Atherosclerosis, Cardiovascular Diseases, Lipoprotein(a)
Conditions
Keywords
Cardiovascular Diseases, Atherosclerosis, Lipoprotein(a)
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
Interventions
DRUGSLN360
SLN360 is a double-stranded small interfering ribonucleic acid (siRNA) targeting LPA messenger RNA (mRNA)
DRUGPlacebo
Sodium chloride, solution for injection
Sponsors
Silence Therapeutics plc
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 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 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. |
| 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. |
Countries
Australia, Czechia, Denmark, Netherlands, Slovakia, South Africa, United Kingdom
Participant flow
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.
Pre-assignment details
A total of 253 participants were screened for inclusion, 73 participants failed screening.
Participants by arm
| Arm | Count |
|---|---|
| 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) | 42 |
| 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) | 44 |
| 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) | 45 |
| Placebo Q16W Placebo administered subcutaneously at Weeks 0, 16 and 32 (dosing every 16 weeks \[Q16W\])
Placebo: Sodium chloride, solution for injection | 23 |
| 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 | 24 |
| Total | 178 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 2 | 0 | 0 | 0 | 0 |
| Overall Study | Hepatitis A screening result | 2 | 0 | 0 | 0 | 0 |
| Overall Study | Lost to Follow-up | 0 | 0 | 1 | 0 | 1 |
| Overall Study | Withdrawal by Subject | 1 | 1 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | SLN360 300 mg Q24W | Total | Placebo Q24W | SLN360 300 mg Q16W | Placebo Q16W | SLN360 450 mg Q24W |
|---|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 21 Participants | 87 Participants | 9 Participants | 23 Participants | 11 Participants | 23 Participants |
| Age, Categorical Between 18 and 65 years | 23 Participants | 91 Participants | 15 Participants | 19 Participants | 12 Participants | 22 Participants |
| Age, Continuous | 64.5 years STANDARD_DEVIATION 8.67 | 63.7 years STANDARD_DEVIATION 9.41 | 62.1 years STANDARD_DEVIATION 9.43 | 63.1 years STANDARD_DEVIATION 9.81 | 65.0 years STANDARD_DEVIATION 8.79 | 63.8 years STANDARD_DEVIATION 10.23 |
| Body Mass Index | 28.240 kg/m2 | 26.905 kg/m2 | 26.160 kg/m2 | 27.060 kg/m2 | 26.930 kg/m2 | 26.470 kg/m2 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 44 Participants | 178 Participants | 24 Participants | 42 Participants | 23 Participants | 45 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Height | 175.0 centimetres | 175.0 centimetres | 174.5 centimetres | 177.0 centimetres | 170.0 centimetres | 173.0 centimetres |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 2 Participants | 8 Participants | 1 Participants | 1 Participants | 0 Participants | 4 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 3 Participants | 0 Participants | 1 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) More than one race | 5 Participants | 13 Participants | 1 Participants | 2 Participants | 2 Participants | 3 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 36 Participants | 153 Participants | 22 Participants | 38 Participants | 21 Participants | 36 Participants |
| Region of Enrollment Australia | 5 participants | 16 participants | 4 participants | 3 participants | 1 participants | 3 participants |
| Region of Enrollment Czechia | 1 participants | 11 participants | 3 participants | 2 participants | 3 participants | 2 participants |
| Region of Enrollment Denmark | 9 participants | 25 participants | 3 participants | 7 participants | 3 participants | 3 participants |
| Region of Enrollment Netherlands | 15 participants | 60 participants | 8 participants | 13 participants | 8 participants | 16 participants |
| Region of Enrollment Slovakia | 0 participants | 5 participants | 0 participants | 2 participants | 0 participants | 3 participants |
| Region of Enrollment South Africa | 8 participants | 29 participants | 3 participants | 6 participants | 3 participants | 9 participants |
| Region of Enrollment United Kingdom | 6 participants | 32 participants | 3 participants | 9 participants | 5 participants | 9 participants |
| Sex: Female, Male Female | 13 Participants | 46 Participants | 6 Participants | 11 Participants | 5 Participants | 11 Participants |
| Sex: Female, Male Male | 31 Participants | 132 Participants | 18 Participants | 31 Participants | 18 Participants | 34 Participants |
| Time from the initial date of elevated Lipoprotein(a) to randomisation date | 5.45 months | 4.45 months | 5.35 months | 6.10 months | 3.60 months | 3.70 months |
| Weight | 82.60 kilograms | 82.85 kilograms | 84.10 kilograms | 84.15 kilograms | 81.00 kilograms | 80.20 kilograms |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 42 | 0 / 44 | 0 / 45 | 0 / 23 | 0 / 24 |
| other Total, other adverse events | 42 / 42 | 43 / 44 | 42 / 45 | 18 / 23 | 22 / 24 |
| serious Total, serious adverse events | 6 / 42 | 2 / 44 | 5 / 45 | 1 / 23 | 3 / 24 |
Outcome results
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.
