A Safety and Efficacy Extension Study of a Recombinant Fusion Protein Linking Coagulation Factor IX With Albumin (rIX-FP) in Patients With Hemophilia B

A Phase 3b Open-label, Multicenter, Safety and Efficacy Extension Study of a Recombinant Coagulation Factor IX Albumin Fusion Protein (rIX-FP) in Subjects With Hemophilia B

This study will examine the long-term safety and efficacy of rIX-FP for the control and prevention of bleeding episodes in children and adults with severe hemophilia B. The study will include subjects who have not previously been treated with Factor IX products, subjects who previously completed a CSL-sponsored rIX-FP lead-in study and subjects requiring major non-emergency surgery who have not previously completed a CSL-sponsored rIX-FP lead-in study.

A surgical prophylaxis substudy will examine the efficacy of rIX-FP in subjects with hemophilia B who are undergoing non-emergency major or minor surgery. An additional substudy will examine the safety and PK of subcutaneous (SC) administration of rIX-FP.

Inclusion criteria:

Main study inclusion criteria:

For previously treated subjects, either:

• Completed a CSL-sponsored rIX-FP (CSL654) study, including study CSL654_3001 [NCT01496274] or study CSL654_3002 [NCT01662531].

Or:

• Scheduled to have a major non-emergency surgery within approximately 8 weeks from the anticipated date of receiving the first rIX-FP injection.
• Not previously completed a CSL-sponsored rIX-FP lead-in study.
• Male, 12 to 70 years of age.
• Documented severe hemophilia B (FIX activity of ≤ 2%), or confirmed at screening by the central laboratory.
• Subjects who have received FIX products (plasma-derived and / or recombinant FIX) for > 150 exposure days (EDs), confirmed by their treating physician.
• No confirmed history of FIX inhibitor formation at screening by the central laboratory

For previously untreated subjects:

• Male, up to 18 years of age.
• Documented severe hemophilia B (FIX activity of ≤ 2%), or confirmed at screening by the central laboratory.
• Never previously been treated with FIX clotting factor products (except previous exposure to blood components).
• No confirmed history of FIX inhibitor formation

Surgery substudy inclusion criterion:

• Must require non-emergency surgery

Subcutaneous substudy inclusion criteria:

• Male, at least 18 years of age.
• Subjects currently enrolled in Study CSL654_3003
• Subjects who have received rIX-FP for ≥ 100 EDs (single-dose cohorts) or for ≥ 50 EDs (repeated-dose cohort)

Exclusion criteria:

Main study exclusion criteria:

• Currently receiving a therapy not permitted during the study.
• Any issue that, in the opinion of the investigator, would render the subject unsuitable for participation in the study.

For subjects who have previously completed a CSL-sponsored rIX-FP study:

• Unwilling to participate in the study for a total of 100 exposure days.

For subjects requiring major non-emergency surgery who have not previously completed a CSL-sponsored rIX-FP lead-in study:

• Known hypersensitivity (ie, allergic reaction or anaphylaxis) to any FIX product or hamster protein.
• Known congenital or acquired coagulation disorder other than congenital FIX deficiency.
• Currently receiving IV immunomodulating agents such as immunoglobulin or chronic systemic corticosteroid treatment.
• Low platelet count, kidney or liver disease.
• Human immunodeficiency virus positive with a CD4 count < 200/mm3.

For previously untreated subjects:

• Known congenital or acquired coagulation disorder other than congenital FIX deficiency (except for vitamin K deficiency of the newborn).
• Known kidney or liver dysfunction or any condition which, in the investigator's opinion, place the patient at unjustifiable risk.

The surgical substudy does not have any additional exclusion criteria, although subject(s) in France will not be eligible for the surgery sub-study.

Subcutaneous substudy exclusion criteria:

• Intravenous use of rIX-FP within 14 days of subcutaneous administration of rIX-FP.
• Life-threatening bleeding episode or major surgery during the 3 months prior to substudy entry