Clinical trial NCT02053792: A Safety and Efficacy Extension Study of a Recombinant Fusion Protein Linking Coagulation Factor IX With Albumin (rIX-FP) in Patients With Hemophilia B
Official title: A Phase 3b Open-label, Multicenter, Safety and Efficacy Extension Study of a Recombinant Coagulation Factor IX Albumin Fusion Protein (rIX-FP) in Subjects With Hemophilia B
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Hemophilia B
Lead sponsor: CSL Behring
Sponsor class: INDUSTRY
First posted: 2014-02-04
Enrollment: 97
Sex: MALE
Maximum age (years): 70
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This study will examine the long-term safety and efficacy of rIX-FP for the control and prevention of bleeding episodes in children and adults with severe hemophilia B. The study will include subjects who have not previously been treated with Factor IX products, subjects who previously completed a CSL-sponsored rIX-FP lead-in study and subjects requiring major non-emergency surgery who have not previously completed a CSL-sponsored rIX-FP lead-in study.

A surgical prophylaxis substudy will examine the efficacy of rIX-FP in subjects with hemophilia B who are undergoing non-emergency major or minor surgery. An additional substudy will examine the safety and PK of subcutaneous (SC) administration of rIX-FP.


Eligibility criteria: Inclusion criteria:

Main study inclusion criteria:

For previously treated subjects, either:

* Completed a CSL-sponsored rIX-FP (CSL654) study, including study CSL654_3001 \[NCT01496274\] or study CSL654_3002 \[NCT01662531\].

Or:

* Scheduled to have a major non-emergency surgery within approximately 8 weeks from the anticipated date of receiving the first rIX-FP injection.
* Not previously completed a CSL-sponsored rIX-FP lead-in study.
* Male, 12 to 70 years of age.
* Documented severe hemophilia B (FIX activity of ≤ 2%), or confirmed at screening by the central laboratory.
* Subjects who have received FIX products (plasma-derived and / or recombinant FIX) for \> 150 exposure days (EDs), confirmed by their treating physician.
* No confirmed history of FIX inhibitor formation at screening by the central laboratory

For previously untreated subjects:

* Male, up to 18 years of age.
* Documented severe hemophilia B (FIX activity of ≤ 2%), or confirmed at screening by the central laboratory.
* Never previously been treated with FIX clotting factor products (except previous exposure to blood components).
* No confirmed history of FIX inhibitor formation

Surgery substudy inclusion criterion:

* Must require non-emergency surgery

Subcutaneous substudy inclusion criteria:

* Male, at least 18 years of age.
* Subjects currently enrolled in Study CSL654_3003
* Subjects who have received rIX-FP for ≥ 100 EDs (single-dose cohorts) or for ≥ 50 EDs (repeated-dose cohort)

Exclusion criteria:

Main study exclusion criteria:

* Currently receiving a therapy not permitted during the study.
* Any issue that, in the opinion of the investigator, would render the subject unsuitable for participation in the study.

For subjects who have previously completed a CSL-sponsored rIX-FP study:

* Unwilling to participate in the study for a total of 100 exposure days.

For subjects requiring major non-emergency surgery who have not previously completed a CSL-sponsored rIX-FP lead-in study:

* Known hypersensitivity (ie, allergic reaction or anaphylaxis) to any FIX product or hamster protein.
* Known congenital or acquired coagulation disorder other than congenital FIX deficiency.
* Currently receiving IV immunomodulating agents such as immunoglobulin or chronic systemic corticosteroid treatment.
* Low platelet count, kidney or liver disease.
* Human immunodeficiency virus positive with a CD4 count \< 200/mm3.

For previously untreated subjects:

* Known congenital or acquired coagulation disorder other than congenital FIX deficiency (except for vitamin K deficiency of the newborn).
* Known kidney or liver dysfunction or any condition which, in the investigator's opinion, place the patient at unjustifiable risk.

The surgical substudy does not have any additional exclusion criteria, although subject(s) in France will not be eligible for the surgery sub-study.

Subcutaneous substudy exclusion criteria:

* Intravenous use of rIX-FP within 14 days of subcutaneous administration of rIX-FP.
* Life-threatening bleeding episode or major surgery during the 3 months prior to substudy entry

