A Study to Evaluate COR-1004 in Adult Volunteers.

This is a randomized, double-blind, placebo-controlled, single-ascending-dose study of COR 1004 administered SC to participants with LDL-C ≥100 mg/dL who are otherwise healthy and not on lipid-lowering therapy.

Each cohort will be comprised of 10 participants randomized 4:1 to receive a single dose of study drug or placebo, respectively.

Monitoring will continue on an outpatient basis, with participants returning to the clinical study site for safety, tolerability, PK, PD, and exploratory biomarker monitoring at specified time points through Day 90. Following Day 90, participants will continue to be monitored for adverse events, blood pressure, liver function tests, PD, and exploratory biomarkers through Month 12.

Dosing in Cohorts 1 to 5 will use a sentinel dosing approach, with the first two participants (one active and one placebo) receiving COR-1004 or placebo 24 hours prior to the remainder of the cohort. If deemed safe and tolerated after 24 hours, and no dose-limiting toxicity is observed by the investigator, the remainder of the cohort will be dosed as planned. The sentinel dosing approach will not be utilized for Cohort 6.

Inclusion criteria

• Serum LDL-C ≥100 mg/dL (≥2.6 mmol/L) at Screening.
• Female participants who are of childbearing potential must be willing to use two highly effective methods of contraception, one of which should be a barrier method.
• Post-menopausal females must be post-menopausal for 12 months.
• Male participants and their partners of child-bearing potential, or same-sex partners, must be willing to use two highly effective methods of contraception, one of which must be a barrier method (eg, condom) for 90 days after study drug administration.
• Able to participate, and willing to give written informed consent and to comply with the study restrictions.

Exclusion criteria

• Any active or chronic disease.
• Active or history of serious mental illness or psychiatric disorder.
• Clinically significant illness within seven days before study drug administration.
• Having risk of atherosclerotic cardiovascular disease (ASCVD) ≥7.5% based on the ASCVD Risk Estimator Plus.
• Having fasting triglyceride level ≥400 mg/dL (≥4.52 mmol/L).
• Clinically significant abnormalities on physical examination, vital signs, or laboratory test results (except for serum LDL-C) during Screening or prior to admission to the study unit.
• Participants with any risk factors or family history for QT or Fridericia-corrected QT interval (QTcF) prolongation or ECG abnormalities or any abnormality in the ECG.
• Confirmed systolic blood pressure (SBP) >140 mmHg or diastolic blood pressure (DBP) >90 mmHg at Screening, Day -1, or pre-dose.
• Mean resting pulse rate <40 bpm or >90 bpm at Screening.
• Abnormal renal function including serum creatinine greater than the upper limit of normal (ULN) or calculated creatinine clearance <60 mL/min (using the Cockcroft-Gault formula).
• Alanine aminotransferase (ALT) and/or total bilirubin above the ULN. Aspartate aminotransferase (AST), alkaline phosphatase (ALP), or gamma glutamyl transferase (GGT) >2 × ULN. International normalized ratio (INR) above the upper bound of the normal reference range (as per the local laboratory reference range) at Screening.
• Positive hepatitis B surface antigen, hepatitis B virus, hepatitis C virus, or human immunodeficiency virus infection.
• Pregnant or lactating women, or males with female partners who are pregnant or lactating.
• History of multiple drug allergies or history of allergic reaction to an oligonucleotide, N-acetylgalactosamine (GalNAc), or inclisiran.
• Participation in an investigational drug or device study within 45 days or five half-lives (whichever time period is longer) or six months for biologic therapies prior to study drug administration.
• Received small interfering ribonucleic acid (siRNA) as an investigational or approved product prior to study drug administration.
• Use of any medications (prescription or over-the-counter) or herbal supplements within two weeks or five half-lives (whichever is longer) prior to study drug administration (six months for biologic therapies), with exception of acetaminophen/paracetamol up to 2 g per day up to 48 hours prior to dosing or medications for contraception. Other exceptions will only be made if the rationale is discussed and clearly documented between the Clinical Research Organization and Sponsor.
• Received any medication, herbal supplements, or nutraceutical known to alter serum lipids within 30 days before Screening (eg, niacin).