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

CSL Behring17 enrolled

Overview

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 Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Hemophilia B

Interventions

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.

Eligibility

Sex: MALEMin age: 12 YearsMax age: 65 Years

Medical Language ↔ Plain English

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

Outcomes

Primary Outcomes

Number of Subjects With Treatment-related Adverse Events

The causal relationship of each adverse event to rIX-FP was assessed by the Investigator.

Time frame: 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.

Time frame: 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).

Time frame: Pre-dose, Day 10 and Weeks 4, 12, and 20

Secondary Outcomes

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.

Time frame: Pre-dose and up to 14 days after rIX-FP infusion.

Half-life (t1/2) of a Single Dose of rIX-FP

Time frame: 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.

Time frame: 30 minutes after infusion

Clearance of a Single Dose of rIX-FP

Time frame: 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

Time frame: Week 9 to approximately Week 20