Clinical trial NCT01496274: 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
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Hemophilia B
Lead sponsor: CSL Behring
Sponsor class: INDUSTRY
First posted: 2011-12-21
Enrollment: 63
Sex: MALE
Minimum age (years): 12
Maximum age (years): 65
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Change in Frequency of Spontaneous Bleeding Events Between On-demand and Prophylaxis Treatments (Annualized)
timeFrame: Up to 26 weeks for on-demand regimen, and between 1 and 17 months for prophylaxis regimen.
measure: Number of Subjects Developing Inhibitors Against Factor IX (FIX)
timeFrame: Up to 27.7 months (maximum)
Secondary outcomes:
measure: The Frequency of Related Adverse Events
timeFrame: For the duration of the study; median 20.27 months.
measure: Number of Subjects Developing Antibodies Against rIX-FP
timeFrame: For the duration of the study; median 20.27 months.
measure: Proportion of Bleeding Episodes Requiring One or ≤ Two Injections of rIX-FP to Achieve Hemostasis
timeFrame: For the duration of the study; median 20.27 months.
measure: 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)
timeFrame: For the duration of the study; median 20.27 months
measure: rIX-FP Consumed Per Month While Maintaining Assigned Prophylactic Treatment Interval During Routine Prophylaxis.
timeFrame: Median 269, 240, 386 and 316 days, respectively (see Description)
measure: Incremental Recovery of rIX-FP
timeFrame: 336 hours
measure: Half-life (t1/2) of a Single Dose of rIX-FP
timeFrame: 336 hours
measure: Area Under the Curve (AUC)
timeFrame: 336 hours
measure: Clearance of a Single Dose of rIX-FP
timeFrame: 336 hours
measure: 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)
timeFrame: Up to 14 days after surgery
measure: Annualized Spontaneous Bleeding Events Compared Between 7 Day Prophylactic and Extended Regimens
timeFrame: During treatment, between median 240 and 386 days per subject.
Other outcomes:
Locations:
city: Chicago
country: United States
facility: Rush University Medical Center
state: Illinois
city: Indianapolis
country: United States
facility: Indiana Hemophilia and Thrombosis Center, Inc.
state: Indiana
city: Philadelphia
country: United States
facility: Hospital of the University of Pennsylvania
state: Pennsylvania
city: Milwaukee
country: United States
facility: BloodCenter of Wisconsin
state: Wisconsin
city: Wien
country: Austria
facility: AKH Wien [Hämatologie, Hämostaseol
city: Sophia
country: Bulgaria
facility: SHAT "Joan Pavel" OOD [Hemorrhagic Diathesis and Anemia]
city: Brest
country: France
facility: Centre Hospitalier Universitaire de Brest/CHU Morvan
city: Le Kremlin-Bicêtre
country: France
facility: C.R.T.H. Hôp. Bicêtre-Hémophilie
city: Lyon
country: France
facility: CHU de Lyon - Hôpital Edouard Herriot [Hemophilie]
city: Paris
country: France
facility: Hôpital Necker-CRTH
city: Bonn
country: Germany
facility: Instit. für Experimentelle - Hämato & Transfusionsmedizin
city: Bremen
country: Germany
facility: Zentralkrankenhaus Prof. Hess-Kinderklinik
city: Frankfurt
country: Germany
facility: Unikinderklinik Frankfurt/Main [Kinderheilkunde]
city: Hamburg
country: Germany
facility: Universitätsklinikum Hamburg-Eppendorf, Abt für Pädiatr. Hämatologie
city: Hannover
country: Germany
facility: Werlhof-Inst. Hannover
city: Tel Aviv
country: Israel
facility: Chaim Sheba Medical Center
city: Milano
country: Italy
facility: IRCCS Ospedale Maggiore[Centro emofilia e Trombosi]
city: Parma
country: Italy
facility: A.O.U. di Parma [Centro di Rif. Reg. per la cura dell'Emofil
city: Vicenza
country: Italy
facility: Osp. S.Bortolo ULSS N.6 [Terapie Cell. ed Ematologia]
city: Kashihara
country: Japan
facility: Nara Medical University Hospital [PEDIATRICS]
city: Kitakyushu
country: Japan
facility: University of Occupational and Environmental Health
city: Nagoya
country: Japan
facility: Nagoya University Hospital
city: Nishinomiya
country: Japan
facility: The Hospital of Hyogo College of Medicine
city: Tokyo
country: Japan
facility: Ogikubo Hospital
city: Tokyo
country: Japan
facility: Tokyo Medical University Hospital
city: Yokohama
country: Japan
facility: St. Marianna University, School of Medicine, Yokohama Seibu
city: Kirov
country: Russian Federation
facility: FGU "Kirov Research Institute of Haemotology and Blood Trans
city: A Coruna
country: Spain
facility: C.H.U. A Coruña [Hematología]
city: Barcelona
country: Spain
facility: H.U.Vall d'Hebrón [Hemofillia]
city: Madrid
country: Spain
facility: H.U. La Paz [Coagulopatias Congénitas]
Study officials:
affiliation: CSL Behring
name: Program Director
role: STUDY_DIRECTOR
References:
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.