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A Safety and Efficacy Extension 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: NCT02053792
Recruitment Status : Recruiting
First Posted : February 4, 2014
Last Update Posted : August 28, 2019
Sponsor:
Information provided by (Responsible Party):
CSL Behring

Tracking Information
First Submitted Date  ICMJE January 29, 2014
First Posted Date  ICMJE February 4, 2014
Last Update Posted Date August 28, 2019
Actual Study Start Date  ICMJE February 6, 2014
Estimated Primary Completion Date January 31, 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 1, 2017)
  • Main study: Total number of subjects who develop inhibitors against factor IX (FIX) [ Time Frame: Approximately 5 years ]
  • Surgery substudy: Investigator's overall clinical assessment of hemostatic efficacy for surgical prophylaxis [ Time Frame: Immediately after surgery (0 hours) and at up to 3 timepoints thereafter up to 72 hours or discharge, whichever is earliest. ]
    Clinical assessment of hemostatic efficacy to be based on a four point ordinal scale (excellent, good, moderate, poor / none)
  • Incremental recovery in previously untreated patients (PUPs) [ Time Frame: Approximately 30 minutes after infusion ]
    Incremental recovery expressed as IU/dL per IU/kg
Original Primary Outcome Measures  ICMJE
 (submitted: February 2, 2014)
  • Main study: Total number of subjects who develop inhibitors against factor IX (FIX) [ Time Frame: Approximately 3 years ]
  • Surgery substudy: Investigator's overall clinical assessment of hemostatic efficacy for surgical prophylaxis [ Time Frame: Immediately after surgery (0 hours) and at up to 3 timepoints thereafter up to 72 hours or discharge, whichever is earliest. ]
    Clinical assessment of hemostatic efficacy to be based on a four point ordinal scale (excellent, good, moderate, poor / none)
Change History Complete list of historical versions of study NCT02053792 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: May 1, 2017)
  • Main study: Comparison of annualized bleeding rate between different prophylaxis treatment intervals. [ Time Frame: Approximately 5 years ]
    Comparison of annualized bleeding rate by prophylaxis treatment interval for spontaneous treated bleeds and total treated bleeds.
  • Main study: Comparison of annualized bleeding rate between 2 different prophylaxis treatment intervals and on-demand treatment. [ Time Frame: Approximately 5 years ]
    For subjects from the lead-in study (CSL654_3001 [NCT01496274]), comparison of the annualized bleeding rate of spontaneous treated bleeds and total treated bleeds between routine prophylaxis treatment in this study (CSL654_3003) and:
    • On-demand treatment during the lead-in study (CSL654_3001).
    • Routine prophylaxis treatment with the different treatment interval used by the subject in the lead-in study (CSL654_3001).
  • Main study: rIX-FP consumed per month per subject during routine prophylaxis treatment. [ Time Frame: Approximately 5 years ]
  • Surgery substudy: The frequency of adverse events (AEs) related to rIX-FP [ Time Frame: 28 days after surgery (major surgery) or up to hospital discharge (minor surgery) ]
  • Surgery substudy: Total number of subjects who develop inhibitors against FIX [ Time Frame: 28 days after surgery (major surgery) or up to hospital discharge (minor surgery) ]
  • Surgery substudy: Total number of subjects who develop antibodies against rIX-FP. [ Time Frame: 28 days after surgery (major surgery) or up to hospital discharge (minor surgery) ]
  • Surgery substudy: Predicted and intraoperative estimated blood loss. [ Time Frame: Predicted blood loss and intraoperative estimated blood loss to be determined before surgery and at the end of surgery, respectively ]
    The predicted blood loss (mL) is based on blood loss expected from a non-hemophilic individual undergoing the same type / extent of procedure. The estimated blood loss (mL) is the anesthesiologist's record of estimated blood loss during the procedure.
  • Surgery substudy: Predicted and actual transfusion requirements. [ Time Frame: Predicted and actual transfusion requirements to be determined before and at the end of surgery, respectively ]
  • Surgery substudy: Change in hemoglobin levels between baseline, intraoperatively and postoperatively (major surgery only). [ Time Frame: Before, during and up to 28 days after surgery ]
  • Overall adverse events (AEs) and rIX-FP-related AEs [ Time Frame: Approximately 5 years ]
    The overall percentage of subjects with at least one AE, and the overall percentage of subjects with at least one rIX-FP-related AE
  • Hemostatic response to rIX-FP treatment in PUPs [ Time Frame: Hemostatic response of rIX-FP treatment during the course of the study (up to 5 years) ]
    The investigator will rate the efficacy of the rIX-FP treatment based on a hemostatic efficacy four point rating scale of "excellent, good, moderate or poor/no response".
Original Secondary Outcome Measures  ICMJE
 (submitted: February 2, 2014)
  • Main study: Comparison of annualized bleeding rate between different prophylaxis treatment intervals. [ Time Frame: Approximately 3 years ]
    Comparison of annualized bleeding rate by prophylaxis treatment interval for spontaneous treated bleeds and total treated bleeds.
  • Main study: Comparison of annualized bleeding rate between 2 different prophylaxis treatment intervals and on-demand treatment. [ Time Frame: At least 3 months and up to 6 months ]
    For subjects from the lead-in study (CSL654_3001 [NCT01496274] on-demand arm), comparison of the annualized bleeding rate of spontaneous treated bleeds between routine prophylaxis treatment in this study (CSL654_3003) and:
    • On-demand treatment during the lead-in study (CSL654_3001).
    • Routine prophylaxis treatment with the different treatment interval used by the subject in the lead-in study (CSL654_3001).
  • Main study: rIX-FP consumed per month per subject during routine prophylaxis treatment. [ Time Frame: Approximately 3 years ]
  • Surgery substudy: The frequency of adverse events (AEs) related to rIX-FP [ Time Frame: 28 days after surgery (major surgery) or up to hospital discharge (minor surgery) ]
  • Surgery substudy: Total number of subjects who develop inhibitors against FIX [ Time Frame: 28 days after surgery (major surgery) or up to hospital discharge (minor surgery) ]
  • Surgery substudy: Total number of subjects who develop antibodies against rIX-FP. [ Time Frame: 28 days after surgery (major surgery) or up to hospital discharge (minor surgery) ]
  • Surgery substudy: Predicted and intraoperative estimated blood loss. [ Time Frame: Predicted blood loss and intraoperative estimated blood loss to be determined before surgery and at the end of surgery, respectively ]
    The predicted blood loss (mL) is based on blood loss expected from a non-hemophilic individual undergoing the same type / extent of procedure. The estimated blood loss (mL) is the anesthesiologist's record of estimated blood loss during the procedure.
  • Surgery substudy: Predicted and actual transfusion requirements. [ Time Frame: Predicted and actual transfusion requirements to be determined before and at the end of surgery, respectively ]
  • Surgery substudy: Change in hemoglobin levels between baseline, intraoperatively and postoperatively (major surgery only). [ Time Frame: Before, during and up to 28 days after surgery ]
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 Extension Study of a Recombinant Fusion Protein Linking Coagulation Factor IX With Albumin (rIX-FP) in Patients With Hemophilia B
Official Title  ICMJE A Phase 3b Open-label, Multicenter, Safety and Efficacy Extension Study of a Recombinant Coagulation Factor IX Albumin Fusion Protein (rIX-FP) in Subjects With Hemophilia B
Brief Summary

