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

Malaria Infection Clinical Trial

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)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05974267
• Other study ID #: MS201618_0034
• Status: Recruiting
• Phase: Phase 2
• Start date: November 28, 2023
• Est. completion date: April 30, 2024

Study information

• Verified date: February 2024
• Source: Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany
• Contact: Communication Center
• Phone: +49 6151 72 5200
• Email: service[@]emdgroup.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 192
• Est. completion date: April 30, 2024
• Est. primary completion date: April 30, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 12 Years to 55 Years

Eligibility

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

Related Conditions & MeSH terms

• Communicable Diseases
• Infections
• Malaria
• Malaria Infection

Intervention

Drug:
• M5717 60 mg
Participants will receive single oral dose (Capsules) of 60 mg M5717 on Day 1 under fasting condition
• 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
• Atovaquone-Proguanil
Participants will Receive Atovaquone-Proguanil tablets 1000/400 mg once daily in a 3-day treatment regimen.
• M5717 200 mg
Participants will receive single oral dose (Capsules) of 200 mg M5717 on Day 1 under fasting condition
• M5717 660mg
Participants will receive single oral dose (Capsules) of 660 mg M5717 on Day 1 under fasting condition

Locations

Country	Name	City	State
Burkina Faso	Groupe de Recherche Action en Sante (GRAS)	Ouagadougou 06
Gambia	MRC Unit The Gambia at LSHTM	Banjul
Kenya	Kisumu County Referral Hospital	Kisumu
Zambia	Ndola Teaching Hospital	Ndola

Sponsors (1)

Lead Sponsor	Collaborator
Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany

Countries where clinical trial is conducted

Burkina Faso,  Gambia,  Kenya,  Zambia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Time to Parasitemia Since Negative Blood Smear after Treatment		From Study Start Day 1 up to End of Study (approximately 12 weeks)
Secondary	Percentage of Participants with Parasitemia (positive blood smear).		From Study Start Day 1 up to End of Study (approximately 12 week)
Secondary	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)
Secondary	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)
Secondary	Parasite Clearance Time		Time from dosing to the first negative (no parasites) blood film (microscopy) , assessed up to 12 weeks
Secondary	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)
Secondary	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

External Links

•   Trial Awareness and Transparency website