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

Silence Therapeutics

Status and phase: Completed; Phase 1

Conditions: Elevated Lp(a); Hyperlipidemias; Dyslipidemias

Treatments: Drug: SLN360; Drug: Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT04606602

SLN360-001

Details and patient eligibility

About

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

Full 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.

Enrollment: 70 patients

Sex: All

Ages: 18+ years old

Volunteers: No 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.

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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70 participants in 11 patient groups, including a placebo group

30 mg

Experimental group

Treatment:

Drug: SLN360

Placebo

Placebo Comparator group

Treatment:

Drug: Placebo

100 mg

Experimental group

Treatment:

Drug: SLN360

300 mg

Experimental group

Treatment:

Drug: SLN360

600 mg

Experimental group

Treatment:

Drug: SLN360

900 mg

Experimental group

Treatment:

Drug: SLN360

100 mg multi dose

Experimental group

Treatment:

Drug: SLN360

200 mg multi dose

Experimental group

Treatment:

Drug: SLN360

300 mg multi dose

Experimental group

Treatment:

Drug: SLN360

600 mg multi dose

Experimental group

Treatment:

Drug: SLN360

Placebo multi dose

Placebo Comparator group

Treatment:

Drug: Placebo