Evaluate SLN360 in Participants With Elevated Lipoprotein(a) at High Risk of Atherosclerotic Cardiovascular Disease Events

A Multi-centre, Randomised, Double-blind, Placebo-controlled, Phase 2 Study to Investigate Efficacy, Safety and Tolerability of SLN360 in Participants With Elevated Lipoprotein(a) at High Risk of Atherosclerotic Cardiovascular Disease Events

Phase 2 study to evaluate the efficacy, safety and tolerability of SLN360 administered subcutaneously (SC) compared with placebo in adult participants with elevated lipoprotein(a) at high risk of atherosclerotic cardiovascular disease events

Study Overview

• Status: Completed
• Conditions: Cardiovascular Diseases; Atherosclerosis; Lipoprotein(a)
• Intervention / Treatment: Drug: SLN360; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 180
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • Adelaide, Australia
    • Royal Adelaide Hospital
  • Melbourne, Australia
    • Monash Health
  • Nedlands, Australia
    • Linear Clinical Research
• Czechia
  • Brandýs Nad Labem, Czechia
    • Medicus Services sro
  • Náchod, Czechia
    • Edumed s.r.o., Kardiologicka, endokrinologicka, diabetologicka a interni ambulance Nachod
  • Pardubice, Czechia
    • Pratia Pardubice a.s.
  • Prague, Czechia
    • Endokrinologie Cerny Most s.r.o.
• Denmark
  • Hellerup, Denmark
    • Gentofte Hospital
  • Herning, Denmark
    • Regionshospitalet Godstrup
  • Viborg, Denmark
    • Viborg Regional Hospital
• Netherlands
  • Amsterdam, Netherlands
    • Onze Lieve Vrouwe Gasthuis
  • Amsterdam, Netherlands
    • Academic Medical Center - Department of Vascular Medicine
  • Roosendaal, Netherlands
    • Bravis Ziekenhuis - Bergen op Zoom
  • Utrecht, Netherlands
    • Universitair Medisch Centrum Utrecht
  • Venlo, Netherlands
    • VieCuri Medisch Centrum
• Slovakia
  • Bardejov, Slovakia
    • Alian, s.r.o., Kardiologicka ambulancia
  • Lučenec, Slovakia
    • Kardiomed s.r.o.
• South Africa
  • Bloemfontein, South Africa
    • Iatros International
  • Cape Town, South Africa
    • Tiervlei Trial Centre (TTC)
  • Cape Town, South Africa
    • TREAD Research - Department of Cardiology
  • Cape Town, South Africa
    • University of Cape Town - Lipid Laboratory
  • Paarl, South Africa
    • Paarl Research Centre
  • Somerset West, South Africa
    • Dr JM Engelbrecht Trial Site
  • Somerset West, South Africa
    • Helderberg Research Institute
• United Kingdom
  • Brighton, United Kingdom
    • Royal Sussex County Hospital
  • London, United Kingdom
    • Chelsea and Westminster Hospital
  • London, United Kingdom
    • Panthera - London North
  • Rochdale, United Kingdom
    • Panthera - Manchester
  • Sheffield, United Kingdom
    • Panthera - Sheffield

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Lipoprotein(a) at screening equal to or greater than 125 nmol/L
• At high risk of ASCVD events
• A body mass index at screening in the range of 18.0 to 32.0 kg/m², inclusive

Exclusion Criteria:

• Renal dysfunction with estimated glomerular filtration rate less than 30 mL/min/1.73 m² at screening
• History or clinical evidence of hepatic dysfunction
• Malignancy within the 5 years before screening
• Fasting triglycerides >400 mg/dL (4.5 mmol/L) at screening
• Currently receiving or <12 weeks at Day 1 since receiving >200 mg/day niacin or niacin derivative drugs
• Treatment with lipid/lipoprotein apheresis within the 12 weeks before screening
• Any previous use of approved or experimental small interfering RNA (siRNA) therapy (e.g. inclisiran). NB: use of messenger RNA (mRNA) based vaccines for infectious diseases is permitted

Study Plan

How is the study designed?

