Cardiovascular DiseasesPhase 2NCT05537571
Evaluate SLN360 in Participants With Elevated Lipoprotein(a) at High Risk of Atherosclerotic Cardiovascular Disease Events
A Phase 2 study testing SLN360 in people with Cardiovascular Diseases and Atherosclerosis, run by Silence Therapeutics plc at 29 sites in 7 countries.
Trial 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 Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Cardiovascular Diseases, Atherosclerosis, Lipoprotein(a)
- What is being tested?
- SLN360
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 180 participants
- Where
- 29 sitesin 7 countries
- Study dates
- 13 Dec 2022to 1 Jul 2024
- Phase
- Phase 2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
29 sites in 7 countries.
29 sites in 7 countries
South Africa7 sites
Iatros International
Bloemfontein
Tiervlei Trial Centre (TTC)
Cape Town
TREAD Research - Department of Cardiology
Cape Town
University of Cape Town - Lipid Laboratory
Cape Town
Paarl Research Centre
Paarl
Dr JM Engelbrecht Trial Site
Somerset West
Helderberg Research Institute
Somerset West
Netherlands5 sites
Academic Medical Center - Department of Vascular Medicine
Amsterdam
Onze Lieve Vrouwe Gasthuis
Amsterdam
Bravis Ziekenhuis - Bergen op Zoom
Roosendaal
Universitair Medisch Centrum Utrecht
Utrecht
VieCuri Medisch Centrum
Venlo
United Kingdom5 sites
Royal Sussex County Hospital
Brighton
Chelsea and Westminster Hospital
London
Panthera - London North
London
Panthera - Manchester
Rochdale
Panthera - Sheffield
Sheffield
Czechia4 sites
Medicus Services SRO
Brandýs nad Labem
Edumed s.r.o., Kardiologicka, endokrinologicka, diabetologicka a interni ambulance Nachod
Náchod
Pratia Pardubice a.s.
Pardubice
Endokrinologie Cerny Most s.r.o.
Prague
Australia3 sites
Royal Adelaide Hospital
Adelaide
Monash Health
Melbourne
Linear Clinical Research
Nedlands
Denmark3 sites
Gentofte Hospital
Hellerup
Regionshospitalet Godstrup
Herning
Viborg Regional Hospital
Viborg
Slovakia2 sites
Alian, s.r.o., Kardiologicka ambulancia
Bardejov
Kardiomed s.r.o.
Lučenec
About this study
Official title: 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
- Conditions
- Cardiovascular Diseases, Atherosclerosis, Lipoprotein(a)
- Being tested
- SLN360, Placebo
- Keywords
- Cardiovascular Diseases, Atherosclerosis, Lipoprotein(a)
- Medical subject headings
- Cardiovascular Diseases, Atherosclerosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SLN360Drug
Also called Zerlasiran
SLN360 is a double-stranded small interfering ribonucleic acid (siRNA) targeting LPA messenger RNA (mRNA)
PlaceboDrug
Sodium chloride, solution for injection
| Study group | Role | What they receive |
|---|---|---|
| SLN360 300 mg Q16W | Experimental | SLN360 300 mg administered subcutaneously at Weeks 0, 16 and 32 (Q16W) Receives: Drug: SLN360 |
| SLN360 300 mg Q24W | Experimental | SLN360 300 mg administered subcutaneously at Weeks 0 and 24 (Q24W) Receives: Drug: SLN360 |
| SLN360 450 mg Q24W | Experimental | SLN360 450 mg administered subcutaneously at Weeks 0 and 24 (Q24W) Receives: Drug: SLN360 |
| Placebo Q16W | Placebo comparator | Placebo administered subcutaneously at Weeks 0, 16 and 32 (Q16W) Receives: 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) Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Week 36
Secondary outcomes (8)
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: Week 60
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Sep 2022
- Study start13 Dec 2022
- Primary completion11 Jan 2024
- Study completion1 Jul 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Cardiovascular DiseasesStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 180 participants (actual)
Sponsor and investigators
- Lead sponsor
- Silence Therapeutics plc
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05537571
- Sponsor's protocol ID
- SLN360-002
- Status last verified
- Jun 2025
- First submitted
- 6 Sep 2022
- Last updated
- 1 Jul 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
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.
PubMed 39556769Nicholls 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.
PubMed 40699211Nicholls 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.
PubMed 39329200Dimitriadis 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.
PubMed 38682459