Hemophilia BPhase 3NCT01662531
A Safety, Efficacy and Pharmacokinetics Study of a Recombinant Fusion Protein Linking Coagulation Factor IX With Albumin (rIX-FP) in Children With Hemophilia B
A Phase 3 study testing rIX-FP in people with Hemophilia B, run by CSL Behring at 17 sites in 10 countries.
Trial summary
This study will examine the pharmacokinetics, safety and efficacy of rIX-FP for the control and prevention of bleeding episodes in children who have previously received factor replacement therapy for hemophilia B. Read more about this study
- Who is it for?
- Ages Up to 11 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
- 27 participants
- Where
- 17 sitesin 10 countries
- Study dates
- Jan 2013to Oct 2014
- Phase
- Phase 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 Up to 11 years
- Men only
- No healthy volunteers
- Child
Who may be able to join
- Male subjects, younger than 12 years old.
- Severe hemophilia B (Factor IX [FIX] activity of ≤ 2%).
- Body weight ≥ 10 kg.
- Subjects who have received FIX products (plasma-derived and/or recombinant FIX) for > 150 exposure days (EDs) (6 to < 12 years), and > 50 EDs (< 6 years).
- 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.
Who cannot join
- Known hypersensitivity to any FIX product or hamster protein.
- Known congenital or acquired coagulation disorder other than congenital FIX deficiency.
- Kidney or liver disease.
- Recent life-threatening bleeding episode.
Trial locations and contacts
17 sites in 10 countries.
17 sites in 10 countries
Czechia3 sites
Fakultni nemocnice Brno
Brno, 625 00
Fakultni nemocnice Ostrava
Ostrava, 708 52
Fakultni nemocnice Motole
Prague, 150 06
France3 sites
C.R.T.H. Hopital de Bicentre (Hemophilie)
Le Kremlin-Bicentre, 94275
Hospital Edouard Herriot
Lyon, 69437
Hôpital d'enfants La Timone
Marseille, 13385
Australia2 sites
The Royal Children's Hospital, Melbourne
Parkville, Victoria, 3052
The Children's Hospital at Westmead
Westmead, 2145
Germany2 sites
CRC Coagulation Research Center GmbH
Duisburg/Altstadt, 47051
Universitätsklinikum Düsseldorf
Düsseldorf, 40225
Italy2 sites
AOU Careggi
Florence, 50134
IRCCS Ospendale Maggiore (Centro emofilia e Trombosi)
Milan, 20122
Russia1 site
FGU "Kirov Research Institute of Haemotology and Blood Trans)
Kirov, 610027
About this study
Official title: A Phase III Open-label, Multicenter, Pharmacokinetic, Safety and Efficacy Study of a Recombinant Fusion Protein Linking Coagulation Factor IX With Albumin (rIX-FP) in Previously Treated Children With Hemophilia B
This study will examine the pharmacokinetics, safety and efficacy of rIX-FP for the control and prevention of bleeding episodes in children 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 Fusion Protein Linking Coagulation Factor IX with Albumin (rIX-FP)
| Study group | Role | What they receive |
|---|---|---|
| rIX-FP | Experimental | Recombinant Fusion Protein Linking Coagulation Factor IX with Albumin (rIX-FP) will be administered by IV infusion as routine weekly prophylaxis and episodic treatment for bleeding episodes. Receives: Biological: rIX-FP |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incremental Recovery Following a Single Intravenous Dose of 50 IU/kg rIX-FP or Previous FIX Product
Incremental recovery (IU/dL/IU/kg) is defined as the FIX activity (IU/dL) obtained 30 minutes following infusion, per dose of (IU/kg) infusion. FIX activity was measured at a central laboratory using validated one-stage clotting method. Recovery values were baseline-corrected for pre-infusion plasma FIX activity. Incremental recovery was measured following a single intravenous dose of 50 IU/kg rIX-FP on Day 1. Analysis of previous FIX product was conducted at the beginning of the study in a subset of subjects who had no historical pharmacokinetic (PK) data of their previous FIX product. For the PK assessment, the previous FIX product was administered by IV infusion after approximately 4 days following the last FIX treatment, prior to any dosing of rIX-FP. The formal PK population consisted of subjects who received at least 1 dose of rIX-FP for PK assessment and for whom a sufficient number of analyzable PK samples had been obtained to permit the evaluation of the PK profile of rIX-FP.
Measured: 30 minutes after infusion
Half-life (t1/2) Following a Single Intravenous Dose of 50 IU/kg rIX-FP or Previous FIX Product
FIX activity was measured at a central laboratory using validated one-stage clotting method. FIX levels were not corrected for baseline values.
Measured: Pre-dose, 30 minutes, 3, 24, 48, 72 120, 168, 240 and 336 hours post-dose
Area Under the Concentration Versus Time Curve From Time Point Zero to the Last Sample With Quantifiable Drug Concentration (AUClast)
AUClast following a single intravenous dose of 50 IU/kg rIX-FP or previous FIX product.
