the Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamic Effects in Adult Subjects With Elevated LDL-C

A Phase 1, Randomized, Single-blinded, Placebo-controlled, Single-ascending-dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamic Effects in Adult Subjects With Elevated LDL-C

This is a randomized, placebo-controlled, single ascending-dose (SAD) study of administered SC to adult subjects with elevated LDL-C. Subjects who have signed an Ethics Committee (EC)-approved informed consent form (ICF) and have met all the protocol eligibility criteria during screening may be enrolled into the study.

Study Overview

• Status: Not yet recruiting
• Conditions: To Reduce the LDL-C Level in Hypercholesteremia Patients
• Intervention / Treatment: Drug: RN0191

• Study Type: Interventional
• Enrollment (Estimated): 32
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Esther JIANG; Phone Number: +8613916015172; Email: esther.jiang@ronatherapeutics.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

1. Male and female subjects, aged 18 to 60 years, inclusive
2. Body mass index between 18 and 32 kg/m2, inclusive, with body weight > 45 kg for females and >50 kg for males
3. Serum LDL-C ≥100 mg/dL (2.6 mmol/L) at screening and Day -1
4. Fasting triglycerides < 400 mg/dL (<4.52 mmol/L) at screening and Day -1

Exclusion Criteria:

1. Known underlying disease or medical condition that may have a potential impact on general safety assessment, lipid metabolism, or glucose metabolism, or surgical condition (including, but not limited to, bariatric surgery) that, in the opinion of the investigator, may interfere with the interpretation of the results of the clinical study
2. Received any medication including, but not limited to, statins, ezetimibe, or lipid-altering nutrients within 30 days prior to screening, or PCSK9 antibody within 90 days prior to screening, or any LDL-C-lowering siRNA therapy within 12 months prior to screening
3. History of multiple drug allergies or allergic reactions to oligonucleotides or N-acetylglucosamine (GalNAc)
4. Subjects with alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) > 1.5 times the upper limit of normal (ULN) at the time of screening (one repeat of the screening assay is permitted) with clinically significant ALT and/or AST > ULN and ≤ 1.5 times the ULN as determined by the investigator
5. Any medical condition that, in the opinion of the Investigator, makes the subject unsuitable for enrollment or may interfere with the subject's participation in or completion of the study. This includes, but is not limited to: history or presence of cardiovascular disease (including peripheral arterial and cerebrovascular disease); diabetes mellitus (except for diabetes mellitus of pregnancy in remission); cerebrovascular accidents; and abnormal thyroid function.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Single

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: cohort 1; or placebo	Drug: RN0191; This is a randomized, placebo-controlled, single ascending-dose (SAD) study of RN0191 administered SC to adult subjects with elevated LDL-C. Subjects who have signed an Ethics Committee (EC)-approved informed consent form (ICF) and have met all the protocol eligibility criteria during screening may be enrolled into the study.
Experimental: Cohort 2; or placebo	Drug: RN0191; This is a randomized, placebo-controlled, single ascending-dose (SAD) study of RN0191 administered SC to adult subjects with elevated LDL-C. Subjects who have signed an Ethics Committee (EC)-approved informed consent form (ICF) and have met all the protocol eligibility criteria during screening may be enrolled into the study.
Experimental: Cohort 3; or placebo	Drug: RN0191; This is a randomized, placebo-controlled, single ascending-dose (SAD) study of RN0191 administered SC to adult subjects with elevated LDL-C. Subjects who have signed an Ethics Committee (EC)-approved informed consent form (ICF) and have met all the protocol eligibility criteria during screening may be enrolled into the study.
Experimental: Cohort 4; or placebo	Drug: RN0191; This is a randomized, placebo-controlled, single ascending-dose (SAD) study of RN0191 administered SC to adult subjects with elevated LDL-C. Subjects who have signed an Ethics Committee (EC)-approved informed consent form (ICF) and have met all the protocol eligibility criteria during screening may be enrolled into the study.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To determine the safety and tolerability of RN0191 administered as escalating single subcutaneous (SC) doses in adult subjects with elevated low-density lipoprotein-cholesterol (LDL-C)	This is a randomized, placebo-controlled, single ascending-dose (SAD) study of RN0191 administered SC to adult subjects with elevated LDL-C. Subjects who have signed an Ethics Committee (EC)-approved informed consent form (ICF) and have met all the protocol eligibility criteria during screening may be enrolled into the study.	For each subject in the study, the duration of the study clinic visits is approximately 18 weeks from screening to Day 85 EOS examination.

Collaborators and Investigators

• Sponsor: Ikaria Bioscience Pty Ltd
• Collaborators: SHANGHAI RONA Therapeutics Co.,Ltd.

Study record dates

Study Major Dates

• Study Start (Estimated): February 1, 2024
• Primary Completion (Estimated): October 1, 2024
• Study Completion (Estimated): December 1, 2024

Study Registration Dates

• First Submitted: November 6, 2023
• First Submitted That Met QC Criteria: November 13, 2023
• First Posted (Actual): November 15, 2023

Study Record Updates

• Last Update Posted (Estimated): January 26, 2024
• Last Update Submitted That Met QC Criteria: January 24, 2024
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Metabolic Diseases; Lipid Metabolism Disorders; Hyperlipidemias; Dyslipidemias; Hypercholesterolemia
• Other Study ID Numbers: RN0191-102

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No