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
  Purpose

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.


Condition Intervention Phase
Hemophilia B
Biological: Recombinant Coagulation Factor IX Albumin Fusion Protein
Biological: Plasma derived FIX [pdFIX]
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by CSL Behring:

Primary Outcome Measures:
  • 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 ]

Secondary Outcome Measures:
  • 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


Enrollment: 25
Study Start Date: October 2010
Study Completion Date: July 2011
Primary Completion Date: July 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Cohort 1
25 IU/kg dose
Biological: Recombinant Coagulation Factor IX Albumin Fusion Protein
Single dose of 25, 50 or 75 IU/kg of rIX-FP, given as intravenous infusion
Experimental: Cohort 2
50 IU/kg dose
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 3
75 IU/kg dose
Biological: Recombinant Coagulation Factor IX Albumin Fusion Protein
Single dose of 25, 50 or 75 IU/kg of rIX-FP, given as intravenous infusion

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.

  Eligibility

Ages Eligible for Study:   12 Years to 65 Years
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01233440

Locations
Austria
Study site
Vienna, Austria
France
Study site
Le Kremlin-Bicetre, France
Study Site
Lyon, France
Study site
Nantes, France
Study site
Paris, France
Germany
Study Site
Berlin, Germany
Study Site
Hamburg, Germany
Study Site
Hannover, Germany
Study site
Munster, Germany
Israel
Study Site
Tel Hashomer, Israel
Italy
Study Site
Catania, Italy
Study Site
Firenze, Italy
Study Site
Genova, Italy
Study site
Milan, Italy
Study Site
Napoli, Italy
Study Site
Parma, Italy
Study Site
Vicenza, Italy
Spain
Study Site
A Coruna, Spain
Study Site
Barcelona, Spain
Study Site
Madrid, Spain
Sponsors and Collaborators
CSL Behring
Investigators
Study Director: Iris Jacobs, MD CSL Behring
  More Information

Additional Information:
No publications provided by CSL Behring

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: CSL Behring
ClinicalTrials.gov Identifier: NCT01233440     History of Changes
Other Study ID Numbers: CSL654_2001, 1508, 2010-018477-38
Study First Received: November 2, 2010
Last Updated: January 26, 2012
Health Authority: Austria: Agency for Health and Food Safety
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Germany: Paul-Ehrlich-Institut
Israel: Ministry of Health
Italy: National Institute of Health
Spain: Agencia Española de Medicamentos y Productos Sanitarios
United Kingdom: Medicines and Healthcare Products Regulatory Agency

Additional relevant MeSH terms:
Hemophilia B
Blood Coagulation Disorders, Inherited
Blood Coagulation Disorders
Hematologic Diseases
Coagulation Protein Disorders
Hemorrhagic Disorders
Genetic Diseases, Inborn
Genetic Diseases, X-Linked

ClinicalTrials.gov processed this record on October 19, 2014