Back to resultsA Safety and Efficacy Study of a Recombinant Fusion Protein Linking Coagulation Factor IX With Albumin (rIX-FP) in Patients With Hemophilia B
Primary Purpose
Hemophilia B
Status
Completed
Phase
Phase 2
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, 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
- On-demand subjects only, who have experienced a minimum average of 2 non-trauma induced bleeding episodes requiring treatment with a FIX product during the previous 6 or 3 months
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, kidney or liver dysfunction
- Recent life-threatening bleeding episode
Sites / Locations
- Rush University Medical Center
- Indiana Hemophilia and Thrombosis Center, Inc.
- Hospital of the University of Pennsylvania
- BloodCenter of Wisconsin
- AKH Wien [Hämatologie, Hämostaseol
- SHAT "Joan Pavel" OOD [Hemorrhagic Diathesis and Anemia]
- Centre Hospitalier Universitaire de Brest/CHU Morvan
- C.R.T.H. Hôp. Bicêtre-Hémophilie
- CHU de Lyon - Hôpital Edouard Herriot [Hemophilie]
- Hôpital Necker-CRTH
- Instit. für Experimentelle - Hämato & Transfusionsmedizin
- Zentralkrankenhaus Prof. Hess-Kinderklinik
- Unikinderklinik Frankfurt/Main [Kinderheilkunde]
- Universitätsklinikum Hamburg-Eppendorf, Abt für Pädiatr. Hämatologie
- Werlhof-Inst. Hannover
- Chaim Sheba Medical Center
- IRCCS Ospedale Maggiore[Centro emofilia e Trombosi]
- A.O.U. di Parma [Centro di Rif. Reg. per la cura dell'Emofil
- Osp. S.Bortolo ULSS N.6 [Terapie Cell. ed Ematologia]
- Nara Medical University Hospital [PEDIATRICS]
- University of Occupational and Environmental Health
- Nagoya University Hospital
- The Hospital of Hyogo College of Medicine
- Ogikubo Hospital
- Tokyo Medical University Hospital
- St. Marianna University, School of Medicine, Yokohama Seibu
- FGU "Kirov Research Institute of Haemotology and Blood Trans
- C.H.U. A Coruña [Hematología]
- H.U.Vall d'Hebrón [Hemofillia]
- H.U. La Paz [Coagulopatias Congénitas]
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
Prophylaxis
On-demand
Arm Description
Routine weekly prophylaxis and episodic treatment for bleeding episodes. An individualized dosing interval may be tested in sub-group subjects during the 2nd part of the trial. Subjects may participate in a surgical 'sub-study' in which rIX-FP may be administered prior to, during and after surgical intervention.
Episodic treatment for bleeding episodes during the first 6 months then switch to routine weekly prophylaxis for a further 6 months Subjects may participate in a surgical 'sub-study' in which rIX-FP may be administered prior to, during and after surgical intervention.
Outcomes
Primary Outcome Measures
Change in Frequency of Spontaneous Bleeding Events Between On-demand and Prophylaxis Treatments (Annualized)
Subjects in the on-demand arm received on-demand dosing with rIX-FP for up to 26 weeks (on-demand regimen), and then received weekly prophylaxis with rIX-FP for the remainder of the study (prophylaxis regimen). The effectiveness of prophylaxis in comparison to on-demand therapy was investigated by comparing the same subject's annualized spontaneous bleeding rate (AsBR) during the on-demand regimen and during the prophylaxis regimen.
Number of Subjects Developing Inhibitors Against Factor IX (FIX)
The number of participants developing inhibitors against factor IX (FIX) along with the 95% Clopper-Pearson confidence interval, are summarized for subjects with 50 or more exposure days (EDs) to rIX-FP, and for all participants in the study.
Secondary Outcome Measures
The Frequency of Related Adverse Events
The percentage of participants experiencing treatment-related adverse-events (TEAEs).
Number of Subjects Developing Antibodies Against rIX-FP
Proportion of Bleeding Episodes Requiring One or ≤ Two Injections of rIX-FP to Achieve Hemostasis
Number of injections required to achieve hemostasis expressed as a percentage of the bleeding episodes requiring treatment.
