Safety and Dose Finding Study of DTX101 (AAVrh10FIX) in Adults With Moderate/Severe to Severe Hemophilia B

Hemophilia B is an X-linked recessive genetic bleeding disorder caused by mutations in the
factor IX (FIX) gene. FIX is produced in the liver and is critical for fibrin clot formation.
Hemophilia B is characterized by frequent, spontaneous internal bleeding that can lead to
chronic arthropathy (joint damage), intracranial hemorrhage, and even death. In patients with
moderate/severe to severe hemophilia B, the majority of bleeding episodes occur in the joints
and, if not treated, lead to debilitating damage and a decreased quality of life.

This study will evaluate the safety and efficacy of the adeno-associated virus (AAV) to
deliver human factor IX (hFIX) gene, the healthy gene necessary to make FIX, to the liver
where FIX is normally produced. This study will determine if AAVrh10 can produce clinically
meaningful FIX levels in patients with moderately/severe or severe hemophilia B.

This study was previously posted by Dimension Therapeutics, which has been acquired by
Ultragenyx in November 2017.

Inclusion Criteria:

1. Male ≥ 18 years of age.

2. Moderate/severe or severe hemophilia B (baseline FIX activity ≤ 2% of normal or
documented history of FIX activity ≤2%).

3. At least 3 bleeding episodes per year that require on-demand treatment with FIX OR are
treated with a prophylactic regimen of FIX.

4. At least 100 days exposure history to FIX.

5. No documented history of inhibitors (neutralizing antibodies) to exogenous FIX.

6. No known allergic reaction to exogenous FIX or any component of DTX101.

7. Willing to stop prophylactic treatment with recombinant FIX at specified time points
during the study.

Exclusion Criteria:

1. History of significant liver disease (ie, portal hypertension).

2. Significant hepatic inflammation or cirrhosis.

3. Evidence of active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection.

4. History of human immunodeficiency virus (HIV) infection AND any of the following: CD4+
cell count < 350 cells/mm^3, change in antiretroviral therapy regimen within 6 months
prior to Day 0, or plasma viral load > 200 copies/mL, on 2 separate occasions, as
measured by polymerase chain reaction.

5. Anti-AAVrh10 neutralizing antibody titer > 1:5.

6. Participation (current or previous) in another gene therapy study.

7. Participation in another investigational medicine study within 3 months before
screening.

NOTE: Other protocol defined inclusion/exclusion criteria may apply.