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

Study Overview
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Brief Summary
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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.

Official Title
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A Phase I/II Open-label, Multicenter, Safety and Efficacy Study of a Recombinant Coagulation Factor IX Albumin Fusion Protein (rIX-FP) in Subjects With Hemophilia B

Conditions
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Hemophilia B

Intervention / Treatment
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* Biological: Recombinant Coagulation Factor IX Albumin Fusion Protein


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 12 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: On-demand<br>The routine prophylactic therapy interval is targeted at every 7 days. | Biological: Recombinant Coagulation Factor IX Albumin Fusion Protein<br>* Study subjects will receive a single dose of 25IU/kg of rIX_FP for pharmacokinetic analysis. Subjects will then be treated for approximately 5 months. The treatment dose will be based on the subject's PK profile and the subject's bleeding phenotype.<br>* Other names: CSL654;|
| Experimental: Prophylactic<br>On-demand subjects will receive rIX-FP only for the treatment of a bleeding episode. | Biological: Recombinant Coagulation Factor IX Albumin Fusion Protein<br>* Study subjects will receive a single dose of 25IU/kg of rIX_FP for pharmacokinetic analysis. Subjects will then be treated for approximately 5 months. The treatment dose will be based on the subject's PK profile and the subject's bleeding phenotype.<br>* Other names: CSL654;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Subjects With Treatment-related Adverse Events | The causal relationship of each adverse event to rIX-FP was assessed by the Investigator. | Approximately 20 weeks | 
| Number of Subjects With Inhibitors Against Factor IX (FIX) | 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. | Baseline, Day 10 and Weeks 4, 12 and 20 | 
| Number of Subjects Who Developed Antibodies to rIX-FP | Antibodies against rIX-FP were detected using a direct binding enzyme-linked immunosorbent assay (ELISA). | Pre-dose, Day 10 and Weeks 4, 12, and 20 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area Under the Curve to the Last Sample With Quantifiable Drug Concentration (AUC0-t) After a Single Dose of rIX-FP | 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. | 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 | 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. | 30 minutes after infusion | 
| Clearance of a Single Dose of rIX-FP |  | Pre-dose and up to 14 days after rIX-FP infusion | 
| Breakthrough Bleeding Events | Number of breakthrough bleeding events (spontaneous bleeding events) requiring treatment per subject in subjects receiving prophylactic treatment regimen with rIX-FP | Week 9 to approximately Week 20 |