Time frame: Week 36
Population: The pharmacodynamic population included all participants who received at least 1 dose of study drug and had evaluable pharmacodynamic data.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| SLN360 300 mg Q16W | Time-averaged Percent Change In Lipoprotein(a) Molar Concentration From Baseline to Week 36 | -80.5 Percentage | Standard Error 1.99 |
| SLN360 300 mg Q24W | Time-averaged Percent Change In Lipoprotein(a) Molar Concentration From Baseline to Week 36 | -79.1 Percentage | Standard Error 1.94 |
| SLN360 450 mg Q24W | Time-averaged Percent Change In Lipoprotein(a) Molar Concentration From Baseline to Week 36 | -83.3 Percentage | Standard Error 1.92 |
| Pooled Placebo | Time-averaged Percent Change In Lipoprotein(a) Molar Concentration From Baseline to Week 36 | 2.3 Percentage | Standard Error 1.88 |
Comparison: 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.p-value: <0.000195% CI: [-86.68, -76]ANOVA
Comparison: 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.p-value: <0.000195% CI: [-88.19, -77.39]ANOVA
Comparison: 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.p-value: <0.000195% CI: [-90.88, -80.26]ANOVA
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.
Time frame: Week 36
Population: The pharmacodynamic population included all participants who received at least 1 dose of study drug and had evaluable pharmacodynamic data.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| SLN360 300 mg Q16W | Time-averaged Percent Change In Apolipoprotein B Concentration From Baseline to Week 36 | -16.9 Percentage | Standard Error 1.93 |
| SLN360 300 mg Q24W | Time-averaged Percent Change In Apolipoprotein B Concentration From Baseline to Week 36 | -13.5 Percentage | Standard Error 1.88 |
| SLN360 450 mg Q24W | Time-averaged Percent Change In Apolipoprotein B Concentration From Baseline to Week 36 | -18.6 Percentage | Standard Error 1.86 |
| Pooled Placebo | Time-averaged Percent Change In Apolipoprotein B Concentration From Baseline to Week 36 | -3.6 Percentage | Standard Error 1.82 |
Comparison: 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.p-value: <0.000195% CI: [-18.55, -8.09]ANOVA
Comparison: 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.p-value: =0.000295% CI: [-15.02, -4.68]ANOVA
Comparison: 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.p-value: <0.000195% CI: [-20.1, -9.82]ANOVA
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.
