Study to Investigate Safety, Tolerability, PK and PD Response of SLN360 in Subjects With Elevated Lipoprotein(a)

Dyslipidemias Clinical Trial

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04606602
• Other study ID #: SLN360-001
• Status: Completed
• Phase: Phase 1
• Start date: November 18, 2020
• Est. completion date: August 23, 2023

Study information

• Verified date: October 2023
• Source: Silence Therapeutics plc
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study will investigate the safety and tolerability of SLN360 in patients with elevated Lp(a).

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 70
• Est. completion date: August 23, 2023
• Est. primary completion date: August 23, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Dyslipidemias
• Elevated Lp(a)
• Hyperlipidemias
• Hyperlipoproteinemias

Intervention

Drug:
• SLN360
SLN360 for subcutaneous (s.c.) injection
• Placebo
Sodium chloride for subcutaneous (s.c.) injection

Locations

Country	Name	City	State
Australia	Monash Medical Centre	Clayton
Australia	Linear Clinical Research	Perth	Western Australia
Netherlands	Amsterdam Medical Centre	Amsterdam
United Kingdom	Hammersmith Medicines Research	London
United States	Metabolic and Atherosclerosis Research Center	Cincinnati	Ohio
United States	Cleveland Clinic	Cleveland	Ohio
United States	Jacksonville Center for Clinical Research Ltd.	Jacksonville	Florida
United States	Progressive Medical Research	Port Orange	Florida

Sponsors (2)

Lead Sponsor	Collaborator
Silence Therapeutics plc	Medpace, Inc.

Countries where clinical trial is conducted

United States,  Australia,  Netherlands,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of treatment-emergent adverse events	safety and tolerability will be reported separately following single-dose administration.	Day 150
Primary	Incidence of treatment-emergent adverse events	safety and tolerability will be reported separately following multiple-dose administration.	Day 201
Secondary	Pharmacokinetic: peak plasma concentration (Cmax)	safety and tolerability will be reported separately following single-dose and multiple-dose administration.	Day 150 and Day 201
Secondary	Pharmacokinetic: area under the plasma concentration (AUC)	safety and tolerability will be reported separately following single-dose and multiple-dose administration.	Day 150 and Day 201
Secondary	Pharmacokinetic: apparent total clearance from plasma after s.c injection (CL/F)	safety and tolerability will be reported separately following single-dose and multiple-dose administration.	Day 150 and Day 201
Secondary	Pharmacodynamic: Change in Lp(a)	safety and tolerability will be reported separately following single-dose and multiple-dose administration.	Day 150 and Day 201