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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

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ClinicalTrials.gov Identifier: NCT01496274
Recruitment Status : Completed
First Posted : December 21, 2011
Results First Posted : May 9, 2016
Last Update Posted : May 9, 2016
Sponsor:
Information provided by (Responsible Party):
CSL Behring

Tracking Information
First Submitted Date  ICMJE December 19, 2011
First Posted Date  ICMJE December 21, 2011
Results First Submitted Date  ICMJE April 3, 2016
Results First Posted Date  ICMJE May 9, 2016
Last Update Posted Date May 9, 2016
Study Start Date  ICMJE February 2012
Actual Primary Completion Date July 2014   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 3, 2016)
  • 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. ]
    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) ]
    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.
Original Primary Outcome Measures  ICMJE
 (submitted: December 19, 2011)
  • Change in Frequency of Spontaneous Bleeding Events Between On-demand and Prophylaxis Treatments (Annualized) [ Time Frame: Approximately 14 months ]
  • Number of Subjects Developing Inhibitors Against Factor IX (FIX) [ Time Frame: Approximately 14 months ]
Change History Complete list of historical versions of study NCT01496274 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: April 3, 2016)
  • The Frequency of Related Adverse Events [ Time Frame: For the duration of the study; median 20.27 months. ]
    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. ]
  • 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. ]
    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 ]
    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) ]
    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 ]
    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 ]
    PK data are presented for a single 50 IU/kg dose of rIX-FP.
  • Area Under the Curve (AUC) [ Time Frame: 336 hours ]
    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 ]
    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 ]
    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. ]
    Median number of spontaneous bleeds per year per subject comparing 7-, 10- and 14- day prophylactic regimens.
Original Secondary Outcome Measures  ICMJE
 (submitted: December 19, 2011)
  • The Frequency of Related Adverse Events [ Time Frame: Approximately 14 months ]
  • Number of Subjects Developing Antibodies Against rIX-FP [ Time Frame: Approximately 14 months ]
  • Proportion of bleeding episodes requiring one or ≤ two infusions of rIX-FP to achieve hemostasis [ Time Frame: Approximately 14 months ]
  • Investigator's overall clinical assessment of hemostatic efficacy for treatment of bleeding episodes, based on a four point ordinal scales (excellent, good, moderate, poor/ none) [ Time Frame: Approximately 14 months ]
  • rIX-FP Consumed Per Month While Maintaining Assigned Prophylactic Treatment Interval During Routine Prophylaxis. [ Time Frame: Approximately 14 months ]
  • Incremental Recovery of rIX-FP [ Time Frame: 30 minutes ]
  • Half-life (t1/2) of a Single Dose of rIX-FP [ Time Frame: 240 hours ]
  • Area Under the Curve (AUC) [ Time Frame: 240 hours ]
    AUC to the last sample with quantifiable drug concentration (AUC0-t) of a single dose of rIX-FP
  • Clearance of a Single Dose of rIX-FP [ Time Frame: 240 hours ]
  • 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/ none) [ Time Frame: Approximately 14 days ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Safety and Efficacy Study of a Recombinant Fusion Protein Linking Coagulation Factor IX With Albumin (rIX-FP) in Patients With Hemophilia B
Official Title  ICMJE 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
Brief Summary 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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Phase 3
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Hemophilia B
Intervention  ICMJE 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
Study Arms  ICMJE
  • 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.

    Intervention: Biological: rIX-FP
  • 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.
    Intervention: Biological: rIX-FP
Publications * Santagostino E, Martinowitz U, Lissitchkov T, Pan-Petesch B, Hanabusa H, Oldenburg J, Boggio L, Negrier C, Pabinger I, von Depka Prondzinski M, Altisent C, Castaman G, Yamamoto K, Álvarez-Roman MT, Voigt C, Blackman N, Jacobs I; PROLONG-9FP Investigators Study Group. Long-acting recombinant coagulation factor IX albumin fusion protein (rIX-FP) in hemophilia B: results of a phase 3 trial. Blood. 2016 Apr 7;127(14):1761-9. doi: 10.1182/blood-2015-09-669234. Epub 2016 Jan 11.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: August 26, 2014)
63
Original Estimated Enrollment  ICMJE
 (submitted: December 19, 2011)
60
Study Completion Date  ICMJE Not Provided
Actual Primary Completion Date July 2014   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: Male
Ages  ICMJE 12 Years to 65 Years   (Child, Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Austria,   Bulgaria,   France,   Germany,   Israel,   Italy,   Japan,   Russian Federation,   Spain,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01496274
Other Study ID Numbers  ICMJE CSL654_3001
2011-002415-28 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party CSL Behring
Study Sponsor  ICMJE CSL Behring
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Program Director CSL Behring
PRS Account CSL Behring
Verification Date April 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP