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

NCT ID: NCT01233440

Last Updated: 2012-01-31

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 25 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-10-31
• Study Completion Date: 2011-07-31

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.

Conditions

Hemophilia B

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Cohort 1

25 IU/kg dose

Group Type: EXPERIMENTAL

Recombinant Coagulation Factor IX Albumin Fusion Protein

Intervention Type: BIOLOGICAL

Single dose of 25, 50 or 75 IU/kg of rIX-FP, given as intravenous infusion

Cohort 2

50 IU/kg dose

Group Type: EXPERIMENTAL

Recombinant Coagulation Factor IX Albumin Fusion Protein

Intervention Type: BIOLOGICAL

Single dose of 25, 50 or 75 IU/kg of rIX-FP, given as intravenous infusion

Plasma derived FIX [pdFIX]

Intervention Type: BIOLOGICAL

Single dose of 50 IU/kg of reference product, given as intravenous infusion

Cohort 3

75 IU/kg dose

Group Type: EXPERIMENTAL

Recombinant Coagulation Factor IX Albumin Fusion Protein

Intervention Type: BIOLOGICAL

Single dose of 25, 50 or 75 IU/kg of rIX-FP, given as intravenous infusion

Interventions

Recombinant Coagulation Factor IX Albumin Fusion Protein

Single dose of 25, 50 or 75 IU/kg of rIX-FP, given as intravenous infusion

Intervention Type: BIOLOGICAL

Plasma derived FIX [pdFIX]

Single dose of 50 IU/kg of reference product, given as intravenous infusion

Intervention Type: BIOLOGICAL

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

• Minimum Eligible Age: 12 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: No

Sponsors

CSL Behring

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Iris Jacobs, MD

Role: STUDY_DIRECTOR

CSL Behring

Locations

Study site

Vienna, , Austria

Study site

Le Kremlin-Bicêtre, , France

Study Site

Lyon, , France

Study site

Nantes, , France

Study site

Paris, , France

Study Site

Berlin, , Germany

Study Site

Hamburg, , Germany

Study Site

Hanover, , Germany

Study site

Münster, , Germany

Study Site

Tel Litwinsky, , Israel

Study Site

Catania, , Italy

Study Site

Florence, , Italy

Study Site

Genova, , Italy

Study site

Milan, , Italy

Study Site

Napoli, , Italy

Study Site

Parma, , Italy

Study Site

Vicenza, , Italy

Study Site

A Coruña, , Spain

Study Site

Barcelona, , Spain

Study Site

Madrid, , Spain

Countries

Austria; France; Germany; Israel; Italy; Spain

References

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.

Reference Type: DERIVED

PMID: 22859609 (View on PubMed)

Other Identifiers

1508

Identifier Type: OTHER

Identifier Source: secondary_id

2010-018477-38

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CSL654_2001

Identifier Type: -

Identifier Source: org_study_id