This study will examine the long-term safety and efficacy of rIX-FP for the control and prevention of bleeding episodes in children and adults with severe hemophilia B. The study will include subjects who have not previously been treated with Factor IX products, subjects who previously completed a CSL-sponsored rIX-FP lead-in study and subjects requiring major non-emergency surgery who have not previously completed a CSL-sponsored rIX-FP lead-in study.

A surgical prophylaxis substudy will examine the efficacy of rIX-FP in subjects with hemophilia B who are undergoing non-emergency major or minor surgery. An additional substudy will examine the safety and PK of subcutaneous (SC) administration of rIX-FP.

Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Hemophilia B
Intervention  ICMJE Biological: rIX-FP
Recombinant Fusion Protein Linking Coagulation Factor IX with Albumin (rIX-FP)
Study Arms  ICMJE Experimental: rIX-FP

Subjects will administer rIX-FP by intravenous infusion as routine prophylaxis, prevention, and on-demand treatment during a treatment period of approximately 3 years.

The routine prophylaxis treatment interval for previously treated patients may be changed at each scheduled 6-month follow-up assessment. On-demand treatment with rIX-FP will be used for all bleeding episodes requiring treatment. Subjects (other than those in France) may participate in a surgical 'substudy' in which rIX-FP may be administered before, during and after surgery. An additional substudy will examine the safety and PK of subcutaneous administration of rIX-FP.

