Hypercholesterolemia
Conditions
Brief summary
IBI306 is a fully human monoclonal antibody that binds proprotein convertase substilisin/kexin type 9 (PCSK-9), preventing its interaction with the low-density lipoprotein cholesterol receptor (LDL-R) and thereby restoring LDL-R recycling and low-density lipoprotein cholesterol（LDL-C）uptake. In phase I study IBI306 was shown to be safe and well tolerated. There was robust reduction in LDL-C, Apo(B), non-HDL-C and lipoprotein (a) in healthy subjects. This study is a randomized, double-blind, placebo-controlled, repeated-dosing, multiple ascending dose trial to evaluate the safety and tolerability of a novel PCSK-9 anti-body, IBI306, in Chinese patients with hypercholesterolemia.
Detailed description
A total of 60 patients who meet the criteria for admission and have a clinical diagnosis of hypercholesterolemia and have received statin for at least 4 weeks will be randomized and receive different dose groups of IBI306 or matching placebo. Ascending dose design includes 6 dose levels: 75 mg Q2W, 140 mgQ2W, 300 mg Q4W，420mg Q4W, 450 mg Q6W，and 600 mg Q6W. Total duration of the study per subject is 12 weeks.
Interventions
DRUGIBI306
Cohort 1: 75mg Q2W Cohort 2: 140mg Q2W Cohort 3: 300mg Q4W Cohort 4: 420mg Q4W Cohort 5: 450mg Q6W Cohort 6: 600mg Q6W
DRUGplacebo
Cohort 1: 75mg Q2W Cohort 2: 140mg Q2W Cohort 3: 300mg Q4W Cohort 4: 420mg Q4W Cohort 5: 450mg Q6W Cohort 6: 600mg Q6W
Sponsors
Innovent Biologics (Suzhou) Co. Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* Subjects must meet all of the following inclusion criteria in order to be included in the study: * Provide a signed and dated informed consent form; * Men or women with an age of 18 to 70 years of age at screening (Inclusive); * BMI between18kg/m2 and 30kg/m2(Inclusive); * Diagnosis of hyperlipidemia, and taking statins with moderate doses or above for at least 4 weeks; * Fasting LDL-C between 100 mg / dl (2.6 mmol / L) and 220 mg / dl (5.7 mmol / L) at screening (Inclusive); * Fasting triglycerides ≤ 400 mg (4.5 mmol / L) at screening.
Exclusion criteria
* Subjects who do not meet any of the following
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| AEs/SAEs | up to 12 weeks | • Percentage of participants with adverse events and severity of adverse events from the first dose to the last visit |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| half-life (T1/2) | up to 12 weeks | — |
| clearance (CL) | up to 12 weeks | — |
| accumulation factor (AR) | up to 12 weeks | — |
| Tmax | up to 12 weeks | — |
| Cmax | up to 12 weeks | — |
| area under curve (AUC) | up to 12 weeks | — |
| changes in blood PCSK-9 concentrations at different time points before and after administration relative to baseline | up to 12 weeks | — |
| ADA | up to 12 weeks | The occurrence of anti-IBI306 antibody (ADA) in serum before and after administration |
| NAb | up to 12 weeks | The occurrence of neutralizing antibody (NAb) in serum before and after administration |
| volume of distribution (Vd) | up to 12 weeks | — |
| Changes in LDL-C levels from baseline at 12 weeks | baseline and week 12 | — |
| Percent change in non-HDL-C cholesterol levels from baseline at 12 weeks | baseline and week 12 | — |
| Percent change in ApoB from baseline at 12 weeks | baseline and week 12 | — |
| Percent change in ApoB/ApoA1 ratio from baseline at 12 weeks | baseline and week 12 | — |
| Percent of patients with a 15% or more decrease in LDL-C levels from baseline at 12 weeks | baseline and week 12 | — |
| Percent change in Lp(a) from baseline at 12 weeks | baseline and week 12 | — |
| Percent change in mean LDL-C levels at week 6 and 12 relative to baseline | baseline, week 6 and 12 | — |
| Percent change in mean ApoB levels at week 6 and 12 relative to baseline | baseline, week 6 and 12 | — |
| Percent change in mean Lp(a) levels at week 6 and 12 relative to baseline | baseline, week 6 and 12 | — |
| Percent change in LDL-C from baseline at 12 weeks | baseline and week 12 | — |
Countries
China
Outcome results
None listed