Hemophilia BPhase 2/3NCT01496274
A Safety and Efficacy Study of a Recombinant Fusion Protein Linking Coagulation Factor IX With Albumin (rIX-FP) in Patients With Hemophilia B
A Phase 2/3 study testing rIX-FP in people with Hemophilia B, run by CSL Behring at 30 sites in 10 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 12 to 65 years, men only
- Conditions the study is for
- Hemophilia B
- What is being tested?
- rIX-FP
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 63 participants
- Where
- 30 sitesin 10 countries
- Study dates
- Feb 2012to Jul 2014
- Phase
- Phase 2/3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 12 to 65 years
- Men only
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
30 sites in 10 countries.
30 sites in 10 countries
Japan7 sites
Nara Medical University Hospital [PEDIATRICS]
Kashihara, 634-8522
University of Occupational and Environmental Health
Kitakyushu
Nagoya University Hospital
Nagoya, 466-8550
The Hospital of Hyogo College of Medicine
Nishinomiya
Ogikubo Hospital
Tokyo, 167-0035
Tokyo Medical University Hospital
Tokyo
St. Marianna University, School of Medicine, Yokohama Seibu
Yokohama, 241-0811
Germany5 sites
Instit. für Experimentelle - Hämato & Transfusionsmedizin
Bonn
Zentralkrankenhaus Prof. Hess-Kinderklinik
Bremen, 28205
Unikinderklinik Frankfurt/Main [Kinderheilkunde]
Frankfurt
Universitätsklinikum Hamburg-Eppendorf, Abt für Pädiatr. Hämatologie
Hamburg, 20246
Werlhof-Inst. Hannover
Hanover
United States4 sites
Rush University Medical Center
Chicago, Illinois, 60612
Indiana Hemophilia and Thrombosis Center, Inc.
Indianapolis, Indiana, 46260
BloodCenter of Wisconsin
Milwaukee, Wisconsin, 53201
Hospital of the University of Pennsylvania
Philadelphia, Pennsylvania, 19104
France4 sites
Centre Hospitalier Universitaire de Brest/CHU Morvan
Brest, 29609
C.R.T.H. Hôp. Bicêtre-Hémophilie
Le Kremlin-Bicêtre, 94275
CHU de Lyon - Hôpital Edouard Herriot [Hemophilie]
Lyon, 03 69437
Hôpital Necker-CRTH
Paris, 75015
Italy3 sites
IRCCS Ospedale Maggiore[Centro emofilia e Trombosi]
Milan
A.O.U. di Parma [Centro di Rif. Reg. per la cura dell'Emofil
Parma, 43126
Osp. S.Bortolo ULSS N.6 [Terapie Cell. ed Ematologia]
Vicenza, 36100
Spain3 sites
C.H.U. A Coruña [Hematología]
A Coruña
H.U.Vall d'Hebrón [Hemofillia]
Barcelona
H.U. La Paz [Coagulopatias Congénitas]
Madrid, 28046
Bulgaria1 site
SHAT "Joan Pavel" OOD [Hemorrhagic Diathesis and Anemia]
Sofia, 1233
Russia1 site
FGU "Kirov Research Institute of Haemotology and Blood Trans
Kirov, 610027
About this study
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
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.
- Conditions
- Hemophilia B
- Being tested
- rIX-FP
- Medical subject headings
- Hemophilia B
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
rIX-FPBiological
Recombinant IX-FP (rIX-FP) is a fusion protein linking coagulation factor IX with albumin, and will be administered by intravenous administration
| Study group | Role | What they receive |
|---|---|---|
| Prophylaxis | Experimental | 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. Receives: Biological: rIX-FP |
| On-demand | Experimental | 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. Receives: Biological: rIX-FP |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Frequency of Spontaneous Bleeding Events Between On-demand and Prophylaxis Treatments (Annualized)
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.
Measured: 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)
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.
Measured: Up to 27.7 months (maximum)
Secondary outcomes (11)
The Frequency of Related Adverse Events
The percentage of participants experiencing treatment-related adverse-events (TEAEs).
Measured: For the duration of the study; median 20.27 months.
Number of Subjects Developing Antibodies Against rIX-FP
Measured: 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
Number of injections required to achieve hemostasis expressed as a percentage of the bleeding episodes requiring treatment.
Measured: 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)
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.
Measured: 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: 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.
