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

Silence Therapeutics plc180 enrolled

Overview

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 Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Enrollment

180

Conditions

Cardiovascular Diseases Atherosclerosis Lipoprotein(a)

Interventions

SLN360DRUG

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

PlaceboDRUG

Sodium chloride, solution for injection

Eligibility

Sex: ALLMin age: 18 YearsMax age: 80 Years

Medical Language ↔ Plain English

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

Locations (29)

Royal Adelaide Hospital

Outcomes

Primary Outcomes

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.

Time frame: Week 36

Secondary Outcomes

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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Data from ClinicalTrials.gov

This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.