Evaluate SLN360 in Participants With Elevated Lipoprotein... | NCT05537571 | Trialant
NCT05537571
Sponsor
Silence Therapeutics plc
Status
Completed
Last Update Posted
Jul 1, 2025Actual
Enrollment
180Actual
Phase
Phase 2
Conditions
Cardiovascular Diseases
Atherosclerosis
Lipoprotein(a)
Interventions
SLN360
Placebo
Countries
Australia
Czechia
Denmark
Netherlands
Slovakia
South Africa
United Kingdom
Protocol Section
Identification Module
NCT ID
NCT05537571
Obsolete or Duplicate NCT IDs
Not provided
Organization Study
SLN360-002
Secondary IDs
Not provided
Brief Title
Evaluate SLN360 in Participants With Elevated Lipoprotein(a) at High Risk of Atherosclerotic Cardiovascular Disease Events
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
Acronym
Not provided
Organization
Silence Therapeutics plcINDUSTRY
Status Module
Record Verification Date
Jun 2025
Overall Recruitment Status or Expanded Access Status
Completed
Last Known Status
Not provided
Delayed Posting
Not provided
Why Stopped
Not provided
Expanded Access Info
No
Start Date
Dec 13, 2022Actual
Primary Completion Date
Jan 11, 2024Actual
Completion Date
Jul 1, 2024Actual
First Submitted Date
Sep 6, 2022
First Submission Date that Met QC Criteria
Sep 12, 2022
First Posted Date
Sep 13, 2022Actual
Results Waived
Not provided
Results First Submitted Date
Jun 4, 2025
Results First Submitted that Met QC Criteria
Jun 27, 2025
Results First Posted Date
Jul 1, 2025Actual
Certification/Extension (aka Delayed Results) First Submitted Date
Not provided
Certification/Extension First Submitted that Passed QC Review
Not provided
Certification/Extension First Posted Date
Not provided
Last Update Submitted Date
Jun 27, 2025
Last Update Posted Date
Jul 1, 2025Actual
Sponsor/Collaborators Module
Responsible Party, by Official Title
Sponsor
Lead Sponsor
Silence Therapeutics plcINDUSTRY
Collaborators
Not provided
Oversight Module
Has Data Monitoring Committee (DMC)
Yes
Is FDA Regulated Drug
No
Is FDA Regulated Device
No
Is Unapproved Device
Not provided
Pediatric Postmarket Surveillance of a Device Product
Not provided
Product Exported from US
No
FDAAA801 Violation
Not provided
Description Module
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 provided
Conditions Module
Conditions
Cardiovascular Diseases
Atherosclerosis
Lipoprotein(a)
Keywords
Cardiovascular Diseases
Atherosclerosis
Lipoprotein(a)
Design Module
Study Type
Interventional
Number of References to an Expanded Access Study
Not provided
Expanded Access Types
Not provided
Patient Registry
Not provided
Target Follow-Up Duration
Not provided
Phases
Phase 2
Interventional Study Design
Allocation
Biospecimen
No data available
No data is available for this block.
Enrollment
180Actual
Arms/Interventions Module
Arm Groups
Label
Type
Description
Intervention Names
SLN360 300 mg Q16W
Experimental
SLN360 300 mg administered subcutaneously at Weeks 0, 16 and 32 (Q16W)
Drug: SLN360
SLN360 300 mg Q24W
Experimental
SLN360 300 mg administered subcutaneously at Weeks 0 and 24 (Q24W)
Drug: SLN360
SLN360 450 mg Q24W
Experimental
SLN360 450 mg administered subcutaneously at Weeks 0 and 24 (Q24W)
Drug: SLN360
Placebo Q16W
Placebo Comparator
Placebo administered subcutaneously at Weeks 0, 16 and 32 (Q16W)
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)
Drug: Placebo
Interventions
Name
Type
Description
Arm Group Labels
Other Names
SLN360
Drug
SLN360 is a double-stranded small interfering ribonucleic acid (siRNA) targeting LPA messenger RNA (mRNA)
SLN360 300 mg Q16W
SLN360 300 mg Q24W
Outcomes Module
Primary Outcomes
Measure
Description
Time Frame
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.
Week 36
Secondary Outcomes
Measure
Description
Time Frame
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.
Week 48
Time-averaged Percent Change In Lipoprotein(a) Molar Concentration From Baseline to Week 60
Other Outcomes
Not provided
Eligibility Module
Eligibility Criteria
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
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.
