Back to resultsA Safety and Efficacy Study of a Recombinant Factor IX in Patients With Severe Hemophilia B
Primary Purpose
Hemophilia B
Status
Completed
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
Recombinant Coagulation Factor IX Albumin Fusion Protein
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 obtained before undergoing any study specific procedures
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, abnormal kidney function, or liver disease
- On-demand subjects experiencing less than 12 or 6 non-trauma induced bleeding episodes requiring treatment with a FIX product during the previous 6 or 3 months, respectively
- Planned major surgical intervention during the study period
Sites / Locations
- Study Site
- Study Site
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
On-demand
Prophylactic
Arm Description
The routine prophylactic therapy interval is targeted at every 7 days.
On-demand subjects will receive rIX-FP only for the treatment of a bleeding episode.
Outcomes
Primary Outcome Measures
Number of Subjects With Treatment-related Adverse Events
The causal relationship of each adverse event to rIX-FP was assessed by the Investigator.
Number of Subjects With Inhibitors Against Factor IX (FIX)
The presence of inhibitors against FIX was assessed by the central laboratory by a FIX potency assay. To quantify anti-FIX neutralizing antibodies, the Bethesda assay with the Nijmegen modification was used, and the results expressed as Bethesda Units per mL (BU/mL). A positive inhibitor test is >=0.6 BU/mL.
Number of Subjects Who Developed Antibodies to rIX-FP
Antibodies against rIX-FP were detected using a direct binding enzyme-linked immunosorbent assay (ELISA).
Secondary Outcome Measures
Area Under the Curve to the Last Sample With Quantifiable Drug Concentration (AUC0-t) After a Single Dose of rIX-FP
The plasma concentrations of rIX-FP were measured as FIX activity using a validated, 1-stage assay in a central laboratory for a quantification range from 0.25 to 150% (or 0.25 IU/dL to 150 IU/dL). The PK population comprised all subjects who received at least 1 dose of rIX-FP and for whom a sufficient number of analyzable PK samples had been obtained in order to permit the evaluation of the PK profile of rIX-FP, and who did not receive a dose of rIX-FP or any other FIX product for the treatment of a bleed during the PK sampling period.
Half-life (t1/2) of a Single Dose of rIX-FP
Incremental Recovery of rIX-FP at 30 Minutes Following Infusion of rIX-FP
Incremental recovery (IU/mL/IU/kg) is defined as FIX activity (IU/mL) obtained 30 minutes following infusion, per dose of (IU/kg) infusion. FIX activity was measured at a central laboratory using validated one-stage clotting method.
Clearance of a Single Dose of rIX-FP
Breakthrough Bleeding Events
Number of breakthrough bleeding events (spontaneous bleeding events) requiring treatment per subject in subjects receiving prophylactic treatment regimen with rIX-FP
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01361126
Brief Title
A Safety and Efficacy Study of a Recombinant Factor IX in Patients With Severe Hemophilia B
Official Title
A Phase I/II 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
July 2011 (undefined)
Primary Completion Date
June 2012 (Actual)
Study Completion Date
July 2012 (Actual)
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 and efficacy of a Recombinant Coagulation Factor IX Albumin Fusion Protein (rIX-FP) for the control and prevention of bleeding episodes in subjects who have previously received factor replacement therapy for hemophilia B. The study consists of a screening period, a pharmacokinetic (PK) period, followed by approximately a 5 month treatment period. Subjects will receive weekly routine prophylactic therapy and on-demand treatment for bleeding episodes. In addition, subjects who are not on routine factor replacement therapy prior to the study will receive only on-demand treatment for bleeding episodes.
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 1, Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
17 (Actual)
8. Arms, Groups, and Interventions
Arm Title
On-demand
Arm Type
Experimental
Arm Description
The routine prophylactic therapy interval is targeted at every 7 days.
Arm Title
Prophylactic
Arm Type
Experimental
Arm Description
On-demand subjects will receive rIX-FP only for the treatment of a bleeding episode.
Intervention Type
Biological
Intervention Name(s)
Recombinant Coagulation Factor IX Albumin Fusion Protein
Other Intervention Name(s)
CSL654
Intervention Description
Study subjects will receive a single dose of 25IU/kg of rIX_FP for pharmacokinetic analysis. Subjects will then be treated for approximately 5 months. The treatment dose will be based on the subject's PK profile and the subject's bleeding phenotype.
Primary Outcome Measure Information:
Title
Number of Subjects With Treatment-related Adverse Events
Description
The causal relationship of each adverse event to rIX-FP was assessed by the Investigator.
Time Frame
Approximately 20 weeks
Title
Number of Subjects With Inhibitors Against Factor IX (FIX)
Description
The presence of inhibitors against FIX was assessed by the central laboratory by a FIX potency assay. To quantify anti-FIX neutralizing antibodies, the Bethesda assay with the Nijmegen modification was used, and the results expressed as Bethesda Units per mL (BU/mL). A positive inhibitor test is >=0.6 BU/mL.
Time Frame
Baseline, Day 10 and Weeks 4, 12 and 20
Title
Number of Subjects Who Developed Antibodies to rIX-FP
Description
Antibodies against rIX-FP were detected using a direct binding enzyme-linked immunosorbent assay (ELISA).
Time Frame
Pre-dose, Day 10 and Weeks 4, 12, and 20
Secondary Outcome Measure Information:
Title
Area Under the Curve to the Last Sample With Quantifiable Drug Concentration (AUC0-t) After a Single Dose of rIX-FP
Description
The plasma concentrations of rIX-FP were measured as FIX activity using a validated, 1-stage assay in a central laboratory for a quantification range from 0.25 to 150% (or 0.25 IU/dL to 150 IU/dL). The PK population comprised all subjects who received at least 1 dose of rIX-FP and for whom a sufficient number of analyzable PK samples had been obtained in order to permit the evaluation of the PK profile of rIX-FP, and who did not receive a dose of rIX-FP or any other FIX product for the treatment of a bleed during the PK sampling period.
Time Frame
Pre-dose and up to 14 days after rIX-FP infusion.
Title
Half-life (t1/2) of a Single Dose of rIX-FP
Time Frame
Pre-dose and up to 14 days after infusion
Title
Incremental Recovery of rIX-FP at 30 Minutes Following Infusion of rIX-FP
Description
Incremental recovery (IU/mL/IU/kg) is defined as FIX activity (IU/mL) obtained 30 minutes following infusion, per dose of (IU/kg) infusion. FIX activity was measured at a central laboratory using validated one-stage clotting method.
Time Frame
30 minutes after infusion
Title
Clearance of a Single Dose of rIX-FP
Time Frame
Pre-dose and up to 14 days after rIX-FP infusion
Title
Breakthrough Bleeding Events
Description
Number of breakthrough bleeding events (spontaneous bleeding events) requiring treatment per subject in subjects receiving prophylactic treatment regimen with rIX-FP
Time Frame
Week 9 to approximately Week 20
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 obtained before undergoing any study specific procedures
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, abnormal kidney function, or liver disease
On-demand subjects experiencing less than 12 or 6 non-trauma induced bleeding episodes requiring treatment with a FIX product during the previous 6 or 3 months, respectively
Planned major surgical intervention during the study period
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Iris Jacobs, MD
Organizational Affiliation
CSL Behring
Official's Role
Study Director
Facility Information:
Facility Name
Study Site
City
Sofia
Country
Bulgaria
Facility Name
Study Site
City
Tel Aviv
Country
Israel
12. IPD Sharing Statement
Learn more about this trial
A Safety and Efficacy Study of a Recombinant Factor IX in Patients With Severe Hemophilia B
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