a study to evaluate the efficacy and safety of factor ix gene therapy with pf-06838435 in adult males with moderately severe to severe hemophilia b

Conditions: Hemophilia B

Summary: this study will evaluate the efficacy and safety of pf-06838435 (a gene therapy drug) in adult male participants with moderately severe to severe hemophilia b (participants that have a factor ix circulating activity of 2% or less). the gene therapy is designed to introduce genetic material into cells to compensate for missing or non-functioning factor ix. eligible study participants will have completed a minimum 6 months of routine factor ix prophylaxis therapy during the lead in study (c0371004). participants will be dosed once (intravenously) and will be evaluated over the course of 6 years. the main objective of the study will evaluate the annualized bleeding rate \[abr\] for participants treated with gene therapy versus standard of care (soc) therapy (fix prophylaxis replacement regimen).


Eligibility criteria:
inclusion criteria * males who completed 6 months of factor ix prophylaxis therapy during the lead-in study (c0371004) prior to providing consent at the screening visit for this study. * documented moderately severe to severe hemophilia b (factor ix activity \< =2%) * previous experience with fix therapy (=\>50 documented exposure days to a fix protein product) * suspension of prophylaxis therapy for hemophilia b after administration of the study drug * laboratory values (hemoglobin, platelets and creatinine) within study specified limits * agree to contraception until components of the drug are eliminated from their body * capable of giving signed informed consent exclusion criteria * anti-aavrh74var neutralizing antibodies (nab) titer above the established threshold (ie, positive for nab). * history of inhibitor to factor ix or inhibitor detected during screening. clinical signs or symptoms of decreased response to factor ix * hypersensitivity to factor ix replacement product or iv immunoglobulin administration * history of chronic infection or other chronic disease * any conditions associated with increased thromboembolic risk * concurrent clinically significant major disease or condition unsuitable for participation and/or may interfere with the interpretation of study results * laboratory values at screening visit that are abnormal or outside acceptable study limits * current unstable liver or biliary disease * currently on antiviral therapy for hepatitis b or c * planned surgical procedure requiring factor ix surgical prophylactic factor treatment 15 months from screening visit * use of restricted therapies (e.g., blood products, acetylsalicylic acid \[aspirin\] or ibuprofen, other investigational therapy, and by-passing agents) * previously dosed in a gene therapy research trial at any time or in an interventional clinical study within 12 weeks of screening visit * active hepatitis b or c; hepatitis b surface antigen, hepatitis b virus deoxyribonucleic acid positivity, or hepatitis c virus ribonucleic acid positivity * significant liver disease * serological evidence of hiv1 or hiv2 infection with either cd4+ cell count \ 20 copies/ml * study and sponsor staff involved in the conduct of the study and their families * unable to comply with study procedures * sensitivity to heparin or heparin induced thrombocytopenia * sensitivity to any of the study interventions, or components thereof, or drug or other allergy

Keywords: pf 06838435 hemophilia hemophilia b factor ix fix gene therapy infusion raav spark100 hfix padua raav spark100-hfix-r338l r338l benegene 2 hematological diseases annualized bleeding rate (abr)