NL-OMON47467已完成不适用
AAV8-mediated Low Density Lipoprotein Receptor (LDLR) Gene Replacement in Subjects with Homozygous Familial Hypercholesterolemia (HoFH) - AAV8.TBG.hLDLR for FH
适应症
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 2
研究概览
简要总结
暂无简介。
研究设计
- 研究类型
- Interventional
入排标准
- 年龄范围
- 18 至 99（—）
入选标准
- •1. Male or female * 18 years of age.
- •2. Untreated and/or treated LDL-C levels and clinical presentation consistent with the
- •diagnosis of homozygous FH
- •3. Molecularly defined LDLR mutations at both LDLR alleles.
- •4. Concurrent allowed lipid lowering medication must be stable for * 4 weeks before the
- •baseline visit and must remain stable until 18 weeks after vector administration (or 4 weeks
- •post steroid termination). These include but are not limited to: statins, ezetimibe, bile acid
- •sequestrants, PCSK9 inhibitors, and LDL and/or plasma apheresis. Subjects on other
- •lipid-lowering medications are eligible for the study but must wash out of these medications
- •for the pre-specified time period.
- •5. Females of childbearing potential must have a negative pregnancy test at screening and
- •baseline visits and be willing to have additional pregnancy tests during the study.
- •6. Sexually active subjects (both female and male) must be willing to use a medically accepted
- •method of contraception from screening visit until 6 months after vector administration
- •7. A baseline serum AAV8 NAb titer * 1:10.
排除标准
- •1. Unwilling to wash out of the following lipid lowering therapies for the pre-specified time
- •a. niacin > 250 mg/day: within 6 weeks of baseline
- •b. fibrates: within 4 weeks of baseline
- •c. lomitapide: within 8 weeks of baseline
- •d. mipomersen: within 24 weeks of baseline
- •2. Heart failure defined by the NYHA classification as functional Class III with history of
- •hospitalization(s) within 12 weeks of the baseline visit or functional Class IV.
- •3. History within 12 weeks of the baseline visit of a myocardial infarction (MI), unstable
- •angina leading to hospitalization, coronary artery bypass graft surgery (CABG),
- •percutaneous coronary intervention (PCI), uncontrolled cardiac arrhythmia, carotid surgeryor stenting, stroke, transient ischemic attack, carotid revascularization, endovascular
- •procedure or surgical intervention.
- •4. Uncontrolled hypertension defined as: systolic blood pressure > 180 mmHg, diastolic blood
- •pressure > 95 mmHg.
- •5. Uncontrolled diabetes defined as HbA1c > 8.5% or an average fasting glucose * 160 mg/dl.
- •6. Known hypersensitivity to prednisone
- •7. History of cirrhosis or chronic liver disease based on documented histological evaluation
- •or non-invasive imaging or testing.
- •8. Documented diagnosis of any of the following liver diseases:
- •a. Nonalcoholic steatohepatitis (biopsy-proven)
- •b. Alcoholic liver disease
- •c. Autoimmune hepatitis
- •d. Liver cancer
- •e. Primary biliary cirrhosis
- •f. Primary sclerosing cholangitis
- •g. Wilson*s disease
- •h. Hemochromatosis
- •i. *1 anti-trypsin deficiency
- •9. Abnormal liver function tests (LFTs) at screening (AST or ALT > 2 × upper limit of normal
- •(ULN) and/or Total Bilirubin of * 1.5 × ULN unless patient has unconjugated
- •hyperbilirubinemia due to Gilbert*s syndrome).
- •10. Hepatitis B as defined by positive for HepB SAg, or Hep B Core Ab, and/or viral DNA
- •11. Chronic active Hepatitis C as defined by positive for HCV Ab and viral RNA.
- •12. History of chronic alcohol abuse within 52 weeks of the screening visit.
- •13. Certain prohibited medications known to be potentially hepatotoxic, especially those that
- •can induce microvesicular or macrovesicular steatosis. These include but are not limited to:
- •Accutane (isotretinoin), amiodarone, HAART medications, heavy acetaminophen use
- •(2 g/day more than 3 times a week), isoniazid, methotrexate, tetracyclines, tamoxifen, or
- •14. Active tuberculosis, systemic fungal disease, or other chronic infection.
- •15. History of immunodeficiency diseases, including a positive HIV test result.
- •16. Chronic renal insufficiency defined as estimated GFR < 30 mL/min/1.73m2.
- •17. History of cancer within the past 5 years, except for adequately treated basal cell skin
- •cancer, squamous cell skin cancer, or in situ cervical cancer.
- •18. Previous organ transplantation.
- •19. Administration of an investigational drug within 12 weeks or 5 half-lives of the drug
- •(whichever is longer) prior to the screening visit and until 52 weeks after receivingAAV8.TBG.hLDLR. Subjects are not prohibited from receiving investigational drugs after
- •20. Any major surgical procedure occurring less than 3 months prior to the screening visit, or
- •any planned future surgical procedure within 3 months of baseline.
- •21. Serious or unstable medical or psychological conditions that, in the opinion of th
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