Clinical Studies

Clinical Studies

1) AAV2-hFIX Summary The Center conducts a Phase 1/2 clinical study to evaluate the safety, tolerability and potential effectiveness of gene therapy vector AAV2-hFIX for the treatment of severe hemophilia B, a rare X-linked clotting disorder. The study is a continuation of an earlier study conducted by The Children’s Hospital of Philadelphia, University of Pittsburgh, Stanford University, State University of Campinas (Brazil), and Royal Prince Alfred Hospital (Australia) that enrolled seven adult males with the disease from August 2001 to February 2004. Important findings of the earlier study are summarized in Manno et al., Nature Medicine, 2006 and Mingozzi et al., Nature Medicine, 2007.

Immunomodulation has been added to the protocol in an effort to prevent the immune response
to AAV capsid protein that the investigators hypothesize resulted in the early clearance of
AAV-transduced hepatocytes observed in subjects included in the earlier protocol; the goal of blocking this response is to achieve sustained expression of FIX in circulation. The Center began enrolling adults with severe hemophilia B under the revised protocol in January 2009 and has observed safe delivery of AAV2-hFIX vector in the context of transient immunomodulation. The Center is also conducting long-term follow-up visits for the individuals enrolled in the earlier study. Please see for additional information.

2) AAV2-hRPE65v2 Summary The Center completed enrollment for a Phase 1/2 clinical study to evaluate the safety and potential effectiveness of gene therapy vector AAV2-hRPE65v2 for the treatment of Leber congenital amaurosis (LCA) Type 2, a very rare form of early onset blindness. Administration of the vector was safe with respect to ocular and systemic toxicity in individuals as young as eight years of age, at all doses tested. All participants reported improved vision, and showed objective evidence of visual function improvement, approximately two to four weeks after receiving the gene therapy vector; the clinical benefit observed has been sustained for more than three years in the initial participants, and for the duration of follow-up in all others. The study is among the first reports of sustained efficacy from in vivo gene delivery and was the first gene therapy clinical trial performed in pediatric population for a non-lethal disease. Important findings of the study are summarized in Maguire et al., New England Journal of Medicine, 2008, Maguire et al., Lancet, 2009; Simonelli et al., Molecular Therapy, 2010.

3) A follow-on study, to evaluate the safety and efficacy of administration to the previously uninjected eye of the Phase 1/2 study participants, was initiated in November 2010. The Center is also pursuing pivotal studies to convincingly demonstrate both efficacy and continued safety of the gene therapy vector AAV2-hRPE65v2 for potential product licensure. There has never been an approved product for an inherited retinal degeneration such as LCA, nor has a gene therapy product ever been approved in an ICH region, such the United States or the European Union. Please see (Phase 1/2 study), (Phase 1/2 follow-on study), and (planned Phase 3 study) for additional information.

You are here: Home Clinical Studies