A Single and Multiple Ascending Doses Study to Evaluate the Safety and Pharmacokinetics of RBD5044

Inclusion criteria

A subject will be eligible for inclusion in this study only if all of the following criteria are met:

• Willing to comply with protocol required visit schedule and visit requirements and provide written informed consent.
• Male and female subjects, aged 18 to 65 years (inclusive).
• Body mass index between 18 and 32 kg/m2, inclusive.
• Fasting TG ≥ 0.9 mmol/L (80 mg/dL) and ≤ 3.4 mmol/L (300 mg/dL) at screening.
• Fasting LDL-C < 4.9 mmol/L (<190 mg/dL) at screening.
• Healthy as determined by pre-study medical history, physical examination, clinical laboratory assessments, and 12-lead electrocardiogram (ECG).
• Satisfy one of the following:

• Females: must be non-pregnant and non-lactating; surgically sterile, post-menopausal, abstinent, or if engaged in sexual relations of child-bearing potential, the subject is using an acceptable contraceptive method (refer to Section 4.6.3) for four weeks before, during, and for at least 6 months after the last dose of study drug administration.
• Males: must be surgically sterile, abstinent, or if engaged in sexual relations of child-bearing potential, the subject is utilizing an acceptable contraceptive method (refer to Section 4.6.3)) during and for at least 6 months after the last dose of study drug administration.
• Non-smokers and non-nicotine users for at least 90 days before screening

Exclusion criteria

A subject meeting any of the following exclusion criteria will not be allowed to participate in this study:

• Any uncontrolled or serious disease, or any medical or surgical condition, may interfere with participation in the clinical study and/or put the subject at significant risk (according to the investigator's judgment) if he/she participates in the clinical study.
• History or presence of cardiovascular disease (including peripheral artery and cerebrovascular disease).
• Systolic blood pressure (SBP) > 140 mmHg and/or diastolic blood pressure (DBP) > 90 mmHg after 10 minutes of supine rest, unless determined by the investigator to be not clinically relevant.
• Diagnosis of diabetes mellitus.
• Received any medication or nutraceutical to alter serum lipids within 30 days before screening.
• Active serious mental illness or psychiatric disorder, including but not limited to schizophrenia, bipolar disorder, or severe depression, which require current pharmacological intervention.
• Alanine aminotransferase (ALT) and/or total bilirubin are above the upper limit of normal reference range (ULN); no investigator discretion and repeat assessments are allowed.
• Aspartate aminotransferase (AST), alkaline phosphatase (ALP), or gamma-glutamyl transferase (GGT) > 2 × ULN (no investigator discretion); or, if AST, ALP, or GGT > ULN, but ≤ 2 × ULN and considered clinically relevant by the investigator.
• Used prescription drugs within 14 days or 7 half-lives (whichever is longer) before the first dose of study drug.
• Used over-the-counter medication, excluding routine vitamins, within 7 days before the first dose of the study drug, unless determined by the investigator to be not clinically relevant, and unlikely to impact blood lipids level.
• Received an investigational product within 30 days or 7 half-lives (whichever is longer) before the first dose of the study drug or are in the follow-up of another clinical study. If subjects used advanced therapy (ASO/siRNA/gene therapy/cell therapy), it should be judged by the investigator.
• Hepatitis B virus, hepatitis C virus, human immunodeficiency virus (HIV), syphilis infection, or positive hepatitis B surface antigen (HBsAg), hepatitis B core antibody (HBcAb), hepatitis C virus antibody (HCVAb), HIV antibody (HIVAb), treponema pallidum antibody (TP-Ab) at screening.
• Clinically significant illness within 7 days before the first dose of the study drug.
• Consume more than 14 (female) or 21 (male) units of alcohol per week (unit: 1 glass of wine [125 mL] = 1 measure of spirits = ½ pint of beer) within the 12 months before screening or positive screen for alcohol abuse.
• History or clinical evidence of drug abuse within the 12 months before screening or positive screen for drug abuse. Drug abuse is defined as compulsive, repetitive, and/or chronic use of drugs or other substances with or without problems related to their use and/or where stopping or a dose reduction will lead to withdrawal symptoms.
• Donated more than 500 mL of blood within 90 days before the first dose of the study drug.
• History of multiple drug allergies or history of allergic reaction to an oligonucleotide or N-acetylgalactosamine (GalNAc).
• History of intolerance to subcutaneous (SC) injection or relevant abdominal scarring (surgical, burns, etc.).
• Any conditions which would make the subject unsuitable for enrollment or could interfere with the subject's participation in or completion of the study in the opinion of the investigator.