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

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

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.

Study Overview

• Status: Completed
• Conditions: Hemophilia B
• Intervention / Treatment: Biological: rIX-FP

• Study Type: Interventional
• Enrollment (Actual): 27
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • Westmead, Australia, 2145
    • The Children's Hospital at Westmead
  • Victoria
    • Parkville, Victoria, Australia, 3052
      • The Royal Children's Hospital, Melbourne
• Austria
  • Wien, Austria
    • AKH Wien (Paediatrics)
• Canada
  • Ontario
    • Hamilton, Ontario, Canada, L8N3Z5
      • McMaster Children's Hospital
• Czech Republic
  • Brno, Czech Republic, 625 00
    • Fakultni nemocnice Brno
  • Ostrava, Czech Republic, 708 52
    • Fakultni Nemocnice Ostrava
  • Praha 5, Czech Republic, 150 06
    • Fakultni nemocnice Motole
• France
  • Le Kremlin-Bicentre, France, 94275
    • C.R.T.H. Hopital de Bicentre (Hemophilie)
  • Lyon, France, 69437
    • Hospital Edouard Herriot
  • Marseille, France, 13385
    • Hopital d'Enfants la Timone
• Germany
  • Duisburg/Altstadt, Germany, 47051
    • CRC Coagulation Research Center GmbH
  • Düsseldorf, Germany, 40225
    • Universitätsklinikum Düsseldorf
• Israel
  • Tel Hashomer, Israel, 52621
    • Sheba Medical Center
• Italy
  • Firenze, Italy, 50134
    • AOU Careggi
  • Milano, Italy, 20122
    • IRCCS Ospendale Maggiore (Centro emofilia e Trombosi)
• Russian Federation
  • Kirov, Russian Federation, 610027
    • FGU "Kirov Research Institute of Haemotology and Blood Trans)
• Spain
  • Madrid, Spain, 28046
    • H.U. La Paz

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 11 years (CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: 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.	Biological: rIX-FP; Recombinant Fusion Protein Linking Coagulation Factor IX with Albumin (rIX-FP)

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

Collaborators and Investigators

• Sponsor: CSL Behring

Publications and helpful links

General Publications

• Kenet G, Chambost H, Male C, Lambert T, Halimeh S, Chernova T, Mancuso ME, Curtin J, Voigt C, Li Y, Jacobs I, Santagostino E; PROLONG-9FP Investigator Study Group. Long-acting recombinant fusion protein linking coagulation factor IX with albumin (rIX-FP) in children. Results of a phase 3 trial. Thromb Haemost. 2016 Sep 27;116(4):659-68. doi: 10.1160/TH16-03-0179. Epub 2016 Sep 1.

Study record dates

Study Major Dates

• Study Start: January 1, 2013
• Primary Completion (ACTUAL): October 1, 2014

Study Registration Dates

• First Submitted: August 7, 2012
• First Submitted That Met QC Criteria: August 7, 2012
• First Posted (ESTIMATE): August 10, 2012

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_3002; 2011-006032-23 (EUDRACT_NUMBER)