Hemophilia BPhase 1/2NCT01361126
A Safety and Efficacy Study of a Recombinant Factor IX in Patients With Severe Hemophilia B
A Phase 1/2 study testing Recombinant Coagulation Factor IX Albumin Fusion Protein in people with Hemophilia B, run by CSL Behring at 2 sites in 2 countries.
Trial summary
This study will examine the safety and efficacy of a Recombinant Coagulation Factor IX Albumin Fusion Protein (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?
- Recombinant Coagulation Factor IX Albumin Fusion Protein
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 17 participants
- Where
- 2 sitesin 2 countries
- Study dates
- Jul 2011to Jul 2012
- Phase
- Phase 1/2
- 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 obtained before undergoing any study specific procedures
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, abnormal kidney function, or liver disease
- On-demand subjects experiencing less than 12 or 6 non-trauma induced bleeding episodes requiring treatment with a FIX product during the previous 6 or 3 months, respectively
- Planned major surgical intervention during the study period
Trial locations and contacts
2 sites in 2 countries.
2 sites in 2 countries
About this study
Official title: A Phase I/II 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 and efficacy of a Recombinant Coagulation Factor IX Albumin Fusion Protein (rIX-FP) for the control and prevention of bleeding episodes in subjects who have previously received factor replacement therapy for hemophilia B. The study consists of a screening period, a pharmacokinetic (PK) period, followed by approximately a 5 month treatment period. Subjects will receive weekly routine prophylactic therapy and on-demand treatment for bleeding episodes. In addition, subjects who are not on routine factor replacement therapy prior to the study will receive only on-demand treatment for bleeding episodes.
- Conditions
- Hemophilia B
- Being tested
- Recombinant Coagulation Factor IX Albumin Fusion Protein
- Medical subject headings
- Hemophilia B
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Recombinant Coagulation Factor IX Albumin Fusion ProteinBiological
Also called CSL654
Study subjects will receive a single dose of 25IU/kg of rIX_FP for pharmacokinetic analysis. Subjects will then be treated for approximately 5 months. The treatment dose will be based on the subject's PK profile and the subject's bleeding phenotype.
| Study group | Role | What they receive |
|---|---|---|
| On-demand | Experimental | The routine prophylactic therapy interval is targeted at every 7 days. Receives: Biological: Recombinant Coagulation Factor IX Albumin Fusion Protein |
| Prophylactic | Experimental | On-demand subjects will receive rIX-FP only for the treatment of a bleeding episode. Receives: Biological: Recombinant Coagulation Factor IX Albumin Fusion Protein |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Subjects With Treatment-related Adverse Events
The causal relationship of each adverse event to rIX-FP was assessed by the Investigator.
Measured: Approximately 20 weeks
Number of Subjects With Inhibitors Against Factor IX (FIX)
The presence of inhibitors against FIX was assessed by the central laboratory by a FIX potency assay. To quantify anti-FIX neutralizing antibodies, the Bethesda assay with the Nijmegen modification was used, and the results expressed as Bethesda Units per mL (BU/mL). A positive inhibitor test is >=0.6 BU/mL.
Measured: Baseline, Day 10 and Weeks 4, 12 and 20
Number of Subjects Who Developed Antibodies to rIX-FP
Antibodies against rIX-FP were detected using a direct binding enzyme-linked immunosorbent assay (ELISA).
Measured: Pre-dose, Day 10 and Weeks 4, 12, and 20
Secondary outcomes (5)
Area Under the Curve to the Last Sample With Quantifiable Drug Concentration (AUC0-t) After a Single Dose of rIX-FP
The plasma concentrations of rIX-FP were measured as FIX activity using a validated, 1-stage assay in a central laboratory for a quantification range from 0.25 to 150% (or 0.25 IU/dL to 150 IU/dL). The PK population comprised all subjects who received at least 1 dose of rIX-FP and for whom a sufficient number of analyzable PK samples had been obtained in order to permit the evaluation of the PK profile of rIX-FP, and who did not receive a dose of rIX-FP or any other FIX product for the treatment of a bleed during the PK sampling period.
Measured: Pre-dose and up to 14 days after rIX-FP infusion.
Half-life (t1/2) of a Single Dose of rIX-FP
Measured: Pre-dose and up to 14 days after infusion
Incremental Recovery of rIX-FP at 30 Minutes Following Infusion of rIX-FP
Incremental recovery (IU/mL/IU/kg) is defined as FIX activity (IU/mL) 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.
