Evaluate the Efficacy and Safety of IBI306 in Subjects With Homozygous Familial Hypercholesterolemia

NCT04948008 | Unknown Phase 2

• 1 other identifier: LQY-PCSK9-Homozygous
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Familial Hypercholesterolemia - Homozygous; Lipid Metabolism Disorders; Proprotein Convertase Subtilisin/Kexin 9

Outcome Measures

Primary Outcomes (3)

• LDL-C

  Percentage decrease in LDL-C from baseline

  baseline,12 weeks and 24 weeks

• non HDL-C

  Percentage decrease in non HDL-C from baseline

  baseline,12 weeks and 24 weeks

• ApoB

  Percentage decrease in ApoB from baseline

  baseline,12 weeks and 24 weeks

Study Arms (2)

Treatment group 1

EXPERIMENTAL

The subjects received IBI306 150 mg Q2W subcutaneously injected into the abdomen each time for 12 weeks;

Biological: IBI306

Treatment group 2

EXPERIMENTAL

The subjects received IBI306 300 mg Q4W subcutaneously injected into the abdomen each time for 12 weeks;

Biological: IBI306

Interventions

IBI306 BIOLOGICAL

IBI306 is a kind of Proprotein convertase subtilisin/kexin 9

Treatment group 1; Treatment group 2

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• 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.
• 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 familial hypercholesterolemia.
• 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.
• The fasting LDL cholesterol concentration of the local laboratory at the time of screening was ≥3.4 mmol/L.
• Fasting triglycerides ≤4.5 mmol/L during screening by the local laboratory.
• The subjects indicated their willingness and cooperation to complete all the steps in the research and the research intervention period.

You may not qualify if:

• 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 tachycardia.
• 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: 1μmol/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.

Sponsors & Collaborators

• Shenzhen People's Hospital: lead

Study Sites (1)

xili People's Hospital

Shenzhen, Guangdong, 518020, China

RECRUITING

MeSH Terms

Conditions

Homozygous Familial Hypercholesterolemia; Lipid Metabolism Disorders

Condition Hierarchy (Ancestors)

Hyperlipoproteinemia Type II; Lipid Metabolism, Inborn Errors; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Hyperlipoproteinemias; Hyperlipidemias; Dyslipidemias; Metabolic Diseases; Nutritional and Metabolic Diseases

Study Officials

• dong shaohong, doctor

  Shenzhen People's Hospital

  STUDY CHAIR

Central Study Contacts

liu qiyun, master

CONTACT

13923810637; liuqiyun7@163.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: The first phase of this research is the randomized design of open labels. The second stage is an open, single-arm design.

Study Record Dates

• First Submitted: June 29, 2021
• First Posted: July 1, 2021
• Study Start: November 5, 2019
• Primary Completion: July 15, 2020
• Study Completion: December 31, 2022
• Last Updated: July 1, 2021

Record last verified: 2021-06

Locations

CN (1)