FIX activity was measured at a central laboratory using validated one-stage clotting method. FIX levels were not corrected for baseline values.
Measured: Pre-dose, 30 minutes, 3, 24, 48, 72 120, 168, 240 and 336 hours post-dose
Clearance for FIX Activity Following a Single Intravenous Dose of 50 IU/kg rIX-FP or Previous FIX Product
FIX activity was measured at a central laboratory using validated one-stage clotting method. FIX levels were not corrected for baseline values. Clearance is normalized for body weight.
Measured: Pre-dose, 30 minutes, 3, 24, 48, 72 120, 168, 240 and 336 hours post-dose
Number of Subjects Developing Inhibitors to Factor IX (FIX)
Inhibitor formation was defined as any inhibitor (≥0.6 BU [Bethesda Units]/mL) identified and confirmed by retesting.
Measured: 12 months
Secondary outcomes (4)
Number of Subjects With Treatment-related Adverse Events
Measured: 12 months
Number of Subjects Developing Antibodies Against rIX-FP
Antibodies to rIX-FP were measured using a direct-binding enzyme-linked immunosorbent assay (ELISA).
Measured: 12 months
Number of Bleeding Episodes Requiring One, Two or More Than Two Infusions of rIX-FP to Achieve Hemostasis
For each bleeding episode that required treatment, the number of episodes that required one, two or more than two infusions of rIX-FP to achieve hemostasis
Measured: Approximately 12 months
Consumption of rIX-FP During Routine Prophylaxis
Consumption of rIX-FP during routine prophylaxis is expressed as the total prophylaxis dose per month.
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Aug 2012 (estimated)
- Study startJan 2013
- Primary completionOct 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 (3)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 3
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 27 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
- NCT01662531
- Sponsor's protocol ID
- CSL654_3002
- Other IDs
- 2011-006032-23
- Status last verified
- Apr 2016
- First submitted
- 7 Aug 2012
- Last updated
- 9 May 2016
- Results posted
- Yes, on ClinicalTrials.gov
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 40386832Alvarez-Roman MT, Merchan RD, Mellado RCR, Jimenez-Yuste V. Switching and increasing prophylaxis regimen with a genetically recombinant fusion of coagulation factor IX and albumin in haemophilia B: a case report. Curr Opin Hematol. 2023 Sep 1;30(5):175-179. doi: 10.1097/MOH.0000000000000775.
PubMed 37522479Kenet G, Chambost H, Male C, Lambert T, Halimeh S, Chernova T, Mancuso ME, Curtin J, Voigt C, Li Y, Jacobs I, Santagostino E; PROLONG-9FP Investigator Study Group. Long-acting recombinant fusion protein linking coagulation factor IX with albumin (rIX-FP) in children. Results of a phase 3 trial. Thromb Haemost. 2016 Sep 27;116(4):659-68. doi: 10.1160/TH16-03-0179. Epub 2016 Sep 1.
PubMed 27583313
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 III Open-label, Multicenter, Pharmacokinetic, Safety and Efficacy Study of a Recombinant Fusion Protein Linking Coagulation Factor IX With Albumin (rIX-FP) in Previously Treated Children With Hemophilia B
- ClinicalTrials.gov ID
- NCT01662531
- Acronym / sponsor ID
- CSL654_3002
- Conditions
- Hemophilia B
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 27 participants (actual)
- Lead sponsor
- CSL BehringIndustry (pharma, biotech, devices)
- Study start
- Jan 2013
- Primary completion
- Oct 2014 (actual)
- First posted
- 10 Aug 2012 (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 pharmacokinetics, safety and efficacy of rIX-FP for the control and prevention of bleeding episodes in children who have previously received factor replacement therapy for hemophilia B.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| rIX-FP | Experimental | Biological: rIX-FPRecombinant Fusion Protein Linking Coagulation Factor IX with Albumin (rIX-FP) will be administered by IV infusion as routine weekly prophylaxis and episodic treatment for bleeding episodes. |
Who may qualify
- Ages
- Up to 11 years
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (6 listed)
- Male subjects, younger than 12 years old.
- Severe hemophilia B (Factor IX [FIX] activity of ≤ 2%).
- Body weight ≥ 10 kg.
- Subjects who have received FIX products (plasma-derived and/or recombinant FIX) for > 150 exposure days (EDs) (6 to < 12 years), and > 50 EDs (< 6 years).
- No history of FIX inhibitor formation, no detectable inhibitors at Screening and no family history of inhibitors against FIX.
Key exclusion criteria (4 listed)
- Known hypersensitivity to any FIX product or hamster protein.
- Known congenital or acquired coagulation disorder other than congenital FIX deficiency.
- Kidney or liver disease.