A total of 253 participants were screened for inclusion, 73 participants failed screening.
Recruitment Details
Participants were screened from 05 December 2022, first randomised participant signed informed consent on 13 December 2022 and last participant was randomised 27 April 2023.
Type of Units Analyzed
Not provided
Arm/Group Information
ID
Title
Description
FG000
SLN360 300 mg Q16W
SLN360 300 mg administered subcutaneously at Weeks 0, 16 and 32 (Q16W)
SLN360: SLN360 is a double-stranded small interfering ribonucleic acid (siRNA) targeting LPA messenger RNA (mRNA)
FG001
SLN360 300 mg Q24W
Periods
Title
Milestones
Reasons Not Completed
Overall Study
Type
Comment
Milestone Data
STARTED
Baseline Characteristics Module
Baseline Analysis Population Description
Outcome Measures Module
Outcome Measures
Adverse Events Module
Frequency Threshold
5
More Info Module
Limitations and Caveats
Not provided
Annotation Section
No data available
No data is available for this block.
Document Section
Large Document Module
Document Has No Statistical Analysis Plan (SAP)
Not provided
Uploaded Document Information
Type
Includes Protocol
Includes SAP
Includes ICF
Document Label
Document Date
Document Uploaded Date
Document File Name
Prot
Yes
No
No
Study Protocol
Aug 9, 2022
Jun 3, 2025
Derived Section
Miscellaneous Info Module
Version Holder
Jul 10, 2026
Removed Countries
Not provided
Submission Tracking
No data available
No data is available for this block.
Condition Browse Module
MeSH Terms
Intervention Browse Module
No data available
No data is available for this block.
Randomized
Intervention Model
Parallel Assignment
Intervention Model Description
Not provided
Primary Purpose
Treatment
Observational Model
Not provided
Time Perspective
Not provided
Masking Info
Masking
Double
Masking Description
Not provided
Who Masked
ParticipantInvestigator
SLN360 450 mg Q24W
Zerlasiran
Placebo
Drug
Sodium chloride, solution for injection
Placebo Q16W
Placebo Q24W
Time-averaged secondary endpoints were calculated and analysed using the same conventions as the primary endpoint.
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.
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.
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.
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.
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.
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.
Week 60
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
Academic Medical Center - Department of Vascular Medicine
Amsterdam
Netherlands
Onze Lieve Vrouwe Gasthuis
Amsterdam
Netherlands
Bravis Ziekenhuis - Bergen op Zoom
Roosendaal
Netherlands
Universitair Medisch Centrum Utrecht
Utrecht
Netherlands
VieCuri Medisch Centrum
Venlo
Netherlands
Alian, s.r.o., Kardiologicka ambulancia
Bardejov
Slovakia
Kardiomed s.r.o.
Lučenec
Slovakia
Iatros International
Bloemfontein
South Africa
Tiervlei Trial Centre (TTC)
Cape Town
South Africa
TREAD Research - Department of Cardiology
Cape Town
South Africa
University of Cape Town - Lipid Laboratory
Cape Town
South Africa
Paarl Research Centre
Paarl
South Africa
Dr JM Engelbrecht Trial Site
Somerset West
South Africa
Helderberg Research Institute
Somerset West
South Africa
Royal Sussex County Hospital
Brighton
United Kingdom
Chelsea and Westminster Hospital
London
United Kingdom
Panthera - London North
London
United Kingdom
Panthera - Manchester
Rochdale
United Kingdom
Panthera - Sheffield
Sheffield
United Kingdom
Derived
Nicholls 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.
Dimitriadis 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.
SLN360 300 mg administered subcutaneously at Weeks 0 and 24 (Q24W)
SLN360: SLN360 is a double-stranded small interfering ribonucleic acid (siRNA) targeting LPA messenger RNA (mRNA)
FG002
SLN360 450 mg Q24W
SLN360 450 mg administered subcutaneously at Weeks 0 and 24 (Q24W)
SLN360: SLN360 is a double-stranded small interfering ribonucleic acid (siRNA) targeting LPA messenger RNA (mRNA)
FG003
Placebo Q16W
Placebo administered subcutaneously at Weeks 0, 16 and 32 (Q16W)
Placebo: Sodium chloride, solution for injection
FG004
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)
Placebo: Sodium chloride, solution for injection
FG00044 subjects
FG00144 subjects
FG00245 subjects
FG00323 subjects
FG00424 subjects
COMPLETED
FG00039 subjects
FG00143 subjects
FG00244 subjects
FG00323 subjects
FG00423 subjects
NOT COMPLETED
FG0005 subjects
FG0011 subjects
FG0021 subjects
FG0030 subjects
FG0041 subjects
Type
Comment
Reasons
Withdrawal by Subject
FG0001 subjects
FG0011 subjects
FG0020 subjects
FG0030 subjects
FG0040 subjects
Adverse Event
FG0002 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG004
Hepatitis A screening result
FG0002 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG004
Lost to Follow-up
FG0000 subjects
FG0010 subjects
FG0021 subjects
FG0030 subjects
FG004
The baseline data are based on the set of unique participants who were randomised and treated. This excludes 2 participant numbers that enrolled but were not treated, due to hepatitis A screening results, but were later rescreened and re-randomised / treated.
