First-in-Human Trial of Single Ascending Dose, Multiple Ascending Dose and Malaria Challenge Model in Healthy Participants

Merck KGaA, Darmstadt, Germany88 enrolled

Overview

The primary purpose of this study was to investigate the safety and tolerability of M5717 and to characterize the Pharmacokinetics (PK) /Pharmacodynamic relationship between M5717 PK and parasite clearance in healthy participants following infection with Plasmodium falciparum.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

OTHER

Masking

DOUBLE

Enrollment

Conditions

Healthy

Interventions

M5717DRUG

Participants received single ascending oral dose of M5717 after at least 8 hours of fasting together with water on Day 1, followed by a 4-hour post-dose fast

PlaceboDRUG

Participants received placebo matched to M5717

M5717DRUG

Participants received single ascending oral dose of M5717 from Part A after at least 8 hours of fasting together with water on Day 1, followed by a 4-hour post-dose fast

Eligibility

Sex: ALLMin age: 18 YearsMax age: 55 YearsHealthy volunteers:

Medical Language ↔ Plain English

Inclusion Criteria: * Adult men and women of non-childbearing potential, with total body weight greater than or equal to 50.0 kilogram and body mass index (BMI) between 19.0 kilogram per meter square(kg/m\^2) and 29.9 kg/m\^2. * Healthy as assessed by the Investigator with no clinically significant abnormality identified on physical examination or laboratory evaluation and no active clinically significant disorder, condition, infection or disease that would pose a risk to participant safety or interfere with the trial evaluation, procedures, or completion. * Other protocol defined inclusion criteria could apply. Exclusion Criteria: * Participants with history or presence of clinically relevant respiratory, gastrointestinal, renal, hepatic, hematological, lymphatic, neurological, cardiovascular, psychiatric, musculoskeletal, genitourinary, immunological dermatological, connective tissue diseases or disorders. * Participants with history of relevant drug hypersensitivity, ascertained or presumptive allergy/hypersensitivity to the active drug substance and/or formulation ingredients; history of serious allergic reactions leading to hospitalization or any other allergic reaction in general, which the Investigator considers may affect the safety of the participant and/or outcome of the trial. * Participants who have any history of malaria. * Participants who have participated in a previous malaria vaccine trial. * Participants who have participated in a previous human malaria challenge trial.

Locations (1)

Q-Pharm Pty Ltd

Brisbane, Australia

Outcomes

Primary Outcomes

Part A: Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, and TEAEs Leading to Discontinuation of Study Treatment

An adverse event (AE) was defined as any untoward medical occurrence in a participant administered with study drug which does not necessarily have 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. The term TEAE is defined as AEs starting or worsening after the first intake of the study drug. TEAEs included both Serious TEAEs and non-serious TEAEs.

Time frame: Baseline up to Day 55

Part A: Number of Participants With Clinically Significant Changes From Baseline in Laboratory Assessments

Laboratory assessments included hematology, biochemistry, urinalysis, and coagulation. Number of participants with clinically significant change from baseline in laboratory parameters were reported. Clinical significance was decided by the investigator.

Time frame: Baseline up to Day 55

Part A: Number of Participants With Clinically Significant Changes From Baseline in 12-lead Electrocardiograms (ECGs) Findings

The 12-lead ECGs were recorded after the participants had rested for at least 5 minutes in supine position. Number of participants with clinically significant change from baseline in ECGs was reported. Clinical significance was decided by the investigator.

Time frame: Baseline up to Day 55

Part A: Number of Participants With Clinically Significant Changes From Baseline in Vital Signs

Vital signs included oral body temperature, systolic blood pressure, diastolic blood pressure, and pulse rate. Number of participants with clinically significant change from baseline in vital signs was reported. Clinical significance was decided by the investigator.

Data from ClinicalTrials.gov

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Time frame: Baseline up to Day 55

Part C: Parasite Reduction Ratio (PRR) Assessed Through Quantitative Polymerase Chain Reaction (qPCR) Analysis

The parasite reduction ratio (PRR) of asexual parasites based on quantitative polymerase chain reaction (qPCR) after administration of M5717 is a mathematical representation of the ratio of the parasite density between drug administration and for a defined period of time. The PRR for asexual forms was estimated using the slope of the optimal fit of the log-linear relationship of the parasitemia decay; ie, the time point where steady exponential decay in parasitemia occurs which may happen after a lag-phase. Lag phase is defined as an initial period after dosing that precedes a steady exponential decline in the parasite count. It was observed that the decline of parasitemia had a biphasic profile, with the first phase, followed by a second phase (the main clearance phase).

Time frame: Day 1 to Day 22

Part C: Maximum Observed Plasma Concentration (Cmax) of M5717

Cmax was obtained directly from the concentration versus time curve.