A Safety and Efficacy Study of a Recombinant Fusion Protein Linking Coagulation Factor IX With Albumin (rIX-FP) in Patients With Hemophilia B
- Conditions
- Hemophilia B
- Interventions
- Biological: rIX-FP
- Registration Number
- NCT01496274
- Lead Sponsor
- CSL Behring
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- Male
- Target Recruitment
- 63
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description On-demand rIX-FP 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. Prophylaxis rIX-FP 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.
- Primary Outcome Measures
Name Time Method Change in Frequency of Spontaneous Bleeding Events Between On-demand and Prophylaxis Treatments (Annualized) Up to 26 weeks for on-demand regimen, and between 1 and 17 months for prophylaxis regimen. 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) Up to 27.7 months (maximum) 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
Name Time Method Area Under the Curve (AUC) 336 hours 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 336 hours PK data are presented for a single 50 IU/kg dose of rIX-FP.
Annualized Spontaneous Bleeding Events Compared Between 7 Day Prophylactic and Extended Regimens During treatment, between median 240 and 386 days per subject. Median number of spontaneous bleeds per year per subject comparing 7-, 10- and 14- day prophylactic regimens.
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) For the duration of the study; median 20.27 months 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.
Incremental Recovery of rIX-FP 336 hours 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 336 hours 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) Up to 14 days after surgery 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.
Proportion of Bleeding Episodes Requiring One or ≤ Two Injections of rIX-FP to Achieve Hemostasis For the duration of the study; median 20.27 months. Number of injections required to achieve hemostasis expressed as a percentage of the bleeding episodes requiring treatment.
rIX-FP Consumed Per Month While Maintaining Assigned Prophylactic Treatment Interval During Routine Prophylaxis. Median 269, 240, 386 and 316 days, respectively (see 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.
The Frequency of Related Adverse Events For the duration of the study; median 20.27 months. The percentage of participants experiencing treatment-related adverse-events (TEAEs).
Number of Subjects Developing Antibodies Against rIX-FP For the duration of the study; median 20.27 months.
Trial Locations
- Locations (30)
Rush University Medical Center
🇺🇸Chicago, Illinois, United States
Hospital of the University of Pennsylvania
🇺🇸Philadelphia, Pennsylvania, United States
Indiana Hemophilia and Thrombosis Center, Inc.
🇺🇸Indianapolis, Indiana, United States
BloodCenter of Wisconsin
🇺🇸Milwaukee, Wisconsin, United States
AKH Wien [Hämatologie, Hämostaseol
🇦🇹Wien, Austria
Centre Hospitalier Universitaire de Brest/CHU Morvan
🇫🇷Brest, France
C.R.T.H. Hôp. Bicêtre-Hémophilie
🇫🇷Le Kremlin-Bicêtre, France
Instit. für Experimentelle - Hämato & Transfusionsmedizin
🇩🇪Bonn, Germany
CHU de Lyon - Hôpital Edouard Herriot [Hemophilie]
🇫🇷Lyon, France
Hôpital Necker-CRTH
🇫🇷Paris, France
H.U.Vall d'Hebrón [Hemofillia]
🇪🇸Barcelona, Spain
Zentralkrankenhaus Prof. Hess-Kinderklinik
🇩🇪Bremen, Germany
Unikinderklinik Frankfurt/Main [Kinderheilkunde]
🇩🇪Frankfurt, Germany
Chaim Sheba Medical Center
🇮🇱Tel Aviv, Israel
Universitätsklinikum Hamburg-Eppendorf, Abt für Pädiatr. Hämatologie
🇩🇪Hamburg, Germany
IRCCS Ospedale Maggiore[Centro emofilia e Trombosi]
🇮🇹Milano, Italy
Werlhof-Inst. Hannover
🇩🇪Hannover, Germany
A.O.U. di Parma [Centro di Rif. Reg. per la cura dell'Emofil
🇮🇹Parma, Italy
University of Occupational and Environmental Health
🇯🇵Kitakyushu, Japan
Nara Medical University Hospital [PEDIATRICS]
🇯🇵Kashihara, Japan
Nagoya University Hospital
🇯🇵Nagoya, Japan
The Hospital of Hyogo College of Medicine
🇯🇵Nishinomiya, Japan
Tokyo Medical University Hospital
🇯🇵Tokyo, Japan
St. Marianna University, School of Medicine, Yokohama Seibu
🇯🇵Yokohama, Japan
Ogikubo Hospital
🇯🇵Tokyo, Japan
C.H.U. A Coruña [Hematología]
🇪🇸A Coruna, Spain
H.U. La Paz [Coagulopatias Congénitas]
🇪🇸Madrid, Spain
Osp. S.Bortolo ULSS N.6 [Terapie Cell. ed Ematologia]
🇮🇹Vicenza, Italy
FGU "Kirov Research Institute of Haemotology and Blood Trans
🇷🇺Kirov, Russian Federation
SHAT "Joan Pavel" OOD [Hemorrhagic Diathesis and Anemia]
🇧🇬Sophia, Bulgaria