Type of Units Analyzed
Not provided
Arm/Group Information
ID
Title
Description
BG000
SLN360 300 mg Q16W
SLN360 300 mg administered subcutaneously at Weeks 0, 16 and 32 (Q16W)
SLN360: SLN360 is a double-stranded small interfering ribonucleic acid (siRNA) targeting LPA messenger RNA (mRNA)
BG001
SLN360 300 mg Q24W
SLN360 300 mg administered subcutaneously at Weeks 0 and 24 (Q24W)
SLN360: SLN360 is a double-stranded small interfering ribonucleic acid (siRNA) targeting LPA messenger RNA (mRNA)
BG002
SLN360 450 mg Q24W
SLN360 450 mg administered subcutaneously at Weeks 0 and 24 (Q24W)
SLN360: SLN360 is a double-stranded small interfering ribonucleic acid (siRNA) targeting LPA messenger RNA (mRNA)
BG003
Placebo Q16W
Placebo administered subcutaneously at Weeks 0, 16 and 32 (dosing every 16 weeks [Q16W])
Placebo: Sodium chloride, solution for injection
BG004
Placebo Q24W
Placebo administered subcutaneously at Weeks 0 and 24 (dosing every 24 weeks [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: Sodium chloride, solution for injection
BG005
Total
Total of all reporting groups
Denominators
Units
Counts
Participants
BG00042
BG00144
BG00245
BG00323
BG00424
BG005178
Baseline Measures
Title
Description
Population Description
Parameter Type
Dispersion Type
Unit of Measure
Calculate Percentage
Denominator Units Selected
Denominators
Classes
Age, Categorical
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
<=18 years
BG0000
BG0010
BG0020
BG003
Age, Continuous
Mean
Standard Deviation
years
Title
Denominators
Categories
Title
Measurements
BG00063.1± 9.81
BG00164.5± 8.67
BG002
Sex: Female, Male
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
Female
BG00011
BG00113
BG002
Ethnicity (NIH/OMB)
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
Hispanic or Latino
BG0000
BG0010
BG002
Race (NIH/OMB)
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
American Indian or Alaska Native
BG0000
BG0010
BG002
Region of Enrollment
Number
participants
Title
Denominators
Categories
Netherlands
Title
Measurements
BG00013
BG00115
BG002
Time from the initial date of elevated Lipoprotein(a) to randomisation date
Median
Inter-Quartile Range
months
Title
Denominators
Categories
Title
Measurements
BG0006.10(1.30 to 12.10)
BG0015.45(1.05 to 17.95)
BG002
Weight
Median
Inter-Quartile Range
kilograms
Title
Denominators
Categories
Title
Measurements
BG00084.15(78.00 to 94.80)
BG00182.60(73.65 to 95.70)
BG002
Body Mass Index
Median
Inter-Quartile Range
kg/m2
Title
Denominators
Categories
Title
Measurements
BG00027.060(25.080 to 29.750)
BG00128.240(23.655 to 30.235)
BG002
Height
Median
Inter-Quartile Range
centimetres
Title
Denominators
Categories
Title
Measurements
BG000177.0(170.0 to 182.0)
BG001175.0(167.5 to 183.0)
BG002
Type
Title
Description
Population Description
Reporting Status
Anticipated Posting Date
Parameter Type
Dispersion Type
Unit of Measure
Calculate Percentage
Time Frame
Units Analyzed
Denominator Units Selected
Arm/Group Information
Denominators
Classes
Analyses
Primary
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.
The pharmacodynamic population included all participants who received at least 1 dose of study drug and had evaluable pharmacodynamic data.
