Dose Escalation of SNK-396 in Participants With Elevated Low-Density Lipoprotein Cholesterol

Phase 1, Single Multiple Dose Escalation Study in a Randomized, Double-blind, Placebo Controlled Design to Investigate Safety, Tolerability, PK and PD of SC Administered SNK-396 in Subjects With Elevated Low-Density Lipoprotein Cholesterol

This is a Phase 1, multi-center, randomized, double-blinded, placebo-controlled single and multiple dose escalation study with SC doses of SNK-396 in participants with elevated LDL-C. The study will be divided into two parts:

• SAD cohorts
• MAD cohorts

Study Overview

• Status: Completed
• Conditions: Elevated Low-Density Lipoprotein Cholesterol
• Intervention / Treatment: Drug: SNK-396 - SAD cohort; Drug: SNK-396 - MAD Cohort

Detailed Description

The SAD part will consist of up to 8 cohorts of eligible participants with elevated LDL-C as defined as serum LDL levels between 2.6 - 4.9 mmol/L (inclusive)

The MAD part will consist of up to 8 cohorts of eligible participants with elevated LDL-C as defined as serum LDL levels between 2.6 - 4.9 mmol/L (inclusive)

• Study Type: Interventional
• Enrollment (Actual): 41
• Phase: Phase 1

Contacts and Locations

Study Locations

• Australia
  • Queensland
    • Herston, Queensland, Australia, 4006
      • Nucleus Network Pty Ltd
  • South Australia
    • Adelaide, South Australia, Australia, 5000
      • CMAX Clinical Research
  • Victoria
    • Melbourne, Victoria, Australia, 3004
      • Nucleus Network Pty Ltd

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria -

1. Male or female, ≥18 and ≤65 years of age, with BMI ≥18.5 and ≤35.0 kg/m2.
2. Participants must be either non smoking (no use of tobacco or nicotine products within 3 months prior to screening) or social smoker as defined by smoking no more than 5 cigarettes (or nicotine equivalent) a week and no smoking during screening period or on study.
3. Participants must be with elevated LDL-C defined as serum LDL levels between 2.6 - 4.9 mmol/L (inclusive) at screening.
4. Healthy (except for the LDL-C status) participants.
5. Participants must have fasting triglyceride level <4.52 mmol/L (<400mg/dL) at screening.
6. Sexually active females of childbearing potential and non-sterile males must be willing to use an acceptable contraceptive method throughout the study as detailed in section 8.1.
7. Able to understand the study procedures and provide signed informed consent to participate in the study.

Exclusion Criteria -

1. Any clinically significant abnormal finding at physical examination in the opinion of the investigator.
2. Subjects with a history or presence of cardiovascular disease (including cerebrovascular accident (stroke or TIA) or disease, uncontrolled hypertension, familial hypercholesterolaemia, obstructive sleep apnoea, and peripheral artery), a diagnosis of diabetes mellitus given potential for hyperglycaemia defined as HbA1c greater or equal to 6.5%, or a non-alcoholic fatty liver disease.
3. Received Leqvio (inclisiran) treatment in less than 6 months ago.
4. Any reason which, in the opinion of the Investigator, would prevent the participant from participating in the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: SAD Cohort; SAD Cohort 1 - 8 : Subjects in each cohort will be randomised will receive a single SC dose of SNK-396 within the dose range of 25 to 800 mg, or matching placebo.	Drug: SNK-396 - SAD cohort; A single dose of SNK-396 within the dose range of 25 to 800 mg, or matching placebo.
Experimental: MAD cohort; MAD Cohort 1 - 8 : Subjects in each cohort will be randomized will receive the active SNK-396 with dose range of SNK-396 anticipated to be from 25 to 800 mg or matching placebo	Drug: SNK-396 - MAD Cohort; Multiple doses of SNK-396 within the dose range of from 25 to 800 mg, or matching placebo.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Treatment emergent adverse events	Number of Subjects with Treatment Emergent Adverse Events	SAD - Up to Day 57 (end of study visit)
Treatment emergent adverse events	Number of Subjects with Treatment Emergent Adverse Events	MAD - Up to Day 85 (end of study visit)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetic Assessment	Cmax will be assessd	Upto Day 57 for SAD , Upto Day 85 for MAD
Pharmacokinetic Assessment	tmax will be assessd	Upto Day 57 for SAD , Upto Day 85 for MAD
Pharmacokinetic Assessment	AUC will be assessd	Upto Day 57 for SAD , Upto Day 85 for MAD
Pharmacokinetic Assessment	T 1/2 will be assessd	Upto Day 57 for SAD , Upto Day 85 for MAD
Pharmacodynamic (PD) effect assessment	LDL-C serum concentration will be assessed.	Upto Day 57 for SAD , Upto Day 85 for MAD
Pharmacodynamic (PD) effect assessment	PCSK9 plasma levels concentration will be assessed.	Upto Day 57 for SAD , Upto Day 85 for MAD

Collaborators and Investigators

• Sponsor: Syneos Health
• Collaborators: SynerK Pharmatech (Suzhou) Limited

Study record dates

Study Major Dates

• Study Start (Actual): April 27, 2023
• Primary Completion (Actual): February 23, 2024
• Study Completion (Actual): February 23, 2024

Study Registration Dates

• First Submitted: March 14, 2023
• First Submitted That Met QC Criteria: June 6, 2023
• First Posted (Actual): June 9, 2023

Study Record Updates

• Last Update Posted (Actual): June 21, 2024
• Last Update Submitted That Met QC Criteria: June 19, 2024
• Last Verified: June 1, 2024

More Information

Terms related to this study

• Other Study ID Numbers: SNK-396-101

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No