- 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 Fusion Protein Linking Coagulation Factor IX with Albumin (rIX-FP) | Biological | rIX-FP |
Primary outcome
Incremental Recovery Following a Single Intravenous Dose of 50 IU/kg rIX-FP or Previous FIX Product
Time frame: 30 minutes after infusion
Incremental recovery (IU/dL/IU/kg) is defined as the FIX activity (IU/dL) obtained 30 minutes following infusion, per dose of (IU/kg) infusion. FIX activity was measured at a central laboratory using validated one-stage clotting method. Recovery values were baseline-corrected for pre-infusion plasma FIX activity. Incremental recovery was measured following a single intravenous dose of 50 IU/kg rIX-FP on Day 1. Analysis of previous FIX product was conducted at the beginning of the study in a subset of subjects who had no historical pharmacokinetic (PK) data of their previous FIX product. For the PK assessment, the previous FIX product was administered by IV infusion after approximately 4 days following the last FIX treatment, prior to any dosing of rIX-FP. The formal PK population consisted of subjects who received at least 1 dose of rIX-FP for PK assessment and for whom a sufficient number of analyzable PK samples had been obtained to permit the evaluation of the PK profile of rIX-FP.
Half-life (t1/2) Following a Single Intravenous Dose of 50 IU/kg rIX-FP or Previous FIX Product
Time frame: Pre-dose, 30 minutes, 3, 24, 48, 72 120, 168, 240 and 336 hours post-dose
FIX activity was measured at a central laboratory using validated one-stage clotting method. FIX levels were not corrected for baseline values.
Area Under the Concentration Versus Time Curve From Time Point Zero to the Last Sample With Quantifiable Drug Concentration (AUClast)
Time frame: Pre-dose, 30 minutes, 3, 24, 48, 72 120, 168, 240 and 336 hours post-dose
AUClast following a single intravenous dose of 50 IU/kg rIX-FP or previous FIX product. FIX activity was measured at a central laboratory using validated one-stage clotting method. FIX levels were not corrected for baseline values.
Clearance for FIX Activity Following a Single Intravenous Dose of 50 IU/kg rIX-FP or Previous FIX Product
Time frame: Pre-dose, 30 minutes, 3, 24, 48, 72 120, 168, 240 and 336 hours post-dose
FIX activity was measured at a central laboratory using validated one-stage clotting method. FIX levels were not corrected for baseline values. Clearance is normalized for body weight.
Number of Subjects Developing Inhibitors to Factor IX (FIX)
Time frame: 12 months
Inhibitor formation was defined as any inhibitor (≥0.6 BU [Bethesda Units]/mL) identified and confirmed by retesting.
4 secondary outcomes
Number of Subjects With Treatment-related Adverse Events
Time frame: 12 months
Number of Subjects Developing Antibodies Against rIX-FP
Time frame: 12 months
Number of Bleeding Episodes Requiring One, Two or More Than Two Infusions of rIX-FP to Achieve Hemostasis
Time frame: Approximately 12 months
Consumption of rIX-FP During Routine Prophylaxis
Time frame: 12 months
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 37522479Alvarez-Roman MT, Merchan RD, Mellado RCR, Jimenez-Yuste V. Switching and increasing prophylaxis regimen with a genetically recombinant fusion of coagulation factor IX and albumin in haemophilia B: a case report. Curr Opin Hematol. 2023 Sep 1;30(5):175-179. doi: 10.1097/MOH.0000000000000775.
- Derived from this study: PubMed 27583313Kenet G, Chambost H, Male C, Lambert T, Halimeh S, Chernova T, Mancuso ME, Curtin J, Voigt C, Li Y, Jacobs I, Santagostino E; PROLONG-9FP Investigator Study Group. Long-acting recombinant fusion protein linking coagulation factor IX with albumin (rIX-FP) in children. Results of a phase 3 trial. Thromb Haemost. 2016 Sep 27;116(4):659-68. doi: 10.1160/TH16-03-0179. Epub 2016 Sep 1.
Related trials for Hemophilia B
Active, not recruitingObservational study
A Study to Learn About the Study Medicine -Hympavzi in Congenital Hemophilia Patients Without Inhibitors in Japan.
Hemophilia A or B
Active, not recruitingPhase 3
A Study to Evaluate the Efficacy and Safety of Factor IX Gene Therapy With PF-06838435 in Adult Males With Moderately Severe to Severe Hemophilia B
Hemophilia B
Not yet recruiting
Safety of Intraosseous Anaesthesia in Children With Haemophilia
Haemophilia A, Haemophilia B
Not yet recruitingPhase 1
Lentiviral FIX Gene Therapy
Hemophilia B
RecruitingPhase 3
A Study to Investigate the Efficacy and Safety of Fitusiran Prophylaxis in Male Participants Aged 1 to Less Than 12 Years With Hemophilia A or B
Hemophilia
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
17 sites in 10 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing rIX-FP in people with Hemophilia B, run by CSL Behring at 17 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 4 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 17 sites in Czechia, France, Australia, Germany, 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 phase mean?
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?
Incremental Recovery Following a Single Intravenous Dose of 50 IU/kg rIX-FP or Previous FIX Product (time frame: 30 minutes after infusion). The study lists 5 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 NCT01662531, which also lists 3 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.