Posted
Least Squares Mean
Standard Error
Percentage
Week 36
ID
Title
Description
OG000
SLN360 300 mg Q16W
SLN360 300 mg administered subcutaneously at Weeks 0, 16 and 32 (Q16W)
SLN360: SLN360 is a double-stranded small interfering ribonucleic acid (siRNA) targeting LPA messenger RNA (mRNA)
OG001
SLN360 300 mg Q24W
SLN360 300 mg administered subcutaneously at Weeks 0 and 24 (Q24W)
SLN360: SLN360 is a double-stranded small interfering ribonucleic acid (siRNA) targeting LPA messenger RNA (mRNA)
OG002
SLN360 450 mg Q24W
SLN360 450 mg administered subcutaneously at Weeks 0 and 24 (Q24W)
SLN360: SLN360 is a double-stranded small interfering ribonucleic acid (siRNA) targeting LPA messenger RNA (mRNA)
OG003
Pooled Placebo
Pooled data from both placebo groups
Placebo: Sodium chloride, solution for injection
Units
Counts
Participants
OG00042
OG00144
OG00245
OG003
Title
Denominators
Categories
Title
Measurements
OG000-80.5± 1.99
OG001-79.1± 1.94
OG002-83.3± 1.92
OG003
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG003
Analysis of variance (ANOVA) was used to test for differences between each active treatment group and the pooled placebo groups in the primary outcome measure.
ANOVA
<0.0001
Mean Difference (Final Values)
-82.8
2-Sided
95
-88.19
-77.39
Superiority
OG001
OG003
Secondary
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.
The pharmacodynamic population included all participants who received at least 1 dose of study drug and had evaluable pharmacodynamic data.
Posted
Least Squares Mean
Standard Error
Percentage
Week 48
ID
Title
Description
OG000
SLN360 300 mg Q16W
SLN360 300 mg administered subcutaneously at Weeks 0, 16 and 32 (Q16W)
SLN360: SLN360 is a double-stranded small interfering ribonucleic acid (siRNA) targeting LPA messenger RNA (mRNA)
OG001
SLN360 300 mg Q24W
SLN360 300 mg administered subcutaneously at Weeks 0 and 24 (Q24W)
SLN360: SLN360 is a double-stranded small interfering ribonucleic acid (siRNA) targeting LPA messenger RNA (mRNA)
OG002
SLN360 450 mg Q24W
SLN360 450 mg administered subcutaneously at Weeks 0 and 24 (Q24W)
SLN360: SLN360 is a double-stranded small interfering ribonucleic acid (siRNA) targeting LPA messenger RNA (mRNA)
OG003
Secondary
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.
The pharmacodynamic population included all participants who received at least 1 dose of study drug and had evaluable pharmacodynamic data.
Posted
Least Squares Mean
Standard Error
Percentage
Week 60
ID
Title
Description
OG000
SLN360 300 mg Q16W
SLN360 300 mg administered subcutaneously at Weeks 0, 16 and 32 (Q16W)
SLN360: SLN360 is a double-stranded small interfering ribonucleic acid (siRNA) targeting LPA messenger RNA (mRNA)
OG001
SLN360 300 mg Q24W
SLN360 300 mg administered subcutaneously at Weeks 0 and 24 (Q24W)
SLN360: SLN360 is a double-stranded small interfering ribonucleic acid (siRNA) targeting LPA messenger RNA (mRNA)
OG002
SLN360 450 mg Q24W
SLN360 450 mg administered subcutaneously at Weeks 0 and 24 (Q24W)
SLN360: SLN360 is a double-stranded small interfering ribonucleic acid (siRNA) targeting LPA messenger RNA (mRNA)
OG003
Secondary
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.
The pharmacodynamic population included all participants who received at least 1 dose of study drug and had evaluable pharmacodynamic data.
Posted
Least Squares Mean
Standard Error
Percentage
Week 36
ID
Title
Description
OG000
SLN360 300 mg Q16W
SLN360 300 mg administered subcutaneously at Weeks 0, 16 and 32 (Q16W)
SLN360: SLN360 is a double-stranded small interfering ribonucleic acid (siRNA) targeting LPA messenger RNA (mRNA)
OG001
SLN360 300 mg Q24W
SLN360 300 mg administered subcutaneously at Weeks 0 and 24 (Q24W)
SLN360: SLN360 is a double-stranded small interfering ribonucleic acid (siRNA) targeting LPA messenger RNA (mRNA)
OG002
SLN360 450 mg Q24W
SLN360 450 mg administered subcutaneously at Weeks 0 and 24 (Q24W)
SLN360: SLN360 is a double-stranded small interfering ribonucleic acid (siRNA) targeting LPA messenger RNA (mRNA)
OG003
Secondary
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.
