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A Safety and Efficacy Extension 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 3
Locations
International
Study Type
Interventional
Intervention
rIX-FP
Sponsored by
CSL Behring
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Hemophilia B

Eligibility Criteria

undefined - 70 Years (Child, Adult, Older Adult)MaleDoes not accept healthy volunteers

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

Sites / Locations

  • University of Colorado
  • Indiana Hemophilia & Thrombosis Center Inc.
  • Hospital of the University of Pennsylvania
  • University of Utah
  • Royal Children's Hospital
  • The Children's Hospital Westmead
  • Department of Pediatrics, Medical University of Vienna
  • Medical University of Vienna, Vienna General Hospital
  • SHAT "Joan Pavel" ODD [Hemorrhagic Diathesis & Anemia]
  • McMaster University
  • Fakultni nemocnice Brno
  • Fakultni Nemocrice Ostrava
  • Fakultni nemocnice v Motole
  • CHRU Hopital Morvan
  • Hopital Louis Pradel
  • Hopital Bicetre - Centre de Traitement del'Hemophilia
  • Hopital d'Enfants La Timonepital
  • Hopital Necker-Enfants Malades
  • Institut fur experimentelle Hamatologie
  • Prof. Hess Kinderklinik
  • CRC Coagulation Research Centre GmbH
  • Heinrich Heine University Dusseldorf
  • Universtatsklinikum Hamburg-Eppendorf
  • Werlhof-Institute for Haemostasis and Thrombosis
  • Kurpfalzkrankenhaus Heidlerberg GmbH
  • Chaim Sheba Medical Center
  • IRCCS Ospedale Maggiore[Centro emofilia e Trobosi]
  • UOS Gestione e Organizzazione Funzlone Hub Emofilia
  • Centro Malattie Emorragiche e Trombotiche Ospedale
  • Nara Medical University Hospital
  • University of Occupational and Environmental Health
  • Nagoya University Hospital
  • The Hospital of Hyogo College of Medicine
  • Tokyo Medical University Hospital
  • Ogikubo Hospital
  • St. Marianna University, School of Medicine, Seibu Hospital
  • National Blood Center
  • Perpetual Succour Hospital
  • Haemophilia Comprehensive Care Centre
  • C.H.U. A Coruna
  • Hospital Vall Hebron
  • H.U. La Paz

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

rIX-FP

Arm Description

Subjects will administer rIX-FP by intravenous infusion as routine prophylaxis, prevention, and on-demand treatment during a treatment period of approximately 3 years. The routine prophylaxis treatment interval for previously treated patients may be changed at each scheduled 6-month follow-up assessment. On-demand treatment with rIX-FP will be used for all bleeding episodes requiring treatment. Subjects (other than those in France) may participate in a surgical 'substudy' in which rIX-FP may be administered before, during and after surgery. An additional substudy will examine the safety and PK of subcutaneous administration of rIX-FP. For previously untreated patients, subjects will administer rIX-FP intravenously as weekly prophylaxis and/or on-demand treatment during the first 12 months, and as weekly routine prophylaxis thereafter. The dose of rIX-FP administered will be based on the subject's previous rIX-FP use and/or pharmacokinetic data.

Outcomes

Primary Outcome Measures

Total Number of Participants Who Developed Inhibitors Against Factor IX (FIX)
Mean Incremental Recovery of a 50 IU/kg Dose of CSL654 in Previously Untreated Patients (PUPs)
Incremental Recovery: The increase in plasma concentration per IU/kg of factor administered.

Secondary Outcome Measures

Total Annualized Bleeding Rate (ABR) by Prophylaxis Regimen in Previously Treated Patients (PTPs)
Spontaneous ABR by Prophylaxis Regimen in PTPs
Average Amount of CSL654 (rIX-FP) Consumed Per Month Per Subject During Routine Prophylaxis Treatment.
Percentage of Participants With at Least One Treatment Emergent Adverse Event (TEAE) and the Percentage of Participants With at Least One CSL654-related TEAE
Number of Participants With Investigator's Overall Clinical Assessment of Hemostatic Efficacy for the Treatment of Major Bleeding Events With CSL654 in PUPs
The investigator will rate the efficacy of the rIX-FP treatment based on a hemostatic efficacy four point rating scale of excellent, good, moderate, or poor/no response.
Total ABR for On-demand Regimen vs. 14-Day Regimen in PTPs
Spontaneous ABR for On-demand Regimen vs. 14-Day Regimen in PTPs
Total ABR for Subjects >=12 Years: 7-Day Regimen vs. 14-Day Regimen in PTPs
Spontaneous ABR for Subjects >=12 Years: 7-Day Regimen vs. 14-Day Regimen in PTPs
Total ABR for Subjects >=12 Years: 7-Day Regimen vs. (10 or 14)-Day Regimen in PTPs
Spontaneous ABR for Subjects >=12 Years: 7-Day Regimen vs. (10 or 14)-Day Regimen in PTPs

Full Information

First Posted
January 29, 2014
Last Updated
July 12, 2022
Sponsor
CSL Behring
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1. Study Identification

Unique Protocol Identification Number
NCT02053792
Brief Title
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

2. Study Status

Record Verification Date
July 2022
Overall Recruitment Status
Completed
Study Start Date
February 6, 2014 (Actual)
Primary Completion Date
June 2, 2021 (Actual)
Study Completion Date
June 2, 2021 (Actual)

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 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.

