Hyperlipidemias
Conditions
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.
Interventions
DRUGSGB-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.
OTHERAtorvastatin
The dosage of atorvastatin was determined by the investigator
OTHERPlacebo
Normal saline 0.9%
Sponsors
Suzhou Sanegene Bio Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of participants with adverse events (AEs) | 57 days | To evaluate the safety and tolerability of SGB-3403 when administered subcutaneously as a single dose to healthy volunteers |
| Number of participants with abnormal laboratory tests results | 57 days | To evaluate the safety and tolerability of SGB-3403 when administered subcutaneously as a single dose to healthy volunteers |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Maximum observed plasma concentration (Cmax) | 48 hours | To characterize the pharmacokinetics of SGB-3403 in healthy volunteers and subjects with elevated LDL-C |
| Area under the concentration-time curve (AUC) | 48 hours | To characterize the pharmacokinetics of SGB-3403 in healthy volunteers and subjects with elevated LDL-C |
| LDL-C change from baseline | 180 days | To evaluate the pharmacodynamic effect of SGB-3403 on serum levels of LDL-C in healthy volunteers |
| PCSK9 change from baseline | 180 days | To evaluate the pharmacodynamic effect of SGB-3403 on plasma levels of proprotein convertase subtilisin/kexin type 9 in healthy volunteers |
Contacts
Primary ContactXiaolin He, Master
Backup ContactXuekun Yao, Master
Outcome results
None listed