The pharmacodynamic population included all participants who received at least 1 dose of study drug and had evaluable pharmacodynamic data.
Posted
Least Squares Mean
Standard Error
Percentage
Week 48
ID
Title
Description
OG000
SLN360 300 mg Q16W
SLN360 300 mg administered subcutaneously at Weeks 0, 16 and 32 (Q16W)
SLN360: SLN360 is a double-stranded small interfering ribonucleic acid (siRNA) targeting LPA messenger RNA (mRNA)
OG001
SLN360 300 mg Q24W
SLN360 300 mg administered subcutaneously at Weeks 0 and 24 (Q24W)
SLN360: SLN360 is a double-stranded small interfering ribonucleic acid (siRNA) targeting LPA messenger RNA (mRNA)
OG002
SLN360 450 mg Q24W
SLN360 450 mg administered subcutaneously at Weeks 0 and 24 (Q24W)
SLN360: SLN360 is a double-stranded small interfering ribonucleic acid (siRNA) targeting LPA messenger RNA (mRNA)
OG003
Secondary
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.
The pharmacodynamic population included all participants who received at least 1 dose of study drug and had evaluable pharmacodynamic data.
Posted
Least Squares Mean
Standard Error
Percentage
Week 60
ID
Title
Description
OG000
SLN360 300 mg Q16W
SLN360 300 mg administered subcutaneously at Weeks 0, 16 and 32 (Q16W)
SLN360: SLN360 is a double-stranded small interfering ribonucleic acid (siRNA) targeting LPA messenger RNA (mRNA)
OG001
SLN360 300 mg Q24W
SLN360 300 mg administered subcutaneously at Weeks 0 and 24 (Q24W)
SLN360: SLN360 is a double-stranded small interfering ribonucleic acid (siRNA) targeting LPA messenger RNA (mRNA)
OG002
SLN360 450 mg Q24W
SLN360 450 mg administered subcutaneously at Weeks 0 and 24 (Q24W)
SLN360: SLN360 is a double-stranded small interfering ribonucleic acid (siRNA) targeting LPA messenger RNA (mRNA)
OG003
Secondary
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.
The pharmacodynamic population included all participants who received at least 1 dose of study drug and had evaluable pharmacodynamic data.
Posted
Least Squares Mean
Standard Error
Percentage
Week 36
ID
Title
Description
OG000
SLN360 300 mg Q16W
SLN360 300 mg administered subcutaneously at Weeks 0, 16 and 32 (Q16W)
SLN360: SLN360 is a double-stranded small interfering ribonucleic acid (siRNA) targeting LPA messenger RNA (mRNA)
OG001
SLN360 300 mg Q24W
SLN360 300 mg administered subcutaneously at Weeks 0 and 24 (Q24W)
SLN360: SLN360 is a double-stranded small interfering ribonucleic acid (siRNA) targeting LPA messenger RNA (mRNA)
OG002
SLN360 450 mg Q24W
SLN360 450 mg administered subcutaneously at Weeks 0 and 24 (Q24W)
SLN360: SLN360 is a double-stranded small interfering ribonucleic acid (siRNA) targeting LPA messenger RNA (mRNA)
OG003
Secondary
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.
The pharmacodynamic population included all participants who received at least 1 dose of study drug and had evaluable pharmacodynamic data.
Posted
Least Squares Mean
Standard Error
Percentage
Week 48
ID
Title
Description
OG000
SLN360 300 mg Q16W
SLN360 300 mg administered subcutaneously at Weeks 0, 16 and 32 (Q16W)
SLN360: SLN360 is a double-stranded small interfering ribonucleic acid (siRNA) targeting LPA messenger RNA (mRNA)
OG001
SLN360 300 mg Q24W
SLN360 300 mg administered subcutaneously at Weeks 0 and 24 (Q24W)
SLN360: SLN360 is a double-stranded small interfering ribonucleic acid (siRNA) targeting LPA messenger RNA (mRNA)
OG002
SLN360 450 mg Q24W
SLN360 450 mg administered subcutaneously at Weeks 0 and 24 (Q24W)
SLN360: SLN360 is a double-stranded small interfering ribonucleic acid (siRNA) targeting LPA messenger RNA (mRNA)
OG003
Secondary
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.
