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

Study Overview
=================
Brief Summary
-----------------
This study will examine the pharmacokinetics, safety and efficacy of rIX-FP for the control and prevention of bleeding episodes in children who have previously received factor replacement therapy for hemophilia B.

Official Title
-----------------
A Phase III Open-label, Multicenter, Pharmacokinetic, Safety and Efficacy Study of a Recombinant Fusion Protein Linking Coagulation Factor IX With Albumin (rIX-FP) in Previously Treated Children With Hemophilia B

Conditions
-----------------
Hemophilia B

Intervention / Treatment
-----------------
* Biological: rIX-FP


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Male subjects, younger than 12 years old. Severe hemophilia B (Factor IX [FIX] activity of ≤ 2%). Body weight ≥ 10 kg. Subjects who have received FIX products (plasma-derived and/or recombinant FIX) for > 150 exposure days (EDs) (6 to < 12 years), and > 50 EDs (< 6 years). 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. Exclusion Criteria: Known hypersensitivity to any FIX product or hamster protein. Known congenital or acquired coagulation disorder other than congenital FIX deficiency. Kidney or liver disease. Recent life-threatening bleeding episode.

Ages Eligible for Study
-----------------
Maximum Age: 11 Years

Sexes Eligible for Study
-----------------
Male

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: rIX-FP<br>Recombinant Fusion Protein Linking Coagulation Factor IX with Albumin (rIX-FP) will be administered by IV infusion as routine weekly prophylaxis and episodic treatment for bleeding episodes. | Biological: rIX-FP<br>* Recombinant Fusion Protein Linking Coagulation Factor IX with Albumin (rIX-FP)<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incremental Recovery Following a Single Intravenous Dose of 50 IU/kg rIX-FP or Previous FIX Product | Incremental recovery (IU/dL/IU/kg) is defined as the FIX activity (IU/dL) 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. Recovery values were baseline-corrected for pre-infusion plasma FIX activity. Incremental recovery was measured following a single intravenous dose of 50 IU/kg rIX-FP on Day 1. Analysis of previous FIX product was conducted at the beginning of the study in a subset of subjects who had no historical pharmacokinetic (PK) data of their previous FIX product. For the PK assessment, the previous FIX product was administered by IV infusion after approximately 4 days following the last FIX treatment, prior to any dosing of rIX-FP. The formal PK population consisted of subjects who received at least 1 dose of rIX-FP for PK assessment and for whom a sufficient number of analyzable PK samples had been obtained to permit the evaluation of the PK profile of rIX-FP. | 30 minutes after infusion | 
| Half-life (t1/2) Following a Single Intravenous Dose of 50 IU/kg rIX-FP or Previous FIX Product | FIX activity was measured at a central laboratory using validated one-stage clotting method. FIX levels were not corrected for baseline values. | Pre-dose, 30 minutes, 3, 24, 48, 72 120, 168, 240 and 336 hours post-dose | 
| Area Under the Concentration Versus Time Curve From Time Point Zero to the Last Sample With Quantifiable Drug Concentration (AUClast) | AUClast following a single intravenous dose of 50 IU/kg rIX-FP or previous FIX product. FIX activity was measured at a central laboratory using validated one-stage clotting method. FIX levels were not corrected for baseline values. | Pre-dose, 30 minutes, 3, 24, 48, 72 120, 168, 240 and 336 hours post-dose | 
| Clearance for FIX Activity Following a Single Intravenous Dose of 50 IU/kg rIX-FP or Previous FIX Product | FIX activity was measured at a central laboratory using validated one-stage clotting method. FIX levels were not corrected for baseline values. Clearance is normalized for body weight. | Pre-dose, 30 minutes, 3, 24, 48, 72 120, 168, 240 and 336 hours post-dose | 
| Number of Subjects Developing Inhibitors to Factor IX (FIX) | Inhibitor formation was defined as any inhibitor (≥0.6 BU [Bethesda Units]/mL) identified and confirmed by retesting. | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Subjects With Treatment-related Adverse Events |  | 12 months | 
| Number of Subjects Developing Antibodies Against rIX-FP | Antibodies to rIX-FP were measured using a direct-binding enzyme-linked immunosorbent assay (ELISA). | 12 months | 
| Number of Bleeding Episodes Requiring One, Two or More Than Two Infusions of rIX-FP to Achieve Hemostasis | For each bleeding episode that required treatment, the number of episodes that required one, two or more than two infusions of rIX-FP to achieve hemostasis | Approximately 12 months | 
| Consumption of rIX-FP During Routine Prophylaxis | Consumption of rIX-FP during routine prophylaxis is expressed as the total prophylaxis dose per month. | 12 months |