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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
CSL Behring
ClinicalTrials.gov Identifier:
NCT01233440
First received: November 2, 2010
Last updated: January 26, 2012
Last verified: January 2012

November 2, 2010
January 26, 2012
October 2010
July 2011   (final data collection date for primary outcome measure)
  • Frequency of adverse events (AEs) [ Time Frame: up to 14 days after drug administration ] [ Designated as safety issue: Yes ]
  • Frequency of serious adverse events (SAEs) [ Time Frame: up to 28 days after drug administration ] [ Designated as safety issue: Yes ]
  • Occurrence of inhibitor against FIX [ Time Frame: up to 28 days after drug administration ] [ Designated as safety issue: Yes ]
  • Occurrence of antibodies against rIX-FP [ Time Frame: up to 28 days after drug administration ] [ Designated as safety issue: Yes ]
Same as current
Complete list of historical versions of study NCT01233440 on ClinicalTrials.gov Archive Site
  • AUC to the last sample with quantifiable drug concentration (AUC0-t) [ Time Frame: From time of dosing up to 7 days after the dose ] [ Designated as safety issue: No ]
    Following 50 IU/kg rIX-FP infusion
  • AUC extrapolated to infinity (AUCt-∞) [ Time Frame: From time of dosing up to 7 days after the dose ] [ Designated as safety issue: No ]
    Following 50 IU/kg rIX-FP infusion
  • Half-life (t1/2) [ Time Frame: From time of dosing up to 7 days after the dose ] [ Designated as safety issue: No ]
    Following 50 IU/kg rIX-FP infusion
  • Incremental recovery (IU/mL/IU/kg) [ Time Frame: From time of dosing up to 7 days after the dose ] [ Designated as safety issue: No ]
    Defined as FIX activity (IU/mL) obtained 30 minutes following infusion, per dose of (IU/kg) infusion.
  • Clearance [ Time Frame: From time of dosing up to 7 days after the dose ] [ Designated as safety issue: No ]
    Following 50 IU/kg rIX-FP infusion
Same as current
Not Provided
Not Provided
 
Safety and Pharmacokinetic Study of a Recombinant Coagulation Factor IX Albumin Fusion Protein in Subjects With Hemophilia B
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

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.

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.

Interventional
Phase 1
Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Hemophilia B
  • Biological: Recombinant Coagulation Factor IX Albumin Fusion Protein
    Single dose of 25, 50 or 75 IU/kg of rIX-FP, given as intravenous infusion
  • Biological: Plasma derived FIX [pdFIX]
    Single dose of 50 IU/kg of reference product, given as intravenous infusion
  • Experimental: Cohort 1
    25 IU/kg dose
    Intervention: Biological: Recombinant Coagulation Factor IX Albumin Fusion Protein
  • Experimental: Cohort 2
    50 IU/kg dose
    Interventions:
    • Biological: Recombinant Coagulation Factor IX Albumin Fusion Protein
    • Biological: Plasma derived FIX [pdFIX]
  • Experimental: Cohort 3
    75 IU/kg dose
    Intervention: Biological: Recombinant Coagulation Factor IX Albumin Fusion Protein
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. Epub 2012 Aug 2.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
25
July 2011
July 2011   (final data collection date for primary outcome measure)

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
Male
12 Years to 65 Years
No
Contact information is only displayed when the study is recruiting subjects
Austria,   France,   Germany,   Israel,   Italy,   Spain
 
NCT01233440
CSL654_2001, 1508, 2010-018477-38
Yes
CSL Behring
CSL Behring
Not Provided
Study Director: Iris Jacobs, MD CSL Behring
CSL Behring
January 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP