Hemophilia B
Conditions
Brief summary
This study will examine the long-term safety and efficacy of rIX-FP for the control and prevention of bleeding episodes in children and adults with severe hemophilia B. The study will include subjects who have not previously been treated with Factor IX products, subjects who previously completed a CSL-sponsored rIX-FP lead-in study and subjects requiring major non-emergency surgery who have not previously completed a CSL-sponsored rIX-FP lead-in study. A surgical prophylaxis substudy will examine the efficacy of rIX-FP in subjects with hemophilia B who are undergoing non-emergency major or minor surgery. An additional substudy will examine the safety and PK of subcutaneous (SC) administration of rIX-FP.
Interventions
BIOLOGICALrIX-FP
Recombinant Fusion Protein Linking Coagulation Factor IX with Albumin (rIX-FP)
Sponsors
CSL Behring
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
No minimum to 70 Years
Healthy volunteers
No
Inclusion criteria
Main study inclusion criteria: For previously treated subjects, either: * Completed a CSL-sponsored rIX-FP (CSL654) study, including study CSL654\_3001 \[NCT01496274\] or study CSL654\_3002 \[NCT01662531\]. Or: * Scheduled to have a major non-emergency surgery within approximately 8 weeks from the anticipated date of receiving the first rIX-FP injection. * Not previously completed a CSL-sponsored rIX-FP lead-in study. * Male, 12 to 70 years of age. * Documented severe hemophilia B (FIX activity of ≤ 2%), or confirmed at screening by the central laboratory. * Subjects who have received FIX products (plasma-derived and / or recombinant FIX) for \> 150 exposure days (EDs), confirmed by their treating physician. * No confirmed history of FIX inhibitor formation at screening by the central laboratory For previously untreated subjects: * Male, up to 18 years of age. * Documented severe hemophilia B (FIX activity of ≤ 2%), or confirmed at screening by the central laboratory. * Never previously been treated with FIX clotting factor products (except previous exposure to blood components). * No confirmed history of FIX inhibitor formation Surgery substudy inclusion criterion: * Must require non-emergency surgery Subcutaneous substudy inclusion criteria: * Male, at least 18 years of age. * Subjects currently enrolled in Study CSL654\_3003 * Subjects who have received rIX-FP for ≥ 100 EDs (single-dose cohorts) or for ≥ 50 EDs (repeated-dose cohort)
Exclusion criteria
Main study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Total Number of Participants Who Developed Inhibitors Against Factor IX (FIX) | For PTPs: up to 5 years or the time it takes to achieve 100 exposure days (EDs). For PUPs: up to 3 years or the time it takes to achieve 50 EDs. | — |
| Mean Incremental Recovery of a 50 IU/kg Dose of CSL654 in Previously Untreated Patients (PUPs) | Approximately 30 minutes after infusion of CSL654 | Incremental Recovery: The increase in plasma concentration per IU/kg of factor administered. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Average Amount of CSL654 (rIX-FP) Consumed Per Month Per Subject During Routine Prophylaxis Treatment. | For PTPs: up to 5 years or the time it takes to achieve 100 exposure days (EDs). For PUPs: up to 3 years or the time it takes to achieve 50 EDs. | — |
| Percentage of Participants With at Least One Treatment Emergent Adverse Event (TEAE) and the Percentage of Participants With at Least One CSL654-related TEAE | For PTPs: up to 5 years or the time it takes to achieve 100 exposure days (EDs). For PUPs: up to 3 years or the time it takes to achieve 50 EDs. | — |
| Number of Participants With Investigator's Overall Clinical Assessment of Hemostatic Efficacy for the Treatment of Major Bleeding Events With CSL654 in PUPs | Up to 3 years or the time it takes to achieve 50 EDs | The investigator will rate the efficacy of the rIX-FP treatment based on a hemostatic efficacy four point rating scale of excellent, good, moderate, or poor/no response. |
| Total ABR for On-demand Regimen vs. 14-Day Regimen in PTPs | For PTPs: up to 5 years or the time it takes to achieve 100 exposure days (EDs). | — |
| Total Annualized Bleeding Rate (ABR) by Prophylaxis Regimen in Previously Treated Patients (PTPs) | For PTPs: up to 5 years or the time it takes to achieve 100 exposure days (EDs). | — |
| Total ABR for Subjects >=12 Years: 7-Day Regimen vs. 14-Day Regimen in PTPs | For PTPs: up to 5 years or the time it takes to achieve 100 exposure days (EDs). | — |
| Spontaneous ABR for Subjects >=12 Years: 7-Day Regimen vs. 14-Day Regimen in PTPs | For PTPs: up to 5 years or the time it takes to achieve 100 exposure days (EDs). | — |
| Total ABR for Subjects >=12 Years: 7-Day Regimen vs. (10 or 14)-Day Regimen in PTPs | For PTPs: up to 5 years or the time it takes to achieve 100 exposure days (EDs). | — |
