A Study to Evaluate SGB-3403 in Healthy Volunteers and Subjects With Elevated Low-Density Lipoprotein Cholesterol (LDL-C)

Hyperlipidemias Clinical Trial

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06239714
• Other study ID #: SGB-3403-001
• Status: Not yet recruiting
• Phase: Phase 1
• Start date: February 18, 2024
• Est. completion date: May 30, 2025

Study information

• Verified date: January 2024
• Source: Suzhou Sanegene Bio Inc.
• Contact: Xiaolin He, Master
• Phone: +086 18132286536
• Email: xiaolin_he[@]sanegenebio.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 64
• Est. completion date: May 30, 2025
• Est. primary completion date: February 18, 2025
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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.

Related Conditions & MeSH terms

• Hyperlipidemias

Intervention

Drug:
• SGB-3403
SGB-3403 is a synthetic, chemically modified small interfering ribonucleic acid (siRNA) targeting proprotein convertase subtilisin kexin type 9 (PCSK9) messenger ribonucleic acid (mRNA) with a covalently attached triantennary N-acetylgalactosamine (GalNAc) ligand.

Other:
• Atorvastatin
The dosage of atorvastatin was determined by the investigator
• Placebo
Normal saline 0.9%

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Suzhou Sanegene Bio Inc.

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of participants with adverse events (AEs)	To evaluate the safety and tolerability of SGB-3403 when administered subcutaneously as a single dose to healthy volunteers	57 days
Primary	Number of participants with abnormal laboratory tests results	To evaluate the safety and tolerability of SGB-3403 when administered subcutaneously as a single dose to healthy volunteers	57 days
Primary	Number of participants with adverse events (AEs)	To evaluate the safety and tolerability of SGB-3403 when administered subcutaneously in multiple-dose to subjects with elevated LDL-C	169 days
Primary	Number of participants with abnormal laboratory tests results	To evaluate the safety and tolerability of SGB-3403 when administered subcutaneously in multiple-dose to subjects with elevated LDL-C	169 days
Secondary	Maximum observed plasma concentration (Cmax)	To characterize the pharmacokinetics of SGB-3403 in healthy volunteers and subjects with elevated LDL-C	48 hours
Secondary	Area under the concentration-time curve (AUC)	To characterize the pharmacokinetics of SGB-3403 in healthy volunteers and subjects with elevated LDL-C	48 hours
Secondary	LDL-C change from baseline	To evaluate the pharmacodynamic effect of SGB-3403 on serum levels of LDL-C in healthy volunteers	180 days
Secondary	LDL-C change from baseline	To evaluate the pharmacodynamic effect of SGB-3403 on serum levels of LDL-C in subjects with elevated LDL-C	265 days
Secondary	PCSK9 change from baseline	To evaluate the pharmacodynamic effect of SGB-3403 on plasma levels of proprotein convertase subtilisin/kexin type 9 in healthy volunteers	180 days
Secondary	PCSK9 change from baseline	To evaluate the pharmacodynamic effect of SGB-3403 on plasma levels of proprotein convertase subtilisin/kexin type 9 in subjects with elevated LDL-C	265 days