Investigator's Overall Clinical Assessment of Hemostatic Efficacy for Treatment of Bleeding Episodes, Based on a Four Point Ordinal Scales (Excellent, Good, Moderate, Poor/No Response)
Number of bleeding episodes requiring treatment that resulted in hemostatic efficacy of excellent, good, moderate, poor/no response, according to the Investigator's clinical assessment of hemostatic efficacy, expressed as a percentage of the bleeding episodes requiring treatment.
rIX-FP Consumed Per Month While Maintaining Assigned Prophylactic Treatment Interval During Routine Prophylaxis.
Time frame: For Prophylaxis Arm 7-, 10- and 14-day regimens, median 269, 240 and 386 days respectively. For On-demand Arm, prophylaxis regimen, median 316 days.
Incremental Recovery of rIX-FP
Pharmacokinetic (PK) data are presented for a single 50 IU/kg dose of rIX-FP.
Half-life (t1/2) of a Single Dose of rIX-FP
PK data are presented for a single 50 IU/kg dose of rIX-FP.
Area Under the Curve (AUC)
AUC to the last sample with quantifiable drug concentration (AUClast) of a single dose of rIX-FP. PK data are presented for a single 50 IU/kg dose of rIX-FP.
Clearance of a Single Dose of rIX-FP
PK data are presented for a single 50 IU/kg dose of rIX-FP.
Investigator's (or Surgeon's) Overall Clinical Assessment of Hemostatic Efficacy for Surgical Prophylaxis, Based on a Four Point Ordinal Scale (Excellent, Good, Moderate, Poor/No Response)
Number of surgical events treated prophylactically with rIX-FP that resulted in hemostatic efficacy of excellent, good, moderate, poor/no response, according to the Investigator's (surgeon's) overall assessment of hemostatic efficacy for surgical prophylaxis.
Annualized Spontaneous Bleeding Events Compared Between 7 Day Prophylactic and Extended Regimens
Median number of spontaneous bleeds per year per subject comparing 7-, 10- and 14- day prophylactic regimens.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01496274
Brief Title
A Safety and Efficacy Study of a Recombinant Fusion Protein Linking Coagulation Factor IX With Albumin (rIX-FP) in Patients With Hemophilia B
Official Title
A Phase II/III Open-label, Multicenter, Safety and Efficacy Study of a Recombinant Coagulation Factor IX Albumin Fusion Protein (rIX-FP) in Subjects With Hemophilia B
Study Type
Interventional
2. Study Status
Record Verification Date
April 2016
Overall Recruitment Status
Completed
Study Start Date
February 2012 (undefined)
Primary Completion Date
July 2014 (Actual)
Study Completion Date
undefined (undefined)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
CSL Behring
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
This study will examine the safety, pharmacokinetics and efficacy of rIX-FP for the control and prevention of bleeding episodes in subjects 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 2, Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
63 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Prophylaxis
Arm Type
Experimental
Arm Description
Routine weekly prophylaxis and episodic treatment for bleeding episodes. An individualized dosing interval may be tested in sub-group subjects during the 2nd part of the trial.
Subjects may participate in a surgical 'sub-study' in which rIX-FP may be administered prior to, during and after surgical intervention.
Arm Title
On-demand
Arm Type
Experimental
Arm Description
Episodic treatment for bleeding episodes during the first 6 months then switch to routine weekly prophylaxis for a further 6 months Subjects may participate in a surgical 'sub-study' in which rIX-FP may be administered prior to, during and after surgical intervention.
Intervention Type
Biological
Intervention Name(s)
rIX-FP
Intervention Description
Recombinant IX-FP (rIX-FP) is a fusion protein linking coagulation factor IX with albumin, and will be administered by intravenous administration
Primary Outcome Measure Information:
Title
Change in Frequency of Spontaneous Bleeding Events Between On-demand and Prophylaxis Treatments (Annualized)
Description
Subjects in the on-demand arm received on-demand dosing with rIX-FP for up to 26 weeks (on-demand regimen), and then received weekly prophylaxis with rIX-FP for the remainder of the study (prophylaxis regimen). The effectiveness of prophylaxis in comparison to on-demand therapy was investigated by comparing the same subject's annualized spontaneous bleeding rate (AsBR) during the on-demand regimen and during the prophylaxis regimen.
Time Frame
Up to 26 weeks for on-demand regimen, and between 1 and 17 months for prophylaxis regimen.
