Application of PCSK9 Inhibitors in Patients With Heterozygous Familial Hypercholesterolemia

NCT04759534 | Unknown Phase 3

• 1 other identifier: LQY-PCSK9-heterozygous
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

This study plans to enroll several patients with heterozygous familial hypercholesterolemia, randomly assigned to different dose groups, and randomly receiving subcutaneous injection of IBI306150 mg or placebo every two weeks: or subcutaneous injection of IBI306 450mg every four weeks (n=49) or placebo (n=25) treatment, treatment lasted for 12 weeks. During randomization, the LDL-C level (\<4.8mmol/L or ≥4.8mmol/L) observed during the screening period visit (VI), and whether ezetimibe was used for stratification. After 12 weeks, each group entered the 12-week open-period treatment, in which subjects in the IBI306 group continued to receive IBI306 treatment, and subjects in the placebo group stopped using placebo and received IBI306 treatment. The exploratory endpoint is the population pharmacokinetic characteristics of IBI306 in Chinese heterozygous familial hypercholesterolemia population.

Conditions

Efficacy and Safety; Heterozygous Familial Hypercholesterolemia; PCSK9

Keywords

PCSK9 inhibitor; heterozygous familial hypercholesterolemia

Outcome Measures

Primary Outcomes (6)

• LDL-C

  Percentage decrease in LDL-C from baseline

  12 weeks after baseline

• LDL-C

  Percentage decrease in LDL-C from baseline

  24 weeks after baseline

• non HDL-C

  Percentage decrease in non HDL-C from baseline

  12 weeks after baseline

• non HDL-C

  Percentage decrease in non HDL-C from baseline

  24 weeks after baseline

• ApoB

  Percentage decrease in ApoB from baseline

  12 weeks after baseline

• ApoB

  Percentage decrease in ApoB from baseline

  24 weeks after baseline

Secondary Outcomes (2)

• safty

  12 weeks after baseline

• safty

  24 weeks after baseline

Study Arms (4)

Treatment group 1

EXPERIMENTAL

Received abdominal subcutaneous injection of IBI306 150 mg Q2W

Biological: protein convertase subtilisin/kexin type 9 inhibitor

Treatment group 2

EXPERIMENTAL

Received abdominal subcutaneous injection of IBI306 150 mg Q4W

Biological: protein convertase subtilisin/kexin type 9 inhibitor

Placebo Group 1

PLACEBO COMPARATOR

Received a subcutaneous injection of placebo Q2W in the abdomen

Biological: protein convertase subtilisin/kexin type 9 inhibitor

Placebo Group 2

PLACEBO COMPARATOR

Received a subcutaneous injection of placebo Q4W in the abdomen

Biological: protein convertase subtilisin/kexin type 9 inhibitor

Interventions

protein convertase subtilisin/kexin type 9 inhibitor BIOLOGICAL

IBI306 is a kind of protein convertase subtilisin/kexin type 9 inhibitor.Received abdominal subcutaneous injection of IBI306 150 mg Q2W or 300 mg Q4W

Placebo Group 1; Placebo Group 2; Treatment group 1; Treatment group 2

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Provide a signed and dated informed consent form.
• Men or women aged ≥18 and ≤80 at the time of screening.
• Body weight ≥ 40 kg at the time of screening.
• According to British Simon Broome (SBR) standards, HeFH is diagnosed or suspected:
• Diagnosis of HeFH: Total cholesterol\> 7.5 mmol/L, or LDL-C concentration\> 4.9 mmol/L, and at least one of the following two can be diagnosed: 1) The patient has tendon xanthoma, or his relatives (first-degree or At least one person at Level 2) has tendon xanthoma; 2) has evidence of LDL receptor, ApoB-100 or PCSK9 gene mutation; Suspected HeFH: Total cholesterol\> 7.5 mmol/L, or LDL-C concentration\> 4.9 mmol/L, and at least one of the following two is suspected HeFH: 1) Second-degree relatives before 50 years old or first-degree relatives 60 years old Previous history of myocardial infarction; 2) First-degree or second-degree adult relatives have a history of total cholesterol\>7.5mmol/L or children, brothers, sisters have a history of total cholesterol\>6.7mmol/L before the age of 16 or 16 years old.
• Maintain a low-fat diet and stably take the current lipid-lowering therapy (taking moderate-intensity or above statins, except for statin intolerance, with or without ezetimibe, niacin, and omega fatty acids) for at least 4 weeks. If you are taking fibrates, the fibrates are treated stably for at least 6 weeks.
• The fasting LDL cholesterol concentration of patients with a history of atherosclerotic cardiovascular disease at the time of screening was ≥1.8 mmol/L; the fasting LDL cholesterol concentration of patients without a history of atherosclerotic cardiovascular disease was ≥2.6 mmol/L.
• The subject indicated that they are willing and cooperate to complete all the steps in the study and the study intervention period.

You may not qualify if:

• Patients diagnosed as homozygous familial hypercholesterolemia.
• He had undergone dialysis or plasma exchange within 4 months before screening.
• Patients who have received liver transplant surgery in the past.
• Adjust the treatment plan or dose of statins, ezetimibe, niacin, and omega fatty acids within 4 weeks before the screening of subjects (these subjects can stabilize the current lipid-lowering drug dosage for 1 month, and then Re-filter).
• New York Heart Association (NYHA) grade III or IV heart failure, or recently detected left ventricular ejection fraction ≤ 30%.
• Poorly controlled severe arrhythmia, defined as recurrent and highly symptomatic ventricular tachycardia, atrial fibrillation with rapid ventricular rate or supraventricular tachycardia.
• Myocardial infarction, unstable angina, percutaneous coronary intervention, coronary artery bypass grafting or stroke occurred within 3 months before enrollment.
• Plan to perform percutaneous coronary intervention, coronary artery bypass grafting or other heart surgery during the study period.
• Type 1 diabetes or poor blood sugar control (HbA1c\>8.5%), or type 2 diabetes requiring multiple injections of insulin daily.
• There are uncontrolled clinical diseases that may affect blood lipids or lipoprotein levels (in patients with thyroid hormone replacement therapy, the thyroid hormone dose needs to be stable for at least 6 weeks before the screening visit). Poorly controlled hypothyroidism or hyperthyroidism is defined as TSH \<the lower limit of normal, or\> 1.5 times the upper limit of normal.
• Poorly controlled hypertension is defined as a sitting systolic blood pressure\> 180 mmHg or diastolic blood pressure\> 110 mmHg confirmed by repeated measurements.
• Moderate to severe renal insufficiency, defined as the estimated glomerular filtration rate \<30 ml / min / 1.73 m2 during the screening period.
• 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) ≥ 3 times of ULN during screening.
• As judged by the investigator, there is a known active infection or major blood, kidney, metabolic, gastrointestinal, or endocrine dysfunction.

Sponsors & Collaborators

• Shenzhen People's Hospital: lead
• Innovent Biopharmaceutical Co., Ltd.: collaborator

Study Sites (1)

xili People's Hospital

Shenzhen, Guangdong, 518020, China

Location

Study Officials

• dong shaohong, doctor

  Shenzhen People's Hospital

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: Central laboratory uses random number table to generate random sequence
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 10, 2021
• First Posted: February 18, 2021
• Study Start: September 10, 2020
• Primary Completion: October 30, 2021
• Study Completion: November 30, 2021
• Last Updated: August 25, 2021

Record last verified: 2021-08

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)