The pharmacodynamic population included all participants who received at least 1 dose of study drug and had evaluable pharmacodynamic data.
Posted
Least Squares Mean
Standard Error
Percentage
Week 60
ID
Title
Description
OG000
SLN360 300 mg Q16W
SLN360 300 mg administered subcutaneously at Weeks 0, 16 and 32 (Q16W)
SLN360: SLN360 is a double-stranded small interfering ribonucleic acid (siRNA) targeting LPA messenger RNA (mRNA)
OG001
SLN360 300 mg Q24W
SLN360 300 mg administered subcutaneously at Weeks 0 and 24 (Q24W)
SLN360: SLN360 is a double-stranded small interfering ribonucleic acid (siRNA) targeting LPA messenger RNA (mRNA)
OG002
SLN360 450 mg Q24W
SLN360 450 mg administered subcutaneously at Weeks 0 and 24 (Q24W)
SLN360: SLN360 is a double-stranded small interfering ribonucleic acid (siRNA) targeting LPA messenger RNA (mRNA)
OG003
Time Frame
05 December 2022 (first participant screened) to 01 July 2024 (last participant last visit). Median duration of exposure was 24.43 weeks. Adverse event data were collected over the 60-week study period (95.6% of participants completed to Week 60).
Description
Serious treatment-emergent and non-serious treatment-emergent adverse events are summarised for the safety population: all participants who received at least 1 dose of study drug. Safety data were summarised by actual treatment received based on the safety population.
All-Cause Mortality Comment
Not provided
Arm/Groups
ID
Title
Description
Deaths (Affected)
Deaths (At Risk)
Serious Events (Affected)
Serious Events (At Risk)
Other Events (Affected)
Other Events (At Risk)
EG000
SLN360 300 mg Q16W
SLN360 300 mg administered subcutaneously at Weeks 0, 16 and 32 (Q16W).
SLN360: SLN360 is a double-stranded small interfering ribonucleic acid (siRNA) targeting LPA messenger RNA (mRNA)
0
42
6
42
42
42
EG001
SLN360 300 mg Q24W
SLN360 300 mg administered subcutaneously at Weeks 0 and 24 (Q24W).
SLN360: SLN360 is a double-stranded small interfering ribonucleic acid (siRNA) targeting LPA messenger RNA (mRNA)
0
44
2
44
43
44
EG002
SLN360 450 mg Q24W
SLN360 450 mg administered subcutaneously at Weeks 0 and 24 (Q24W).
SLN360: SLN360 is a double-stranded small interfering ribonucleic acid (siRNA) targeting LPA messenger RNA (mRNA)
0
45
5
45
42
45
EG003
Placebo Q16W
Placebo administered subcutaneously at Weeks 0, 16 and 32 (dosing every 16 weeks [Q16W]).
Placebo: Sodium chloride, solution for injection
0
23
1
23
18
23
EG004
Placebo Q24W
Placebo administered subcutaneously at Weeks 0 and 24 (dosing every 24 weeks [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: Sodium chloride, solution for injection
0
24
3
24
22
24
Serious Adverse Events
Term
Organ System
Source Vocabulary
Assessment Type
Notes
Statistical Information
Prostate cancer
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA (25.1)
Systematic Assessment
EG0001 events1 affected42 at risk
EG0010 events0 affected44 at risk
EG0020 events0 affected45 at risk
EG0030 events0 affected23 at risk
EG004
Malignant polyp
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Analysis of variance (ANOVA) was used to test for differences between each active treatment group and the pooled placebo groups in the primary outcome measure.
ANOVA
<0.0001
Mean Difference (Final Values)
-81.3
2-Sided
95
-86.68
-76.0
Superiority
OG002
OG003
Analysis of variance (ANOVA) was used to test for differences between each active treatment group and the pooled placebo groups in the primary outcome measure.
ANOVA
<0.0001
Mean Difference (Final Values)
-85.6
2-Sided
95
-90.88
-80.26
Superiority
Pooled Placebo
Pooled data from both placebo groups
Placebo: Sodium chloride, solution for injection
Units
Counts
Participants
OG00042
OG00144
OG00245
OG00347
Title
Denominators
Categories
Title
Measurements
OG000-81.6± 2.05
OG001-77.2± 2.00
OG002-81.5± 1.98
OG0031.5± 1.94
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG003
Analysis of variance (ANOVA) was used to test for differences between each active treatment group and the pooled placebo groups in the primary outcome measure.
