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

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

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.

Study Overview

• Status: Completed
• Conditions: Hemophilia B
• Intervention / Treatment: Biological: Recombinant Coagulation Factor IX Albumin Fusion Protein

• Study Type: Interventional
• Enrollment (Actual): 17
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Bulgaria
  • Sofia, Bulgaria
    • Study Site
• Israel
  • Tel Aviv, Israel
    • Study Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years to 65 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: On-demand; The routine prophylactic therapy interval is targeted at every 7 days.	Biological: Recombinant Coagulation Factor IX Albumin Fusion Protein; 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.; Other Names: CSL654
Experimental: Prophylactic; On-demand subjects will receive rIX-FP only for the treatment of a bleeding episode.	Biological: Recombinant Coagulation Factor IX Albumin Fusion Protein; 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.; Other Names: CSL654

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: CSL Behring
• Investigators: Study Director: Iris Jacobs, MD, CSL Behring

Study record dates

Study Major Dates

• Study Start: July 1, 2011
• Primary Completion (Actual): June 1, 2012
• Study Completion (Actual): July 1, 2012

Study Registration Dates

• First Submitted: May 25, 2011
• First Submitted That Met QC Criteria: May 25, 2011
• First Posted (Estimate): May 26, 2011

Study Record Updates

• Last Update Posted (Estimate): May 9, 2016
• Last Update Submitted That Met QC Criteria: April 3, 2016
• Last Verified: April 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Hematologic Diseases; Blood Coagulation Disorders, Inherited; Coagulation Protein Disorders; Hemorrhagic Disorders; Genetic Diseases, Inborn; Genetic Diseases, X-Linked; Blood Coagulation Disorders; Hemophilia A; Hemophilia B
• Other Study ID Numbers: CSL654_2004; 2010-023793-39 (EudraCT Number)