Design Details

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

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: SLN360 300 mg Q16W; SLN360 300 mg administered subcutaneously at Weeks 0, 16 and 32 (Q16W)	Drug: SLN360; SLN360 is a double-stranded small interfering ribonucleic acid (siRNA) targeting LPA messenger RNA (mRNA); Other Names: Zerlasiran
Experimental: SLN360 300 mg Q24W; SLN360 300 mg administered subcutaneously at Weeks 0 and 24 (Q24W)	Drug: SLN360; SLN360 is a double-stranded small interfering ribonucleic acid (siRNA) targeting LPA messenger RNA (mRNA); Other Names: Zerlasiran
Experimental: SLN360 450 mg Q24W; SLN360 450 mg administered subcutaneously at Weeks 0 and 24 (Q24W)	Drug: SLN360; SLN360 is a double-stranded small interfering ribonucleic acid (siRNA) targeting LPA messenger RNA (mRNA); Other Names: Zerlasiran
Placebo Comparator: Placebo Q16W; Placebo administered subcutaneously at Weeks 0, 16 and 32 (Q16W)	Drug: Placebo; Sodium chloride, solution for injection
Placebo Comparator: Placebo Q24W; Placebo administered subcutaneously at Weeks 0 and 24 (Q24W). This group was stratified so that half of participants were dosed to match the SLN360 300 mg Q24W group and half were dosed to match the SLN360 450 mg Q24W group (with respect to injected volume)	Drug: Placebo; Sodium chloride, solution for injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time-averaged Percent Change In Lipoprotein(a) Molar Concentration From Baseline to Week 36	Clinical trial results (relative to Day 1 pre-dose) was calculated for each participant by estimating the sum of the area under the curve with the linear trapezoidal method for all scheduled assessments from Week 4 to Week 36, inclusive, divided by the total time interval between the Week 4 and Week 36 assessments. Analysis of variance was used to test for differences between each active treatment group and the pooled placebo groups in the primary outcome measure. Time-averaged percent change in lipoprotein(a) to Week 36 was the dependent variable, and treatment group was included as the predictor variable. The least squares means, standard errors, and 2-sided 95% confidence intervals for each treatment group and for the pairwise comparisons between the SLN360 and placebo groups were estimated.	Week 36

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time-averaged Percent Change In Lipoprotein(a) Molar Concentration From Baseline to Week 48	Time-averaged secondary endpoints were calculated and analysed using the same conventions as the primary endpoint.	Week 48
Time-averaged Percent Change In Lipoprotein(a) Molar Concentration From Baseline to Week 60	Time-averaged secondary endpoints were calculated and analysed using the same conventions as the primary endpoint.	Week 60
Time-averaged Percent Change In Apolipoprotein B Concentration From Baseline to Week 36	Time-averaged secondary endpoints were calculated and analysed using the same conventions as the primary endpoint.	Week 36
Time-averaged Percent Change In Apolipoprotein B Concentration From Baseline to Week 48	Time-averaged secondary endpoints were calculated and analysed using the same conventions as the primary endpoint.	Week 48
Time-averaged Percent Change In Apolipoprotein B Concentration From Baseline to Week 60	Time-averaged secondary endpoints were calculated and analysed using the same conventions as the primary endpoint.	Week 60
Time-averaged Percent Change In Low-density Lipoprotein Cholesterol Concentration From Baseline to Week 36	Time-averaged secondary endpoints were calculated and analysed using the same conventions as the primary endpoint.	Week 36
Time-averaged Percent Change In Low-density Lipoprotein Cholesterol Concentration From Baseline to Week 48	Time-averaged secondary endpoints were calculated and analysed using the same conventions as the primary endpoint.	Week 48
Time-averaged Percent Change In Low-density Lipoprotein Cholesterol Concentration From Baseline to Week 60	Time-averaged secondary endpoints were calculated and analysed using the same conventions as the primary endpoint.	Week 60

Collaborators and Investigators

• Sponsor: Silence Therapeutics plc

Publications and helpful links

General Publications

• Nissen SE, Wang Q, Nicholls SJ, Navar AM, Ray KK, Schwartz GG, Szarek M, Stroes ESG, Troquay R, Dorresteijn JAN, Fok H, Rider DA, Romano S, Wolski K, Rambaran C. Zerlasiran-A Small-Interfering RNA Targeting Lipoprotein(a): A Phase 2 Randomized Clinical Trial. JAMA. 2024 Dec 17;332(23):1992-2002. doi: 10.1001/jama.2024.21957.

Helpful Links

• PubMed Publication

Study record dates

Study Major Dates

• Study Start (Actual): December 13, 2022
• Primary Completion (Actual): January 11, 2024
• Study Completion (Actual): July 1, 2024

Study Registration Dates

• First Submitted: September 6, 2022
• First Submitted That Met QC Criteria: September 12, 2022
• First Posted (Actual): September 13, 2022

Study Record Updates

• Last Update Posted (Estimated): July 1, 2025
• Last Update Submitted That Met QC Criteria: June 27, 2025
• Last Verified: June 1, 2025

More Information

Terms related to this study

• Keywords: Cardiovascular Diseases; Atherosclerosis; Lipoprotein(a)
• Additional Relevant MeSH Terms: Vascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Cardiovascular Diseases; Atherosclerosis
• Other Study ID Numbers: SLN360-002

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No