| Spontaneous ABR for Subjects >=12 Years: 7-Day Regimen vs. (10 or 14)-Day Regimen in PTPs | For PTPs: up to 5 years or the time it takes to achieve 100 exposure days (EDs). | — |
| Spontaneous ABR for On-demand Regimen vs. 14-Day Regimen in PTPs | For PTPs: up to 5 years or the time it takes to achieve 100 exposure days (EDs). | — |
| Spontaneous ABR by Prophylaxis Regimen in PTPs | For PTPs: up to 5 years or the time it takes to achieve 100 exposure days (EDs). | — |
Countries
Australia, Austria, Bulgaria, Canada, Czechia, France, Germany, Israel, Italy, Japan, Malaysia, Philippines, South Africa, Spain, United States
Participant flow
Pre-assignment details
Approximately 115 male previously treated patients (PTPs) and previously untreated patients (PUPs) with hemophilia B were planned to be enrolled, including all eligible PTPs from CSLB-sponsored rIX-FP lead-in studies, approximately 10 PTPs who required major, nonemergency surgery, and approximately 20 PUPs.
Participants by arm
| Arm | Count |
|---|---|
| CSL654 (PTPs) Previously treated patients (PTPs) will administer CSL654 (rIX-FP) by intravenous infusion as routine prophylaxis, prevention, and on-demand treatment during a treatment period of approximately 5 years or the time it took to reach 100 exposure days (EDs). The dose of rIX-FP administered will be based on the subject's previous rIX-FP use and/or pharmacokinetic data. | 83 |
| CSL654 (PUPs) Previously untreated patients (PUPs) administered CSL654 (rIX-FP) intravenously as weekly prophylaxis and/or on-demand treatment during the first 12 months, and as weekly routine prophylaxis thereafter up to 3 years or the time it takes to achieve 50 EDs. The dose of rIX-FP administered will be based on the subject's previous rIX-FP use and/or pharmacokinetic data. | 14 |
| Total | 97 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 |
| Overall Study | Development of High titer FIX inhibitor | 0 | 1 |
| Overall Study | Lack of Efficacy | 1 | 0 |
| Overall Study | Patient reached minimum number of exposure days and was allowed to stop | 1 | 0 |
| Overall Study | Physician Decision | 0 | 1 |
| Overall Study | The patient was not compliant to the study procedure | 1 | 0 |
| Overall Study | Withdrawal by Subject | 2 | 2 |
Baseline characteristics
| Characteristic | CSL654 (PTPs) | Total | CSL654 (PUPs) |
|---|---|---|---|
| Age, Categorical <=18 years | 30 Participants | 44 Participants | 14 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 53 Participants | 53 Participants | 0 Participants |
| Age, Continuous CSL654 (PTPs) | 27.7 years STANDARD_DEVIATION 17.81 | 27.7 years STANDARD_DEVIATION 17.81 | — |
| Age, Continuous CSL654 (PUPs) | — | 1.3 years STANDARD_DEVIATION 3.11 | 1.3 years STANDARD_DEVIATION 3.11 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants | 2 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 81 Participants | 93 Participants | 12 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 12 Participants | 13 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants | 3 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) White | 68 Participants | 78 Participants | 10 Participants |
| Region of Enrollment Australia | 2 participants | 5 participants | 3 participants |
| Region of Enrollment Austria | 4 participants | 5 participants | 1 participants |
| Region of Enrollment Bulgaria | 4 participants | 4 participants | 0 participants |
| Region of Enrollment Canada | 1 participants | 1 participants | 0 participants |
| Region of Enrollment Czechia | 3 participants | 3 participants | 0 participants |
| Region of Enrollment France | 14 participants | 14 participants | 0 participants |
| Region of Enrollment Germany | 8 participants | 11 participants | 3 participants |
| Region of Enrollment Israel | 15 participants | 15 participants | 0 participants |
| Region of Enrollment Italy | 10 participants | 12 participants | 2 participants |
| Region of Enrollment Japan | 9 participants | 9 participants | 0 participants |
| Region of Enrollment Malaysia | 2 participants | 2 participants | 0 participants |
| Region of Enrollment Philippines | 1 participants | 2 participants | 1 participants |
| Region of Enrollment South Africa | 2 participants | 2 participants | 0 participants |
| Region of Enrollment Spain | 6 participants | 6 participants | 0 participants |
| Region of Enrollment United States | 2 participants | 6 participants | 4 participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 83 Participants | 97 Participants | 14 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 1 / 83 | 0 / 12 |
| other Total, other adverse events | 69 / 83 | 11 / 12 |
| serious Total, serious adverse events | 17 / 83 | 5 / 12 |
Outcome results
Primary
Mean Incremental Recovery of a 50 IU/kg Dose of CSL654 in Previously Untreated Patients (PUPs)
Incremental Recovery: The increase in plasma concentration per IU/kg of factor administered.
