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

Phase 2

Completed

• Conditions: Lipoprotein(a); Atherosclerosis; Cardiovascular Diseases
• Interventions: Drug: SLN360; Drug: Placebo

• Registration Number: NCT05537571
• Lead Sponsor: Silence Therapeutics plc

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

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2022-09-06
• Study First Submitted QC: 2022-09-12
• Study First Posted: 2022-09-13
• Study Start: 2022-12-13
• Primary Completion: 2024-01-11
• Study Completion: 2024-07-01
• Status Verified: 2025-06
• Results First Submitted: 2025-06-04
• Results First Submitted QC: 2025-06-27
• Last Update Submitted: 2025-06-27
• Results First Posted: 2025-07-01
• Last Update Posted: 2025-07-01

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 180

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
SLN360 300 mg Q16W	SLN360	SLN360 300 mg administered subcutaneously at Weeks 0, 16 and 32 (Q16W)
SLN360 300 mg Q24W	SLN360	SLN360 300 mg administered subcutaneously at Weeks 0 and 24 (Q24W)
SLN360 450 mg Q24W	SLN360	SLN360 450 mg administered subcutaneously at Weeks 0 and 24 (Q24W)
Placebo Q16W	Placebo	Placebo administered subcutaneously at Weeks 0, 16 and 32 (Q16W)
Placebo Q24W	Placebo	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)
Placebo Dose 1	Placebo	Sodium chloride for subcutaneous injection
SLN360 Dose 1	SLN360	SLN360 for subcutaneous injection
Placebo Dose 2 and 3	Placebo	Sodium chloride for subcutaneous injection
SLN360 Dose 2	SLN360	SLN360 for subcutaneous injection
SLN360 Dose 3	SLN360	SLN360 for subcutaneous injection

Primary Outcome Measures

Name	Time	Method
Time-averaged Percent Change In Lipoprotein(a) Molar Concentration From Baseline to Week 36	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.

Secondary Outcome Measures

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

Trial Locations

Locations (29)

Royal Adelaide Hospital; 🇦🇺 Adelaide, Australia

Monash Health; 🇦🇺 Melbourne, Australia

Linear Clinical Research; 🇦🇺 Nedlands, Australia

Medicus Services SRO; 🇨🇿 Brandýs Nad Labem, Czechia

Edumed s.r.o., Kardiologicka, endokrinologicka, diabetologicka a interni ambulance Nachod; 🇨🇿 Náchod, Czechia

Pratia Pardubice a.s.; 🇨🇿 Pardubice, Czechia

Endokrinologie Cerny Most s.r.o.; 🇨🇿 Prague, Czechia

Gentofte Hospital; 🇩🇰 Hellerup, Denmark

Regionshospitalet Godstrup; 🇩🇰 Herning, Denmark

Viborg Regional Hospital; 🇩🇰 Viborg, Denmark

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