Clinical trial NCT04606602: Study to Investigate Safety, Tolerability, PK and PD Response of SLN360 in Subjects With Elevated Lipoprotein(a)
Official title: A Randomised, Double-blind, Placebo Controlled, First-in-human Study to Investigate the Safety, Tolerability, Pharmacokinetic and Pharmacodynamic Response of SLN360 in Subjects With Elevated Lipoprotein(a)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Hyperlipidemias
Dyslipidemias
Elevated Lp(a)
Keywords: Dyslipidemia, Dyslipoproteinemia, Hyperlipidemia, Hyperlipoproteinemia, Hyperlipoproteinemia (a), Lipoprotein, Lipoprotein (a)
Lead sponsor: Silence Therapeutics plc
Sponsor class: INDUSTRY
Collaborators: name: Medpace, Inc.
First posted: 2020-10-28
Enrollment: 70
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Incidence of treatment-emergent adverse events
timeFrame: Day 150
measure: Incidence of treatment-emergent adverse events
timeFrame: Day 201
Secondary outcomes:
measure: Pharmacokinetic: peak plasma concentration (Cmax)
timeFrame: Day 150 and Day 201
measure: Pharmacokinetic: area under the plasma concentration (AUC)
timeFrame: Day 150 and Day 201
measure: Pharmacokinetic: apparent total clearance from plasma after s.c injection (CL/F)
timeFrame: Day 150 and Day 201
measure: Pharmacodynamic: Change in Lp(a)
timeFrame: Day 150 and Day 201
Other outcomes:
Locations:
city: Jacksonville
country: United States
facility: Jacksonville Center for Clinical Research Ltd.
state: Florida
city: Port Orange
country: United States
facility: Progressive Medical Research
state: Florida
city: Cincinnati
country: United States
facility: Metabolic and Atherosclerosis Research Center
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Perth
country: Australia
facility: Linear Clinical Research
state: Western Australia
city: Clayton
country: Australia
facility: Monash Medical Centre
city: Amsterdam
country: Netherlands
facility: Amsterdam Medical Centre
city: London
country: United Kingdom
facility: Hammersmith Medicines Research
Study officials:
References:
citation: Nissen SE, Wolski K, Balog C, Swerdlow DI, Scrimgeour AC, Rambaran C, Wilson RJ, Boyce M, Ray KK, Cho L, Watts GF, Koren M, Turner T, Stroes ES, Melgaard C, Campion GV. Single Ascending Dose Study of a Short Interfering RNA Targeting Lipoprotein(a) Production in Individuals With Elevated Plasma Lipoprotein(a) Levels. JAMA. 2022 May 3;327(17):1679-1687. doi: 10.1001/jama.2022.5050.
citation: Nissen SE, Wolski K, Watts GF, Koren MJ, Fok H, Nicholls SJ, Rider DA, Cho L, Romano S, Melgaard C, Rambaran C. Single Ascending and Multiple-Dose Trial of Zerlasiran, a Short Interfering RNA Targeting Lipoprotein(a): A Randomized Clinical Trial. JAMA. 2024 May 14;331(18):1534-1543. doi: 10.1001/jama.2024.4504.