atherosclerosis elevated lipoprotein (a)
Conditions
Interventions
SLN360 is a GalNAc conjugated 19-mer double stranded fully modified short
interfering RNA (siRNA) targeting LPA messenger RNA (mRNA).
SLN360 will be provided as a solution for injection for s.c. use
Sponsors
Silence Therapeutics plc
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: i. Male and female subjects aged 18 years to 70 years. ii. Body mass index of >= 18 kg/m2 and
Exclusion criteria
Exclusion criteria: i. Comorbidity; a. For the SAD part only: any history of clinically overt cardiovascular disease, defined as acute coronary syndromes, myocardial infarction, stable angina, coronary or other revascularization, ischemic stroke or transient ischemic attack and atherosclerotic peripheral arterial disease. b. For the MD part only: recent history of acute cardiovascular disease events within 6 months of screening (including, but not limited to, acute myocardial infarction, unstable angina, acute stroke and acute limb ischemia). c. Any uncontrolled or serious disease, or any medical or surgical condition including evidence of unstable cardiovascular disease, that may interfere with participation in the clinical study, significantly interfere with the interpretation of the results and/or put the subject at significant risk (according to Investigator*s judgement) if he/she participates in the clinical study. d. Moderate or severe hepatic cirrhosis with Child-Pugh grade B or C, or other current or previous liver disease that may increase the risk of drug-induced liver injury or influence the pharmacology of SLN360. e. Active serious mental illness or psychiatric disorder, including but not limited to schizophrenia, bipolar disorder, or severe depression requiring current pharmacological intervention. f. Clinically significant illness within 7 days before the first dose of study drug. g. Any conditions which, in the opinion of the Investigator, would make the subject unsuitable for enrolment in the study or could interfere with the subject*s participation in, or completion of the study. h. Positive nucleic acid test for SARS-CoV-2 (the virus causing Covid-19) during screening. i. Positive test for hepatitis B surface antigen (HBsAg), hepatitis B core antibody (anti HBC), hepatitis C virus antibody (HCV Ab) or human immunodeficiency virus (HIV). ii. Biochemical and hematological parameters: a. Clinically significant abnormalities in screening blood tests (excluding lipid profile) that are judged to affect the suitability for inclusion, including: i. ALT or AST >1.5 × ULN. ii. Total bilirubin > ULN, except in previously confirmed cases of Gilbert*s syndrome. iii. Platelet count = 8 weeks prior to screening and no planned medication or dose adjustment during the study. b. Statins and/or ezetimibe unless on a stable dose or off treatment for at least 8 weeks prior to screening and no planned medication or dose adjustment during the study. c. Lipid or lipoprote
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Safety and tolerability parameters of single or multiple doses SLN360 in subjects with elevated Lp(a) levels. Please see Appendices 2 and 3 of the protocol for detailed information on safety and laboratory parameters. | — |
Secondary
| Measure | Time frame |
|---|---|
| PD and PK parameters of single and multiple doses of SLN360 on Lp(a). Extent and duration of reduction in Lp(a) following single and multiple doses of SLN360. Impact of dose schedule of SLN360 on extent and duration of reduction in Lp(a). Impact of single and multiple doses of SLN360 on lipid profile including apoB, OxPLs, inflammatory markers, and plasminogen. Please see Appendices 2 and 3 of the protocol for detailed information on safety and laboratory parameters. | — |
Countries
Netherlands
Outcome results
None listed