For previously untreated patients, subjects will administer rIX-FP intravenously as weekly prophylaxis and/or on-demand treatment during the first 12 months, and as weekly routine prophylaxis thereafter.

The dose of rIX-FP administered will be based on the subject's previous rIX-FP use and/or pharmacokinetic data.

Intervention: Biological: rIX-FP
Publications * Not Provided

*   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 Recruiting
Estimated Enrollment  ICMJE
 (submitted: June 10, 2015)
115
Original Estimated Enrollment  ICMJE
 (submitted: February 2, 2014)
95
Estimated Study Completion Date  ICMJE January 31, 2022
Estimated Primary Completion Date January 31, 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion criteria:

Main study inclusion criteria:

For previously treated subjects, either:

  • Completed a CSL-sponsored rIX-FP (CSL654) study, including study CSL654_3001 [NCT01496274] or study CSL654_3002 [NCT01662531].

Or:

  • Scheduled to have a major non-emergency surgery within approximately 8 weeks from the anticipated date of receiving the first rIX-FP injection.
  • Not previously completed a CSL-sponsored rIX-FP lead-in study.
  • Male, 12 to 70 years of age.
  • Documented severe hemophilia B (FIX activity of ≤ 2%), or confirmed at screening by the central laboratory.
  • Subjects who have received FIX products (plasma-derived and / or recombinant FIX) for > 150 exposure days (EDs), confirmed by their treating physician.
  • No confirmed history of FIX inhibitor formation at screening by the central laboratory

For previously untreated subjects:

  • Male, up to 18 years of age.
  • Documented severe hemophilia B (FIX activity of ≤ 2%), or confirmed at screening by the central laboratory.
  • Never previously been treated with FIX clotting factor products (except previous exposure to blood components).
  • No confirmed history of FIX inhibitor formation

Surgery substudy inclusion criterion:

  • Must require non-emergency surgery

Subcutaneous substudy inclusion criteria:

  • Male, at least 18 years of age.
  • Subjects currently enrolled in Study CSL654_3003
  • Subjects who have received rIX-FP for ≥ 100 EDs (single-dose cohorts) or for ≥ 50 EDs (repeated-dose cohort)

Exclusion criteria:

Main study exclusion criteria:

  • Currently receiving a therapy not permitted during the study.
  • Any issue that, in the opinion of the investigator, would render the subject unsuitable for participation in the study.

For subjects who have previously completed a CSL-sponsored rIX-FP study:

  • Unwilling to participate in the study for a total of 100 exposure days.

For subjects requiring major non-emergency surgery who have not previously completed a CSL-sponsored rIX-FP lead-in study:

  • Known hypersensitivity (ie, allergic reaction or anaphylaxis) to any FIX product or hamster protein.
  • Known congenital or acquired coagulation disorder other than congenital FIX deficiency.
  • Currently receiving IV immunomodulating agents such as immunoglobulin or chronic systemic corticosteroid treatment.
  • Low platelet count, kidney or liver disease.
  • Human immunodeficiency virus positive with a CD4 count < 200/mm3.

For previously untreated subjects:

  • Known congenital or acquired coagulation disorder other than congenital FIX deficiency (except for vitamin K deficiency of the newborn).
  • Known kidney or liver dysfunction or any condition which, in the investigator's opinion, place the patient at unjustifiable risk.

The surgical substudy does not have any additional exclusion criteria, although subject(s) in France will not be eligible for the surgery sub-study.

Subcutaneous substudy exclusion criteria:

  • Intravenous use of rIX-FP within 14 days of subcutaneous administration of rIX-FP.
  • Life-threatening bleeding episode or major surgery during the 3 months prior to substudy entry
Sex/Gender  ICMJE
Sexes Eligible for Study: Male
Ages  ICMJE up to 70 Years   (Child, Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Clinical Trial Registration Coordinator clinicaltrials@cslbehring.com
Listed Location Countries  ICMJE United States,   Australia,   Austria,   Bulgaria,   Canada,   Czechia,   France,   Germany,   Israel,   Italy,   Japan,   Malaysia,   Philippines,   South Africa,   Spain
Removed Location Countries Czech Republic
 
Administrative Information
NCT Number  ICMJE NCT02053792
Other Study ID Numbers  ICMJE CSL654_3003
2012-005489-37 ( EudraCT Number )
Has Data Monitoring Committee Not Provided
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 August 2019

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