Title
Number of Subjects Developing Inhibitors Against Factor IX (FIX)
Description
The number of participants developing inhibitors against factor IX (FIX) along with the 95% Clopper-Pearson confidence interval, are summarized for subjects with 50 or more exposure days (EDs) to rIX-FP, and for all participants in the study.
Time Frame
Up to 27.7 months (maximum)
Secondary Outcome Measure Information:
Title
The Frequency of Related Adverse Events
Description
The percentage of participants experiencing treatment-related adverse-events (TEAEs).
Time Frame
For the duration of the study; median 20.27 months.
Title
Number of Subjects Developing Antibodies Against rIX-FP
Time Frame
For the duration of the study; median 20.27 months.
Title
Proportion of Bleeding Episodes Requiring One or ≤ Two Injections of rIX-FP to Achieve Hemostasis
Description
Number of injections required to achieve hemostasis expressed as a percentage of the bleeding episodes requiring treatment.
Time Frame
For the duration of the study; median 20.27 months.
Title
Investigator's Overall Clinical Assessment of Hemostatic Efficacy for Treatment of Bleeding Episodes, Based on a Four Point Ordinal Scales (Excellent, Good, Moderate, Poor/No Response)
Description
Number of bleeding episodes requiring treatment that resulted in hemostatic efficacy of excellent, good, moderate, poor/no response, according to the Investigator's clinical assessment of hemostatic efficacy, expressed as a percentage of the bleeding episodes requiring treatment.
Time Frame
For the duration of the study; median 20.27 months
Title
rIX-FP Consumed Per Month While Maintaining Assigned Prophylactic Treatment Interval During Routine Prophylaxis.
Description
Time frame: For Prophylaxis Arm 7-, 10- and 14-day regimens, median 269, 240 and 386 days respectively. For On-demand Arm, prophylaxis regimen, median 316 days.
Time Frame
Median 269, 240, 386 and 316 days, respectively (see Description)
Title
Incremental Recovery of rIX-FP
Description
Pharmacokinetic (PK) data are presented for a single 50 IU/kg dose of rIX-FP.
Time Frame
336 hours
Title
Half-life (t1/2) of a Single Dose of rIX-FP
Description
PK data are presented for a single 50 IU/kg dose of rIX-FP.
Time Frame
336 hours
Title
Area Under the Curve (AUC)
Description
AUC to the last sample with quantifiable drug concentration (AUClast) of a single dose of rIX-FP. PK data are presented for a single 50 IU/kg dose of rIX-FP.
Time Frame
336 hours
Title
Clearance of a Single Dose of rIX-FP
Description
PK data are presented for a single 50 IU/kg dose of rIX-FP.
Time Frame
336 hours
Title
Investigator's (or Surgeon's) Overall Clinical Assessment of Hemostatic Efficacy for Surgical Prophylaxis, Based on a Four Point Ordinal Scale (Excellent, Good, Moderate, Poor/No Response)
Description
Number of surgical events treated prophylactically with rIX-FP that resulted in hemostatic efficacy of excellent, good, moderate, poor/no response, according to the Investigator's (surgeon's) overall assessment of hemostatic efficacy for surgical prophylaxis.
Time Frame
Up to 14 days after surgery
Title
Annualized Spontaneous Bleeding Events Compared Between 7 Day Prophylactic and Extended Regimens
Description
Median number of spontaneous bleeds per year per subject comparing 7-, 10- and 14- day prophylactic regimens.
Time Frame
During treatment, between median 240 and 386 days per subject.
10. Eligibility
Sex
Male
Minimum Age & Unit of Time
12 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
On-demand subjects only, who have experienced a minimum average of 2 non-trauma induced bleeding episodes requiring treatment with a FIX product during the previous 6 or 3 months
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, kidney or liver dysfunction
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
Rush University Medical Center
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60612
Country
United States
Facility Name
Indiana Hemophilia and Thrombosis Center, Inc.
