Lentiviral FIX Gene Therapy

Study Overview
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Brief Summary
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This study is a Phase I trial using an advanced lentiviral vector to deliver a functional gene for human clotting factor IX into patients with hemophilia B, to evaluate the safety and efficacy of infusion of lentiviral gene modified autologous stem cells in patients.

Detailed Description
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Hemophilia B is a genetic bleeding disorder caused by the lack of ability to produce blood-clotting factor IX (FIX). Individuals with hemophilia B suffer repeated bleeding episodes, which can cause chronic joint disease and sometimes even death due to the inability for blood to clot efficiently. The current treatment is intravenous infusion of clotting factor concentrates, either prophylactically or in response to bleeding. The procedure is life time long and expensive while still cannot achieve a cure.Gene therapy is a novel technology that has been successfully demonstrated in a number of clinical studies for diseases such as cancer and genetic diseases. In this study, an advanced lentiviral vector system NHP/TYF will be used to deliver a functional FIX gene to overcome human clotting FIX gene defect in patients with hemophilia B. This study is a Phase I trial evaluating the safety and efficacy for infusion of gene modified autologous stem cells in patients with hemophilia B.

Official Title
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Lentiviral FIX Gene Therapy for Hemophilia B

Conditions
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Hemophilia B

Intervention / Treatment
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* Biological: YUVA-GT-F901


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 1. Able to provide informed consent and comply with requirements of the study. 2. Males ≥2 years with confirmed diagnosis of hemophilia B (endogenous factor IX ≤2 IU/dL or ≤2% of normal). 3. A minimum average of 4 bleeding events per year requiring episodic treatment of factor IX infusions or prophylactic factor IX infusions. 4. No measurable factor IX inhibitor as assessed by the central laboratory and have no prior history of inhibitors to factor IX protein. 5. Agree to use reliable barrier contraception until 3 consecutive samples are negative for vector sequences. Exclusion Criteria: 1. Significant liver dysfunction as defined by abnormal alanine transaminase, bilirubin and alkaline phosphatase. 2. History of inhibitor against factor IX. 3. Evidence of active hepatitis B or C and currently on antiviral therapy. 4. Have serological evidence of HIV-1 or HIV-2 with CD4 counts ≤200/mm3 (subjects who are HIV+ and stable with CD4 count >200/mm3 and undetectable viral load are eligible to enroll). 5. Any evidence of active infection or any immunosuppressive disorder. 6. Participated in a gene transfer trial within the last 6 months or in a clinical trial with an investigational drug within the last 12 weeks. 7. Unable or unwilling to comply with study assessments.

Ages Eligible for Study
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Minimum Age: 2 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: YUVA-GT-F901<br>Gene transfer to treat Hemophilia B | Biological: YUVA-GT-F901<br>* Lentiviral factor IX gene modified autologous hematopoietic and mesenchymal stem cells<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants experiencing drug-related adverse events | As assessed by physical exam, vital signs, standard clinical labs, and Bethesda assay for FIX inhibitor | a year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes from baseline in circulating FIX activity (IU/dL or % normal) |  | a year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hemophilia B, factor IX, Gene therapylentiviral vector