A Safety, Efficacy and Pharmacokinetics Study of a Recombinant Fusion Protein Linking Coagulation Factor IX With Albumin (rIX-FP) in Children With Hemophilia B
- Conditions
- Hemophilia B
- Interventions
- Biological: rIX-FP
- Registration Number
- NCT01662531
- Lead Sponsor
- CSL Behring
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- Male
- Target Recruitment
- 27
- 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.
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description rIX-FP rIX-FP 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.
- Primary Outcome Measures
Name Time Method Incremental Recovery Following a Single Intravenous Dose of 50 IU/kg rIX-FP or Previous FIX Product 30 minutes after infusion 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.
Number of Subjects Developing Inhibitors to Factor IX (FIX) 12 months Inhibitor formation was defined as any inhibitor (≥0.6 BU \[Bethesda Units\]/mL) identified and confirmed by retesting.
Half-life (t1/2) Following a Single Intravenous Dose of 50 IU/kg rIX-FP or Previous FIX Product Pre-dose, 30 minutes, 3, 24, 48, 72 120, 168, 240 and 336 hours post-dose FIX activity was measured at a central laboratory using validated one-stage clotting method. FIX levels were not corrected for baseline values.
Clearance for FIX Activity Following a Single Intravenous Dose of 50 IU/kg rIX-FP or Previous FIX Product Pre-dose, 30 minutes, 3, 24, 48, 72 120, 168, 240 and 336 hours post-dose 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.
Area Under the Concentration Versus Time Curve From Time Point Zero to the Last Sample With Quantifiable Drug Concentration (AUClast) Pre-dose, 30 minutes, 3, 24, 48, 72 120, 168, 240 and 336 hours post-dose 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.
- Secondary Outcome Measures
Name Time Method Number of Subjects With Treatment-related Adverse Events 12 months Number of Subjects Developing Antibodies Against rIX-FP 12 months Antibodies to rIX-FP were measured using a direct-binding enzyme-linked immunosorbent assay (ELISA).
Number of Bleeding Episodes Requiring One, Two or More Than Two Infusions of rIX-FP to Achieve Hemostasis Approximately 12 months 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
Consumption of rIX-FP During Routine Prophylaxis 12 months Consumption of rIX-FP during routine prophylaxis is expressed as the total prophylaxis dose per month.
Trial Locations
- Locations (17)
McMaster Children's Hospital
🇨🇦Hamilton, Ontario, Canada
Fakultni nemocnice Motole
🇨🇿Praha 5, Czech Republic
The Royal Children's Hospital, Melbourne
🇦🇺Parkville, Victoria, Australia
AKH Wien (Paediatrics)
🇦🇹Wien, Austria
C.R.T.H. Hopital de Bicentre (Hemophilie)
🇫🇷Le Kremlin-Bicentre, France
FGU "Kirov Research Institute of Haemotology and Blood Trans)
🇷🇺Kirov, Russian Federation
Sheba Medical Center
🇮🇱Tel Hashomer, Israel
The Children's Hospital at Westmead
🇦🇺Westmead, Australia
H.U. La Paz
🇪🇸Madrid, Spain
Hospital Edouard Herriot
🇫🇷Lyon, France
Fakultni nemocnice Brno
🇨🇿Brno, Czech Republic
CRC Coagulation Research Center GmbH
🇩🇪Duisburg/Altstadt, Germany
AOU Careggi
🇮🇹Firenze, Italy
Fakultni nemocnice Ostrava
🇨🇿Ostrava, Czech Republic
Hôpital d'enfants La Timone
🇫🇷Marseille, France
Universitätsklinikum Düsseldorf
🇩🇪Düsseldorf, Germany
IRCCS Ospendale Maggiore (Centro emofilia e Trombosi)
🇮🇹Milano, Italy