Clinical Trial: Hemophilia B Gene Therapy With AAV8 Vector

Study Status: Terminated
Recruit Status: Terminated
Study Type: Interventional

Official Title: A Phase 1 Safety Study in Subjects With Severe Hemophilia B (Factor IX Deficiency) Using a Single-Stranded, Adeno-Associated Pseudotype 8 Vira

Brief Summary: Hemophilia B is a bleeding disease in males due to very low levels of coagulation factor IX (FIX) in the blood. The current treatment is intravenous injection of FIX clotting factor concentrates, in response to bleeding. This study will focus on the severe, most common type of hemophilia B. This study plans to use a virus called adeno-associated virus (AAV), which in nature causes no disease, and can be engineered to deliver the human FIX gene (AAV8-hFIX19 vector) to liver cells, where FIX is normally made. This study will use the AAV8-hFIX19 vector.

Detailed Summary:

Hemophilia B is a bleeding disease in males due to very low levels of coagulation factor IX (FIX) in the blood. The major effect on health is joint disease caused by repeated bleeds into joints like the knee, hip, ankles and elbows. Rarely, the disease causes death due to bleeding into the brain or other important organs. The current treatment is intravenous injection of FIX clotting factor concentrates, in response to bleeding. This study will focus on the severe, most common type of hemophilia B.

This study plans to use a virus called adeno-associated virus (AAV), which in nature causes no disease, and can be engineered to deliver the human FIX gene (AAV8-hFIX19 vector) to liver cells, where FIX is normally made. Medical researchers in the United States and England have recently used an AAV vector similar to the one planned for this study, and found that after a single intravenous injection of the vector, blood levels of FIX reached levels greater than 1%, high enough to change the course of disease from severe to moderate. This means that the need to take FIX clotting factor concentrates has decreased, or even stopped. While these are important results, it needs to be noted that two of the six subjects who received the vector at higher doses developed inflammation of the liver. These subjects were treated with a steroid medication called Prednisolone, which is commonly used for serious types of inflammation. Prednisolone seemed to decrease the liver inflammation, as measured by a decrease in blood levels of elevated liver enzymes, and stability of FIX levels at greater than 1% of normal.

This study will use the AAV8-hFIX19 vector. The vector will be injected once into a peripheral vein of each subject, while the subject is in the hospital. If everything is fine, the subject will be discharged from the hospital the next
Sponsor: Spark Therapeutics

Current Primary Outcome: Number of subjects with adverse events related to investigational product [ Time Frame: One year (with 15-year follow-up) ]

Physical exams; clinical labs, including evaluation of FIX inhibitor; and adverse event reporting.


Original Primary Outcome: Number of subjects with adverse events related to investigational product [ Time Frame: One year ]

Physical exams; clinical labs, including evaluation of FIX inhibitor; and adverse event reporting.


Current Secondary Outcome: Circulating plasma factor IX levels [ Time Frame: One year (with 15-year follow-up) ]

Factor IX activity and antigen; PT; and aPTT.


Original Secondary Outcome: Same as current

Information By: Spark Therapeutics

Dates:
Date Received: June 12, 2012
Date Started: October 2012
Date Completion:
Last Updated: May 10, 2017
Last Verified: May 2017