Phase 1 study in healthy volunteers comparing the safety and pharmacokinetics of MAR001 and MAR005

INTERVENTION: Up to 6 healthy participants will be receiving MAR005. MAR005 is a monoclonal antibody designed to block angiopoietin‐like 4. MAR005 is structurally identical to MAR001 aside from two additional amino acid substitutions in the Fc domain of MAR005 that are designed to improve the half‐life of the drug. Investigational product: 300 mg dose of MAR005 for subcutaneous (SC) injection administered by site staff on Day 1 and Day 29. Dosing will be staggered with 1 participant from the MAR005 arm dosed at least 47 hours before the remaining participants. Participants will be screened within 28 days before their first dose of trial intervention. They will reside in the Clinical Unit from the day before dosing until the day after dosing for each dosing instance. Safety assessments will be conducted throughout the trial, and participants will attend 11 outpatient visits. Adherence to the intervention will be monitored through direct administration of all doses by qualified study personnel at the Clinical Research Unit. Dosing will be documented in source records and drug accountability records, and participants will be monitored according to the protocol‐defined schedule. CONDITION: Hypertriglyceridaemia; ; Hypertriglyceridaemia Metabolic and Endocrine ‐ Metabolic disorders PRIMARY OUTCOME: Assessment of safety and tolerability following multiple dose subcutaneous administration of MAR005 compared with MAR001, evaluated by the incidence of adverse events (AEs), changes in vital signs, electrocardiograms (ECGs), clinical laboratory parameters, physical assessments in healthy participants (Composite primary outcome)[AEs: Adverse events (AEs) will be assessed by monitoring the incidence, severity, seriousness, timing, duration, and relationship to MAR005 compared with MAR001, with all treatment‐emergent AEs recorded from dosing through end of follow‐up in accordance with the protocol; ; Vital Signs: Pulse rate will be measured using a calibrated digital monitor or cardiac monitor; blood pressure will be measured using an automated sphygmomanometer; oxygen saturation will be assessed using pulse oximetry; respiratory rate will be measured by direct observation (breaths per minute); and body temperature will be measured using a digital thermometer. Measurements will be taken in a seated or supine position, as appropriate, after adequate rest; ; Electrocardiograms (ECGs): Pulse rate, PR interval, QRS duration, QT interval, QTcF interval ECG will be performed in a supine position, and in triplicate. Triplicate ECG readings will be taken and are to be within 2to 5 minutes of each other Mean (average of the 3). ; ; Laboratory parameters: Clinical Chemistry, Hematology, Coagulation, Urinalysis.; ; Physical Examination: Physical exams will be performed by a qualified study clinician at protocol specified time points. Complete physical examinations will include general appearance, head, ears, eyes, nose, throat, mouth / dental (if required), neck (incl. thyroid & nodes), cardiovascular, respiratory, gastrointestinal, renal, musculoskeletal, skin, other; From Day 1 to Day 85 (EOT)] INCLUSION CRITERIA: 1. BMI in the range 18.0 to 32.0 kg/m2 (inclusive). 2. In good health as determined by past medical history, physical examination, vital signs, electrocardiogram, and laboratory tests at screening. 3. Body weight more than 50 kg 4. Negative pregnancy test at screening and admission (female participants only). 5. Stable diet (as judged by the Investigator) for a minimum of 3 months prior to screening and with no plans to change diet through the duration of the trial. SECONDARY OUTCOME: Pharmacokinetics (PK) of MAR005 compared with MAR001 following multiple Subcutaneous doses in healthy participants (Composite secondary outcome)[Plasma pharmacokinetics will be evaluated using serial plasma samples collected at predefined timepoints. Pharmacokinetic parameters, including: ; AUCinf – Area Under the Plasma Concentration‐Time Curve from time zero extrapolated to infinity. ; AUCinf/D – AUCinf normalized by dose. ; AUClast – Area Under the Plasma Concentration‐Time Curve from time zero to the last measurable concentration. ; AUClast/D – AUClast normalized by dose. ; Cma X– Maximum (peak) observed plasma concentration. ; Tma X– Time to reach the maximum plasma concentration (Cmax). ; Tlast – Time of the last measurable plasma concentration. ; t½ (Terminal Half‐Life) – Time required for the plasma concentration of the drug to decrease by 50% during the terminal elimination phase. Pre dose on Day 1, Post dose at 6 hr and 12 hr on Day 1, Day 2, Day 4, Day 8, Day 10, Day 15, Day 22, Pre dose on Day 29, Post dose on at 6 hr and 12 hr on Day 29, Day 30, Day 32, Day 36, Day 43, Day 50, Day 57, and Day 85 (EOT)]