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

NCT ID: NCT05537571

Last Updated: 2025-07-01

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

180 participants

Study Classification

INTERVENTIONAL

Study Start Date

2022-12-13

Study Completion Date

2024-07-01

Brief Summary

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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

Detailed Description

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Conditions

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Cardiovascular Diseases Atherosclerosis Lipoprotein(a)

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Participants Investigators

Study Groups

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SLN360 300 mg Q16W

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

Group Type EXPERIMENTAL

SLN360

Intervention Type DRUG

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

SLN360 300 mg Q24W

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

Group Type EXPERIMENTAL

SLN360

Intervention Type DRUG

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

SLN360 450 mg Q24W

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

Group Type EXPERIMENTAL

SLN360

Intervention Type DRUG

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

Placebo Q16W

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

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

Sodium chloride, solution for injection

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)

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

Sodium chloride, solution for injection

Interventions

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SLN360

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

Intervention Type DRUG

Placebo

Sodium chloride, solution for injection

Intervention Type DRUG

Other Intervention Names

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Zerlasiran

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Maximum Eligible Age

80 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Silence Therapeutics plc

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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Royal Adelaide Hospital

Adelaide, , Australia

Site Status

Monash Health

Melbourne, , Australia

Site Status

Linear Clinical Research

Nedlands, , Australia

Site Status

Medicus Services SRO

Brandýs nad Labem, , Czechia

Site Status

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

Náchod, , Czechia

Site Status

Pratia Pardubice a.s.

Pardubice, , Czechia

Site Status

Endokrinologie Cerny Most s.r.o.

Prague, , Czechia

Site Status

Gentofte Hospital

Hellerup, , Denmark

Site Status

Regionshospitalet Godstrup

Herning, , Denmark

Site Status

Viborg Regional Hospital

Viborg, , Denmark

Site Status

Academic Medical Center - Department of Vascular Medicine

Amsterdam, , Netherlands

Site Status

Onze Lieve Vrouwe Gasthuis

Amsterdam, , Netherlands

Site Status

Bravis Ziekenhuis - Bergen op Zoom

Roosendaal, , Netherlands

Site Status

Universitair Medisch Centrum Utrecht

Utrecht, , Netherlands

Site Status

VieCuri Medisch Centrum

Venlo, , Netherlands

Site Status

Alian, s.r.o., Kardiologicka ambulancia

Bardejov, , Slovakia

Site Status

Kardiomed s.r.o.

Lučenec, , Slovakia

Site Status

Iatros International

Bloemfontein, , South Africa

Site Status

Tiervlei Trial Centre (TTC)

Cape Town, , South Africa

Site Status

TREAD Research - Department of Cardiology

Cape Town, , South Africa

Site Status

University of Cape Town - Lipid Laboratory

Cape Town, , South Africa

Site Status

Paarl Research Centre

Paarl, , South Africa

Site Status

Dr JM Engelbrecht Trial Site

Somerset West, , South Africa

Site Status

Helderberg Research Institute

Somerset West, , South Africa

Site Status

Royal Sussex County Hospital

Brighton, , United Kingdom

Site Status

Chelsea and Westminster Hospital

London, , United Kingdom

Site Status

Panthera - London North

London, , United Kingdom

Site Status

Panthera - Manchester

Rochdale, , United Kingdom

Site Status

Panthera - Sheffield

Sheffield, , United Kingdom

Site Status

Countries

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Australia Czechia Denmark Netherlands Slovakia South Africa United Kingdom

References

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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.

Reference Type RESULT
PMID: 39556769 (View on PubMed)

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.

Reference Type DERIVED
PMID: 40699211 (View on PubMed)

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.

Reference Type DERIVED
PMID: 39329200 (View on PubMed)

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.

Reference Type DERIVED
PMID: 38682459 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

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Other Identifiers

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SLN360-002

Identifier Type: -

Identifier Source: org_study_id

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