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
97 (Actual)

8. Arms, Groups, and Interventions

Arm Title
rIX-FP
Arm Type
Experimental
Arm Description
Subjects will administer rIX-FP by intravenous infusion as routine prophylaxis, prevention, and on-demand treatment during a treatment period of approximately 3 years. The routine prophylaxis treatment interval for previously treated patients may be changed at each scheduled 6-month follow-up assessment. On-demand treatment with rIX-FP will be used for all bleeding episodes requiring treatment. Subjects (other than those in France) may participate in a surgical 'substudy' in which rIX-FP may be administered before, during and after surgery. An additional substudy will examine the safety and PK of subcutaneous administration of rIX-FP. For previously untreated patients, subjects will administer rIX-FP intravenously as weekly prophylaxis and/or on-demand treatment during the first 12 months, and as weekly routine prophylaxis thereafter. The dose of rIX-FP administered will be based on the subject's previous rIX-FP use and/or pharmacokinetic data.
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
Total Number of Participants Who Developed Inhibitors Against Factor IX (FIX)
Time Frame
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.
Title
Mean Incremental Recovery of a 50 IU/kg Dose of CSL654 in Previously Untreated Patients (PUPs)
Description
Incremental Recovery: The increase in plasma concentration per IU/kg of factor administered.
Time Frame
Approximately 30 minutes after infusion of CSL654
Secondary Outcome Measure Information:
Title
Total Annualized Bleeding Rate (ABR) by Prophylaxis Regimen in Previously Treated Patients (PTPs)
Time Frame
For PTPs: up to 5 years or the time it takes to achieve 100 exposure days (EDs).
Title
Spontaneous ABR by Prophylaxis Regimen in PTPs
Time Frame
For PTPs: up to 5 years or the time it takes to achieve 100 exposure days (EDs).
Title
Average Amount of CSL654 (rIX-FP) Consumed Per Month Per Subject During Routine Prophylaxis Treatment.
Time Frame
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.
Title
Percentage of Participants With at Least One Treatment Emergent Adverse Event (TEAE) and the Percentage of Participants With at Least One CSL654-related TEAE
Time Frame
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.
Title
Number of Participants With Investigator's Overall Clinical Assessment of Hemostatic Efficacy for the Treatment of Major Bleeding Events With CSL654 in PUPs
Description
The investigator will rate the efficacy of the rIX-FP treatment based on a hemostatic efficacy four point rating scale of excellent, good, moderate, or poor/no response.
Time Frame
Up to 3 years or the time it takes to achieve 50 EDs
Title
Total ABR for On-demand Regimen vs. 14-Day Regimen in PTPs
Time Frame
For PTPs: up to 5 years or the time it takes to achieve 100 exposure days (EDs).
Title
Spontaneous ABR for On-demand Regimen vs. 14-Day Regimen in PTPs
Time Frame
For PTPs: up to 5 years or the time it takes to achieve 100 exposure days (EDs).
Title
Total ABR for Subjects >=12 Years: 7-Day Regimen vs. 14-Day Regimen in PTPs
Time Frame
For PTPs: up to 5 years or the time it takes to achieve 100 exposure days (EDs).
Title
Spontaneous ABR for Subjects >=12 Years: 7-Day Regimen vs. 14-Day Regimen in PTPs
Time Frame
For PTPs: up to 5 years or the time it takes to achieve 100 exposure days (EDs).
Title
Total ABR for Subjects >=12 Years: 7-Day Regimen vs. (10 or 14)-Day Regimen in PTPs
Time Frame
For PTPs: up to 5 years or the time it takes to achieve 100 exposure days (EDs).
Title
Spontaneous ABR for Subjects >=12 Years: 7-Day Regimen vs. (10 or 14)-Day Regimen in PTPs
Time Frame
For PTPs: up to 5 years or the time it takes to achieve 100 exposure days (EDs).

