A Safety and Efficacy Study of a Recombinant Factor IX in Patients With Severe Hemophilia B

Phase 1

Completed

Interventions: Biological: Recombinant Coagulation Factor IX Albumin Fusion Protein

Brief Summary: This study will examine the safety and efficacy of a Recombinant Coagulation Factor IX Albumin Fusion Protein (rIX-FP) for the control and prevention of bleeding episodes in subjects who have previously received factor replacement therapy for hemophilia B. The study consists of a screening period, a pharmacokinetic (PK) period, followed by approximately a 5 month treatment period. Subjects will receive weekly routine prophylactic therapy and on-demand treatment for bleeding episodes. In addition, subjects who are not on routine factor replacement therapy prior to the study will receive only on-demand treatment for bleeding episodes.

Recruitment & Eligibility

Inclusion Criteria

Male subjects, 12 to 65 years old
Severe hemophilia B (FIX activity of ≤ 2%)
Subjects who have received FIX products (plasma-derived and/or recombinant FIX) for > 150 exposure days (EDs)
No history of FIX inhibitor formation, no detectable inhibitors at Screening and no family history of inhibitors against FIX
Written informed consent for study participation obtained before undergoing any study specific procedures

Exclusion Criteria

Known hypersensitivity to any FIX product or hamster protein
Known congenital or acquired coagulation disorder other than congenital FIX deficiency
HIV positive subjects with a CD4 count < 200/mm3
Low platelet count, abnormal kidney function, or liver disease
On-demand subjects experiencing less than 12 or 6 non-trauma induced bleeding episodes requiring treatment with a FIX product during the previous 6 or 3 months, respectively
Planned major surgical intervention during the study period

Arm && Interventions

Group	Intervention	Description
Prophylactic	Recombinant Coagulation Factor IX Albumin Fusion Protein	On-demand subjects will receive rIX-FP only for the treatment of a bleeding episode.
On-demand	Recombinant Coagulation Factor IX Albumin Fusion Protein	The routine prophylactic therapy interval is targeted at every 7 days.

Primary Outcome Measures

Name	Time	Method
Number of Subjects Who Developed Antibodies to rIX-FP	Pre-dose, Day 10 and Weeks 4, 12, and 20	Antibodies against rIX-FP were detected using a direct binding enzyme-linked immunosorbent assay (ELISA).
Number of Subjects With Treatment-related Adverse Events	Approximately 20 weeks	The causal relationship of each adverse event to rIX-FP was assessed by the Investigator.
Number of Subjects With Inhibitors Against Factor IX (FIX)	Baseline, Day 10 and Weeks 4, 12 and 20	The presence of inhibitors against FIX was assessed by the central laboratory by a FIX potency assay. To quantify anti-FIX neutralizing antibodies, the Bethesda assay with the Nijmegen modification was used, and the results expressed as Bethesda Units per mL (BU/mL). A positive inhibitor test is \>=0.6 BU/mL.

Secondary Outcome Measures

Name	Time	Method
Area Under the Curve to the Last Sample With Quantifiable Drug Concentration (AUC0-t) After a Single Dose of rIX-FP	Pre-dose and up to 14 days after rIX-FP infusion.	The plasma concentrations of rIX-FP were measured as FIX activity using a validated, 1-stage assay in a central laboratory for a quantification range from 0.25 to 150% (or 0.25 IU/dL to 150 IU/dL). The PK population comprised all subjects who received at least 1 dose of rIX-FP and for whom a sufficient number of analyzable PK samples had been obtained in order to permit the evaluation of the PK profile of rIX-FP, and who did not receive a dose of rIX-FP or any other FIX product for the treatment of a bleed during the PK sampling period.
Clearance of a Single Dose of rIX-FP	Pre-dose and up to 14 days after rIX-FP infusion
Half-life (t1/2) of a Single Dose of rIX-FP	Pre-dose and up to 14 days after infusion
Incremental Recovery of rIX-FP at 30 Minutes Following Infusion of rIX-FP	30 minutes after infusion	Incremental recovery (IU/mL/IU/kg) is defined as FIX activity (IU/mL) obtained 30 minutes following infusion, per dose of (IU/kg) infusion. FIX activity was measured at a central laboratory using validated one-stage clotting method.
Breakthrough Bleeding Events	Week 9 to approximately Week 20	Number of breakthrough bleeding events (spontaneous bleeding events) requiring treatment per subject in subjects receiving prophylactic treatment regimen with rIX-FP