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46260
Country
United States
Facility Name
Hospital of the University of Pennsylvania
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
Facility Name
BloodCenter of Wisconsin
City
Milwaukee
State/Province
Wisconsin
ZIP/Postal Code
53201
Country
United States
Facility Name
AKH Wien [Hämatologie, Hämostaseol
City
Wien
Country
Austria
Facility Name
SHAT "Joan Pavel" OOD [Hemorrhagic Diathesis and Anemia]
City
Sophia
ZIP/Postal Code
1233
Country
Bulgaria
Facility Name
Centre Hospitalier Universitaire de Brest/CHU Morvan
City
Brest
ZIP/Postal Code
29609
Country
France
Facility Name
C.R.T.H. Hôp. Bicêtre-Hémophilie
City
Le Kremlin-Bicêtre
ZIP/Postal Code
94275
Country
France
Facility Name
CHU de Lyon - Hôpital Edouard Herriot [Hemophilie]
City
Lyon
ZIP/Postal Code
03 69437
Country
France
Facility Name
Hôpital Necker-CRTH
City
Paris
ZIP/Postal Code
75015
Country
France
Facility Name
Instit. für Experimentelle - Hämato & Transfusionsmedizin
City
Bonn
Country
Germany
Facility Name
Zentralkrankenhaus Prof. Hess-Kinderklinik
City
Bremen
ZIP/Postal Code
28205
Country
Germany
Facility Name
Unikinderklinik Frankfurt/Main [Kinderheilkunde]
City
Frankfurt
Country
Germany
Facility Name
Universitätsklinikum Hamburg-Eppendorf, Abt für Pädiatr. Hämatologie
City
Hamburg
ZIP/Postal Code
20246
Country
Germany
Facility Name
Werlhof-Inst. Hannover
City
Hannover
Country
Germany
Facility Name
Chaim Sheba Medical Center
City
Tel Aviv
Country
Israel
Facility Name
IRCCS Ospedale Maggiore[Centro emofilia e Trombosi]
City
Milano
Country
Italy
Facility Name
A.O.U. di Parma [Centro di Rif. Reg. per la cura dell'Emofil
City
Parma
ZIP/Postal Code
43126
Country
Italy
Facility Name
Osp. S.Bortolo ULSS N.6 [Terapie Cell. ed Ematologia]
City
Vicenza
ZIP/Postal Code
36100
Country
Italy
Facility Name
Nara Medical University Hospital [PEDIATRICS]
City
Kashihara
ZIP/Postal Code
634-8522
Country
Japan
Facility Name
University of Occupational and Environmental Health
City
Kitakyushu
Country
Japan
Facility Name
Nagoya University Hospital
City
Nagoya
ZIP/Postal Code
466-8550
Country
Japan
Facility Name
The Hospital of Hyogo College of Medicine
City
Nishinomiya
Country
Japan
Facility Name
Ogikubo Hospital
City
Tokyo
ZIP/Postal Code
167-0035
Country
Japan
Facility Name
Tokyo Medical University Hospital
City
Tokyo
Country
Japan
Facility Name
St. Marianna University, School of Medicine, Yokohama Seibu
City
Yokohama
ZIP/Postal Code
241-0811
Country
Japan
Facility Name
FGU "Kirov Research Institute of Haemotology and Blood Trans
City
Kirov
ZIP/Postal Code
610027
Country
Russian Federation
Facility Name
C.H.U. A Coruña [Hematología]
City
A Coruna
Country
Spain
Facility Name
H.U.Vall d'Hebrón [Hemofillia]
City
Barcelona
Country
Spain
Facility Name
H.U. La Paz [Coagulopatias Congénitas]
City
Madrid
ZIP/Postal Code
28046
Country
Spain
12. IPD Sharing Statement
Citations:
PubMed Identifier
26755710
Citation
Santagostino E, Martinowitz U, Lissitchkov T, Pan-Petesch B, Hanabusa H, Oldenburg J, Boggio L, Negrier C, Pabinger I, von Depka Prondzinski M, Altisent C, Castaman G, Yamamoto K, Alvarez-Roman MT, Voigt C, Blackman N, Jacobs I; PROLONG-9FP Investigators Study Group. Long-acting recombinant coagulation factor IX albumin fusion protein (rIX-FP) in hemophilia B: results of a phase 3 trial. Blood. 2016 Apr 7;127(14):1761-9. doi: 10.1182/blood-2015-09-669234. Epub 2016 Jan 11.
Results Reference
derived
Learn more about this trial
A Safety and Efficacy Study of a Recombinant Fusion Protein Linking Coagulation Factor IX With Albumin (rIX-FP) in Patients With Hemophilia B
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