Clinical trial NCT05896969: Dose Escalation of SNK-396 in Participants With Elevated Low-Density Lipoprotein Cholesterol
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Elevated Low-Density Lipoprotein Cholesterol
Lead sponsor: Syneos Health
Sponsor class: OTHER
Collaborators: name: SynerK Pharmatech (Suzhou) Limited
First posted: 2023-06-09
Enrollment: 41
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: This is a Phase 1, multi-center, randomized, double-blind, 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. The two parts will be completed sequentially. The MAD part may be initiated when safety, tolerability, and PK data are known and deemed acceptable for single doses of at least the 5 planned dose levels of the SAD cohorts.
Primary purpose: TREATMENT

Brief summary: 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

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)

Eligibility criteria: 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.

Primary outcomes:
measure: Treatment emergent adverse events
timeFrame: SAD - Up to Day 57 (end of study visit)
measure: Treatment emergent adverse events
timeFrame: MAD - Up to Day 85 (end of study visit)
Secondary outcomes:
measure: Pharmacokinetic Assessment
timeFrame: Upto Day 57 for SAD , Upto Day 85 for MAD
measure: Pharmacokinetic Assessment
timeFrame: Upto Day 57 for SAD , Upto Day 85 for MAD
measure: Pharmacokinetic Assessment
timeFrame: Upto Day 57 for SAD , Upto Day 85 for MAD
measure: Pharmacokinetic Assessment
timeFrame: Upto Day 57 for SAD , Upto Day 85 for MAD
measure: Pharmacodynamic (PD) effect assessment
timeFrame: Upto Day 57 for SAD , Upto Day 85 for MAD
measure: Pharmacodynamic (PD) effect assessment
timeFrame: Upto Day 57 for SAD , Upto Day 85 for MAD
Other outcomes:
Locations:
city: Herston
country: Australia
facility: Nucleus Network Pty Ltd
state: Queensland
city: Adelaide
country: Australia
facility: Cmax Clinical Research
state: South Australia
city: Melbourne
country: Australia
facility: Nucleus Network Pty Ltd
state: Victoria
Study officials:
References: