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

Phase 2

Completed

• Conditions: Malaria Infection
• Interventions: Drug: M5717 60 mg; Drug: Atovaquone-Proguanil; Drug: M5717 200 mg; Drug: M5717 660mg; Drug: Pyronaridine

• Registration Number: NCT05974267
• Lead Sponsor: Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany

Brief Summary

This study will evaluate 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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2023-07-25
• Study First Submitted QC: 2023-08-02
• Study First Posted: 2023-08-03
• Study Start: 2023-11-28
• Primary Completion: 2024-12-29
• Study Completion: 2024-12-29
• Status Verified: 2025-01
• Last Update Submitted: 2025-01-30
• Last Update Posted: 2025-01-31

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 192

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Cohort 2: M5717 (200 mg) + Pyronaridine	M5717 200 mg	Participants will receive 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.
Cohort 1: M5717 (60 mg) + Pyronaridine	M5717 60 mg	Participants will receive 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.
Cohort 3: M5717 (660 mg)+ Pyronaridine	M5717 660mg	Participants will receive 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.
Cohort 4: Atovaquone-proguanil	Atovaquone-Proguanil	Participants will receive orally 3 doses of Malarone (fixed-dose combination of atovaquone-proguanil) once daily in a 3-day treatment regimen.
Cohort 1: M5717 (60 mg) + Pyronaridine	Pyronaridine	Participants will receive 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.
Cohort 2: M5717 (200 mg) + Pyronaridine	Pyronaridine	Participants will receive 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.
Cohort 3: M5717 (660 mg)+ Pyronaridine	Pyronaridine	Participants will receive 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.

Primary Outcome Measures

Name	Time	Method
Time to Parasitemia Since Negative Blood Smear after Treatment	From Study Start Day 1 up to End of Study (approximately 12 weeks)

Secondary Outcome Measures

Name	Time	Method
Percentage of Participants with Parasitemia (positive blood smear).	From Study Start Day 1 up to End of Study (approximately 12 week)
Percentage of Participants with PCR-adjusted Parasitemia (Thick Smear/Microscopy, after Adjustment for Parasitemia due to Recrudescence as determined by Genotyping using PCR Techniques)	From Study Start Day 1 up to End of Study (approximately 12 weeks)
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)	From Study Start Day 1 up to End of Study (approximately 12 weeks)
Parasite Clearance Time	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 Related TEAEs	From Study Start Day 1 up to End of Study (approximately 12 Weeks)
Pharmacokinetic (PK) Plasma Concentrations of M5717 and Pyronaridine	Predose, 1, 2, 4, 6, 8, and 12 hours on Day 1 and (24 hours) on Day 2

Trial Locations

Locations (4)

Groupe de Recherche Action en Sante (GRAS); 🇧🇫 Ouagadougou 06, Burkina Faso

MRC Unit The Gambia at LSHTM; 🇬🇲 Banjul, Gambia

Kisumu County Referral Hospital; 🇰🇪 Kisumu, Kenya

Ndola Teaching Hospital; 🇿🇲 Ndola, Zambia