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

• 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: CSL Behring
• Information provided by (Responsible Party): CSL Behring

Tracking Information

• First Submitted Date: December 19, 2011
• First Posted Date: December 21, 2011
• Results First Submitted Date: April 3, 2016
• Results First Posted Date: May 9, 2016
• Last Update Posted Date: May 9, 2016
• Study Start Date: February 2012
• Actual Primary Completion Date: July 2014 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (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 (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 ]

Current Secondary Outcome Measures (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 (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: 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: 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: Interventional
• Study Phase: Phase 2; Phase 3
• Study Design: Allocation: Non-Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Hemophilia B

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

Study Arms

• 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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: August 26, 2014): 63
• Original Estimated Enrollment (submitted: December 19, 2011): 60
• Study Completion Date: Not Provided
• Actual Primary Completion Date: July 2014 (Final data collection date for primary outcome measure)

Eligibility 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

Sex/Gender

• Sexes Eligible for Study: Male

• Ages: 12 Years to 65 Years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Austria, Bulgaria, France, Germany, Israel, Italy, Japan, Russian Federation, Spain, United States

Administrative Information

• NCT Number: NCT01496274
• Other Study ID Numbers: CSL654_3001; 2011-002415-28 ( EudraCT Number )
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: CSL Behring
• Study Sponsor: CSL Behring
• Collaborators: Not Provided

Investigators

• Study Director: Program Director; CSL Behring

• PRS Account: CSL Behring
• Verification Date: April 2016