Study of Recombinant Factor IX Product, IB1001, in Subjects With Hemophilia B

Phase I/II/III Pharmacokinetic and Outcome Study of Recombinant Factor IX Product, IB1001, in Subjects With Hemophilia B

Primary Objective:

To evaluate the safety (acute effects associated with infusions, and inhibitor development), pharmacokinetics (PK), and efficacy with respect to breakthrough bleeding during prophylaxis and with respect to control of hemorrhaging in both the prophylaxis and on demand groups of IB1001 in subjects with hemophilia B.

Key Secondary Objectives:

To evaluate the ability of IB1001 to provide coverage against bleeding under surgical circumstances; To evaluate the long-term safety and efficacy of IB1001

Inclusion Criteria:

1. Patient must be willing to give written Institutional Review Board (IRB)/Independent Ethics Committee (IEC)-approved informed consent, make the required study visits, and follow instructions while enrolled in the study

2. Severe (factor IX activity ≤2 U/dL) hemophilia B subjects on demand therapy with a minimum of 3 bleeding episodes over the preceding 6 months or 6 bleeding episodes over the preceding 12 months; subjects on prophylaxis with a bleeding pattern as above demonstrated prior to starting prophylaxis

3. Immunocompetent (CD4 count >400/mm3) and not receiving immune modulating or chemotherapeutic agents

4. Previously treated patients with a minimum of 150 exposure days to a factor IX preparation

5. Platelet count at least 150,000/mm3

6. Liver function: alanine transaminase [ALT] and aspartate transaminase [AST] ≤2 times the upper limit of the normal range

7. Total bilirubin ≤1.5 times the upper limit of the normal range

8. Renal function: serum creatinine ≤1.25 times the upper limit of the normal range

9. Willingness to participate in the trial for up to 12-15 months

10. European Union (EU), Israel, and Canada: Age of at least 12 years and body weight of ≥40 kilograms to participate in any PK Study or the Surgical Sub-study [the Surgical Sub-study does not apply to the UK]; age of at least 12 years for the prophylaxis and on demand components of the Treatment Phase and Continuation Study

    United States (US): Age of at least 12 years and body weight of ≥40 kilograms to participate in any PK Study or the Surgical Sub-study; age of at least 5 years for the prophylaxis and on demand components of the Treatment Phase and Continuation Study

11. Hemoglobin ≥7 g/dL at the time of the blood draw

Exclusion Criteria:

1. History of factor IX inhibitor ≥0.6 Bethesda units (BU)
2. Existence of another coagulation disorder
3. Evidence of thrombotic disease, fibrinolysis, or disseminated intravascular coagulation (DIC)
4. Use of an investigational drug within 30 days prior to study entry
5. On medications that could impact hemostasis, such as aspirin
6. History of poor compliance, a serious medical or social condition, or any other circumstance that, in the opinion of the investigator, would interfere with participation or compliance with the study protocol
7. History of adverse reaction to either plasma-derived factor IX or recombinant factor IX that interfered with the subject's ability to treat bleeding episodes with a factor IX product