Healthy Volunteers, Hypercholesterolemia, LDL-Cholesterol
Conditions
Brief summary
This is a single-center, randomized, double-blind, placebo-controlled, single HST101 SC dose cohort study to evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics in Healthy Chinese Participants with Elevated LDL-C Levels.
Detailed description
The planned 30 study participants will be assigned to low- or high-dose 2 cohorts and 15 participants in each cohort will be randomized to either the HST101 group or the matching dose placebo group and will be administered in subsequent or in-parallel manner. Cohort 1: 15 study participants will receive the low dose of HST101 or placebo at a corresponding dose. Cohort 2: additional 15 study participants will receive the high dose of HST101 or placebo at a corresponding dose.
Interventions
DRUGHST101
HST101 is a novel anti-PCSK9 fusion protein
Sponsors
Hasten Biopharmaceutical Co., Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Intervention model description
the initially enrolled 15 subjects will receive low-dose single SC administration, followed by another 15 subjects will receive high-dose single SC administration.
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
* Men and women who are ≥18 and ≤55 years of age with elevated LDL-C Levels; * LDL-C ≥ 2.6 mmol/L (100 mg/dL) and ≤ 4.9 mmol/L (190 mg/dL) and TG ≤ 2.83 mmol/L (250 mg/dL) who are not on a lipid-lowering therapy 30 days prior to screening; * Body mass index (BMI) ≥18 and≤28 kg/m2
Exclusion criteria
* Positive blood screen for HIV antibody, Treponema pallidum antibody, HBsAg or HCV antibody; * Clinically significant liver function test abnormalities at screening, such as AST or ALT \> 2 × ULN, total bilirubin \> 1.5 × ULN, or ALP \> 2 × ULN based on normal values; * CK \> 3 × ULN at the screening visit, it can be retested if considered to be related to exercise; * History of prescription drug abuse, illicit drug use or alcohol abuse; * Use of any prescription drug, herbal and compound decoction, vitamins, minerals, and OTC drugs and nutritional supplements that alter lipid metabolism within 14 days prior to Check-in and planned use of the above drugs throughout the study; * Prior treatment with PCSK9 inhibitors, including mAbs, siRNA products, or any Adnectin products; * History of allergy to protein-based biologics including, but not limited to, mAbs and vaccine; * Less than 30 days or less than 5 half-lives (drug) since the end of participation in another clinical trial (drug or device), whichever is longer; * Use of any other biologics within 3 months prior to investigational product administration; * Any other significant clinical diseases or psychological diseases that the investigator considers to be inappropriate for participation in this study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The primary objective of this study is to assess the safety and tolerability of a single SC dose of HST101 in Chinese healthy adult study participants with elevated LDL-C level(International Standard Unit: mmol/L) | 57 days | Safety and tolerability will be assessed by the incidence and severity of treatment emergent adverse events |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| To assess the PD effect of a single SC dose of HST101 on serum unbound (free) PCSK9 concentrations and serum LDL-C concentrations | 57 days | Serum free PCSK9 and LDL-C will be measured at baseline and various time points over 57 days |
| To assess the effect of a single SC dose of HST101 on blood lipids including TC, HDL-C, VLDL-C, and TG | 57 days | Serum TC,HDL-C,VLDL-C and TG（ISU:mmol/L）will be measured at baseline and various time points over 57 days to assess percent change from baseline over time |
| To assess the effect of a single SC dose of HST101 on serum ApoB, Apo A1 concentrations | 57 days | Serum Apo B(ISU:mg/dL) , Apo A1(ISU:mg/dL) concentrations will be measured at baseline and various time points over 57 days to assess percent change from baseline over time |
| To assess the pharmacokinetic characteristics and dose proportionality relathionship of HST101 following a single SC dose | 57 days | The PK parameters include Cmax, Tmax, T1/2, AUC0-t, AUCinf and others if necessary |
| To assess the PK-PD relationship following a single SC dose of HST101 | 57 days | The PK-PD relationship will be measured over 57 days |
| To assess immunogenicity (incidence, titer, and duration of ADAs/NAbs) following a single SC dose of HST101 | 57 days | Measurement of ADAs/NAbs will be done at baseline and various intervals after HST101 administration |
| To assess the effect of a single SC dose of HST101 on serum Lp(a) concentrations | 57 days | Serum Lp (a)(ISU: nmol/L) concentrations will be measured at baseline and various time points over 57 days to assess percent change from baseline over time |
Countries
China
Outcome results
None listed