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| ID | Type | Description | Link |
|---|---|---|---|
| 2010-023793-39 | EudraCT Number |
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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| On-demand | Experimental | The routine prophylactic therapy interval is targeted at every 7 days. |
|
| Prophylactic | Experimental | On-demand subjects will receive rIX-FP only for the treatment of a bleeding episode. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Recombinant Coagulation Factor IX Albumin Fusion Protein | Biological | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Subjects With Treatment-related Adverse Events | The causal relationship of each adverse event to rIX-FP was assessed by the Investigator. | 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. | 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). | Pre-dose, Day 10 and Weeks 4, 12, and 20 |
| Measure | Description | Time Frame |
|---|---|---|
| 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. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Iris Jacobs, MD | CSL Behring | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Study Site | Sofia | Bulgaria | ||||
| Study Site |
A total of 17 subjects were screened and enrolled in the study. Fifteen subjects participated in the pharmacokinetic (PK) evaluation period and were administered a dose of 25 IU/kg rIX-FP. Two subjects did not participate in the PK evaluation period because PK data for these 2 subjects were available from the previous phase 1 study (CSL654_2001).
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| ID | Title | Description |
|---|---|---|
| FG000 | Prophylactic | For the PK evaluation, subjects received a single intravenous (IV) infusion of Recombinant Coagulation Factor IX Albumin Fusion Protein (rIX-FP) at a dose of 25 IU/kg. After completion of the PK evaluation period, subjects entered the treatment period and were administered a single IV infusion of rIX-FP once a week at a dose of 15 to 35 IU/kg, or at a dose determined by the investigator. The dose was adjusted up to 75 IU/kg to maintain the trough FIX activity level > 1% between infusions. |
| FG001 | On-demand | For the PK evaluation, subjects received a single IV infusion of rIX-FP at a dose of 25 IU/kg. After completion of the PK evaluation period, subjects entered the treatment period and were administered 1 or more IV infusions of rIX-FP at a dose of at least 25 IU/kg to treat minor, moderate or major bleeding episodes. The dose of rIX-FP was calculated by the investigator. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
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Safety Population
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| ID | Title | Description |
|---|---|---|
| BG000 | Prophylactic | For the PK evaluation, subjects received a single IV infusion of rIX-FP at a dose of 25 IU/kg. After completion of the PK evaluation period, subjects entered the treatment period and were administered a single IV infusion of rIX-FP once a week at a dose of 15 to 35 IU/kg, or at a dose determined by the investigator. The dose was adjusted up to 75 IU/kg to maintain the trough FIX activity level > 1% between infusions. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Number of Subjects With Treatment-related Adverse Events | The causal relationship of each adverse event to rIX-FP was assessed by the Investigator. | Safety Population | Posted | Number | participants | Approximately 20 weeks |
|
|
20 weeks
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | All Subjects | Subjects received rIX-FP administered by IV infusion as prophylactic treatment once a week or on demand to treat bleeding episodes for 20 weeks. |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA 15.0 | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Clinical Trial Disclosure Manager | CSL Behring | Use email contact | clinicaltrials@cslbehring.com |
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| ID | Term |
|---|---|
| D002836 | Hemophilia B |
| ID | Term |
|---|---|
| D025861 | Blood Coagulation Disorders, Inherited |
| D001778 | Blood Coagulation Disorders |
| D006402 | Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
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| ID | Term |
|---|---|
| C000618231 | albutrepenonacog alfa |
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|
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| Pre-dose and up to 14 days after rIX-FP infusion. |
| Half-life (t1/2) of a Single Dose of rIX-FP | 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. | 30 minutes after infusion |
| Clearance of a Single Dose of rIX-FP | 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 | Week 9 to approximately Week 20 |
| Tel Aviv |
| Israel |
| BG001 | On-demand | For the PK evaluation, subjects received a single IV infusion of rIX-FP at a dose of 25 IU/kg. After completion of the PK evaluation period, subjects entered the treatment period and were administered 1 or more IV infusions of rIX-FP at a dose of at least 25 IU/kg to treat minor, moderate or major bleeding episodes. The dose of rIX-FP was calculated by the investigator. |
| BG002 | Total | Total of all reporting groups |
| years |
|
| Age, Customized | Number | participants |
|
| Sex: Female, Male | Count of Participants | Participants |
|
|
| Primary | 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. | Safety Population | Posted | Number | participants | Baseline, Day 10 and Weeks 4, 12 and 20 |
|
|
|
