Back to resultsA Safety, Efficacy and Pharmacokinetics Study of a Recombinant Fusion Protein Linking Coagulation Factor IX With Albumin (rIX-FP) in Children With Hemophilia B
Primary Purpose
Hemophilia B
Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
rIX-FP
Sponsored by
About this trial
This is an interventional treatment trial for Hemophilia B
Eligibility 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.
Sites / Locations
- The Royal Children's Hospital, Melbourne
- The Children's Hospital at Westmead
- AKH Wien (Paediatrics)
- McMaster Children's Hospital
- Fakultni nemocnice Brno
- Fakultni nemocnice Ostrava
- Fakultni nemocnice Motole
- C.R.T.H. Hopital de Bicentre (Hemophilie)
- Hospital Edouard Herriot
- Hôpital d'enfants La Timone
- CRC Coagulation Research Center GmbH
- Universitätsklinikum Düsseldorf
- Sheba Medical Center
- AOU Careggi
- IRCCS Ospendale Maggiore (Centro emofilia e Trombosi)
- FGU "Kirov Research Institute of Haemotology and Blood Trans)
- H.U. La Paz
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
rIX-FP
Arm Description
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.
Outcomes
Primary Outcome Measures
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.
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.
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.
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.
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.
Secondary Outcome Measures
Number of Subjects With Treatment-related Adverse Events
Number of Subjects Developing Antibodies Against rIX-FP
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
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
Consumption of rIX-FP during routine prophylaxis is expressed as the total prophylaxis dose per month.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01662531
Brief Title
A Safety, Efficacy and Pharmacokinetics Study of a Recombinant Fusion Protein Linking Coagulation Factor IX With Albumin (rIX-FP) in Children With Hemophilia B
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
Study Type
Interventional
2. Study Status
Record Verification Date
April 2016
Overall Recruitment Status
Completed
Study Start Date
January 2013 (undefined)
Primary Completion Date
October 2014 (Actual)
Study Completion Date
undefined (undefined)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
CSL Behring
4. Oversight
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hemophilia B
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
27 (Actual)
8. Arms, Groups, and Interventions
Arm Title
rIX-FP
Arm Type
Experimental
Arm Description
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.
Intervention Type
Biological
Intervention Name(s)
rIX-FP
Intervention Description
Recombinant Fusion Protein Linking Coagulation Factor IX with Albumin (rIX-FP)
Primary Outcome Measure Information:
Title
Incremental Recovery Following a Single Intravenous Dose of 50 IU/kg rIX-FP or Previous FIX Product
Description
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.
Time Frame
30 minutes after infusion
Title
Half-life (t1/2) Following a Single Intravenous Dose of 50 IU/kg rIX-FP or Previous FIX Product
Description
FIX activity was measured at a central laboratory using validated one-stage clotting method. FIX levels were not corrected for baseline values.
Time Frame
Pre-dose, 30 minutes, 3, 24, 48, 72 120, 168, 240 and 336 hours post-dose
Title
Area Under the Concentration Versus Time Curve From Time Point Zero to the Last Sample With Quantifiable Drug Concentration (AUClast)
Description
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.
Time Frame
Pre-dose, 30 minutes, 3, 24, 48, 72 120, 168, 240 and 336 hours post-dose
Title
Clearance for FIX Activity Following a Single Intravenous Dose of 50 IU/kg rIX-FP or Previous FIX Product
Description
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.
Time Frame
Pre-dose, 30 minutes, 3, 24, 48, 72 120, 168, 240 and 336 hours post-dose
Title
Number of Subjects Developing Inhibitors to Factor IX (FIX)
Description
Inhibitor formation was defined as any inhibitor (≥0.6 BU [Bethesda Units]/mL) identified and confirmed by retesting.
Time Frame
12 months
Secondary Outcome Measure Information:
Title
Number of Subjects With Treatment-related Adverse Events
Time Frame
12 months
Title
Number of Subjects Developing Antibodies Against rIX-FP
Description
Antibodies to rIX-FP were measured using a direct-binding enzyme-linked immunosorbent assay (ELISA).
Time Frame
12 months
Title
Number of Bleeding Episodes Requiring One, Two or More Than Two Infusions of rIX-FP to Achieve Hemostasis
Description
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
Time Frame
Approximately 12 months
Title
Consumption of rIX-FP During Routine Prophylaxis
Description
Consumption of rIX-FP during routine prophylaxis is expressed as the total prophylaxis dose per month.
Time Frame
12 months
10. Eligibility
Sex
Male
Maximum Age & Unit of Time
11 Years
Accepts Healthy Volunteers
No
Eligibility 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Program Director
Organizational Affiliation
CSL Behring
Official's Role
Study Director
Facility Information:
Facility Name
The Royal Children's Hospital, Melbourne
City
Parkville
State/Province
Victoria
ZIP/Postal Code
3052
Country
Australia
Facility Name
The Children's Hospital at Westmead
City
Westmead
ZIP/Postal Code
2145
Country
Australia
Facility Name
AKH Wien (Paediatrics)
City
Wien
Country
Austria
Facility Name
McMaster Children's Hospital
City
Hamilton
State/Province
Ontario
ZIP/Postal Code
L8N3Z5
Country
Canada
Facility Name
Fakultni nemocnice Brno
City
Brno
ZIP/Postal Code
625 00
Country
Czech Republic
Facility Name
Fakultni nemocnice Ostrava
City
Ostrava
ZIP/Postal Code
708 52
Country
Czech Republic
Facility Name
Fakultni nemocnice Motole
City
Praha 5
ZIP/Postal Code
150 06
Country
Czech Republic
Facility Name
C.R.T.H. Hopital de Bicentre (Hemophilie)
City
Le Kremlin-Bicentre
ZIP/Postal Code
94275
Country
France
Facility Name
Hospital Edouard Herriot
City
Lyon
ZIP/Postal Code
69437
Country
France
Facility Name
Hôpital d'enfants La Timone
City
Marseille
ZIP/Postal Code
13385
Country
France
Facility Name
CRC Coagulation Research Center GmbH
City
Duisburg/Altstadt
ZIP/Postal Code
47051
Country
Germany
Facility Name
Universitätsklinikum Düsseldorf
City
Düsseldorf
ZIP/Postal Code
40225
Country
Germany
Facility Name
Sheba Medical Center
City
Tel Hashomer
ZIP/Postal Code
52621
Country
Israel
Facility Name
AOU Careggi
City
Firenze
ZIP/Postal Code
50134
Country
Italy
Facility Name
IRCCS Ospendale Maggiore (Centro emofilia e Trombosi)
City
Milano
ZIP/Postal Code
20122
Country
Italy
Facility Name
FGU "Kirov Research Institute of Haemotology and Blood Trans)
City
Kirov
ZIP/Postal Code
610027
Country
Russian Federation
Facility Name
H.U. La Paz
City
Madrid
ZIP/Postal Code
28046
Country
Spain
12. IPD Sharing Statement
Citations:
PubMed Identifier
27583313
Citation
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.
Results Reference
derived
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A Safety, Efficacy and Pharmacokinetics Study of a Recombinant Fusion Protein Linking Coagulation Factor IX With Albumin (rIX-FP) in Children With Hemophilia B
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