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

April 3, 2016 updated by: CSL Behring

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

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
63

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Austria
      • Wien, Austria
        • AKH Wien [Hämatologie, Hämostaseol
  • Bulgaria
      • Sophia, Bulgaria, 1233
        • SHAT "Joan Pavel" OOD [Hemorrhagic Diathesis and Anemia]
  • France
      • Brest, France, 29609
        • Centre Hospitalier Universitaire de Brest/CHU Morvan
      • Le Kremlin-Bicêtre, France, 94275
        • C.R.T.H. Hôp. Bicêtre-Hémophilie
      • Lyon, France, 03 69437
        • CHU de Lyon - Hôpital Edouard Herriot [Hemophilie]
      • Paris, France, 75015
        • Hôpital Necker-CRTH
  • Germany
      • Bonn, Germany
        • Instit. für Experimentelle - Hämato & Transfusionsmedizin
      • Bremen, Germany, 28205
        • Zentralkrankenhaus Prof. Hess-Kinderklinik
      • Frankfurt, Germany
        • Unikinderklinik Frankfurt/Main [Kinderheilkunde]
      • Hamburg, Germany, 20246
        • Universitätsklinikum Hamburg-Eppendorf, Abt für Pädiatr. Hämatologie
      • Hannover, Germany
        • Werlhof-Inst. Hannover
  • Israel
      • Tel Aviv, Israel
        • Chaim Sheba Medical Center
  • Italy
      • Milano, Italy
        • IRCCS Ospedale Maggiore[Centro emofilia e Trombosi]
      • Parma, Italy, 43126
        • A.O.U. di Parma [Centro di Rif. Reg. per la cura dell'Emofil
      • Vicenza, Italy, 36100
        • Osp. S.Bortolo ULSS N.6 [Terapie Cell. ed Ematologia]
  • Japan
      • Kashihara, Japan, 634-8522
        • Nara Medical University Hospital [PEDIATRICS]
      • Kitakyushu, Japan
        • University of Occupational and Environmental Health
      • Nagoya, Japan, 466-8550
        • Nagoya University Hospital
      • Nishinomiya, Japan
        • The Hospital of Hyogo College of Medicine
      • Tokyo, Japan, 167-0035
        • Ogikubo Hospital
      • Tokyo, Japan
        • Tokyo Medical University Hospital
      • Yokohama, Japan, 241-0811
        • St. Marianna University, School of Medicine, Yokohama Seibu
  • Russian Federation
      • Kirov, Russian Federation, 610027
        • FGU "Kirov Research Institute of Haemotology and Blood Trans
  • Spain
      • A Coruna, Spain
        • C.H.U. A Coruña [Hematología]
      • Barcelona, Spain
        • H.U.Vall d'Hebrón [Hemofillia]
      • Madrid, Spain, 28046
        • H.U. La Paz [Coagulopatias Congénitas]
  • United States
    • Illinois
      • Chicago, Illinois, United States, 60612
        • Rush University Medical Center
    • Indiana
      • Indianapolis, Indiana, United States, 46260
        • Indiana Hemophilia and Thrombosis Center, Inc.
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19104
        • Hospital of the University of Pennsylvania
    • Wisconsin
      • Milwaukee, Wisconsin, United States, 53201
        • BloodCenter of Wisconsin

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

12 years to 65 years (ADULT, OLDER_ADULT, CHILD)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Male

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: NON_RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: NONE

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
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.
Up to 26 weeks for on-demand regimen, and between 1 and 17 months for 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.
Up to 27.7 months (maximum)

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
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).
For the duration of the study; median 20.27 months.
Number of Subjects Developing Antibodies Against rIX-FP
Time Frame: For the duration of the study; median 20.27 months.
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.
For the duration of the study; median 20.27 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/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.
For the duration of the study; median 20.27 months
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.
Median 269, 240, 386 and 316 days, respectively (see Description)
Incremental Recovery of rIX-FP
Time Frame: 336 hours
Pharmacokinetic (PK) data are presented for a single 50 IU/kg dose of rIX-FP.
336 hours
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.
336 hours
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.
336 hours
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.
336 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/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.
Up to 14 days after surgery
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.
During treatment, between median 240 and 386 days per subject.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
CSL Behring

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
February 1, 2012

Primary Completion (ACTUAL)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
July 1, 2014

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
December 19, 2011

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
December 19, 2011

First Posted (ESTIMATE)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
December 21, 2011

Study Record Updates

Last Update Posted (ESTIMATE)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
May 9, 2016

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 3, 2016

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
April 1, 2016

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • CSL654_3001
  • 2011-002415-28 (EUDRACT_NUMBER)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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