum Blood Concentration (Tmax) of M5717 and Pyronaridine	Time to reach the maximum blood concentration (Tmax) was obtained directly from the concentration versus time curve.	Predose, 1, 2, 4, 6, 8, and 12 hours on Day 1 and 24 hours on Day 2
Apparent Volume of Distribution (Vz/F) During the Terminal Phase of M5717 and Pyronaridine	The Vz/f was defined as the theoretical volume in which the total amount of required to uniformly distribute to produce the desired plasma concentration. Apparent volume of distribution after oral dose (Vz/F) was influenced by the fraction absorbed. The Vz/f was calculated by dividing the dose with area under the concentration time curve from time zero to infinity multiplied with terminal elimination rate constant Lambda(z). Vz/f=Dose/AUC(0-inf) multiply Lambda(z).	Predose, 1, 2, 4, 6, 8, and 12 hours on Day 1 and 24 hours on Day 2

Collaborators and Investigators

• Sponsor: Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany
• Investigators: Study Director: Medical Responsible, Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany

Publications and helpful links

Helpful Links

• Trial Awareness and Transparency website
• Medical Information Location Map - Med Info Contacts

Study record dates

Study Major Dates

• Study Start (Actual): November 28, 2023
• Primary Completion (Actual): December 29, 2024
• Study Completion (Actual): December 29, 2024

Study Registration Dates

• First Submitted: July 25, 2023
• First Submitted That Met QC Criteria: August 2, 2023
• First Posted (Actual): August 3, 2023

Study Record Updates

• Last Update Posted (Actual): February 6, 2026
• Last Update Submitted That Met QC Criteria: February 5, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: Adolescents; Malaria; Plasmodium falciparum; Adults; Chemoprevention; Exposure response; Plasmodium eukaryotic translation elongation factor 2 (PeEF2); Asymptomatic Infection
• Additional Relevant MeSH Terms: Vector Borne Diseases; Mosquito-Borne Diseases; Pathologic Processes; Disease Attributes; Infections; Protozoan Infections; Parasitic Diseases; Asymptomatic Diseases; Pathological Conditions, Signs and Symptoms; Malaria; Malaria, Falciparum; Asymptomatic Infections; Anti-Infective Agents; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites; Antimalarials; Antiprotozoal Agents; Antiparasitic Agents; pyronaridine; atovaquone, proguanil drug combination
• Other Study ID Numbers: MS201618_0034

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: We are committed to enhancing public health through responsible sharing of clinical trial data. Following approval of a new product or a new indication for an approved product in both the US and European Union, the study sponsor and/or its affiliated companies will share study protocols, anonymized patient data and study level data, and redacted clinical study reports with qualified scientific and medical researchers, upon request, as necessary for conducting legitimate research. Further information on how to request data can be found on our website bit.ly/IPD21
• IPD Sharing Time Frame: Within six months after the approval of a new product or a new indication for an approved product in both the United States and the European Union
• IPD Sharing Access Criteria: Qualified scientific and medical researchers can request the data. Such requests must be submitted in writing to the company's portal and will be internally reviewed regarding criteria for researchers' qualification and legitimacy of the research proposal.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ANALYTIC_CODE; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No