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

Study Overview
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Brief Summary
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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.

Official Title
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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)

Conditions
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Malaria Infection

Intervention / Treatment
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* Drug: M5717 60 mg
* Drug: Pyronaridine
* Drug: Atovaquone-Proguanil
* Drug: M5717 200 mg
* Drug: M5717 660mg


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 12 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1: M5717 (60 mg) + Pyronaridine<br>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<br>* Participants will receive single oral dose (Capsules) of 60 mg M5717 on Day 1 under fasting condition<br>Drug: Pyronaridine<br>* 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<br>* Other names: Pyronaridine tetraphosphate;|
| Experimental: Cohort 2: M5717 (200 mg) + Pyronaridine<br>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<br>* 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<br>* Other names: Pyronaridine tetraphosphate;Drug: M5717 200 mg<br>* Participants will receive single oral dose (Capsules) of 200 mg M5717 on Day 1 under fasting condition<br>|
| Experimental: Cohort 3: M5717 (660 mg)+ Pyronaridine<br>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<br>* 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<br>* Other names: Pyronaridine tetraphosphate;Drug: M5717 660mg<br>* Participants will receive single oral dose (Capsules) of 660 mg M5717 on Day 1 under fasting condition<br>|
| Experimental: Cohort 4: Atovaquone-proguanil<br>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<br>* Participants will Receive Atovaquone-Proguanil tablets 1000/400 mg once daily in a 3-day treatment regimen.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Plasmodium falciparum, Chemoprevention, Malaria, Plasmodium eukaryotic translation elongation factor 2 (PeEF2), Exposure response, Adults, Adolescents, Asymptomatic Infection