Gene therapy for Haemophilia B MedDRA version: 19.0 Level: LLT Classification code 10001140 Term: Adeno-associated in vivo gene therapy System Organ Class: 100000004865 MedDRA version: 19.0 Level: PT Classification code 10061992 Term: Haemophilia System Organ Class: 10010331 - Congenital, familial and genetic disorders
Conditions
Interventions
Product Name: scAAV2/8-LP1-hFIXco
Product Code: scAAV
Pharmaceutical Form: Infusion
Sponsors
St. Jude Children’s Research Hospital
Eligibility
Sex/Gender
Male
Inclusion criteria
Inclusion criteria: 1. Males = 18 years of age with established severe HB (FIX:C=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Evidence of active infection with Hepatitis B or C virus as reflected by HBsAg or HCV RNA positivity, respectively. To be considered negative for active infection, two negative assays at a minimum of a six month interval are required. 2. Exposure to Hepatitis B or C who are currently on antiviral therapy. 3. Serological evidence of HTLV or active HIV infection. Individuals who are effectively being treated with antiretroviral therapy are eligible. Specific criteria for effectiveness of treatment include the following: - Documented CD4+ T-cell count of > 350 cells/mm3. - HIV-1 RNA viral load 1) or 14. Received an AAV vector or any other gene transfer agent in the previous 6 months. 15. Presence of lung nodule(s) suspicious of malignancy on screening chest tomography 16. Presence of liver abnormalities suspicious of malignancy on screening liver ultrasound
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Primary Objective: To assess the safety of systemic administration of a novel self complementary AAV vector (scAAV2/8-LP1-hFIXco) in adults with severe hemophilia B at up to four different dose levels. We predict that systemic administration of scAAV2/8-LP1-hFIXco vector pseudotyped with AAV8 capsid protein and encoding the human FIX (hFIX) gene will be safe with absence of persistent Grade III or greater dose limiting toxicity. Any Grade I-II toxicity is likely to be dose dependent and reversible. To test this hypothesis we have developed a comprehensive clinical monitoring plan that will detect and document any adverse events following gene transfer. ;Secondary Objective: a. To estimate the dose of scAAV required to achieve stable expression of hFIX at or above 3% of normal (= 3u/dl) which would significantly ameliorate the severe bleeding phenotype. The kinetics, duration and magnitude of scAAV-mediated hFIX expression in individuals with hemophilia B will be evaluated and related to vector dose. b. To describe the immune responses to the hFIX transgene product and AAV capsid proteins following systemic administration of scAAV2/8-LP1-hFIXco. c. To assess viral shedding in various body fluids after systemic administration of scAAV2/8-LP1-hFIXco. ;Primary end point(s): The primary safety endpoint is the development of dose limiting toxicity including any Grade III-IV adverse events or any Grade II adverse events that persist for more than 7 days and are at least possibly related to the study agent, according to the modified symptom specific NCI toxicity scale in Appendix B which is derived from the NCI Common Terminology Criteria for Adverse Events, v3.0 ( http://ctep.cancer.gov/reporting/ctc_v30.html ). ;Timepoint(s) of evaluation of this end point: 12 months | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Efficacy, a secondary endpoint, will be defined as expression of biologically relevant levels of hFIX (> 3% = 3u/dl = 150ng/ml) in the peripheral blood.;Timepoint(s) of evaluation of this end point: 12 months | — |
Countries
United Kingdom, United States
Contacts
Public ContactUlrike Reiss
St. Jude Children’s Research Hospital
Outcome results
None listed