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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
CSL Behring
ClinicalTrials.gov Identifier:
NCT01662531
First received: August 7, 2012
Last updated: April 3, 2016
Last verified: April 2016
  Purpose
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.

Condition Intervention Phase
Hemophilia B
Biological: rIX-FP
Phase 3

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by CSL Behring:

Primary Outcome Measures:
  • Incremental Recovery Following a Single Intravenous Dose of 50 IU/kg rIX-FP or Previous FIX Product [ Time Frame: 30 minutes after infusion ] [ Designated as safety issue: No ]
    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.

  • Half-life (t1/2) Following a Single Intravenous Dose of 50 IU/kg rIX-FP or Previous FIX Product [ Time Frame: Pre-dose, 30 minutes, 3, 24, 48, 72 120, 168, 240 and 336 hours post-dose ] [ Designated as safety issue: No ]
    FIX activity was measured at a central laboratory using validated one-stage clotting method. FIX levels were not corrected for baseline values.

  • Area Under the Concentration Versus Time Curve From Time Point Zero to the Last Sample With Quantifiable Drug Concentration (AUClast) [ Time Frame: Pre-dose, 30 minutes, 3, 24, 48, 72 120, 168, 240 and 336 hours post-dose ] [ Designated as safety issue: No ]

    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.


  • Clearance for FIX Activity Following a Single Intravenous Dose of 50 IU/kg rIX-FP or Previous FIX Product [ Time Frame: Pre-dose, 30 minutes, 3, 24, 48, 72 120, 168, 240 and 336 hours post-dose ] [ Designated as safety issue: No ]
    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.

  • Number of Subjects Developing Inhibitors to Factor IX (FIX) [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
    Inhibitor formation was defined as any inhibitor (≥0.6 BU [Bethesda Units]/mL) identified and confirmed by retesting.


Secondary Outcome Measures:
  • Number of Subjects With Treatment-related Adverse Events [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
  • Number of Subjects Developing Antibodies Against rIX-FP [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: Approximately 12 months ] [ Designated as safety issue: No ]
    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 [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    Consumption of rIX-FP during routine prophylaxis is expressed as the total prophylaxis dose per month.


Enrollment: 27
Study Start Date: January 2013
Primary Completion Date: October 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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)

  Eligibility

Ages Eligible for Study:   up to 11 Years   (Child)
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01662531

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

Responsible Party: CSL Behring
ClinicalTrials.gov Identifier: NCT01662531     History of Changes
Other Study ID Numbers: CSL654_3002  2011-006032-23 
Study First Received: August 7, 2012
Results First Received: April 3, 2016
Last Updated: April 3, 2016
Health Authority: Australia: Department of Health and Ageing Therapeutic Goods Administration
Austria: Federal Office for Safety in Health Care
Canada: Health Canada
Czech Republic: State Institute for Drug Control
France: Agence Nationale de Sécurité du Médicament et des produits de santé
Germany: Paul-Ehrlich-Institut
Italy: The Italian Medicines Agency
Russia: Ministry of Health of the Russian Federation
Spain: Agencia Española de Medicamentos y Productos Sanitarios

Additional relevant MeSH terms:
Hemophilia A
Hemophilia B
Blood Coagulation Disorders, Inherited
Blood Coagulation Disorders
Hematologic Diseases
Coagulation Protein Disorders
Hemorrhagic Disorders
Genetic Diseases, Inborn
Genetic Diseases, X-Linked

ClinicalTrials.gov processed this record on July 28, 2016