Trial Review

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT05537571




Registration number
NCT05537571
Ethics application status
Date submitted
6/09/2022
Date registered
13/09/2022
Date last updated
1/07/2025

Titles & IDs
Public title
Evaluate SLN360 in Participants With Elevated Lipoprotein(a) at High Risk of Atherosclerotic Cardiovascular Disease Events
Scientific 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
Secondary ID [1] 0 0
SLN360-002
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Cardiovascular Diseases 0 0
Atherosclerosis 0 0
Lipoprotein(a) 0 0
Condition category
Condition code
Cardiovascular 0 0 0 0
Diseases of the vasculature and circulation including the lymphatic system

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - SLN360
Treatment: Drugs - Placebo

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

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

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

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

Placebo comparator: 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)


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

Treatment: Drugs: Placebo
Sodium chloride, solution for injection
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Time-averaged Percent Change In Lipoprotein(a) Molar Concentration From Baseline to Week 36
Assessment method [1] 0 0
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.
Timepoint [1] 0 0
Week 36
Secondary outcome [1] 0 0
Time-averaged Percent Change In Lipoprotein(a) Molar Concentration From Baseline to Week 48
Assessment method [1] 0 0
Time-averaged secondary endpoints were calculated and analysed using the same conventions as the primary endpoint.
Timepoint [1] 0 0
Week 48
Secondary outcome [2] 0 0
Time-averaged Percent Change In Lipoprotein(a) Molar Concentration From Baseline to Week 60
Assessment method [2] 0 0
Time-averaged secondary endpoints were calculated and analysed using the same conventions as the primary endpoint.
Timepoint [2] 0 0
Week 60
Secondary outcome [3] 0 0
Time-averaged Percent Change In Apolipoprotein B Concentration From Baseline to Week 36
Assessment method [3] 0 0
Time-averaged secondary endpoints were calculated and analysed using the same conventions as the primary endpoint.
Timepoint [3] 0 0
Week 36
Secondary outcome [4] 0 0
Time-averaged Percent Change In Apolipoprotein B Concentration From Baseline to Week 48
Assessment method [4] 0 0
Time-averaged secondary endpoints were calculated and analysed using the same conventions as the primary endpoint.
Timepoint [4] 0 0
Week 48
Secondary outcome [5] 0 0
Time-averaged Percent Change In Apolipoprotein B Concentration From Baseline to Week 60
Assessment method [5] 0 0
Time-averaged secondary endpoints were calculated and analysed using the same conventions as the primary endpoint.
Timepoint [5] 0 0
Week 60
Secondary outcome [6] 0 0
Time-averaged Percent Change In Low-density Lipoprotein Cholesterol Concentration From Baseline to Week 36
Assessment method [6] 0 0
Time-averaged secondary endpoints were calculated and analysed using the same conventions as the primary endpoint.
Timepoint [6] 0 0
Week 36
Secondary outcome [7] 0 0
Time-averaged Percent Change In Low-density Lipoprotein Cholesterol Concentration From Baseline to Week 48
Assessment method [7] 0 0
Time-averaged secondary endpoints were calculated and analysed using the same conventions as the primary endpoint.
Timepoint [7] 0 0
Week 48
Secondary outcome [8] 0 0
Time-averaged Percent Change In Low-density Lipoprotein Cholesterol Concentration From Baseline to Week 60
Assessment method [8] 0 0
Time-averaged secondary endpoints were calculated and analysed using the same conventions as the primary endpoint.
Timepoint [8] 0 0
Week 60

Eligibility
Key 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
Minimum age
18 Years
Maximum age
80 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
13/12/2022
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/07/2024
Sample size
Target
Accrual to date
Final
180
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Royal Adelaide Hospital - Adelaide
Recruitment hospital [2] 0 0
Monash Health - Melbourne
Recruitment hospital [3] 0 0
Linear Clinical Research - Nedlands
Recruitment postcode(s) [1] 0 0
- Adelaide
Recruitment postcode(s) [2] 0 0
- Melbourne
Recruitment postcode(s) [3] 0 0
- Nedlands
Recruitment outside Australia
Country [1] 0 0
Czechia
State/province [1] 0 0
Brandýs Nad Labem
Country [2] 0 0
Czechia
State/province [2] 0 0
Náchod
Country [3] 0 0
Czechia
State/province [3] 0 0
Pardubice
Country [4] 0 0
Czechia
State/province [4] 0 0
Prague
Country [5] 0 0
Denmark
State/province [5] 0 0
Hellerup
Country [6] 0 0
Denmark
State/province [6] 0 0
Herning
Country [7] 0 0
Denmark
State/province [7] 0 0
Viborg
Country [8] 0 0
Netherlands
State/province [8] 0 0
Amsterdam
Country [9] 0 0
Netherlands
State/province [9] 0 0
Roosendaal
Country [10] 0 0
Netherlands
State/province [10] 0 0
Utrecht
Country [11] 0 0
Netherlands
State/province [11] 0 0
Venlo
Country [12] 0 0
Slovakia
State/province [12] 0 0
Bardejov
Country [13] 0 0
Slovakia
State/province [13] 0 0
Lucenec
Country [14] 0 0
South Africa
State/province [14] 0 0
Bloemfontein
Country [15] 0 0
South Africa
State/province [15] 0 0
Cape Town
Country [16] 0 0
South Africa
State/province [16] 0 0
Paarl
Country [17] 0 0
South Africa
State/province [17] 0 0
Somerset West
Country [18] 0 0
United Kingdom
State/province [18] 0 0
Brighton
Country [19] 0 0
United Kingdom
State/province [19] 0 0
London
Country [20] 0 0
United Kingdom
State/province [20] 0 0
Rochdale
Country [21] 0 0
United Kingdom
State/province [21] 0 0
Sheffield

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Silence Therapeutics plc
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Email 0 0
Contact person for scientific queries

No information has been provided regarding IPD availability


What supporting documents are/will be available?



Results publications and other study-related documents

TypeCitations or Other Details
Journal Nissen SE, Wang Q, Nicholls SJ, Navar AM, Ray KK, ... [More Details]

Results are available at https://clinicaltrials.gov/study/NCT05537571