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

NCT04606602 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: SLN360-001
• Study Type: interventional
• Target: 70
• Locations: 4 countries
• Sites: 8

Brief Summary

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

Conditions

Hyperlipidemias; Dyslipidemias; Elevated Lp(a)

Keywords

Dyslipidemia, Dyslipoproteinemia, Hyperlipidemia, Hyperlipoproteinemia, Hyperlipoproteinemia (a), Lipoprotein, Lipoprotein (a)

Outcome Measures

Primary Outcomes (2)

• Incidence of treatment-emergent adverse events

  safety and tolerability will be reported separately following single-dose administration.

  Day 150

• Incidence of treatment-emergent adverse events

  safety and tolerability will be reported separately following multiple-dose administration.

  Day 201

Secondary Outcomes (4)

• Pharmacokinetic: peak plasma concentration (Cmax)

  Day 150 and Day 201

• Pharmacokinetic: area under the plasma concentration (AUC)

  Day 150 and Day 201

• Pharmacokinetic: apparent total clearance from plasma after s.c injection (CL/F)

  Day 150 and Day 201

• Pharmacodynamic: Change in Lp(a)

  Day 150 and Day 201

Study Arms (11)

30 mg

EXPERIMENTAL

Drug: SLN360

Placebo

PLACEBO COMPARATOR

Drug: Placebo

100 mg

EXPERIMENTAL

Drug: SLN360

300 mg

EXPERIMENTAL

Drug: SLN360

600 mg

EXPERIMENTAL

Drug: SLN360

900 mg

EXPERIMENTAL

Drug: SLN360

100 mg multi dose

EXPERIMENTAL

Drug: SLN360

200 mg multi dose

EXPERIMENTAL

Drug: SLN360

300 mg multi dose

EXPERIMENTAL

Drug: SLN360

600 mg multi dose

EXPERIMENTAL

Drug: SLN360

Placebo multi dose

PLACEBO COMPARATOR

Drug: Placebo

Interventions

SLN360 DRUG

SLN360 for subcutaneous (s.c.) injection

100 mg; 100 mg multi dose; 200 mg multi dose; 30 mg; 300 mg; 300 mg multi dose; 600 mg; 600 mg multi dose; 900 mg

Placebo DRUG

Sodium chloride for subcutaneous (s.c.) injection

Placebo; Placebo multi dose

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Silence Therapeutics plc: lead
• Medpace, Inc.: collaborator

Study Sites (8)

Jacksonville Center for Clinical Research Ltd.

Jacksonville, Florida, 32216, United States

Location

Progressive Medical Research

Port Orange, Florida, 32127, United States

Location

Metabolic and Atherosclerosis Research Center

Cincinnati, Ohio, 45227, United States

Location

Cleveland Clinic

Cleveland, Ohio, 44195, United States

Location

Linear Clinical Research

Perth, Western Australia, Australia

Location

Monash Medical Centre

Clayton, Australia

Location

Amsterdam Medical Centre

Amsterdam, Netherlands

Location

Hammersmith Medicines Research

London, United Kingdom

Location

Related Publications (2)

• 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.

  PMID: 35368052 RESULT

• 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.

  PMID: 38587822 RESULT

MeSH Terms

Conditions

Hyperlipidemias; Dyslipidemias; Hyperlipoproteinemias

Condition Hierarchy (Ancestors)

Lipid Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 7, 2020
• First Posted: October 28, 2020
• Study Start: November 18, 2020
• Primary Completion: August 23, 2023
• Study Completion: August 23, 2023
• Last Updated: August 12, 2024

Record last verified: 2024-08

Locations

NL (1); GB (1); US (4); AU (2)