Time frame: Approximately 30 minutes after infusion of CSL654
Population: Pharmacokinetic (PK) Population consisted of participants who received ≥ 1 dose of rIX-FP and had a sufficient number of analyzable PK blood samples (ie, ≥ 1 PK parameter calculated) for the PK assessment of rIX-FP. Participants were excluded from the analyses if an insufficient number of analyzable PK samples was obtained to permit the evaluation of ≥ 1 PK parameter. Only PUPs were analyzed for this endpoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| CSL654 (PUPs) | Mean Incremental Recovery of a 50 IU/kg Dose of CSL654 in Previously Untreated Patients (PUPs) | Uncorrected FIX Activity | 1.295 (IU/dL)/(IU/kg) | Standard Deviation 0.3578 |
| CSL654 (PUPs) | Mean Incremental Recovery of a 50 IU/kg Dose of CSL654 in Previously Untreated Patients (PUPs) | Baseline-corrected FIX Activity | 1.231 (IU/dL)/(IU/kg) | Standard Deviation 0.3729 |
Primary
Total Number of Participants Who Developed Inhibitors Against Factor IX (FIX)
Time frame: For PTPs: up to 5 years or the time it takes to achieve 100 exposure days (EDs). For PUPs: up to 3 years or the time it takes to achieve 50 EDs.
Population: Safety Population (SP) consisted of all participants who received ≥ 1 dose of rIX-FP during this study
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| CSL654 (PTPs) | Total Number of Participants Who Developed Inhibitors Against Factor IX (FIX) | 0 Participants |
| CSL654 (PUPs) | Total Number of Participants Who Developed Inhibitors Against Factor IX (FIX) | 1 Participants |
Secondary
Average Amount of CSL654 (rIX-FP) Consumed Per Month Per Subject During Routine Prophylaxis Treatment.
Time frame: For PTPs: up to 5 years or the time it takes to achieve 100 exposure days (EDs). For PUPs: up to 3 years or the time it takes to achieve 50 EDs.
Population: EP
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| CSL654 (PTPs) | Average Amount of CSL654 (rIX-FP) Consumed Per Month Per Subject During Routine Prophylaxis Treatment. | 181.8 IU/kg per month | Standard Deviation 35.16 |
| CSL654 (PUPs) | Average Amount of CSL654 (rIX-FP) Consumed Per Month Per Subject During Routine Prophylaxis Treatment. | 188.53 IU/kg per month | Standard Deviation 24.096 |
Secondary
Number of Participants With Investigator's Overall Clinical Assessment of Hemostatic Efficacy for the Treatment of Major Bleeding Events With CSL654 in PUPs
The investigator will rate the efficacy of the rIX-FP treatment based on a hemostatic efficacy four point rating scale of excellent, good, moderate, or poor/no response.
Time frame: Up to 3 years or the time it takes to achieve 50 EDs
Population: EP. This endpoint was for PUPs only. No major bleeding events were reported. Therefore, no data for this endpoint.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| CSL654 (PUPs) | Number of Participants With Investigator's Overall Clinical Assessment of Hemostatic Efficacy for the Treatment of Major Bleeding Events With CSL654 in PUPs | 0 Participants |
Secondary
Percentage of Participants With at Least One Treatment Emergent Adverse Event (TEAE) and the Percentage of Participants With at Least One CSL654-related TEAE
Time frame: For PTPs: up to 5 years or the time it takes to achieve 100 exposure days (EDs). For PUPs: up to 3 years or the time it takes to achieve 50 EDs.
