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

Sponsor

Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany (Industry)

Overall Status

Not yet recruiting

CT.gov ID

NCT05974267

Collaborator

(none)

192

Enrollment

Location

Arms

8.2

Anticipated Duration (Months)

23.5

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Malaria Infection	Drug: M5717 60 mg Drug: Pyronaridine Drug: Atovaquone-Proguanil Drug: M5717 200 mg Drug: M5717 660mg	Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

192 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

Open LabelOpen Label

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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)

Anticipated Study Start Date :

Aug 25, 2023

Anticipated Primary Completion Date :

Apr 30, 2024

Anticipated Study Completion Date :

Apr 30, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Cohort 1: M5717 (60 mg) + 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.	Drug: M5717 60 mg Participants will receive single oral dose (Capsules) of 60 mg M5717 on Day 1 under fasting condition Drug: Pyronaridine Participants will receive 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 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.	Drug: Pyronaridine Participants will receive 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 will receive single oral dose (Capsules) of 200 mg M5717 on Day 1 under fasting condition
Experimental: Cohort 3: M5717 (660 mg)+ 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.	Drug: Pyronaridine Participants will receive 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 will receive single oral dose (Capsules) of 660 mg M5717 on Day 1 under fasting condition
Experimental: Cohort 4: Atovaquone-proguanil Participants will receive orally 3 doses of Malarone (fixed-dose combination of atovaquone-proguanil) once daily in a 3-day treatment regimen.	Drug: Atovaquone-Proguanil Participants will Receive Atovaquone-Proguanil tablets 1000/400 mg once daily in a 3-day treatment regimen.

Outcome Measures

Primary Outcome Measures

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

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 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)]
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)]
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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

12 Years to 55 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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