Clinical trial NCT01233440: 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
Overall status: COMPLETED
Phase: PHASE1
Conditions: Hemophilia B
Lead sponsor: CSL Behring
Sponsor class: INDUSTRY
First posted: 2010-11-03
Enrollment: 25
Sex: MALE
Minimum age (years): 12
Maximum age (years): 65
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Frequency of adverse events (AEs)
timeFrame: up to 14 days after drug administration
measure: Frequency of serious adverse events (SAEs)
timeFrame: up to 28 days after drug administration
measure: Occurrence of inhibitor against FIX
timeFrame: up to 28 days after drug administration
measure: Occurrence of antibodies against rIX-FP
timeFrame: up to 28 days after drug administration
Secondary outcomes:
measure: AUC to the last sample with quantifiable drug concentration (AUC0-t)
timeFrame: From time of dosing up to 7 days after the dose
measure: AUC extrapolated to infinity (AUCt-∞)
timeFrame: From time of dosing up to 7 days after the dose
measure: Half-life (t1/2)
timeFrame: From time of dosing up to 7 days after the dose
measure: Incremental recovery (IU/mL/IU/kg)
timeFrame: From time of dosing up to 7 days after the dose
measure: Clearance
timeFrame: From time of dosing up to 7 days after the dose
Other outcomes:
Locations:
city: Vienna
country: Austria
facility: Study site
city: Le Kremlin-Bicetre
country: France
facility: Study site
city: Lyon
country: France
facility: Study Site
city: Nantes
country: France
facility: Study site
city: Paris
country: France
facility: Study site
city: Berlin
country: Germany
facility: Study Site
city: Hamburg
country: Germany
facility: Study Site
city: Hannover
country: Germany
facility: Study Site
city: Munster
country: Germany
facility: Study site
city: Tel Hashomer
country: Israel
facility: Study Site
city: Catania
country: Italy
facility: Study Site
city: Firenze
country: Italy
facility: Study Site
city: Genova
country: Italy
facility: Study Site
city: Milan
country: Italy
facility: Study site
city: Napoli
country: Italy
facility: Study Site
city: Parma
country: Italy
facility: Study Site
city: Vicenza
country: Italy
facility: Study Site
city: A Coruna
country: Spain
facility: Study Site
city: Barcelona
country: Spain
facility: Study Site
city: Madrid
country: Spain
facility: Study Site
Study officials:
affiliation: CSL Behring
name: Iris Jacobs, MD
role: STUDY_DIRECTOR
References:
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.