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

NCT05537571 | Completed Phase 2 Results DMC

• 1 other identifier: SLN360-002
• Study Type: interventional
• Target: 180
• Locations: 7 countries
• Sites: 29

Brief Summary

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

Conditions

Cardiovascular Diseases; Atherosclerosis; Lipoprotein(a)

Keywords

Cardiovascular Diseases; Atherosclerosis; Lipoprotein(a)

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (8)

• Time-averaged Percent Change In Lipoprotein(a) Molar Concentration From Baseline to Week 48

  Week 48

• Time-averaged Percent Change In Lipoprotein(a) Molar Concentration From Baseline to Week 60

  Week 60

• Time-averaged Percent Change In Apolipoprotein B Concentration From Baseline to Week 36

  Week 36

• Time-averaged Percent Change In Apolipoprotein B Concentration From Baseline to Week 48

  Week 48

• Time-averaged Percent Change In Apolipoprotein B Concentration From Baseline to Week 60

  Week 60

Study Arms (5)

SLN360 300 mg Q16W

EXPERIMENTAL

SLN360 300 mg administered subcutaneously at Weeks 0, 16 and 32 (Q16W)

Drug: SLN360

SLN360 300 mg Q24W

EXPERIMENTAL

SLN360 300 mg administered subcutaneously at Weeks 0 and 24 (Q24W)

Drug: SLN360

SLN360 450 mg Q24W

EXPERIMENTAL

SLN360 450 mg administered subcutaneously at Weeks 0 and 24 (Q24W)

Drug: SLN360

Placebo Q16W

PLACEBO COMPARATOR

Placebo administered subcutaneously at Weeks 0, 16 and 32 (Q16W)

Drug: Placebo

Placebo Q24W

PLACEBO COMPARATOR

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

Interventions

SLN360 DRUG

SLN360 is a double-stranded small interfering ribonucleic acid (siRNA) targeting LPA messenger RNA (mRNA)

Also known as: Zerlasiran

SLN360 300 mg Q16W; SLN360 300 mg Q24W; SLN360 450 mg Q24W

Placebo DRUG

Sodium chloride, solution for injection

Placebo Q16W; Placebo Q24W

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Silence Therapeutics plc: lead

Study Sites (29)

Royal Adelaide Hospital

Adelaide, Australia

Location

Monash Health

Melbourne, Australia

Location

Linear Clinical Research

Nedlands, Australia

Location

Medicus Services SRO

Brandýs nad Labem, Czechia

Location

Edumed s.r.o., Kardiologicka, endokrinologicka, diabetologicka a interni ambulance Nachod

Náchod, Czechia

Location

Pratia Pardubice a.s.

Pardubice, Czechia

Location

Endokrinologie Cerny Most s.r.o.

Prague, Czechia

Location

Gentofte Hospital

Hellerup, Denmark

Location

Regionshospitalet Godstrup

Herning, Denmark

Location

Viborg Regional Hospital

Viborg, Denmark

Location

Academic Medical Center - Department of Vascular Medicine

Amsterdam, Netherlands

Location

Onze Lieve Vrouwe Gasthuis

Amsterdam, Netherlands

Location

Bravis Ziekenhuis - Bergen op Zoom

Roosendaal, Netherlands

Location

Universitair Medisch Centrum Utrecht

Utrecht, Netherlands

Location

VieCuri Medisch Centrum

Venlo, Netherlands

Location

Alian, s.r.o., Kardiologicka ambulancia

Bardejov, Slovakia

Location

Kardiomed s.r.o.

Lučenec, Slovakia

Location

Iatros International

Bloemfontein, South Africa

Location

Tiervlei Trial Centre (TTC)

Cape Town, South Africa

Location

TREAD Research - Department of Cardiology

Cape Town, South Africa

Location

University of Cape Town - Lipid Laboratory

Cape Town, South Africa

Location

Paarl Research Centre

Paarl, South Africa

Location

Dr JM Engelbrecht Trial Site

Somerset West, South Africa

Location

Helderberg Research Institute

Somerset West, South Africa

Location

Royal Sussex County Hospital

Brighton, United Kingdom

Location

Chelsea and Westminster Hospital

London, United Kingdom

Location

Panthera - London North

London, United Kingdom

Location

Panthera - Manchester

Rochdale, United Kingdom

Location

Panthera - Sheffield

Sheffield, United Kingdom

Location

Related Publications (4)

• 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.

  PMID: 39556769 RESULT

• Nicholls SJ. Therapeutic lowering of lipoprotein(a): implications for improving outcomes in patients with peripheral arterial disease. Curr Opin Lipidol. 2025 Oct 1;36(5):232-237. doi: 10.1097/MOL.0000000000001002. Epub 2025 Jul 21.

  PMID: 40699211 DERIVED

• Nicholls SJ, Nelson AJ, Michael LF. Oral agents for lowering lipoprotein(a). Curr Opin Lipidol. 2024 Dec 1;35(6):275-280. doi: 10.1097/MOL.0000000000000953. Epub 2024 Sep 25.

  PMID: 39329200 DERIVED

• Dimitriadis K, Theofilis P, Iliakis P, Pyrpyris N, Dri E, Sakalidis A, Soulaidopoulos S, Tsioufis P, Fragkoulis C, Chrysohoou C, Tsiachris D, Tsioufis K. Management of dyslipidemia in coronary artery disease: the present and the future. Coron Artery Dis. 2024 Sep 1;35(6):516-524. doi: 10.1097/MCA.0000000000001375. Epub 2024 Apr 29.

  PMID: 38682459 DERIVED

Related Links

• PubMed Publication

MeSH Terms

Conditions

Cardiovascular Diseases; Atherosclerosis

Condition Hierarchy (Ancestors)

Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases

Results Point of Contact

• Title: Global Regulatory
• Organization: Silence Therapeutics plc

global-regulatory@silence-therapeutics.com

+442034576900

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 6, 2022
• First Posted: September 13, 2022
• Study Start: December 13, 2022
• Primary Completion: January 11, 2024
• Study Completion: July 1, 2024
• Last Updated: July 1, 2025
• Results First Posted: July 1, 2025

Record last verified: 2025-06

Locations

CZ (4); SL (2); DK (3); AU (3); ZA (7); GB (5); NL (5)