Time frame: Week 48
Population: The pharmacodynamic population included all participants who received at least 1 dose of study drug and had evaluable pharmacodynamic data.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| SLN360 300 mg Q16W | Time-averaged Percent Change In Apolipoprotein B Concentration From Baseline to Week 48 | -16.4 Percentage | Standard Error 1.94 |
| SLN360 300 mg Q24W | Time-averaged Percent Change In Apolipoprotein B Concentration From Baseline to Week 48 | -12.6 Percentage | Standard Error 1.9 |
| SLN360 450 mg Q24W | Time-averaged Percent Change In Apolipoprotein B Concentration From Baseline to Week 48 | -18.0 Percentage | Standard Error 1.88 |
| Pooled Placebo | Time-averaged Percent Change In Apolipoprotein B Concentration From Baseline to Week 48 | -4.0 Percentage | Standard Error 1.83 |
Comparison: 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.p-value: <0.000195% CI: [-17.62, -7.08]ANOVA
Comparison: 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.p-value: =0.001395% CI: [-13.85, -3.44]ANOVA
Comparison: 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.p-value: <0.000195% CI: [-19.2, -8.84]ANOVA
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.
Time frame: Week 60
Population: The pharmacodynamic population included all participants who received at least 1 dose of study drug and had evaluable pharmacodynamic data.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| SLN360 300 mg Q16W | Time-averaged Percent Change In Apolipoprotein B Concentration From Baseline to Week 60 | -15.0 Percentage | Standard Error 2.04 |
| SLN360 300 mg Q24W | Time-averaged Percent Change In Apolipoprotein B Concentration From Baseline to Week 60 | -10.9 Percentage | Standard Error 1.99 |
| SLN360 450 mg Q24W | Time-averaged Percent Change In Apolipoprotein B Concentration From Baseline to Week 60 | -16.4 Percentage | Standard Error 1.97 |
| Pooled Placebo | Time-averaged Percent Change In Apolipoprotein B Concentration From Baseline to Week 60 | -3.8 Percentage | Standard Error 1.93 |
Comparison: 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.p-value: <0.000195% CI: [-16.81, -5.73]ANOVA
Comparison: 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.p-value: =0.010695% CI: [-12.64, -1.69]ANOVA
Comparison: 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.p-value: <0.000195% CI: [-18.04, -7.15]ANOVA
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.
Time frame: Week 48
Population: The pharmacodynamic population included all participants who received at least 1 dose of study drug and had evaluable pharmacodynamic data.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| SLN360 300 mg Q16W | Time-averaged Percent Change In Lipoprotein(a) Molar Concentration From Baseline to Week 48 | -81.6 Percentage | Standard Error 2.05 |
| SLN360 300 mg Q24W | Time-averaged Percent Change In Lipoprotein(a) Molar Concentration From Baseline to Week 48 | -77.2 Percentage | Standard Error 2 |
| SLN360 450 mg Q24W | Time-averaged Percent Change In Lipoprotein(a) Molar Concentration From Baseline to Week 48 | -81.5 Percentage | Standard Error 1.98 |
| Pooled Placebo | Time-averaged Percent Change In Lipoprotein(a) Molar Concentration From Baseline to Week 48 | 1.5 Percentage | Standard Error 1.94 |
Comparison: 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.p-value: <0.000195% CI: [-88.7, -77.57]ANOVA
Comparison: 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.p-value: <0.000195% CI: [-84.18, -73.17]ANOVA
Comparison: 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.p-value: <0.000195% CI: [-88.43, -77.49]ANOVA
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.
Time frame: Week 60
Population: The pharmacodynamic population included all participants who received at least 1 dose of study drug and had evaluable pharmacodynamic data.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| SLN360 300 mg Q16W | Time-averaged Percent Change In Lipoprotein(a) Molar Concentration From Baseline to Week 60 | -78.0 Percentage | Standard Error 2.24 |
| SLN360 300 mg Q24W | Time-averaged Percent Change In Lipoprotein(a) Molar Concentration From Baseline to Week 60 | -70.7 Percentage | Standard Error 2.19 |
| SLN360 450 mg Q24W | Time-averaged Percent Change In Lipoprotein(a) Molar Concentration From Baseline to Week 60 | -76.0 Percentage | Standard Error 2.16 |
| Pooled Placebo | Time-averaged Percent Change In Lipoprotein(a) Molar Concentration From Baseline to Week 60 | 1.1 Percentage | Standard Error 2.11 |
Comparison: 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.p-value: <0.000195% CI: [-85.25, -73.1]ANOVA
Comparison: 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.p-value: <0.000195% CI: [-77.81, -65.8]ANOVA
Comparison: 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.p-value: <0.000195% CI: [-83.09, -71.15]ANOVA
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.
