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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Experimental: cohort low dose HST101 | Experimental | HST101 single SC administration of 150 mg or placebo; |
|
| Experimental: cohort high dose HST101 | Experimental | HST101 single SC administration of 300 mg or placebo. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| HST101 | Drug | HST101 is a novel anti-PCSK9 fusion protein |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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) | Safety and tolerability will be assessed by the incidence and severity of treatment emergent adverse events | 57 days |
| Measure | Description | Time Frame |
|---|---|---|
| To assess the pharmacokinetic characteristics and dose proportionality relathionship of HST101 following a single SC dose | The PK parameters include Cmax, Tmax, T1/2, AUC0-t, AUCinf and others if necessary | 57 days |
| To assess the PD effect of a single SC dose of HST101 on serum unbound (free) PCSK9 concentrations and serum LDL-C concentrations |
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Inclusion Criteria:
Exclusion Criteria:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| West China Hospital of Sichuan University | Chengdu | Sichuan | 610044 | China |
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| ID | Term |
|---|---|
| D006937 | Hypercholesterolemia |
| ID | Term |
|---|---|
| D006949 | Hyperlipidemias |
| D050171 | Dyslipidemias |
| D052439 | Lipid Metabolism Disorders |
| D008659 | Metabolic Diseases |
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the initially enrolled 15 subjects will receive low-dose single SC administration, followed by another 15 subjects will receive high-dose single SC administration.
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Serum free PCSK9 and LDL-C will be measured at baseline and various time points over 57 days |
| 57 days |
| To assess the effect of a single SC dose of HST101 on blood lipids including TC, HDL-C, VLDL-C, and TG | 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 | 57 days |
| To assess the effect of a single SC dose of HST101 on serum ApoB, Apo A1 concentrations | 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 | 57 days |
| To assess the effect of a single SC dose of HST101 on serum Lp(a) concentrations | 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 | 57 days |
| To assess the PK-PD relationship following a single SC dose of HST101 | The PK-PD relationship will be measured over 57 days | 57 days |
| To assess immunogenicity (incidence, titer, and duration of ADAs/NAbs) following a single SC dose of HST101 | Measurement of ADAs/NAbs will be done at baseline and various intervals after HST101 administration | 57 days |
| D009750 |
| Nutritional and Metabolic Diseases |