Phase 1a Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of RN5681 in Healthy Volunteers

A Phase 1a, Randomized, Placebo-Controlled, Single Ascending Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of RN5681 in Healthy Volunteers

The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics and immunogenicity of single doses of RN5681 in Adult healthy subjects

Inclusion Criteria:

• Body mass index (BMI) 18 to 35 kg/m2
• Fasting LDL-C ≥70 mg/dL (1.81 mmol/L) (all SAD cohorts); fasting LDL-C ≥100 mg/dL (2.59 mmol/L) (POC cohort only)
• Lp(a) at Screening: SAD cohort: ≥25 nmol/L POC cohort: ≥100 nmol/L
• Fasting triglycerides <400 mg/dL (4.51 mmol/L) at Screening
• No clinically significant abnormalities of hepatic or renal function

Exclusion Criteria:

• Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >1.5× the upper limit of normal at screening
• Hemoglobin A1c (HbA1c) ≥6.5% at screening
• Current regular smoker (defined as >2 cigarettes/day or >10 cigarettes/week) within 3 months prior to screening
• Use of any siRNA, antisense oligonucleotide (ASO), cell and gene therapy, or clustered regularly interspaced short palindromic repeats (CRISPR) agent in the prior 12 months
• Received any prescription lipid-lowering medication, including but not limited to statins, ezetimibe, and PCSK9 inhibitors to alter serum lipids within 30 days before screening