ANOVA
<0.0001
Mean Difference (Final Values)
-83.1
2-Sided
95
-88.7
-77.57
Superiority
OG001
OG003
Analysis of variance (ANOVA) was used to test for differences between each active treatment group and the pooled placebo groups in the primary outcome measure.
ANOVA
<0.0001
Mean Difference (Final Values)
-78.7
2-Sided
95
-84.18
-73.17
Superiority
OG002
OG003
Analysis of variance (ANOVA) was used to test for differences between each active treatment group and the pooled placebo groups in the primary outcome measure.
ANOVA
<0.0001
Mean Difference (Final Values)
-83.0
2-Sided
95
-88.43
-77.49
Superiority
Pooled Placebo
Pooled data from both placebo groups
Placebo: Sodium chloride, solution for injection
Units
Counts
Participants
OG00042
OG00144
OG00245
OG00347
Title
Denominators
Categories
Title
Measurements
OG000-78.0± 2.24
OG001-70.7± 2.19
OG002-76.0± 2.16
OG0031.1± 2.11
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG003
Analysis of variance (ANOVA) was used to test for differences between each active treatment group and the pooled placebo groups in the primary outcome measure.
ANOVA
<0.0001
Mean Difference (Final Values)
-79.2
2-Sided
95
-85.25
-73.1
Superiority
OG001
OG003
Analysis of variance (ANOVA) was used to test for differences between each active treatment group and the pooled placebo groups in the primary outcome measure.
ANOVA
<0.0001
Mean Difference (Final Values)
-71.8
2-Sided
95
-77.81
-65.8
Superiority
OG002
OG003
Analysis of variance (ANOVA) was used to test for differences between each active treatment group and the pooled placebo groups in the primary outcome measure.
ANOVA
<0.0001
Mean Difference (Final Values)
-77.1
2-Sided
95
-83.09
-71.15
Superiority
Pooled Placebo
Pooled data from both placebo groups
Placebo: Sodium chloride, solution for injection
Units
Counts
Participants
OG00042
OG00144
OG00245
OG00347
Title
Denominators
Categories
Title
Measurements
OG000-16.9± 1.93
OG001-13.5± 1.88
OG002-18.6± 1.86
OG003-3.6± 1.82
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG003
Analysis of variance (ANOVA) was used to test for differences between each active treatment group and the pooled placebo groups in the primary outcome measure.
ANOVA
<0.0001
Mean Difference (Final Values)
-13.3
2-Sided
95
-18.55
-8.09
Superiority
OG001
OG003
Analysis of variance (ANOVA) was used to test for differences between each active treatment group and the pooled placebo groups in the primary outcome measure.
ANOVA
=0.0002
Mean Difference (Final Values)
-9.9
2-Sided
95
-15.02
-4.68
Superiority
OG002
OG003
Analysis of variance (ANOVA) was used to test for differences between each active treatment group and the pooled placebo groups in the primary outcome measure.
ANOVA
<0.0001
Mean Difference (Final Values)
-15.0
2-Sided
95
-20.1
-9.82
Superiority
Pooled Placebo
Pooled data from both placebo groups
Placebo: Sodium chloride, solution for injection
Units
Counts
Participants
OG00042
OG00144
OG00245
OG00347
Title
Denominators
Categories
Title
Measurements
OG000-16.4± 1.94
OG001-12.6± 1.90
OG002-18.0± 1.88
OG003-4.0± 1.83
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG003
Analysis of variance (ANOVA) was used to test for differences between each active treatment group and the pooled placebo groups in the primary outcome measure.
ANOVA
<0.0001
Mean Difference (Final Values)
-12.3
2-Sided
95
-17.62
-7.08
Superiority
OG001
OG003
Analysis of variance (ANOVA) was used to test for differences between each active treatment group and the pooled placebo groups in the primary outcome measure.
ANOVA
=0.0013
Mean Difference (Final Values)
-8.6
2-Sided
95
-13.85
-3.44
Superiority
OG002
OG003
Analysis of variance (ANOVA) was used to test for differences between each active treatment group and the pooled placebo groups in the primary outcome measure.