Population: SP
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| CSL654 (PTPs) | Percentage of Participants With at Least One Treatment Emergent Adverse Event (TEAE) and the Percentage of Participants With at Least One CSL654-related TEAE | AEs | 89.2 percentage of participants |
| CSL654 (PTPs) | Percentage of Participants With at Least One Treatment Emergent Adverse Event (TEAE) and the Percentage of Participants With at Least One CSL654-related TEAE | Related AEs | 2.4 percentage of participants |
| CSL654 (PUPs) | Percentage of Participants With at Least One Treatment Emergent Adverse Event (TEAE) and the Percentage of Participants With at Least One CSL654-related TEAE | AEs | 91.7 percentage of participants |
| CSL654 (PUPs) | Percentage of Participants With at Least One Treatment Emergent Adverse Event (TEAE) and the Percentage of Participants With at Least One CSL654-related TEAE | Related AEs | 16.7 percentage of participants |
Secondary
Spontaneous ABR by Prophylaxis Regimen in PTPs
Time frame: For PTPs: up to 5 years or the time it takes to achieve 100 exposure days (EDs).
Population: EP. Only PTPs were analyzed for this endpoint. Participants may be assigned under multiple regimens during the study, but will be counted only once in any given regimen group. Annualized Bleeding Rate is derived only for subjects who are on the given regimen for at least 12 weeks.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| CSL654 (PTPs) | Spontaneous ABR by Prophylaxis Regimen in PTPs | 7-Day Regimen | 0.95 Bleeds/Year/Participant | Standard Deviation 1.672 |
| CSL654 (PTPs) | Spontaneous ABR by Prophylaxis Regimen in PTPs | 10-Day Regimen | 0.98 Bleeds/Year/Participant | Standard Deviation 1.689 |
| CSL654 (PTPs) | Spontaneous ABR by Prophylaxis Regimen in PTPs | 14-Day Regimen | 1.32 Bleeds/Year/Participant | Standard Deviation 2.205 |
| CSL654 (PTPs) | Spontaneous ABR by Prophylaxis Regimen in PTPs | 21-Day Regimen | 0.60 Bleeds/Year/Participant | Standard Deviation 1.408 |
Secondary
Spontaneous ABR for On-demand Regimen vs. 14-Day Regimen in PTPs
Time frame: For PTPs: up to 5 years or the time it takes to achieve 100 exposure days (EDs).
Population: EP. Only PTPs were analyzed for this endpoint. Participants may be assigned under multiple regimens during the study, but will be counted only once in any given regimen group. Number of participants analyzed are those who received at least 12 weeks of treatment in the respective regimen.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| CSL654 (PTPs) | Spontaneous ABR for On-demand Regimen vs. 14-Day Regimen in PTPs | On-demand Regimen | 13.17 Bleeds/Year/Subject | Standard Deviation 5.873 |
| CSL654 (PTPs) | Spontaneous ABR for On-demand Regimen vs. 14-Day Regimen in PTPs | 14-Day Regimen | 1.93 Bleeds/Year/Subject | Standard Deviation 3.363 |
Secondary
Spontaneous ABR for Subjects >=12 Years: 7-Day Regimen vs. (10 or 14)-Day Regimen in PTPs
Time frame: For PTPs: up to 5 years or the time it takes to achieve 100 exposure days (EDs).
Population: EP. Only PTPs were analyzed for this endpoint. Participants may be assigned under multiple regimens during the study, but will be counted only once in any given regimen group. Number of participants analyzed are those who received at least 12 weeks of treatment in the respective regimen.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| CSL654 (PTPs) | Spontaneous ABR for Subjects >=12 Years: 7-Day Regimen vs. (10 or 14)-Day Regimen in PTPs | (10 or 14)-Day Regimen | 1.05 Bleeds/Year/Subject | Standard Deviation 2.022 |
| CSL654 (PTPs) | Spontaneous ABR for Subjects >=12 Years: 7-Day Regimen vs. (10 or 14)-Day Regimen in PTPs | 7-Day Regimen | 0.57 Bleeds/Year/Subject | Standard Deviation 1.192 |
Secondary
Spontaneous ABR for Subjects >=12 Years: 7-Day Regimen vs. 14-Day Regimen in PTPs
Time frame: For PTPs: up to 5 years or the time it takes to achieve 100 exposure days (EDs).
Population: EP. Only PTPs were analyzed for this endpoint. Participants may be assigned under multiple regimens during the study, but will be counted only once in any given regimen group. Number of participants analyzed are those who received at least 12 weeks of treatment in the respective regimen.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| CSL654 (PTPs) | Spontaneous ABR for Subjects >=12 Years: 7-Day Regimen vs. 14-Day Regimen in PTPs | 7-Day Regimen | 0.49 Bleeds/Year/Subject | Standard Deviation 1.135 |
| CSL654 (PTPs) | Spontaneous ABR for Subjects >=12 Years: 7-Day Regimen vs. 14-Day Regimen in PTPs | 14-Day Regimen | 1.33 Bleeds/Year/Subject | Standard Deviation 2.349 |
Secondary
Total ABR for On-demand Regimen vs. 14-Day Regimen in PTPs
Time frame: For PTPs: up to 5 years or the time it takes to achieve 100 exposure days (EDs).