Primary outcomes:
measure: Total Number of Participants Who Developed Inhibitors Against Factor IX (FIX)
timeFrame: For PTPs: up to 5 years or the time it takes to achieve 100 exposure days (EDs). For PUPs: up to 3 years or the time it takes to achieve 50 EDs.
measure: Mean Incremental Recovery of a 50 IU/kg Dose of CSL654 in Previously Untreated Patients (PUPs)
timeFrame: Approximately 30 minutes after infusion of CSL654
Secondary outcomes:
measure: Total Annualized Bleeding Rate (ABR) by Prophylaxis Regimen in Previously Treated Patients (PTPs)
timeFrame: For PTPs: up to 5 years or the time it takes to achieve 100 exposure days (EDs).
measure: Spontaneous ABR by Prophylaxis Regimen in PTPs
timeFrame: For PTPs: up to 5 years or the time it takes to achieve 100 exposure days (EDs).
measure: Average Amount of CSL654 (rIX-FP) Consumed Per Month Per Subject During Routine Prophylaxis Treatment.
timeFrame: For PTPs: up to 5 years or the time it takes to achieve 100 exposure days (EDs). For PUPs: up to 3 years or the time it takes to achieve 50 EDs.
measure: Percentage of Participants With at Least One Treatment Emergent Adverse Event (TEAE) and the Percentage of Participants With at Least One CSL654-related TEAE
timeFrame: For PTPs: up to 5 years or the time it takes to achieve 100 exposure days (EDs). For PUPs: up to 3 years or the time it takes to achieve 50 EDs.
measure: Number of Participants With Investigator's Overall Clinical Assessment of Hemostatic Efficacy for the Treatment of Major Bleeding Events With CSL654 in PUPs
timeFrame: Up to 3 years or the time it takes to achieve 50 EDs
measure: Total ABR for On-demand Regimen vs. 14-Day Regimen in PTPs
timeFrame: For PTPs: up to 5 years or the time it takes to achieve 100 exposure days (EDs).
measure: Spontaneous ABR for On-demand Regimen vs. 14-Day Regimen in PTPs
timeFrame: For PTPs: up to 5 years or the time it takes to achieve 100 exposure days (EDs).
measure: Total ABR for Subjects >=12 Years: 7-Day Regimen vs. 14-Day Regimen in PTPs
timeFrame: For PTPs: up to 5 years or the time it takes to achieve 100 exposure days (EDs).
measure: Spontaneous ABR for Subjects >=12 Years: 7-Day Regimen vs. 14-Day Regimen in PTPs
timeFrame: For PTPs: up to 5 years or the time it takes to achieve 100 exposure days (EDs).
measure: Total ABR for Subjects >=12 Years: 7-Day Regimen vs. (10 or 14)-Day Regimen in PTPs
timeFrame: For PTPs: up to 5 years or the time it takes to achieve 100 exposure days (EDs).
measure: Spontaneous ABR for Subjects >=12 Years: 7-Day Regimen vs. (10 or 14)-Day Regimen in PTPs
timeFrame: For PTPs: up to 5 years or the time it takes to achieve 100 exposure days (EDs).
Other outcomes:
Locations:
city: Aurora
country: United States
facility: University of Colorado
state: Colorado
city: Indianapolis
country: United States
facility: Indiana Hemophilia & Thrombosis Center Inc.
state: Indiana
city: Philadelphia
country: United States
facility: Hospital of the University of Pennsylvania
state: Pennsylvania
city: Salt Lake City
country: United States
facility: University of Utah
state: Utah
city: Parkville
country: Australia
facility: Royal Children's Hospital
state: Victoria
city: Westmead
country: Australia
facility: The Children's Hospital Westmead
state: Victoria
city: Vienna
country: Austria
facility: Department of Pediatrics, Medical University of Vienna
city: Vienna
country: Austria
facility: Medical University of Vienna, Vienna General Hospital
city: Sofia
country: Bulgaria
facility: SHAT "Joan Pavel" ODD [Hemorrhagic Diathesis & Anemia]
city: Hamilton
country: Canada
facility: McMaster University
state: Ontario
city: Brno
country: Czechia
facility: Fakultni nemocnice Brno
city: Ostrava-Poruba
country: Czechia
facility: Fakultni Nemocrice Ostrava
city: Praha
country: Czechia
facility: Fakultni nemocnice v Motole
city: Brest
country: France
facility: CHRU Hopital Morvan
city: Bron Cedex
country: France
facility: Hopital Louis Pradel
city: Le Kremlin-Bicetre
country: France
facility: Hopital Bicetre - Centre de Traitement del'Hemophilia
city: Marseille Cedex
country: France
facility: Hopital d'Enfants La Timonepital
city: Paris
country: France
facility: Hopital Necker-Enfants Malades
city: Bonn
country: Germany
facility: Institut fur experimentelle Hamatologie
city: Bremen
country: Germany
facility: Prof. Hess Kinderklinik
city: Duisburg
country: Germany
facility: CRC Coagulation Research Centre GmbH
city: Dusseldorf
country: Germany
facility: Heinrich Heine University Dusseldorf
city: Hamburg
country: Germany
facility: Universtatsklinikum Hamburg-Eppendorf
city: Hannover
country: Germany
facility: Werlhof-Institute for Haemostasis and Thrombosis
city: Heidelberg
country: Germany
facility: Kurpfalzkrankenhaus Heidlerberg GmbH
city: Tel Aviv
country: Israel
facility: Chaim Sheba Medical Center
city: Milano
country: Italy
facility: IRCCS Ospedale Maggiore[Centro emofilia e Trobosi]
city: Parma
country: Italy
facility: UOS Gestione e Organizzazione Funzlone Hub Emofilia
city: Vicenza
country: Italy
facility: Centro Malattie Emorragiche e Trombotiche Ospedale
city: Kashihara
country: Japan
facility: Nara Medical University Hospital
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: Tokyo Medical University Hospital
city: Tokyo
country: Japan
facility: Ogikubo Hospital
city: Yokohama
country: Japan
facility: St. Marianna University, School of Medicine, Seibu Hospital
city: Kuala Lumpur
country: Malaysia
facility: National Blood Center
city: Cebu
country: Philippines
facility: Perpetual Succour Hospital
city: Parktown
country: South Africa
facility: Haemophilia Comprehensive Care Centre
city: A Coruna
country: Spain
facility: C.H.U. A Coruna
city: Barcelona
country: Spain
facility: Hospital Vall Hebron
city: Madrid
country: Spain
facility: H.U. La Paz
Study officials:
affiliation: CSL Behring
name: Program Director
role: STUDY_DIRECTOR
References: