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Safety and Pharmacokinetic Study of a Recombinant Coagulation Factor IX Albumin Fusion Protein in Subjects With Hemophilia B

Primary Purpose

Hemophilia B

Status
Completed
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
Recombinant Coagulation Factor IX Albumin Fusion Protein
Plasma derived FIX [pdFIX]
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

12 Years - 65 Years (Child, Adult, Older Adult)MaleDoes not accept healthy volunteers

Inclusion Criteria:

  • Male, 12 - 65 years, with body weight ≥ 30 kg and ≤ 120 kg
  • Documented severe Hemophilia B (FIX activity of ≤ 2%) or tested by the central laboratory at screening
  • Subjects who have received FIX products for > 150 exposure days (EDs) (estimated)
  • No confirmed prior history of FIX inhibitor (history of positive FIX inhibitor defined as two consecutive positive tests - a confirmatory test on a second, separately drawn sample shortly after the previous positive test) and confirmed no detectable FIX inhibitors (negative FIX inhibitor defined as < 0.6 Bethesda Units [BU] by the central laboratory at screening
  • Subjects can be treated on-demand or under prophylactic therapy
  • Signed Informed Consent/Assent

Exclusion Criteria:

  • Known hypersensitivity (allergic reaction or anaphylaxis) to any FIX product or hamster protein
  • Any known congenital or acquired coagulation disorder other than congenital FIX deficiency
  • Platelet count < 100,000/µL
  • Immunocompromised (CD4 count < 200/mm3), (HIV positive subjects may participate in the study and protease inhibitors and antiviral therapy are permitted, at the discretion of the Investigator)
  • Currently receiving IV immunomodulating agents such as immunoglobulin or chronic systemic corticosteroid treatment
  • Serum aspartate aminotransferase (AST) or serum alanine aminotransferase (ALT) concentration > 5 times (x) the upper limit of normal (ULN)
  • Serum creatinine > 2 x ULN
  • Evidence of thrombosis, including deep vein thrombosis, stroke, pulmonary embolism, myocardial infarction and arterial embolus within 3 months prior to enrollment
  • Use of an Investigational Medicinal Product (IMP) within 30 days prior to the first rIX-FP administration
  • Experienced life-threatening bleeding episode or had major surgery or an orthopedic surgical procedure during the 3 months prior to study entry
  • Subject currently on a dose and/or regimen of FIX that would preclude participation in the study due to possible increased risk of bleeding because of the requirement to withhold treatment during the PK sampling period
  • Suspected inability (e.g., language problem or mental condition) or unwillingness to comply with study procedures or history of noncompliance

Sites / Locations

  • Study site
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Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Experimental

Arm Label

Cohort 1

Cohort 2

Cohort 3

Arm Description

25 IU/kg dose

50 IU/kg dose

75 IU/kg dose

Outcomes

Primary Outcome Measures

Frequency of adverse events (AEs)
Frequency of serious adverse events (SAEs)
Occurrence of inhibitor against FIX
Occurrence of antibodies against rIX-FP

Secondary Outcome Measures

AUC to the last sample with quantifiable drug concentration (AUC0-t)
Following 50 IU/kg rIX-FP infusion
AUC extrapolated to infinity (AUCt-∞)
Following 50 IU/kg rIX-FP infusion
Half-life (t1/2)
Following 50 IU/kg rIX-FP infusion
Incremental recovery (IU/mL/IU/kg)
Defined as FIX activity (IU/mL) obtained 30 minutes following infusion, per dose of (IU/kg) infusion.
Clearance
Following 50 IU/kg rIX-FP infusion

Full Information

First Posted
November 2, 2010
Last Updated
January 26, 2012
Sponsor
CSL Behring
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1. Study Identification

Unique Protocol Identification Number
NCT01233440
Brief Title
Safety and Pharmacokinetic Study of a Recombinant Coagulation Factor IX Albumin Fusion Protein in Subjects With Hemophilia B
Official Title
An Open-label, Multicenter, Dose-Escalation Safety and Pharmacokinetic 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
January 2012
Overall Recruitment Status
Completed
Study Start Date
October 2010 (undefined)
Primary Completion Date
July 2011 (Actual)
Study Completion Date
July 2011 (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
The primary objective of the study is to assess the safety of IV administration of rIX-FP. Safety will be evaluated by adverse events and laboratory changes over time. The secondary objective of the study is to evaluate the pharmacokinetics parameters, following a single intravenous dose of rIX-FP.
Detailed Description
This study is comprised of both a rIX-FP dose-escalation safety segment (25, 50 and 75 IU/kg of rIX-FP), and PK evaluation of rIX-FP after a single dose of 50 IU/kg, as well as PK evaluation after a single dose of 50 IU/kg of the previously given Factor IX (FIX) product (recombinant FIX [rFIX] or plasma derived FIX [pdFIX]) which is used as the reference product.

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
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
25 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Cohort 1
Arm Type
Experimental
Arm Description
25 IU/kg dose
Arm Title
Cohort 2
Arm Type
Experimental
Arm Description
50 IU/kg dose
Arm Title
Cohort 3
Arm Type
Experimental
Arm Description
75 IU/kg dose
Intervention Type
Biological
Intervention Name(s)
Recombinant Coagulation Factor IX Albumin Fusion Protein
Intervention Description
Single dose of 25, 50 or 75 IU/kg of rIX-FP, given as intravenous infusion
Intervention Type
Biological
Intervention Name(s)
Plasma derived FIX [pdFIX]
Intervention Description
Single dose of 50 IU/kg of reference product, given as intravenous infusion
Primary Outcome Measure Information:
Title
Frequency of adverse events (AEs)
Time Frame
up to 14 days after drug administration
Title
Frequency of serious adverse events (SAEs)
Time Frame
up to 28 days after drug administration
Title
Occurrence of inhibitor against FIX
Time Frame
up to 28 days after drug administration
Title
Occurrence of antibodies against rIX-FP
Time Frame
up to 28 days after drug administration
Secondary Outcome Measure Information:
Title
AUC to the last sample with quantifiable drug concentration (AUC0-t)
Description
Following 50 IU/kg rIX-FP infusion
Time Frame
From time of dosing up to 7 days after the dose
Title
AUC extrapolated to infinity (AUCt-∞)
Description
Following 50 IU/kg rIX-FP infusion
Time Frame
From time of dosing up to 7 days after the dose
Title
Half-life (t1/2)
Description
Following 50 IU/kg rIX-FP infusion
Time Frame
From time of dosing up to 7 days after the dose
Title
Incremental recovery (IU/mL/IU/kg)
Description
Defined as FIX activity (IU/mL) obtained 30 minutes following infusion, per dose of (IU/kg) infusion.
Time Frame
From time of dosing up to 7 days after the dose
Title
Clearance
Description
Following 50 IU/kg rIX-FP infusion
Time Frame
From time of dosing up to 7 days after the dose

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, 12 - 65 years, with body weight ≥ 30 kg and ≤ 120 kg Documented severe Hemophilia B (FIX activity of ≤ 2%) or tested by the central laboratory at screening Subjects who have received FIX products for > 150 exposure days (EDs) (estimated) No confirmed prior history of FIX inhibitor (history of positive FIX inhibitor defined as two consecutive positive tests - a confirmatory test on a second, separately drawn sample shortly after the previous positive test) and confirmed no detectable FIX inhibitors (negative FIX inhibitor defined as < 0.6 Bethesda Units [BU] by the central laboratory at screening Subjects can be treated on-demand or under prophylactic therapy Signed Informed Consent/Assent Exclusion Criteria: Known hypersensitivity (allergic reaction or anaphylaxis) to any FIX product or hamster protein Any known congenital or acquired coagulation disorder other than congenital FIX deficiency Platelet count < 100,000/µL Immunocompromised (CD4 count < 200/mm3), (HIV positive subjects may participate in the study and protease inhibitors and antiviral therapy are permitted, at the discretion of the Investigator) Currently receiving IV immunomodulating agents such as immunoglobulin or chronic systemic corticosteroid treatment Serum aspartate aminotransferase (AST) or serum alanine aminotransferase (ALT) concentration > 5 times (x) the upper limit of normal (ULN) Serum creatinine > 2 x ULN Evidence of thrombosis, including deep vein thrombosis, stroke, pulmonary embolism, myocardial infarction and arterial embolus within 3 months prior to enrollment Use of an Investigational Medicinal Product (IMP) within 30 days prior to the first rIX-FP administration Experienced life-threatening bleeding episode or had major surgery or an orthopedic surgical procedure during the 3 months prior to study entry Subject currently on a dose and/or regimen of FIX that would preclude participation in the study due to possible increased risk of bleeding because of the requirement to withhold treatment during the PK sampling period Suspected inability (e.g., language problem or mental condition) or unwillingness to comply with study procedures or history of noncompliance
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
Vienna
Country
Austria
Facility Name
Study site
City
Le Kremlin-Bicetre
Country
France
Facility Name
Study Site
City
Lyon
Country
France
Facility Name
Study site
City
Nantes
Country
France
Facility Name
Study site
City
Paris
Country
France
Facility Name
Study Site
City
Berlin
Country
Germany
Facility Name
Study Site
City
Hamburg
Country
Germany
Facility Name
Study Site
City
Hannover
Country
Germany
Facility Name
Study site
City
Munster
Country
Germany
Facility Name
Study Site
City
Tel Hashomer
Country
Israel
Facility Name
Study Site
City
Catania
Country
Italy
Facility Name
Study Site
City
Firenze
Country
Italy
Facility Name
Study Site
City
Genova
Country
Italy
Facility Name
Study site
City
Milan
Country
Italy
Facility Name
Study Site
City
Napoli
Country
Italy
Facility Name
Study Site
City
Parma
Country
Italy
Facility Name
Study Site
City
Vicenza
Country
Italy
Facility Name
Study Site
City
A Coruna
Country
Spain
Facility Name
Study Site
City
Barcelona
Country
Spain
Facility Name
Study Site
City
Madrid
Country
Spain

12. IPD Sharing Statement

Citations:
PubMed Identifier
22859609
Citation
Santagostino E, Negrier C, Klamroth R, Tiede A, Pabinger-Fasching I, Voigt C, Jacobs I, Morfini M. Safety and pharmacokinetics of a novel recombinant fusion protein linking coagulation factor IX with albumin (rIX-FP) in hemophilia B patients. Blood. 2012 Sep 20;120(12):2405-11. doi: 10.1182/blood-2012-05-429688. Epub 2012 Aug 2.
Results Reference
derived
Links:
URL
http://www.cslbehring.com/clinical-trials/contact-us.htm?registryRefNum=NCT01233440&registryName=ctgov
Description
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Safety and Pharmacokinetic Study of a Recombinant Coagulation Factor IX Albumin Fusion Protein in Subjects With Hemophilia B

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