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

January 26, 2012 updated by: CSL Behring

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

25

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Austria
      • Vienna, Austria
        • Study Site
  • France
      • Le Kremlin-Bicetre, France
        • Study Site
      • Lyon, France
        • Study Site
      • Nantes, France
        • Study Site
      • Paris, France
        • Study Site
  • Germany
      • Berlin, Germany
        • Study Site
      • Hamburg, Germany
        • Study Site
      • Hannover, Germany
        • Study Site
      • Munster, Germany
        • Study Site
  • Israel
      • Tel Hashomer, Israel
        • Study Site
  • Italy
      • 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
        • Study Site
  • Spain
      • A Coruna, Spain
        • Study Site
      • Barcelona, Spain
        • Study Site
      • Madrid, Spain
        • Study Site

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

12 years to 65 years (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Male

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Frequency of adverse events (AEs)
Time Frame: up to 14 days after drug administration
up to 14 days after drug administration
Frequency of serious adverse events (SAEs)
Time Frame: up to 28 days after drug administration
up to 28 days after drug administration
Occurrence of inhibitor against FIX
Time Frame: up to 28 days after drug administration
up to 28 days after drug administration
Occurrence of antibodies against rIX-FP
Time Frame: up to 28 days after drug administration
up to 28 days after drug administration

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
AUC to the last sample with quantifiable drug concentration (AUC0-t)
Time Frame: From time of dosing up to 7 days after the dose
Following 50 IU/kg rIX-FP infusion
From time of dosing up to 7 days after the dose
AUC extrapolated to infinity (AUCt-∞)
Time Frame: From time of dosing up to 7 days after the dose
Following 50 IU/kg rIX-FP infusion
From time of dosing up to 7 days after the dose
Half-life (t1/2)
Time Frame: From time of dosing up to 7 days after the dose
Following 50 IU/kg rIX-FP infusion
From time of dosing up to 7 days after the dose
Incremental recovery (IU/mL/IU/kg)
Time Frame: From time of dosing up to 7 days after the dose
Defined as FIX activity (IU/mL) obtained 30 minutes following infusion, per dose of (IU/kg) infusion.
From time of dosing up to 7 days after the dose
Clearance
Time Frame: From time of dosing up to 7 days after the dose
Following 50 IU/kg rIX-FP infusion
From time of dosing up to 7 days after the dose

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

CSL Behring

Investigators

  • Study Director: Iris Jacobs, MD, CSL Behring

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

October 1, 2010

Primary Completion (Actual)

July 1, 2011

Study Completion (Actual)

July 1, 2011

Study Registration Dates

First Submitted

November 2, 2010

First Submitted That Met QC Criteria

November 2, 2010

First Posted (Estimate)

November 3, 2010

Study Record Updates

Last Update Posted (Estimate)

January 31, 2012

Last Update Submitted That Met QC Criteria

January 26, 2012

Last Verified

January 1, 2012

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CSL654_2001
  • 1508 (Other Identifier: CSL Behring)
  • 2010-018477-38 (EudraCT Number)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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