Measured: Median 269, 240, 386 and 316 days, respectively (see Description)
Incremental Recovery of rIX-FP
Pharmacokinetic (PK) data are presented for a single 50 IU/kg dose of rIX-FP.
Measured: 336 hours
Half-life (t1/2) of a Single Dose of rIX-FP
PK data are presented for a single 50 IU/kg dose of rIX-FP.
Measured: 336 hours
Area Under the Curve (AUC)
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.
Measured: 336 hours
Clearance of a Single Dose of rIX-FP
PK data are presented for a single 50 IU/kg dose of rIX-FP.
Measured: 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)
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.
Measured: Up to 14 days after surgery
Annualized Spontaneous Bleeding Events Compared Between 7 Day Prophylactic and Extended Regimens
Median number of spontaneous bleeds per year per subject comparing 7-, 10- and 14- day prophylactic regimens.
Measured: During treatment, between median 240 and 386 days per subject.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Dec 2011 (estimated)
- Study startFeb 2012
- Primary completionJul 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Hemophilia BStudies of the same condition, open and under way.
- More trials run by CSL BehringThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2/3
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 63 participants (actual)
Sponsor and investigators
- Lead sponsor
- CSL Behring
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Program Director, Study director, CSL Behring
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01496274
- Sponsor's protocol ID
- CSL654_3001
- Other IDs
- 2011-002415-28
- Status last verified
- Apr 2016
- First submitted
- 19 Dec 2011
- Last updated
- 9 May 2016
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Koopman SF, Cnossen MH, Mathot RAA; OPTI-CLOT study group and SYMPHONY consortium. Relationship between Dose, Factor IX Activity Levels and Bleeding Probability for rIX-FP Prophylaxis in Hemophilia B: A Repeated Time-to-Event Analysis. Clin Pharmacol Ther. 2025 Oct;118(4):831-840. doi: 10.1002/cpt.3724. Epub 2025 May 19.
PubMed 40386832Santagostino 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, Alvarez-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.
PubMed 26755710
Study at a glance
From the registry record, last updated by the sponsor on 9 May 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01496274
- Acronym / sponsor ID
- CSL654_3001
- Conditions
- Hemophilia B
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 63 participants (actual)
- Lead sponsor
- CSL BehringIndustry (pharma, biotech, devices)
- Study start
- Feb 2012
- Primary completion
- Jul 2014 (actual)
- First posted
- 21 Dec 2011 (estimated)
- Results
- Posted 9 May 2016
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Prophylaxis | Experimental | Biological: rIX-FPRoutine 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. |
| On-demand | Experimental | Biological: rIX-FPEpisodic 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. |
Who may qualify
- Ages
- 12 to 65 years
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (6 listed)
- 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
Key exclusion criteria (5 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| rIX-FPRecombinant IX-FP (rIX-FP) is a fusion protein linking coagulation factor IX with albumin, and will be administered by intravenous administration | Biological | On-demand, Prophylaxis |
Primary outcome
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.
11 secondary outcomes
The Frequency of Related Adverse Events
Time frame: 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.
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.
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
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)
Incremental Recovery of rIX-FP
Time frame: 336 hours
Half-life (t1/2) of a Single Dose of rIX-FP
Time frame: 336 hours
Area Under the Curve (AUC)
Time frame: 336 hours
Clearance of a Single Dose of rIX-FP
Time frame: 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
Annualized Spontaneous Bleeding Events Compared Between 7 Day Prophylactic and Extended Regimens
Time frame: During treatment, between median 240 and 386 days per subject.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 May 2016.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 40386832Koopman SF, Cnossen MH, Mathot RAA; OPTI-CLOT study group and SYMPHONY consortium. Relationship between Dose, Factor IX Activity Levels and Bleeding Probability for rIX-FP Prophylaxis in Hemophilia B: A Repeated Time-to-Event Analysis. Clin Pharmacol Ther. 2025 Oct;118(4):831-840. doi: 10.1002/cpt.3724. Epub 2025 May 19.
- Derived from this study: PubMed 26755710Santagostino 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, Alvarez-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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Program Director study director
CSL Behring
30 sites in 10 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing rIX-FP in people with Hemophilia B, run by CSL Behring at 30 sites in 10 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 9 May 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 30 sites in Japan, Germany, United States, France, Italy and 5 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 9 May 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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.). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01496274, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 May 2016.