Time frame: Week 36
Population: The pharmacodynamic population included all participants who received at least 1 dose of study drug and had evaluable pharmacodynamic data.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| SLN360 300 mg Q16W | Time-averaged Percent Change In Low-density Lipoprotein Cholesterol Concentration From Baseline to Week 36 | -22.3 Percentage | Standard Error 8.16 |
| SLN360 300 mg Q24W | Time-averaged Percent Change In Low-density Lipoprotein Cholesterol Concentration From Baseline to Week 36 | -20.1 Percentage | Standard Error 7.98 |
| SLN360 450 mg Q24W | Time-averaged Percent Change In Low-density Lipoprotein Cholesterol Concentration From Baseline to Week 36 | -15.5 Percentage | Standard Error 7.89 |
| Pooled Placebo | Time-averaged Percent Change In Low-density Lipoprotein Cholesterol Concentration From Baseline to Week 36 | 9.6 Percentage | Standard Error 7.72 |
Comparison: 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.p-value: =0.005195% CI: [-54.07, -9.72]ANOVA
Comparison: 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.p-value: =0.008195% CI: [-51.62, -7.81]ANOVA
Comparison: 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.p-value: =0.024195% CI: [-46.89, -3.33]ANOVA
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.
Time frame: Week 48
Population: The pharmacodynamic population included all participants who received at least 1 dose of study drug and had evaluable pharmacodynamic data.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| SLN360 300 mg Q16W | Time-averaged Percent Change In Low-density Lipoprotein Cholesterol Concentration From Baseline to Week 48 | -20.9 Percentage | Standard Error 7.01 |
| SLN360 300 mg Q24W | Time-averaged Percent Change In Low-density Lipoprotein Cholesterol Concentration From Baseline to Week 48 | -18.5 Percentage | Standard Error 6.85 |
| SLN360 450 mg Q24W | Time-averaged Percent Change In Low-density Lipoprotein Cholesterol Concentration From Baseline to Week 48 | -17.0 Percentage | Standard Error 6.78 |
| Pooled Placebo | Time-averaged Percent Change In Low-density Lipoprotein Cholesterol Concentration From Baseline to Week 48 | 8.9 Percentage | Standard Error 6.63 |
Comparison: 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.p-value: =0.002395% CI: [-48.86, -10.76]ANOVA
Comparison: 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.p-value: =0.004695% CI: [-46.23, -8.58]ANOVA
Comparison: 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.p-value: =0.006895% CI: [-44.67, -7.24]ANOVA
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.
Time frame: Week 60
Population: The pharmacodynamic population included all participants who received at least 1 dose of study drug and had evaluable pharmacodynamic data.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| SLN360 300 mg Q16W | Time-averaged Percent Change In Low-density Lipoprotein Cholesterol Concentration From Baseline to Week 60 | -19.3 Percentage | Standard Error 7.45 |
| SLN360 300 mg Q24W | Time-averaged Percent Change In Low-density Lipoprotein Cholesterol Concentration From Baseline to Week 60 | -16.8 Percentage | Standard Error 7.28 |
| SLN360 450 mg Q24W | Time-averaged Percent Change In Low-density Lipoprotein Cholesterol Concentration From Baseline to Week 60 | -14.7 Percentage | Standard Error 7.19 |
| Pooled Placebo | Time-averaged Percent Change In Low-density Lipoprotein Cholesterol Concentration From Baseline to Week 60 | 9.3 Percentage | Standard Error 7.04 |
Comparison: 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.p-value: =0.005795% CI: [-48.91, -8.46]ANOVA
Comparison: 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.95% CI: [-46.13, -6.16]
Comparison: 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.p-value: 0.017995% CI: [-43.93, -4.2]ANOVA