Clinical trial NCT06239714: A Study to Evaluate SGB-3403 in Healthy Volunteers and Subjects With Elevated Low-Density Lipoprotein Cholesterol (LDL-C)
Official title: A Phase 1, Randomized, Double-Blind, Placebo-Controlled, SAD and MAD Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Subcutaneously Administered SGB-3403 in Healthy Volunteers and Subjects With Elevated LDL-C
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE1
Conditions: Hyperlipidemias
Lead sponsor: Suzhou Sanegene Bio Inc.
Sponsor class: INDUSTRY
First posted: 2024-02-02
Enrollment: 64
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study is a randomized, double-blind, placebo-controlled, single ascending dose (SAD) and multiple ascending doses (MAD) of SGB-3403 when single administered subcutaneously to healthy volunteers and multiple administered subcutaneously to subjects with elevated LDL-C to evaluate the safety, tolerance, PK, and PD.

Detailed description: This study is a randomized, double-blind, placebo-controlled, single ascending dose (SAD) and multiple ascending doses (MAD) of SGB-3403 when single administered subcutaneously to healthy volunteers and multiple administered subcutaneously to subjects with elevated LDL-C. The study will be performed in 2 phases: SAD and MAD.

Eligibility criteria: Inclusion Criteria in SAD:

* Male and female subjects aged 18 to 55 years are included.
* Body mass index between 19 and 32 kg/m2, inclusive.
* Physical examination, vital signs, 12-lead electrocardiogram, and laboratory tests will be normal or slightly abnormal but not clinically significant according to the Investigator's judgment.
* Willing to comply with the protocol required visit schedule and visit requirements and provide written informed consent.

Exclusion Criteria in SAD:

* An underlying known disease or surgical or medical condition that, in the opinion of the Investigator, might interfere with the interpretation of the clinical study results.
* The positive result of hepatitis B surface antigen (HBsAg), hepatitis C virus antibody (HCV Ab), human immunodeficiency virus (HIV) antibody, or syphilis at screening.
* Alanine aminotransferase (ALT), total bilirubin (TBIL), aspartate aminotransferase (AST), alkaline phosphatase (ALP), or gamma-glutamyl transferase (GGT) \> 1.5 × ULN (upper limit of normal).
* Serum creatinine exceeds the upper limit of normal at screening.
* History of multiple drug allergies or allergic reactions to an oligonucleotide or N acetylgalactosamine (GalNAc).
* History of intolerance to subcutaneous (SC) injection or relevant abdominal scarring (surgical, burns, etc.)
* Received an investigational agent within 28 days or 5 half-lives (whichever is longer) before the first dose of the study drug or are in another clinical study, received INCLISIRAN within 1 year.
* Use any Chinese herbs, vitamins, or supplements known to affect lipid metabolism (e.g., fish oil \> 1000 mg/ day, medicines, or health products containing red yeast rice) within 28 days before receiving the test drug.
* Any conditions which, in the opinion of the Investigator, would make the subject unsuitable for enrollment or could interfere with the subject's participation in or completion of the study.

Inclusion Criteria in MAD:

* Male and female subjects aged 18 to 65 years are included.
* Body mass index between 19 and 35 kg/m2, inclusive.
* Serum LDL-C ≥ 2.6mmol/L (≤ 100 mg/dL) and ≤ 4.9 mmol/L (≤ 190 mg/dL) at screening.
* Fasting triglyceride \< 4.52 mmol/L (\< 400 mg/dL) at screening.

Primary outcomes:
measure: Number of participants with adverse events (AEs)
timeFrame: 57 days
measure: Number of participants with abnormal laboratory tests results
timeFrame: 57 days
measure: Number of participants with adverse events (AEs)
timeFrame: 169 days
measure: Number of participants with abnormal laboratory tests results
timeFrame: 169 days
Secondary outcomes:
measure: Maximum observed plasma concentration (Cmax)
timeFrame: 48 hours
measure: Area under the concentration-time curve (AUC)
timeFrame: 48 hours
measure: LDL-C change from baseline
timeFrame: 180 days
measure: LDL-C change from baseline
timeFrame: 265 days
measure: PCSK9 change from baseline
timeFrame: 180 days
measure: PCSK9 change from baseline
timeFrame: 265 days
Other outcomes:
Locations:
Study officials:
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