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A Safety and Efficacy Study of a Recombinant Factor IX in Patients With Severe Hemophilia B

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
CSL Behring
ClinicalTrials.gov Identifier:
NCT01361126
First received: May 25, 2011
Last updated: April 3, 2016
Last verified: April 2016
  Purpose
This study will examine the safety and efficacy of a Recombinant Coagulation Factor IX Albumin Fusion Protein (rIX-FP) for the control and prevention of bleeding episodes in subjects who have previously received factor replacement therapy for hemophilia B. The study consists of a screening period, a pharmacokinetic (PK) period, followed by approximately a 5 month treatment period. Subjects will receive weekly routine prophylactic therapy and on-demand treatment for bleeding episodes. In addition, subjects who are not on routine factor replacement therapy prior to the study will receive only on-demand treatment for bleeding episodes.

Condition Intervention Phase
Hemophilia B
Biological: Recombinant Coagulation Factor IX Albumin Fusion Protein
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I/II Open-label, Multicenter, Safety and Efficacy 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:
  • Number of Subjects With Treatment-related Adverse Events [ Time Frame: Approximately 20 weeks ] [ Designated as safety issue: Yes ]
    The causal relationship of each adverse event to rIX-FP was assessed by the Investigator.

  • Number of Subjects With Inhibitors Against Factor IX (FIX) [ Time Frame: Baseline, Day 10 and Weeks 4, 12 and 20 ] [ Designated as safety issue: Yes ]
    The presence of inhibitors against FIX was assessed by the central laboratory by a FIX potency assay. To quantify anti-FIX neutralizing antibodies, the Bethesda assay with the Nijmegen modification was used, and the results expressed as Bethesda Units per mL (BU/mL). A positive inhibitor test is >=0.6 BU/mL.

  • Number of Subjects Who Developed Antibodies to rIX-FP [ Time Frame: Pre-dose, Day 10 and Weeks 4, 12, and 20 ] [ Designated as safety issue: Yes ]
    Antibodies against rIX-FP were detected using a direct binding enzyme-linked immunosorbent assay (ELISA).


Secondary Outcome Measures:
  • Area Under the Curve to the Last Sample With Quantifiable Drug Concentration (AUC0-t) After a Single Dose of rIX-FP [ Time Frame: Pre-dose and up to 14 days after rIX-FP infusion. ] [ Designated as safety issue: No ]
    The plasma concentrations of rIX-FP were measured as FIX activity using a validated, 1-stage assay in a central laboratory for a quantification range from 0.25 to 150% (or 0.25 IU/dL to 150 IU/dL). The PK population comprised all subjects who received at least 1 dose of rIX-FP and for whom a sufficient number of analyzable PK samples had been obtained in order to permit the evaluation of the PK profile of rIX-FP, and who did not receive a dose of rIX-FP or any other FIX product for the treatment of a bleed during the PK sampling period.

  • Half-life (t1/2) of a Single Dose of rIX-FP [ Time Frame: Pre-dose and up to 14 days after infusion ] [ Designated as safety issue: No ]
  • Incremental Recovery of rIX-FP at 30 Minutes Following Infusion of rIX-FP [ Time Frame: 30 minutes after infusion ] [ Designated as safety issue: No ]
    Incremental recovery (IU/mL/IU/kg) is defined as FIX activity (IU/mL) obtained 30 minutes following infusion, per dose of (IU/kg) infusion. FIX activity was measured at a central laboratory using validated one-stage clotting method.

  • Clearance of a Single Dose of rIX-FP [ Time Frame: Pre-dose and up to 14 days after rIX-FP infusion ] [ Designated as safety issue: No ]
  • Breakthrough Bleeding Events [ Time Frame: Week 9 to approximately Week 20 ] [ Designated as safety issue: No ]
    Number of breakthrough bleeding events (spontaneous bleeding events) requiring treatment per subject in subjects receiving prophylactic treatment regimen with rIX-FP


Enrollment: 17
Study Start Date: July 2011
Study Completion Date: July 2012
Primary Completion Date: June 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: On-demand
The routine prophylactic therapy interval is targeted at every 7 days.
Biological: Recombinant Coagulation Factor IX Albumin Fusion Protein
Study subjects will receive a single dose of 25IU/kg of rIX_FP for pharmacokinetic analysis. Subjects will then be treated for approximately 5 months. The treatment dose will be based on the subject's PK profile and the subject's bleeding phenotype.
Other Name: CSL654
Experimental: Prophylactic
On-demand subjects will receive rIX-FP only for the treatment of a bleeding episode.
Biological: Recombinant Coagulation Factor IX Albumin Fusion Protein
Study subjects will receive a single dose of 25IU/kg of rIX_FP for pharmacokinetic analysis. Subjects will then be treated for approximately 5 months. The treatment dose will be based on the subject's PK profile and the subject's bleeding phenotype.
Other Name: CSL654

  Eligibility

Ages Eligible for Study:   12 Years to 65 Years   (Child, Adult)
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Male subjects, 12 to 65 years old
  • Severe hemophilia B (FIX activity of ≤ 2%)
  • Subjects who have received FIX products (plasma-derived and/or recombinant FIX) for > 150 exposure days (EDs)
  • No history of FIX inhibitor formation, no detectable inhibitors at Screening and no family history of inhibitors against FIX
  • Written informed consent for study participation obtained before undergoing any study specific procedures

Exclusion Criteria:

  • Known hypersensitivity to any FIX product or hamster protein
  • Known congenital or acquired coagulation disorder other than congenital FIX deficiency
  • HIV positive subjects with a CD4 count < 200/mm3
  • Low platelet count, abnormal kidney function, or liver disease
  • On-demand subjects experiencing less than 12 or 6 non-trauma induced bleeding episodes requiring treatment with a FIX product during the previous 6 or 3 months, respectively
  • Planned major surgical intervention during the study period
  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: NCT01361126

Locations
Bulgaria
Study Site
Sofia, Bulgaria
Israel
Study Site
Tel Aviv, Israel
Sponsors and Collaborators
CSL Behring
Investigators
Study Director: Iris Jacobs, MD CSL Behring
  More Information

Responsible Party: CSL Behring
ClinicalTrials.gov Identifier: NCT01361126     History of Changes
Other Study ID Numbers: CSL654_2004  2010-023793-39 
Study First Received: May 25, 2011
Results First Received: April 3, 2016
Last Updated: April 3, 2016
Health Authority: Bulgaria: Bulgarian Drug Agency
Israel: Ministry of Health

Additional relevant MeSH terms:
Hemophilia A
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 September 27, 2016