Dyslipidemias, Elevated Lp(a), Hyperlipidemias
Conditions
Keywords
Dyslipidemia, Dyslipoproteinemia, Hyperlipidemia, Hyperlipoproteinemia, Hyperlipoproteinemia (a), Lipoprotein, Lipoprotein (a)
Brief summary
This study will investigate the safety and tolerability of SLN360 in patients with elevated Lp(a).
Detailed description
This first-in-human (FIH) study will investigate the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of SLN360 after single ascending s.c. doses and multiple doses in healthy male and female subjects. Up to 9 cohorts of 88 patients with elevated Lp(a) will be enrolled. Each patient will receive single or multiple doses of SLN360 or placebo given by subcutaneous (s.c) injection.
Interventions
DRUGSLN360
SLN360 for subcutaneous (s.c.) injection
DRUGPlacebo
Sodium chloride for subcutaneous (s.c.) injection
Sponsors
Medpace, Inc.
Silence Therapeutics plc
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Elevated plasma Lp(a) ≥ 150nmol/L. * All subjects must agree to adhere to appropriate contraception requirements. * Subjects must provide written informed consent and be able to comply with all study requirements. * Body mass index of ≥ 18 kg/m2 and ≤ 45 kg/m2. * For the MD part: confirmed history of stable atherosclerortic cardiovascular disease.
Exclusion criteria
* Single Ascending Dose 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. * Multiple Dose 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). * Moderate or severe hepatic cirrhosis with Child-Pugh grade B or C, or other current or previous liver disease. * Active serious mental illness or psychiatric disorder, including but not limited to schizophrenia, bipolar disorder, or severe depression requiring current pharmacological intervention. * 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. * Subjects with previous or current use of medication or therapies significantly affecting Lp(a) level or hormone replacement therapy, unless on a stable dose for ≥ 8 weeks prior to screening * History or clinical evidence of alcohol or illegal drug misuse within the 6 months before screening. * History of multiple drug allergies or history of allergic reaction to an oligonucleotide or GalNAc, or intolerance to s.c. injections.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of treatment-emergent adverse events | Day 150 | safety and tolerability will be reported separately following single-dose administration. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetic: peak plasma concentration (Cmax) | Day 150 and Day 201 | safety and tolerability will be reported separately following single-dose and multiple-dose administration. |
| Pharmacokinetic: area under the plasma concentration (AUC) | Day 150 and Day 201 | safety and tolerability will be reported separately following single-dose and multiple-dose administration. |
| Pharmacokinetic: apparent total clearance from plasma after s.c injection (CL/F) | Day 150 and Day 201 | safety and tolerability will be reported separately following single-dose and multiple-dose administration. |
| Pharmacodynamic: Change in Lp(a) | Day 150 and Day 201 | safety and tolerability will be reported separately following single-dose and multiple-dose administration. |
Countries
Australia, Netherlands, United Kingdom, United States
Outcome results
None listed