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

Hemophilia B Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01233440
• Other study ID #: CSL654_2001
• Secondary ID: 15082010-018477-
• Status: Completed
• Phase: Phase 1
• First received: November 2, 2010
• Last updated: January 26, 2012
• Start date: October 2010
• Est. completion date: July 2011

Study information

• Verified date: January 2012
• Source: CSL Behring
• Contact: n/a
• Is FDA regulated: No
• Health authority: Austria: Agency for Health and Food SafetyFrance: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)Germany: Paul-Ehrlich-InstitutIsrael: Ministry of HealthItaly: National Institute of HealthSpain: Agencia Española de Medicamentos y Productos SanitariosUnited Kingdom: Medicines and Healthcare Products Regulatory Agency
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 25
• Est. completion date: July 2011
• Est. primary completion date: July 2011
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 12 Years to 65 Years

Eligibility

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 Design

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

Related Conditions & MeSH terms

• Hemophilia A
• Hemophilia B

Intervention

Biological:
• Recombinant Coagulation Factor IX Albumin Fusion Protein
Single dose of 25, 50 or 75 IU/kg of rIX-FP, given as intravenous infusion
• Plasma derived FIX [pdFIX]
Single dose of 50 IU/kg of reference product, given as intravenous infusion

Locations

Country	Name	City	State
Austria	Study site	Vienna
France	Study site	Le Kremlin-Bicetre
France	Study Site	Lyon
France	Study site	Nantes
France	Study site	Paris
Germany	Study Site	Berlin
Germany	Study Site	Hamburg
Germany	Study Site	Hannover
Germany	Study site	Munster
Israel	Study Site	Tel Hashomer
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
Spain	Study Site	A Coruna
Spain	Study Site	Barcelona
Spain	Study Site	Madrid

Sponsors (1)

Lead Sponsor	Collaborator
CSL Behring

Countries where clinical trial is conducted

Austria,  France,  Germany,  Israel,  Italy,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Frequency of adverse events (AEs)		up to 14 days after drug administration	Yes
Primary	Frequency of serious adverse events (SAEs)		up to 28 days after drug administration	Yes
Primary	Occurrence of inhibitor against FIX		up to 28 days after drug administration	Yes
Primary	Occurrence of antibodies against rIX-FP		up to 28 days after drug administration	Yes
Secondary	AUC to the last sample with quantifiable drug concentration (AUC0-t)	Following 50 IU/kg rIX-FP infusion	From time of dosing up to 7 days after the dose	No
Secondary	AUC extrapolated to infinity (AUCt-8)	Following 50 IU/kg rIX-FP infusion	From time of dosing up to 7 days after the dose	No
Secondary	Half-life (t1/2)	Following 50 IU/kg rIX-FP infusion	From time of dosing up to 7 days after the dose	No
Secondary	Incremental recovery (IU/mL/IU/kg)	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	No
Secondary	Clearance	Following 50 IU/kg rIX-FP infusion	From time of dosing up to 7 days after the dose	No

External Links

•   Click here to request more information about this study