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

Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany192 enrolled

Overview

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 Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

192

Conditions

Malaria Infection

Interventions

M5717 60 mgDRUG

Eligibility

Sex: ALLMin age: 12 YearsMax age: 55 Years

Medical Language ↔ Plain English

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

Locations (4)

Groupe de Recherche Action en Sante (GRAS)

Ouagadougou, Burkina Faso

Kisumu County Referral Hospital

Kisumu, Kenya

MRC Unit The Gambia at LSHTM

Banjul, The Gambia

Ndola Teaching Hospital

Ndola, Zambia

Outcomes

Primary Outcomes

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.

Time frame: From treatment Day 1 up to End of observation period Day 64 (Week 10)

Secondary Outcomes

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).

Time frame: 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.

Time frame: 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.

Time frame: 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 frame: 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.

Time frame: 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.