ANOVA
<0.0001
Mean Difference (Final Values)
-14.0
2-Sided
95
-19.2
-8.84
Superiority
Pooled Placebo
Pooled data from both placebo groups
Placebo: Sodium chloride, solution for injection
Units
Counts
Participants
OG00042
OG00144
OG00245
OG00347
Title
Denominators
Categories
Title
Measurements
OG000-15.0± 2.04
OG001-10.9± 1.99
OG002-16.4± 1.97
OG003-3.8± 1.93
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG003
Analysis of variance (ANOVA) was used to test for differences between each active treatment group and the pooled placebo groups in the primary outcome measure.
ANOVA
<0.0001
Mean Difference (Final Values)
-11.3
2-Sided
95
-16.81
-5.73
Superiority
OG001
OG003
Analysis of variance (ANOVA) was used to test for differences between each active treatment group and the pooled placebo groups in the primary outcome measure.
ANOVA
=0.0106
Mean Difference (Final Values)
-7.2
2-Sided
95
-12.64
-1.69
Superiority
OG002
OG003
Analysis of variance (ANOVA) was used to test for differences between each active treatment group and the pooled placebo groups in the primary outcome measure.
ANOVA
<0.0001
Mean Difference (Final Values)
-12.6
2-Sided
95
-18.04
-7.15
Superiority
Pooled Placebo
Pooled data from both placebo groups
Placebo: Sodium chloride, solution for injection
Units
Counts
Participants
OG00042
OG00144
OG00245
OG00347
Title
Denominators
Categories
Title
Measurements
OG000-22.3± 8.16
OG001-20.1± 7.98
OG002-15.5± 7.89
OG0039.6± 7.72
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG003
Analysis of variance (ANOVA) was used to test for differences between each active treatment group and the pooled placebo groups in the primary outcome measure.
ANOVA
=0.0051
Mean Difference (Final Values)
-31.9
2-Sided
95
-54.07
-9.72
Superiority
OG001
OG003
Analysis of variance (ANOVA) was used to test for differences between each active treatment group and the pooled placebo groups in the primary outcome measure.
ANOVA
=0.0081
Mean Difference (Final Values)
-29.7
2-Sided
95
-51.62
-7.81
Superiority
OG002
OG003
Analysis of variance (ANOVA) was used to test for differences between each active treatment group and the pooled placebo groups in the primary outcome measure.
ANOVA
=0.0241
Mean Difference (Final Values)
-25.1
2-Sided
95
-46.89
-3.33
Superiority
Pooled Placebo
Pooled data from both placebo groups
Placebo: Sodium chloride, solution for injection
Units
Counts
Participants
OG00042
OG00144
OG00245
OG00347
Title
Denominators
Categories
Title
Measurements
OG000-20.9± 7.01
OG001-18.5± 6.85
OG002-17.0± 6.78
OG0038.9± 6.63
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG003
Analysis of variance (ANOVA) was used to test for differences between each active treatment group and the pooled placebo groups in the primary outcome measure.
ANOVA
=0.0023
Mean Difference (Final Values)
-29.8
2-Sided
95
-48.86
-10.76
Superiority
OG001
OG003
Analysis of variance (ANOVA) was used to test for differences between each active treatment group and the pooled placebo groups in the primary outcome measure.
ANOVA
=0.0046
Mean Difference (Final Values)
-27.4
2-Sided
95
-46.23
-8.58
Superiority
OG002
OG003
Analysis of variance (ANOVA) was used to test for differences between each active treatment group and the pooled placebo groups in the primary outcome measure.
ANOVA
=0.0068
Mean Difference (Final Values)
-26.0
2-Sided
95
-44.67
-7.24
Superiority
Pooled Placebo
Pooled data from both placebo groups
Placebo: Sodium chloride, solution for injection
Units
Counts
Participants
OG00042
OG00144
OG00245
OG00347
Title
Denominators
Categories
Title
Measurements
OG000-19.3± 7.45
OG001-16.8± 7.28
OG002-14.7± 7.19
OG0039.3± 7.04
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG003
Analysis of variance (ANOVA) was used to test for differences between each active treatment group and the pooled placebo groups in the primary outcome measure.
ANOVA
=0.0057
Mean Difference (Final Values)
-28.7
2-Sided
95
-48.91
-8.46
Superiority
OG001
OG003
Analysis of variance (ANOVA) was used to test for differences between each active treatment group and the pooled placebo groups in the primary outcome measure.
Mean Difference (Final Values)
-26.1
2-Sided
95
-46.13
-6.16
Superiority
OG002
OG003
Analysis of variance (ANOVA) was used to test for differences between each active treatment group and the pooled placebo groups in the primary outcome measure.