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
Trial Snapshot
- Phase
- Phase 2
- Status
- Completed
- Sponsor
- Silence Therapeutics plc
- Enrollment
- 180
- Locations
- 29
- Primary Endpoint
- Time-averaged Percent Change In Lipoprotein(a) Molar Concentration From Baseline to Week 36
Study Overview
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
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Double (Participant, Investigator)
Eligibility Criteria
- Ages
- 18 Years to 80 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
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
Arms & Interventions
SLN360 300 mg Q16W
SLN360 300 mg administered subcutaneously at Weeks 0, 16 and 32 (Q16W)
Intervention: SLN360 (Drug)
SLN360 300 mg Q24W
SLN360 300 mg administered subcutaneously at Weeks 0 and 24 (Q24W)
Intervention: SLN360 (Drug)
SLN360 450 mg Q24W
SLN360 450 mg administered subcutaneously at Weeks 0 and 24 (Q24W)
Intervention: SLN360 (Drug)
Placebo Q16W
Placebo administered subcutaneously at Weeks 0, 16 and 32 (Q16W)
Intervention: Placebo (Drug)
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)
Intervention: Placebo (Drug)
Outcomes
Primary Outcomes
Time-averaged Percent Change In Lipoprotein(a) Molar Concentration From Baseline to Week 36
Time Frame: 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 Outcomes
- 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)
- Time-averaged Percent Change In Low-density Lipoprotein Cholesterol Concentration From Baseline to Week 36(Week 36)
- Time-averaged Percent Change In Low-density Lipoprotein Cholesterol Concentration From Baseline to Week 48(Week 48)
- Time-averaged Percent Change In Low-density Lipoprotein Cholesterol Concentration From Baseline to Week 60(Week 60)