This is a study to investigate if gene therapy is safe in people with homozygous familial hypercholesterolemia (also called HoFH).

Phase 1

• Conditions: Adults with homozygous familial hypercholesterolemia; Therapeutic area: Diseases [C] - Cardiovascular Diseases [C14]

• Registration Number: EUCTR2016-001446-25-NL
• Lead Sponsor: niversity of Pennsylvania

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2016-09-12
• Last Update Posted: 21 June 2021

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 12

Inclusion Criteria

1. Age: 18 years or older;
2. Molecularly defined LDLR mutations in both LDLR alleles and clinical
presentation consistent with HoFH;
3. No cardiovascular event or cardiovascular intervention within 12 weeks of
enrollment;
4. A baseline serum AAV8 neutralizing antibody titer = 1:10.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 12
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

1. Unwilling to wash out of the following lipid lowering therapies for the pre-specified time period:
niacin > 250 mg/day: within 4 weeks of baseline
fibrates: within 4 weeks of baseline
Lomitapide: within 6 weeks of baseline
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 surgery or 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. History of cirrhosis or chronic liver disease based on documented histological evaluation or non- invasive imaging or testing.
6. Documented diagnosis of any of the following liver diseases:
Nonalcoholic steatohepatitis (biopsy-proven)
Alcoholic liver disease
Autoimmune hepatitis
Liver cancer
Primary biliary cirrhosis
Primary sclerosing cholangitis
Wilson’s disease
Hemochromatosis
a1 anti-trypsin deficiency
7. Abnormal LFTs at screening (AST or ALT >2x upper limit of normal (ULN) and/or Total Bilirubin of
>1.5x ULN unless patient has unconjugated hyperbilirubinemia due to Gilbert’s syndrome).
8. Hepatitis B as defined by positive for HepB SAg, or Hep B Core Ab, and/or viral DNA
9. Chronic active Hepatitis C as defined by positive for HCV Ab and viral RNA.
10. History of alcohol abuse within 52 weeks.
11. Certain prohibited medications known to be potentially hepatotoxic, especially those that can induce microvesicular or macrovesicular steatosis. These include but are not limited to: acutane, amiodarone, HAART medications, heavy acetaminophen use (2g/day more than 3 times a week), isoniazid, methotrexate, tetracyclines, tamoxifen, valproate.
12. Current use of systemic corticosteroids or active tuberculosis, systemic fungal disease, or other chronic infection.
13. History of immunodeficiency diseases, including a positive HIV test result.
14. Chronic renal insufficiency defined as estimated GFR < 30 mL/min.
15. 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.
16. Previous organ transplantation.
17. 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 receiving AAV8.TBG.hLDLR.
18. 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.
19. Serious or unstable medical or psychological conditions that, in the opinion of the investigator, would compromise the subject’s safety or successful participation in the study.
20. A baseline serum AAV8 NAb titer > 1:10.
21. Any other medical condition or finding that would make it not in the subject’s best interest to participate in the study
22. Study staff member or any direct family member.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified