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

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

Detailed Description
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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.

Official Title
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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)

Conditions
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Hyperlipidemias, Dyslipidemias, Elevated Lp(a)

Intervention / Treatment
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* Drug: SLN360
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 30 mg<br> | Drug: SLN360<br>* SLN360 for subcutaneous (s.c.) injection<br>|
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* Sodium chloride for subcutaneous (s.c.) injection<br>|
| Experimental: 100 mg<br> | Drug: SLN360<br>* SLN360 for subcutaneous (s.c.) injection<br>|
| Experimental: 300 mg<br> | Drug: SLN360<br>* SLN360 for subcutaneous (s.c.) injection<br>|
| Experimental: 600 mg<br> | Drug: SLN360<br>* SLN360 for subcutaneous (s.c.) injection<br>|
| Experimental: 900 mg<br> | Drug: SLN360<br>* SLN360 for subcutaneous (s.c.) injection<br>|
| Experimental: 100 mg multi dose<br> | Drug: SLN360<br>* SLN360 for subcutaneous (s.c.) injection<br>|
| Experimental: 200 mg multi dose<br> | Drug: SLN360<br>* SLN360 for subcutaneous (s.c.) injection<br>|
| Experimental: 300 mg multi dose<br> | Drug: SLN360<br>* SLN360 for subcutaneous (s.c.) injection<br>|
| Experimental: 600 mg multi dose<br> | Drug: SLN360<br>* SLN360 for subcutaneous (s.c.) injection<br>|
| Placebo Comparator: Placebo multi dose<br> | Drug: Placebo<br>* Sodium chloride for subcutaneous (s.c.) injection<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetic: peak plasma concentration (Cmax) | safety and tolerability will be reported separately following single-dose and multiple-dose administration. | Day 150 and Day 201 | 
| 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 | 
| 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 | 
| Pharmacodynamic: Change in Lp(a) | safety and tolerability will be reported separately following single-dose and multiple-dose administration. | Day 150 and Day 201 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Dyslipidemia, Dyslipoproteinemia, Hyperlipidemia, Hyperlipoproteinemia, Hyperlipoproteinemia (a), Lipoprotein, Lipoprotein (a)