Population: EP. Only PTPs were analyzed for this endpoint. Participants may be assigned under multiple regimens during the study, but will be counted only once in any given regimen group. Number of participants analyzed are those who received at least 12 weeks of treatment in the respective regimen.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| CSL654 (PTPs) | Total ABR for On-demand Regimen vs. 14-Day Regimen in PTPs | On-demand Regimen | 17.51 Bleeds/Year/Subject | Standard Deviation 7.13 |
| CSL654 (PTPs) | Total ABR for On-demand Regimen vs. 14-Day Regimen in PTPs | 14-Day Regimen | 3.01 Bleeds/Year/Subject | Standard Deviation 4.204 |
Secondary
Total ABR for Subjects >=12 Years: 7-Day Regimen vs. (10 or 14)-Day Regimen in PTPs
Time frame: For PTPs: up to 5 years or the time it takes to achieve 100 exposure days (EDs).
Population: EP. Only PTPs were analyzed for this endpoint. Participants may be assigned under multiple regimens during the study, but will be counted only once in any given regimen group. Number of participants analyzed are those who received at least 12 weeks of treatment in the respective regimen.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| CSL654 (PTPs) | Total ABR for Subjects >=12 Years: 7-Day Regimen vs. (10 or 14)-Day Regimen in PTPs | 7-Day Regimen | 1.31 Bleeds/Year/Subject | Standard Deviation 1.868 |
| CSL654 (PTPs) | Total ABR for Subjects >=12 Years: 7-Day Regimen vs. (10 or 14)-Day Regimen in PTPs | (10 or 14)-Day Regimen | 2.01 Bleeds/Year/Subject | Standard Deviation 2.7 |
Secondary
Total ABR for Subjects >=12 Years: 7-Day Regimen vs. 14-Day Regimen in PTPs
Time frame: For PTPs: up to 5 years or the time it takes to achieve 100 exposure days (EDs).
Population: EP. Only PTPs were analyzed for this endpoint. Participants may be assigned under multiple regimens during the study, but will be counted only once in any given regimen group. Number of participants analyzed are those who received at least 12 weeks of treatment in the respective regimen.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| CSL654 (PTPs) | Total ABR for Subjects >=12 Years: 7-Day Regimen vs. 14-Day Regimen in PTPs | 7-Day Regimen | 1.12 Bleeds/Year/Subject | Standard Deviation 1.697 |
| CSL654 (PTPs) | Total ABR for Subjects >=12 Years: 7-Day Regimen vs. 14-Day Regimen in PTPs | 14-Day Regimen | 2.19 Bleeds/Year/Subject | Standard Deviation 3 |
Secondary
Total Annualized Bleeding Rate (ABR) by Prophylaxis Regimen in Previously Treated Patients (PTPs)
Time frame: For PTPs: up to 5 years or the time it takes to achieve 100 exposure days (EDs).
Population: Efficacy Population (EP) consisted of all participants in the Safety Population (SP). Only PTPs were analyzed for this endpoint. Participants were assigned under multiple regimens during the study, but were counted only once in any given regimen group. Annualized Bleeding Rate was derived only for subjects who were on the given regimen for at least 12 weeks.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| CSL654 (PTPs) | Total Annualized Bleeding Rate (ABR) by Prophylaxis Regimen in Previously Treated Patients (PTPs) | 7-Day Regimen | 2.89 Bleeds/Year/Participant | Standard Deviation 3.115 |
| CSL654 (PTPs) | Total Annualized Bleeding Rate (ABR) by Prophylaxis Regimen in Previously Treated Patients (PTPs) | 10-Day Regimen | 2.72 Bleeds/Year/Participant | Standard Deviation 2.827 |
| CSL654 (PTPs) | Total Annualized Bleeding Rate (ABR) by Prophylaxis Regimen in Previously Treated Patients (PTPs) | 14-Day Regimen | 2.72 Bleeds/Year/Participant | Standard Deviation 3.395 |
| CSL654 (PTPs) | Total Annualized Bleeding Rate (ABR) by Prophylaxis Regimen in Previously Treated Patients (PTPs) | 21-Day Regimen | 1.19 Bleeds/Year/Participant | Standard Deviation 1.572 |