A Gene Therapy Study for Hemophilia B

Gene Therapy, Open-label, Dose-escalation Study of PF-06838435 (SPK-9001) [Adeno-associated Viral Vector With Human Factor IX Gene] in Subjects With Hemophilia B

A Phase 1/2, Open-Label, Non-Randomized, Dose-Escalation Study of SPK-9001 in Subjects with Hemophilia B.

Hemophilia B, or Christmas disease, is a genetic bleeding disorder resulting in the lack of ability to produce blood-clotting factor IX (FIX). Individuals with hemophilia B suffer repeated bleeding events, which can cause chronic joint disease and sometimes leads to death due to the inability for blood to clot efficiently. This chronic joint disease can have significant physical, psychosocial, and quality-of-life effects, including financial burden. The current treatment is intravenous infusion of FIX protein products, either prophylactically or in response to bleeding.

The approach being tested in this study uses a novel recombinant adeno-associated virus (AAV), which in nature causes no disease, to deliver the human factor IX (hFIX) gene to the liver cells where FIX is normally made. Recent data of a gene therapy study showed preliminary encouraging results with the approach of using an AAV vector carrying the factor IX gene. This study will seek to determine the safety and kinetics of a single IV infusion of SPK-9001 (a novel AAV vector carrying a high specific activity factor IX variant).

Inclusion Criteria:

• Able to provide informed consent and comply with requirements of the study
• Males ≥18 y.o. with confirmed diagnosis of hemophilia B (≤2 IU/dL or ≤2% endogenous factor IX)
• Received ≥50 exposure days to factor IX products
• A minimum average of 4 bleeding events per year requiring episodic treatment of factor IX infusions or prophylactic factor IX infusions
• No measurable factor IX inhibitor as assessed by the central laboratory and have no prior history of inhibitors to factor IX protein
• Agree to use reliable barrier contraception until 3 consecutive samples are negative for vector sequences

Exclusion Criteria:

• Evidence of active hepatitis B or C
• Currently on antiviral therapy for hepatitis B or C
• Have significant underlying liver disease
• 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)
• Neutralizing antibodies reactive with AAV-Spark100 above and/or below a defined titre
• Participated in a gene transfer trial within the last 52 weeks or in a clinical trial with an investigational drug within the last 12 weeks
• Unable or unwilling to comply with study assessments