| Primary | Number of Subjects Who Developed Antibodies to rIX-FP | Antibodies against rIX-FP were detected using a direct binding enzyme-linked immunosorbent assay (ELISA). | Safety Population | Posted | Number | participants | Pre-dose, Day 10 and Weeks 4, 12, and 20 |
|
|
|
| Secondary | 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. | PK population | Posted | Geometric Mean | Geometric Coefficient of Variation | h*IU/dL | Pre-dose and up to 14 days after rIX-FP infusion. |
|
|
|
| Secondary | Half-life (t1/2) of a Single Dose of rIX-FP | PK population | Posted | Geometric Mean | Geometric Coefficient of Variation | hours | Pre-dose and up to 14 days after infusion |
|
|
|
| Secondary | 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. | PK population | Posted | Geometric Mean | Geometric Coefficient of Variation | IU/dL/IU/kg | 30 minutes after infusion |
|
|
|
| Secondary | Clearance of a Single Dose of rIX-FP | PK population | Posted | Geometric Mean | Geometric Coefficient of Variation | mL/h/kg | Pre-dose and up to 14 days after rIX-FP infusion |
|
|
|
| Secondary | Breakthrough Bleeding Events | Number of breakthrough bleeding events (spontaneous bleeding events) requiring treatment per subject in subjects receiving prophylactic treatment regimen with rIX-FP | Per protocol population | Posted | Mean | Standard Deviation | Events per subject | Week 9 to approximately Week 20 |
|
|
|
| 0 |
| 17 |
| 14 |
| 17 |
| Synovitis | Musculoskeletal and connective tissue disorders | MedDRA 15.0 | Systematic Assessment |
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| Bone pain | Musculoskeletal and connective tissue disorders | MedDRA 15.0 | Systematic Assessment |
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| Chondropathy | Musculoskeletal and connective tissue disorders | MedDRA 15.0 | Systematic Assessment |
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| Joint range of motion decreased | Musculoskeletal and connective tissue disorders | MedDRA 15.0 | Systematic Assessment |
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| Muscle spasms | Musculoskeletal and connective tissue disorders | MedDRA 15.0 | Systematic Assessment |
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| Hand fracture | Injury, poisoning and procedural complications | MedDRA 15.0 | Systematic Assessment |
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| Laceration | Injury, poisoning and procedural complications | MedDRA 15.0 | Systematic Assessment |
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| Contusion | Injury, poisoning and procedural complications | MedDRA 15.0 | Systematic Assessment |
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| Head injury | Injury, poisoning and procedural complications | MedDRA 15.0 | Systematic Assessment |
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| Injury | Injury, poisoning and procedural complications | MedDRA 15.0 | Systematic Assessment |
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| Limb injury | Injury, poisoning and procedural complications | MedDRA 15.0 | Systematic Assessment |
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| Radius fracture | Injury, poisoning and procedural complications | MedDRA 15.0 | Systematic Assessment |
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| Upper respiratory tract infection | Infections and infestations | MedDRA 15.0 | Systematic Assessment |
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| Pharyngitis | Infections and infestations | MedDRA 15.0 | Systematic Assessment |
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| Tonsillitis | Infections and infestations | MedDRA 15.0 | Systematic Assessment |
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| Injection site swelling | General disorders | MedDRA 15.0 | Systematic Assessment |
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| Injection site erythema | General disorders | MedDRA 15.0 | Systematic Assessment |
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| Injection site haemorrhage | General disorders | MedDRA 15.0 | Systematic Assessment |
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| Headache | Nervous system disorders | MedDRA 15.0 | Systematic Assessment |
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| Dizziness | Nervous system disorders | MedDRA 15.0 | Systematic Assessment |
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| Conjunctivitis | Eye disorders | MedDRA 15.0 | Systematic Assessment |
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| Eye pain | Eye disorders | MedDRA 15.0 | Systematic Assessment |
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| Dyspepsia | Gastrointestinal disorders | MedDRA 15.0 | Systematic Assessment |
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| Weight decreased | Investigations | MedDRA 15.0 | Systematic Assessment |
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| Rash follicular | Skin and subcutaneous tissue disorders | MedDRA 15.0 | Systematic Assessment |
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CSL agreements and restrictions on publishing may vary with individual investigators; however, CSL will not prohibit any investigator from publishing. CSL supports the publication of results from all centers of a multi-center trial and generally requires that reports based on single-site data not precede the primary publication of the entire clinical trial.
| D020147 | Coagulation Protein Disorders |
| D006474 | Hemorrhagic Disorders |
| D030342 | Genetic Diseases, Inborn |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D040181 | Genetic Diseases, X-Linked |