Study to Investigate Safety, Tolerability, PK and PD Response of SLN360 in Subjects With Elevated Lipoprotein(a)

A Randomised, Double-blind, Placebo Controlled, First-in-human Study to Investigate the Safety, Tolerability, Pharmacokinetic and Pharmacodynamic Response of SLN360 in Subjects With Elevated Lipoprotein(a)

This study will investigate the safety and tolerability of SLN360 in patients with elevated Lp(a).

Study Overview

• Status: Completed
• Conditions: Dyslipidemias; Hyperlipidemias; Elevated Lp(a)
• Intervention / Treatment: Drug: SLN360; Drug: Placebo

Detailed Description

This first-in-human (FIH) study will investigate the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of SLN360 after single ascending s.c. doses and multiple doses in healthy male and female subjects.

Up to 9 cohorts of 88 patients with elevated Lp(a) will be enrolled. Each patient will receive single or multiple doses of SLN360 or placebo given by subcutaneous (s.c) injection.

• Study Type: Interventional
• Enrollment (Actual): 70
• Phase: Phase 1

Contacts and Locations

Study Locations

• Australia
  • Clayton, Australia
    • Monash Medical Centre
  • Western Australia
    • Perth, Western Australia, Australia
      • Linear Clinical Research
• Netherlands
  • Amsterdam, Netherlands
    • Amsterdam Medical Centre
• United Kingdom
  • London, United Kingdom
    • Hammersmith Medicines Research
• United States
  • Florida
    • Jacksonville, Florida, United States, 32216
      • Jacksonville Center for Clinical Research Ltd.
    • Port Orange, Florida, United States, 32127
      • Progressive Medical Research
  • Ohio
    • Cincinnati, Ohio, United States, 45227
      • Metabolic and Atherosclerosis Research Center
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion criteria:

• Elevated plasma Lp(a) ≥ 150nmol/L.
• All subjects must agree to adhere to appropriate contraception requirements.
• Subjects must provide written informed consent and be able to comply with all study requirements.
• Body mass index of ≥ 18 kg/m2 and ≤ 45 kg/m2.
• For the MD part: confirmed history of stable atherosclerortic cardiovascular disease.

Exclusion criteria:

• Single Ascending Dose only: any history of clinically overt cardiovascular disease, defined as acute coronary syndromes, myocardial infarction, stable angina, coronary or other revascularization, ischemic stroke or transient ischemic attack and atherosclerotic peripheral arterial disease.
• Multiple Dose only: recent history of acute cardiovascular disease events within 6 months of screening (including, but not limited to, acute myocardial infarction, unstable angina, acute stroke and acute limb ischemia).
• Moderate or severe hepatic cirrhosis with Child-Pugh grade B or C, or other current or previous liver disease.
• Active serious mental illness or psychiatric disorder, including but not limited to schizophrenia, bipolar disorder, or severe depression requiring current pharmacological intervention.
• Any conditions which, in the opinion of the Investigator, would make the subject unsuitable for enrolment in the study or could interfere with the subject's participation in, or completion of the study.
• Subjects with previous or current use of medication or therapies significantly affecting Lp(a) level or hormone replacement therapy, unless on a stable dose for ≥ 8 weeks prior to screening
• History or clinical evidence of alcohol or illegal drug misuse within the 6 months before screening.
• History of multiple drug allergies or history of allergic reaction to an oligonucleotide or GalNAc, or intolerance to s.c. injections.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

11

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo; Sodium chloride for subcutaneous (s.c.) injection
Experimental: 100 mg	Drug: SLN360; SLN360 for subcutaneous (s.c.) injection
Experimental: 30 mg	Drug: SLN360; SLN360 for subcutaneous (s.c.) injection
Experimental: 300 mg	Drug: SLN360; SLN360 for subcutaneous (s.c.) injection
Experimental: 600 mg	Drug: SLN360; SLN360 for subcutaneous (s.c.) injection
Experimental: 900 mg	Drug: SLN360; SLN360 for subcutaneous (s.c.) injection
Experimental: 100 mg multi dose	Drug: SLN360; SLN360 for subcutaneous (s.c.) injection
Experimental: 200 mg multi dose	Drug: SLN360; SLN360 for subcutaneous (s.c.) injection
Experimental: 300 mg multi dose	Drug: SLN360; SLN360 for subcutaneous (s.c.) injection
Experimental: 600 mg multi dose	Drug: SLN360; SLN360 for subcutaneous (s.c.) injection
Placebo Comparator: Placebo multi dose	Drug: Placebo; Sodium chloride for subcutaneous (s.c.) injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of treatment-emergent adverse events	safety and tolerability will be reported separately following single-dose administration.	Day 150
Incidence of treatment-emergent adverse events	safety and tolerability will be reported separately following multiple-dose administration.	Day 201

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetic: peak plasma concentration (Cmax)	safety and tolerability will be reported separately following single-dose and multiple-dose administration.	Day 150 and Day 201
Pharmacokinetic: area under the plasma concentration (AUC)	safety and tolerability will be reported separately following single-dose and multiple-dose administration.	Day 150 and Day 201
Pharmacokinetic: apparent total clearance from plasma after s.c injection (CL/F)	safety and tolerability will be reported separately following single-dose and multiple-dose administration.	Day 150 and Day 201
Pharmacodynamic: Change in Lp(a)	safety and tolerability will be reported separately following single-dose and multiple-dose administration.	Day 150 and Day 201

Collaborators and Investigators

• Sponsor: Silence Therapeutics plc
• Collaborators: Medpace, Inc.

Publications and helpful links

General Publications

• Nissen SE, Wolski K, Balog C, Swerdlow DI, Scrimgeour AC, Rambaran C, Wilson RJ, Boyce M, Ray KK, Cho L, Watts GF, Koren M, Turner T, Stroes ES, Melgaard C, Campion GV. Single Ascending Dose Study of a Short Interfering RNA Targeting Lipoprotein(a) Production in Individuals With Elevated Plasma Lipoprotein(a) Levels. JAMA. 2022 May 3;327(17):1679-1687. doi: 10.1001/jama.2022.5050.
• Nissen SE, Wolski K, Watts GF, Koren MJ, Fok H, Nicholls SJ, Rider DA, Cho L, Romano S, Melgaard C, Rambaran C. Single Ascending and Multiple-Dose Trial of Zerlasiran, a Short Interfering RNA Targeting Lipoprotein(a): A Randomized Clinical Trial. JAMA. 2024 May 14;331(18):1534-1543. doi: 10.1001/jama.2024.4504.

Study record dates

Study Major Dates

• Study Start (Actual): November 18, 2020
• Primary Completion (Actual): August 23, 2023
• Study Completion (Actual): August 23, 2023

Study Registration Dates

• First Submitted: October 7, 2020
• First Submitted That Met QC Criteria: October 22, 2020
• First Posted (Actual): October 28, 2020

Study Record Updates

• Last Update Posted (Actual): August 12, 2024
• Last Update Submitted That Met QC Criteria: August 8, 2024
• Last Verified: August 1, 2024

More Information

Terms related to this study

• Keywords: Dyslipidemia, Dyslipoproteinemia, Hyperlipidemia, Hyperlipoproteinemia, Hyperlipoproteinemia (a), Lipoprotein, Lipoprotein (a)
• Additional Relevant MeSH Terms: Metabolic Diseases; Lipid Metabolism Disorders; Dyslipidemias; Hyperlipidemias; Hyperlipoproteinemias
• Other Study ID Numbers: SLN360-001

Drug and device information, study documents

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