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

Primary Purpose

Hyperlipidemias, Dyslipidemias, Elevated Lp(a)

Status
Completed
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
SLN360
Placebo
Sponsored by
Silence Therapeutics plc
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Hyperlipidemias focused on measuring Dyslipidemia, Dyslipoproteinemia, Hyperlipidemia, Hyperlipoproteinemia, Hyperlipoproteinemia (a), Lipoprotein, Lipoprotein (a)

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Jacksonville Center for Clinical Research Ltd.
  • Progressive Medical Research
  • Metabolic and Atherosclerosis Research Center
  • Cleveland Clinic
  • Linear Clinical Research
  • Monash Medical Centre
  • Amsterdam Medical Centre
  • Hammersmith Medicines Research

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm 7

Arm 8

Arm 9

Arm 10

Arm 11

Arm Type

Experimental

Placebo Comparator

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Placebo Comparator

Arm Label

30 mg

Placebo

100 mg

300 mg

600 mg

900 mg

100 mg multi dose

200 mg multi dose

300 mg multi dose

600 mg multi dose

Placebo multi dose

Arm Description

Outcomes

Primary Outcome Measures

Incidence of treatment-emergent adverse events
safety and tolerability will be reported separately following single-dose administration.
Incidence of treatment-emergent adverse events
safety and tolerability will be reported separately following multiple-dose administration.

Secondary Outcome Measures

Pharmacokinetic: peak plasma concentration (Cmax)
safety and tolerability will be reported separately following single-dose and multiple-dose administration.
Pharmacokinetic: area under the plasma concentration (AUC)
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)
safety and tolerability will be reported separately following single-dose and multiple-dose administration.
Pharmacodynamic: Change in Lp(a)
safety and tolerability will be reported separately following single-dose and multiple-dose administration.

Full Information

First Posted
October 7, 2020
Last Updated
October 2, 2023
Sponsor
Silence Therapeutics plc
Collaborators
Medpace, Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT04606602
Brief Title
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

2. Study Status

Record Verification Date
October 2023
Overall Recruitment Status
Completed
Study Start Date
November 18, 2020 (Actual)
Primary Completion Date
August 23, 2023 (Actual)
Study Completion Date
August 23, 2023 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Silence Therapeutics plc
Collaborators
Medpace, Inc.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hyperlipidemias, Dyslipidemias, Elevated Lp(a)
Keywords
Dyslipidemia, Dyslipoproteinemia, Hyperlipidemia, Hyperlipoproteinemia, Hyperlipoproteinemia (a), Lipoprotein, Lipoprotein (a)

7. Study Design

Primary Purpose
Prevention
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
70 (Actual)

8. Arms, Groups, and Interventions

Arm Title
30 mg
Arm Type
Experimental
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Title
100 mg
Arm Type
Experimental
Arm Title
300 mg
Arm Type
Experimental
Arm Title
600 mg
Arm Type
Experimental
Arm Title
900 mg
Arm Type
Experimental
Arm Title
100 mg multi dose
Arm Type
Experimental
Arm Title
200 mg multi dose
Arm Type
Experimental
Arm Title
300 mg multi dose
Arm Type
Experimental
Arm Title
600 mg multi dose
Arm Type
Experimental
Arm Title
Placebo multi dose
Arm Type
Placebo Comparator
Intervention Type
Drug
Intervention Name(s)
SLN360
Intervention Description
SLN360 for subcutaneous (s.c.) injection
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Sodium chloride for subcutaneous (s.c.) injection
Primary Outcome Measure Information:
Title
Incidence of treatment-emergent adverse events
Description
safety and tolerability will be reported separately following single-dose administration.
Time Frame
Day 150
Title
Incidence of treatment-emergent adverse events
Description
safety and tolerability will be reported separately following multiple-dose administration.
Time Frame
Day 201
Secondary Outcome Measure Information:
Title
Pharmacokinetic: peak plasma concentration (Cmax)
Description
safety and tolerability will be reported separately following single-dose and multiple-dose administration.
Time Frame
Day 150 and Day 201
Title
Pharmacokinetic: area under the plasma concentration (AUC)
Description
safety and tolerability will be reported separately following single-dose and multiple-dose administration.
Time Frame
Day 150 and Day 201
Title
Pharmacokinetic: apparent total clearance from plasma after s.c injection (CL/F)
Description
safety and tolerability will be reported separately following single-dose and multiple-dose administration.
Time Frame
Day 150 and Day 201
Title
Pharmacodynamic: Change in Lp(a)
Description
safety and tolerability will be reported separately following single-dose and multiple-dose administration.
Time Frame
Day 150 and Day 201

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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.
Facility Information:
Facility Name
Jacksonville Center for Clinical Research Ltd.
City
Jacksonville
State/Province
Florida
ZIP/Postal Code
32216
Country
United States
Facility Name
Progressive Medical Research
City
Port Orange
State/Province
Florida
ZIP/Postal Code
32127
Country
United States
Facility Name
Metabolic and Atherosclerosis Research Center
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45227
Country
United States
Facility Name
Cleveland Clinic
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44195
Country
United States
Facility Name
Linear Clinical Research
City
Perth
State/Province
Western Australia
Country
Australia
Facility Name
Monash Medical Centre
City
Clayton
Country
Australia
Facility Name
Amsterdam Medical Centre
City
Amsterdam
Country
Netherlands
Facility Name
Hammersmith Medicines Research
City
London
Country
United Kingdom

12. IPD Sharing Statement

Citations:
PubMed Identifier
35368052
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.
Results Reference
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Learn more about this trial

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

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