Measured: 30 minutes after infusion
Clearance of a Single Dose of rIX-FP
Measured: Pre-dose and up to 14 days after rIX-FP infusion
Breakthrough Bleeding Events
Number of breakthrough bleeding events (spontaneous bleeding events) requiring treatment per subject in subjects receiving prophylactic treatment regimen with rIX-FP
Measured: Week 9 to approximately Week 20
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 May 2011 (estimated)
- Study startJul 2011
- Primary completionJun 2012
- Study completionJul 2012
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 (1)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 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 17 participants (actual)
Sponsor and investigators
- Lead sponsor
- CSL Behring
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Iris Jacobs, MD, Study director, CSL Behring
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01361126
- Sponsor's protocol ID
- CSL654_2004
- Other IDs
- 2010-023793-39
- Status last verified
- Apr 2016
- First submitted
- 25 May 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 40386832
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 I/II 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
- NCT01361126
- Acronym / sponsor ID
- CSL654_2004
- Conditions
- Hemophilia B
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 17 participants (actual)
- Lead sponsor
- CSL BehringIndustry (pharma, biotech, devices)
- Study start
- Jul 2011
- Primary completion
- Jun 2012 (actual)
- Study completion
- Jul 2012 (actual)
- First posted
- 26 May 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 and efficacy of a Recombinant Coagulation Factor IX Albumin Fusion Protein (rIX-FP) for the control and prevention of bleeding episodes in subjects who have previously received factor replacement therapy for hemophilia B. The study consists of a screening period, a pharmacokinetic (PK) period, followed by approximately a 5 month treatment period. Subjects will receive weekly routine prophylactic therapy and on-demand treatment for bleeding episodes. In addition, subjects who are not on routine factor replacement therapy prior to the study will receive only on-demand treatment for bleeding episodes.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| On-demand | Experimental | Biological: Recombinant Coagulation Factor IX Albumin Fusion ProteinThe routine prophylactic therapy interval is targeted at every 7 days. |
| Prophylactic | Experimental | Biological: Recombinant Coagulation Factor IX Albumin Fusion ProteinOn-demand subjects will receive rIX-FP only for the treatment of a bleeding episode. |
Who may qualify
- Ages
- 12 to 65 years
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (5 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 obtained before undergoing any study specific procedures
Key exclusion criteria (6 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, abnormal kidney function, or liver disease
- On-demand subjects experiencing less than 12 or 6 non-trauma induced bleeding episodes requiring treatment with a FIX product during the previous 6 or 3 months, respectively
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 |
|---|---|---|
| Recombinant Coagulation Factor IX Albumin Fusion ProteinAlso: CSL654Study subjects will receive a single dose of 25IU/kg of rIX_FP for pharmacokinetic analysis. Subjects will then be treated for approximately 5 months. The treatment dose will be based on the subject's PK profile and the subject's bleeding phenotype. | Biological | On-demand, Prophylactic |
Primary outcome
Number of Subjects With Treatment-related Adverse Events
Time frame: Approximately 20 weeks
The causal relationship of each adverse event to rIX-FP was assessed by the Investigator.
Number of Subjects With Inhibitors Against Factor IX (FIX)
Time frame: Baseline, Day 10 and Weeks 4, 12 and 20
The presence of inhibitors against FIX was assessed by the central laboratory by a FIX potency assay. To quantify anti-FIX neutralizing antibodies, the Bethesda assay with the Nijmegen modification was used, and the results expressed as Bethesda Units per mL (BU/mL). A positive inhibitor test is >=0.6 BU/mL.
Number of Subjects Who Developed Antibodies to rIX-FP
Time frame: Pre-dose, Day 10 and Weeks 4, 12, and 20
Antibodies against rIX-FP were detected using a direct binding enzyme-linked immunosorbent assay (ELISA).
5 secondary outcomes
Area Under the Curve to the Last Sample With Quantifiable Drug Concentration (AUC0-t) After a Single Dose of rIX-FP
Time frame: Pre-dose and up to 14 days after rIX-FP infusion.
Half-life (t1/2) of a Single Dose of rIX-FP
Time frame: Pre-dose and up to 14 days after infusion
Incremental Recovery of rIX-FP at 30 Minutes Following Infusion of rIX-FP
Time frame: 30 minutes after infusion
Clearance of a Single Dose of rIX-FP
Time frame: Pre-dose and up to 14 days after rIX-FP infusion
Breakthrough Bleeding Events
Time frame: Week 9 to approximately Week 20
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.
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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.
Iris Jacobs, MD study director
CSL Behring
2 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Recombinant Coagulation Factor IX Albumin Fusion Protein in people with Hemophilia B, run by CSL Behring at 2 sites in 2 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 5 inclusion and 6 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 2 sites in Bulgaria, Israel. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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?
Number of Subjects With Treatment-related Adverse Events (time frame: Approximately 20 weeks). The study lists 3 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 NCT01361126, which also lists 1 linked publication.
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.