RN5681 dosing and safety in healthy adults with elevated LDL and Lp(a)

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

This trial will test single doses of RN5681 versus placebo to see if the drug is safe, how the body handles it, and how it changes LDL-C and Lp(a) in healthy adults with elevated levels.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 60 (estimated)
• Ages: 18 Years to 65 Years
• Sex: All
• Sponsor: Ikaria Bioscience Pty Ltd (Industry-sponsored)
• Locations: 2 sites (Brisbane, Queensland and 1 other locations)
• Trial ID: NCT07347678 on ClinicalTrials.gov

What this trial studies

This Phase 1a, randomized, placebo-controlled single ascending dose study gives one dose of RN5681 to healthy adult volunteers who meet specified LDL-C and Lp(a) thresholds to measure safety, tolerability, pharmacokinetics, pharmacodynamics, and immunogenicity. The protocol includes multiple single ascending dose (SAD) cohorts and a proof-of-concept (POC) cohort with higher required Lp(a) levels. Participants receive RN5681 or placebo at clinical research units in Brisbane and Melbourne with serial blood sampling, safety monitoring, and scheduled follow-up visits. People using prescription lipid-lowering medications or with significant liver, kidney, or metabolic abnormalities are excluded to focus on safety and early pharmacology signals.

Who should consider this trial

Good fit: Ideal candidates are healthy adults (BMI 18–35 kg/m2) with fasting LDL-C and Lp(a) meeting the study thresholds, normal liver and kidney tests, non‑smokers, and not taking prescription lipid‑lowering or recent genetic therapies.

Not a fit: People with significant liver or kidney disease, HbA1c ≥6.5%, very high triglycerides, current regular smokers, those on prescription lipid‑lowering medications, or recent recipients of siRNA/ASO/gene therapies are unlikely to be eligible or to benefit from this Phase 1a dosing study.

Why it matters

Potential benefit: If successful, RN5681 could safely reduce Lp(a) and/or LDL-C and potentially provide a new treatment option to lower cardiovascular risk in people with elevated levels.

How similar studies have performed: Other oligonucleotide and siRNA approaches targeting Lp(a) have shown large reductions in Lp(a) in early clinical studies, so this approach builds on prior promising results.

Eligibility criteria

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

Where this trial is running

Brisbane, Queensland and 1 other locations

• Q-Pharm Pty Ltd. — Brisbane, Queensland, Australia (Recruiting)
• Nucleus Network Pty Ltd. — Melbourne, Victoria, Australia (Recruiting)

Study contacts

• Study coordinator: Dan Xiang

Conditions High Cholesterol