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A Safety and Efficacy Study of a Recombinant Fusion Protein Linking Coagulation Factor IX With Albumin (rIX-FP) in Patients With Hemophilia B

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
CSL Behring
ClinicalTrials.gov Identifier:
NCT01496274
First received: December 19, 2011
Last updated: April 3, 2016
Last verified: April 2016
  Purpose
This study will examine the safety, pharmacokinetics and efficacy of rIX-FP for the control and prevention of bleeding episodes in subjects who have previously received factor replacement therapy for hemophilia B.

Condition Intervention Phase
Hemophilia B
Biological: rIX-FP
Phase 2
Phase 3

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 II/III 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:
  • Change in Frequency of Spontaneous Bleeding Events Between On-demand and Prophylaxis Treatments (Annualized) [ Time Frame: Up to 26 weeks for on-demand regimen, and between 1 and 17 months for prophylaxis regimen. ] [ Designated as safety issue: No ]
    Subjects in the on-demand arm received on-demand dosing with rIX-FP for up to 26 weeks (on-demand regimen), and then received weekly prophylaxis with rIX-FP for the remainder of the study (prophylaxis regimen). The effectiveness of prophylaxis in comparison to on-demand therapy was investigated by comparing the same subject's annualized spontaneous bleeding rate (AsBR) during the on-demand regimen and during the prophylaxis regimen.

  • Number of Subjects Developing Inhibitors Against Factor IX (FIX) [ Time Frame: Up to 27.7 months (maximum) ] [ Designated as safety issue: Yes ]
    The number of participants developing inhibitors against factor IX (FIX) along with the 95% Clopper-Pearson confidence interval, are summarized for subjects with 50 or more exposure days (EDs) to rIX-FP, and for all participants in the study.


Secondary Outcome Measures:
  • The Frequency of Related Adverse Events [ Time Frame: For the duration of the study; median 20.27 months. ] [ Designated as safety issue: Yes ]
    The percentage of participants experiencing treatment-related adverse-events (TEAEs).

  • Number of Subjects Developing Antibodies Against rIX-FP [ Time Frame: For the duration of the study; median 20.27 months. ] [ Designated as safety issue: Yes ]
  • Proportion of Bleeding Episodes Requiring One or ≤ Two Injections of rIX-FP to Achieve Hemostasis [ Time Frame: For the duration of the study; median 20.27 months. ] [ Designated as safety issue: No ]
    Number of injections required to achieve hemostasis expressed as a percentage of the bleeding episodes requiring treatment.

  • Investigator's Overall Clinical Assessment of Hemostatic Efficacy for Treatment of Bleeding Episodes, Based on a Four Point Ordinal Scales (Excellent, Good, Moderate, Poor/No Response) [ Time Frame: For the duration of the study; median 20.27 months ] [ Designated as safety issue: No ]
    Number of bleeding episodes requiring treatment that resulted in hemostatic efficacy of excellent, good, moderate, poor/no response, according to the Investigator's clinical assessment of hemostatic efficacy, expressed as a percentage of the bleeding episodes requiring treatment.

  • rIX-FP Consumed Per Month While Maintaining Assigned Prophylactic Treatment Interval During Routine Prophylaxis. [ Time Frame: Median 269, 240, 386 and 316 days, respectively (see Description) ] [ Designated as safety issue: No ]
    Time frame: For Prophylaxis Arm 7-, 10- and 14-day regimens, median 269, 240 and 386 days respectively. For On-demand Arm, prophylaxis regimen, median 316 days.

  • Incremental Recovery of rIX-FP [ Time Frame: 336 hours ] [ Designated as safety issue: No ]
    Pharmacokinetic (PK) data are presented for a single 50 IU/kg dose of rIX-FP.

  • Half-life (t1/2) of a Single Dose of rIX-FP [ Time Frame: 336 hours ] [ Designated as safety issue: No ]
    PK data are presented for a single 50 IU/kg dose of rIX-FP.

  • Area Under the Curve (AUC) [ Time Frame: 336 hours ] [ Designated as safety issue: No ]
    AUC to the last sample with quantifiable drug concentration (AUClast) of a single dose of rIX-FP. PK data are presented for a single 50 IU/kg dose of rIX-FP.

  • Clearance of a Single Dose of rIX-FP [ Time Frame: 336 hours ] [ Designated as safety issue: No ]
    PK data are presented for a single 50 IU/kg dose of rIX-FP.

  • Investigator's (or Surgeon's) Overall Clinical Assessment of Hemostatic Efficacy for Surgical Prophylaxis, Based on a Four Point Ordinal Scale (Excellent, Good, Moderate, Poor/No Response) [ Time Frame: Up to 14 days after surgery ] [ Designated as safety issue: No ]
    Number of surgical events treated prophylactically with rIX-FP that resulted in hemostatic efficacy of excellent, good, moderate, poor/no response, according to the Investigator's (surgeon's) overall assessment of hemostatic efficacy for surgical prophylaxis.

  • Annualized Spontaneous Bleeding Events Compared Between 7 Day Prophylactic and Extended Regimens [ Time Frame: During treatment, between median 240 and 386 days per subject. ] [ Designated as safety issue: No ]
    Median number of spontaneous bleeds per year per subject comparing 7-, 10- and 14- day prophylactic regimens.


Enrollment: 63
Study Start Date: February 2012
Primary Completion Date: July 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Prophylaxis

Routine weekly prophylaxis and episodic treatment for bleeding episodes. An individualized dosing interval may be tested in sub-group subjects during the 2nd part of the trial.

Subjects may participate in a surgical 'sub-study' in which rIX-FP may be administered prior to, during and after surgical intervention.

Biological: rIX-FP
Recombinant IX-FP (rIX-FP) is a fusion protein linking coagulation factor IX with albumin, and will be administered by intravenous administration
Experimental: On-demand
Episodic treatment for bleeding episodes during the first 6 months then switch to routine weekly prophylaxis for a further 6 months Subjects may participate in a surgical 'sub-study' in which rIX-FP may be administered prior to, during and after surgical intervention.
Biological: rIX-FP
Recombinant IX-FP (rIX-FP) is a fusion protein linking coagulation factor IX with albumin, and will be administered by intravenous administration

  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
  • On-demand subjects only, who have experienced a minimum average of 2 non-trauma induced bleeding episodes requiring treatment with a FIX product during the previous 6 or 3 months

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, kidney or liver dysfunction
  • Recent life-threatening bleeding episode
  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: NCT01496274

  Show 30 Study Locations
Sponsors and Collaborators
CSL Behring
Investigators
Study Director: Program Director CSL Behring
  More Information

Responsible Party: CSL Behring
ClinicalTrials.gov Identifier: NCT01496274     History of Changes
Other Study ID Numbers: CSL654_3001  2011-002415-28 
Study First Received: December 19, 2011
Results First Received: April 3, 2016
Last Updated: April 3, 2016
Health Authority: Austria: Federal Office for Safety in Health Care
Bulgaria: Bulgarian Drug Agency
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Germany: Paul-Ehrlich-Institut
Israel: Ministry of Health
Italy: Ministry of Health
Japan: Pharmaceuticals and Medical Devices Agency
Russia: Ministry of Health of the Russian Federation
Spain: Spanish Agency of Medicines
United States: Food and Drug Administration

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 30, 2016