Multiple Ascending Dose Study of PCSK-9 Inhibitor (IBI306) in Chinese Patients With Hypercholesterolemia
Multiple Ascending Dose Study of PCSK-9 Inhibitor (IBI306) in Chinese Patients With Hypercholesterolemia
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.
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.
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 exclusion criteria cannot be included in
 the study:

 -  Subject's current statin treatment are stable less than 4 weeks prior to random
 enrollment

 -  New York Heart Association (NYHA) III or IV heart failure, or last left
 ventricular ejection fraction <30%

 -  Uncontrolled hypertension, defined as repeated measurements confirmed, sitting
 systolic blood pressure ≥ 180 mmHg or diastolic blood pressure ≥ 110 mmHg.

 -  Diabetic patients have one of the following conditions;

 1. Known microvascular and macrovascular complications

 2. HbA1c>7.5% within 4 weeks before screening

 -  Moderate or severe renal insufficiency, defined as the estimated glomerular
 filtration rate <60 ml / min / 1.73 m2 during screening (calculated using the
 MDRD formula)

 -  Active liver disease or impaired liver function, defined as aspartate
 aminotransferase (AST) or alanine aminotransferase (ALT) > 3 times the normal
 upper limit (ULN) at screening.

 -  Have previously undergone liver transplant surgery.

 -  Creatine kinase (CK) ≥ 3 times the upper limit of normal (ULN) at screening.

 -  At the discretion of the investigator, there are known active infections or major
 blood, kidney, metabolism, gastrointestinal or endocrine dysfunction.

 -  Female subject of childbearing potential not willing to use an acceptable
 method(s) of effective birth control during treatment with investigational
 product and for an additional 15 weeks after the end of treatment with
 investigational product. Male subjects are reluctant to inform their female
 sexual partners about their participation in the clinical study.

 -  Female subject is pregnant or breast feeding, planning to become pregnant or
 planning to breastfeed during treatment with investigational product and/or
 within 15 weeks after the end of treatment with investigational product..

 -  Subjects have been treated with PCSK9 inhibitors or have participated in other
 PCSK-9 inhibitor studies

 -  Subject has known sensitivity to the study drug and its excipients

 -  Any conditions which, in the opinion of the Investigator, would make the subject
 unsuitable for enrollment (for example, alcohol or other substance abuse, unable
 or unwilling to comply with the agreement or mental illness).

 -  Currently receiving treatment in another investigational device or drug study, or
 less than 30 days before randomization since ending treatment on another
 investigational device or drug study(s) while participating in this study

 -  In the opinion of the investigator, would pose a risk to subject safety or
 interfere with the study evaluation, procedures or completion.