10. Eligibility

Sex
Male
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
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
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
University of Colorado
City
Aurora
State/Province
Colorado
ZIP/Postal Code
80045
Country
United States
Facility Name
Indiana Hemophilia & 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
University of Utah
City
Salt Lake City
State/Province
Utah
ZIP/Postal Code
84103
Country
United States
Facility Name
Royal Children's Hospital
City
Parkville
State/Province
Victoria
ZIP/Postal Code
3052
Country
Australia
Facility Name
The Children's Hospital Westmead
City
Westmead
State/Province
Victoria
ZIP/Postal Code
2145
Country
Australia
Facility Name
Department of Pediatrics, Medical University of Vienna
City
Vienna
ZIP/Postal Code
1090
Country
Austria
Facility Name
Medical University of Vienna, Vienna General Hospital
City
Vienna
ZIP/Postal Code
1090
Country
Austria
Facility Name
SHAT "Joan Pavel" ODD [Hemorrhagic Diathesis & Anemia]
City
Sofia
ZIP/Postal Code
1233
Country
Bulgaria
Facility Name
McMaster University
City
Hamilton
State/Province
Ontario
ZIP/Postal Code
L8L 2X2
Country
Canada
Facility Name
Fakultni nemocnice Brno
City
Brno
ZIP/Postal Code
62500
Country
Czechia
Facility Name
Fakultni Nemocrice Ostrava
City
Ostrava-Poruba
ZIP/Postal Code
708 52
Country
Czechia
Facility Name
Fakultni nemocnice v Motole
City
Praha
ZIP/Postal Code
15006
Country
Czechia
Facility Name
CHRU Hopital Morvan
City
Brest
ZIP/Postal Code
29609
Country
France
Facility Name
Hopital Louis Pradel
City
Bron Cedex
ZIP/Postal Code
69677
Country
France
Facility Name
Hopital Bicetre - Centre de Traitement del'Hemophilia
City
Le Kremlin-Bicetre
ZIP/Postal Code
94275
Country
France
Facility Name
Hopital d'Enfants La Timonepital
City
Marseille Cedex
ZIP/Postal Code
13385
Country
France
Facility Name
Hopital Necker-Enfants Malades
City
Paris
ZIP/Postal Code
75015
Country
France
Facility Name
Institut fur experimentelle Hamatologie
City
Bonn
ZIP/Postal Code
53127
Country
Germany
Facility Name
Prof. Hess Kinderklinik
City
Bremen
ZIP/Postal Code
28177
Country
Germany
Facility Name
CRC Coagulation Research Centre GmbH
City
Duisburg
ZIP/Postal Code
47051
Country
Germany
Facility Name
Heinrich Heine University Dusseldorf
City
Dusseldorf
ZIP/Postal Code
40225
Country
Germany
Facility Name
Universtatsklinikum Hamburg-Eppendorf
City
Hamburg
ZIP/Postal Code
20246
Country
Germany
Facility Name
Werlhof-Institute for Haemostasis and Thrombosis
City
Hannover
ZIP/Postal Code
30159
Country
Germany
Facility Name
Kurpfalzkrankenhaus Heidlerberg GmbH
City
Heidelberg
Country
Germany
Facility Name
Chaim Sheba Medical Center
City
Tel Aviv
Country
Israel
Facility Name
IRCCS Ospedale Maggiore[Centro emofilia e Trobosi]
City
Milano
ZIP/Postal Code
20122
Country
Italy
Facility Name
UOS Gestione e Organizzazione Funzlone Hub Emofilia
City
Parma
ZIP/Postal Code
43126
Country
Italy
Facility Name
Centro Malattie Emorragiche e Trombotiche Ospedale
City
Vicenza
ZIP/Postal Code
36100
Country
Italy
Facility Name
Nara Medical University Hospital
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
Tokyo Medical University Hospital
City
Tokyo
ZIP/Postal Code
160-0023
Country
Japan
Facility Name
Ogikubo Hospital
City
Tokyo
ZIP/Postal Code
167-0035
Country
Japan
Facility Name
St. Marianna University, School of Medicine, Seibu Hospital
City
Yokohama
ZIP/Postal Code
241-0811
Country
Japan
Facility Name
National Blood Center
City
Kuala Lumpur
ZIP/Postal Code
50400
Country
Malaysia
Facility Name
Perpetual Succour Hospital
City
Cebu
ZIP/Postal Code
6000
Country
Philippines
Facility Name
Haemophilia Comprehensive Care Centre
City
Parktown
ZIP/Postal Code
2193
Country
South Africa
Facility Name
C.H.U. A Coruna
City
A Coruna
Country
Spain
Facility Name
Hospital Vall Hebron
City
Barcelona
ZIP/Postal Code
08035
Country
Spain
Facility Name
H.U. La Paz
City
Madrid
ZIP/Postal Code
28046
Country
Spain

12. IPD Sharing Statement

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A Safety and Efficacy Extension Study of a Recombinant Fusion Protein Linking Coagulation Factor IX With Albumin (rIX-FP) in Patients With Hemophilia B

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