IBI306 is a bio-innovative drug against proprotein convertase subtilisin 9 (PCSK-9)
monoclonal antibody. Currently, cholesterol-lowering drugs with multiple mechanisms of action
are on the market or under development. Among them, anti-PCSK-9 monoclonal antibodies have
received widespread attention due to their good safety and efficacy. The results of existing
preclinical studies show that IBI306 has a clear structure, good stability, and is not
inferior to other drugs of its kind in terms of drug activity, animal pharmacokinetics
(PK)/pharmacodynamics (PD) and safety.
This study is divided into two phases: the dose exploration phase (the first phase) and the
confirmatory phase (the second phase). Each stage is divided into screening period, treatment
period, and safety follow-up period. The first phase of this research is the randomized
design of open labels. The second stage is an open, single-arm design.
The main purpose of the first phase of the study: to evaluate the tolerability and safety of
multiple-dose repeated administration of IBI306 in the Chinese population with
hypercholesterolemia, and to recommend the dose for the second phase. The main purpose of the
second phase of the study: to evaluate the effectiveness of IBI306 in the Chinese homozygous
familial hypercholesterolemia population. Secondary research purpose: To evaluate the safety
and immunogenicity of IBI306 in Chinese homozygous familial hypercholesterolemia population.
- Provide a signed and dated informed consent form.
- Men or women aged 18 and 80 at the time of screening.
- Weight 40 kg at the time of screening.
- Meet at least one of genetic testing confirmation or clinical data to diagnose
homozygous familial hypercholesterolemia.
Clinical diagnosis basis: based on untreated LDL-C concentration> 13 mmol/L or after
treatment (defined as receiving moderate-strength or maximum tolerated dose of statin
for at least 4 weeks, with or without ezetimibe ) LDL-C concentration> 8mmol/L, and
xanthoma occurred before the age of 10 or both parents have a history of heterozygous
5. Maintain a low-fat diet and stably take the current lipid-lowering therapy (taking
moderate-strength statins, except for statin intolerance, with or without ezetimibe,
bile acid chelator, or niacin) for at least 4 weeks.
6. The fasting LDL cholesterol concentration of the local laboratory at the time of
screening was 3.4 mmol/L.
7. Fasting triglycerides 4.5 mmol/L during screening by the local laboratory.
8. The subjects indicated their willingness and cooperation to complete all the steps in
the research and the research intervention period.
- Dialysis or plasma exchange was performed within 8 weeks before screening.
- Patients who have received liver transplant surgery in the past.
- Have used Mipomethamine or Lometapide within 5 months before screening.
- Subjects should adjust their current lipid-lowering drug regimen or doses such as
statins within 4 weeks before screening (these subjects can stabilize the current dose
of lipid-lowering drugs such as statins and can be re-screened for 1 month).
- There are uncontrolled clinical diseases that may affect blood lipids or lipoprotein
levels (for patients with thyroid hormone replacement therapy, the thyroid hormone dose
needs to be stabilized for at least 6 weeks before the screening visit)
- New York Heart Association (NYHA) grade III or IV heart failure, or recently detected
left ventricular ejection fraction <30%.
- Uncontrolled severe arrhythmia, defined as recurrent and highly symptomatic ventricular
tachycardia, atrial fibrillation with rapid ventricular response or supraventricular
- Myocardial infarction, unstable angina, percutaneous coronary intervention, coronary
artery bypass grafting or stroke occurred within 3 months before enrollment.
- Plan to have heart surgery or revascularization within 20 weeks after screening.
- Poorly controlled hypertension is defined as a systolic blood pressure> 180 mmHg or a
diastolic blood pressure> 110 mmHg confirmed by repeated measurements.
- Moderate to severe renal insufficiency, defined as the estimated glomerular filtration
rate <30 ml/min/1.73m2 during the screening period, calculated using the MDRD formula:
eGFR =186 x SCr (mg/dl)-1.154x (age )-0.203x (0.742 [if female]), the unit conversion of
blood creatinine: 1mol/L=0.0113 mg/d.
- Active liver disease or liver function impairment is defined as the screening period
determined by local laboratory analysis, aspartate aminotransferase or alanine
aminotransferase> 3 times the upper limit of normal (ULN).
- Creatine kinase (CK) 5 times of ULN during screening, confirmed by repeated
measurements at least 1 week apart.
- As judged by the investigator, there is a known active infection or major blood, kidney,
metabolic, gastrointestinal or endocrine dysfunction.
- Diagnosed deep vein thrombosis or pulmonary embolism within 3 months before enrollment.
- Except for those who have been sterilized or menopausal, female subjects with potential
for pregnancy, if they are unwilling to inform their sexual partners to participate in
the clinical study, and take effective measures during the use of the study drug and
within 15 weeks after the last dose of the study drug Contraceptive measures. Male
subjects are unwilling to inform their female sexual partners that they participate in
the clinical study.
- Subjects who are pregnant or breastfeeding, or planning to become pregnant or
breastfeeding during the period of study medication or within 15 weeks after the last
dose of study medication.
- Suffered from malignant tumors in the past 5 years (except for non-melanoma skin cancer,
cervical carcinoma in situ, ductal carcinoma in situ of the breast or stage 1 prostate
- Human immunodeficiency virus (HIV) antibodies, hepatitis B surface antigen (HBsAg),
hepatitis C (HCV) antibodies or syphilis antibodies were positive at the time of
- The subject has been treated with a PCSK9 inhibitor or participated in other studies
that inhibit PCSK9.
- Known allergy to study drug and its ingredients.
- Those who are judged by the investigator to be unsuitable to participate in the study
(for example, alcohol or other drug abuse, inability or unwillingness to comply with the
agreement, or mental illness).
- Currently participating in another medical device or drug research, or the previous
medical device or drug clinical research has ended, but the last time to receive other
research drugs is within 30 days of screening.
- In any other circumstances, the investigator or the sponsor after discussing it may
impair the subject's ability or safety to give written informed consent and/or comply
with all necessary research procedures.