| Primary | 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. | This analysis includes only the participants assigned to the on-demand arm who received at least 1 dose of rIX-FP in the on-demand regimen and at least 1 dose of rIX-FP in the prophylaxis regimen. | Posted | | Median | Inter-Quartile Range | bleeds/year/subject | | Up to 26 weeks for on-demand regimen, and between 1 and 17 months for prophylaxis regimen. | | | | ID | Title | Description |
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| OG000 | On-demand Arm, On-demand Regimen | Participants in the On-demand Arm, when receiving episodic treatment for bleeding episodes (on-demand regimen). | | OG001 | On-demand Arm, Prophylaxis Regimen | Participants in the On-demand Arm, when receiving routine weekly prophylaxis (prophylaxis regimen). |
| | | Title | Denominators | Categories |
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| | | Title | Measurements |
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| - OG00015.43(7.98 to 17.96)
- OG0010.00(0.00 to 0.96)
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| | Group IDs | Group Description | Statistical Method | Statistical Comment | P-Value | P-Value Comment | Parameter Type | Parameter Value | Dispersion Type | Dispersion Value | Confidence Interval Sides | Confidence Interval % | CI Lower Limit | CI Upper Limit | CI Lower Limit Comment | CI Upper Limit Comment | Estimate Comment | Tested Non-Inferiority | Non-Inferiority Type | Non-Inferiority Comment | Other Analysis Description |
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| A test of null hypothesis that the ratio of AsBR (prophylaxis regimen/on-demand regimen) was ≥ 0.50 was conducted at the 1-sided 0.025 level. Matched pairs design with 19 subjects and 2 observations per subject. | Wilcoxon signed-rank test | | <0.0001 | P value is based on a Wilcoxon signed-rank test of H0: AsBR ratio (prophylaxis regimen/on-demand regimen) ≥ 0.50. The ratio was based on the original scale. | | | | | | | | | | | | No | Superiority or Other | | |
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| Primary | 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. | | Posted | | Number | 95% Confidence Interval | participants | | Up to 27.7 months (maximum) | | | | ID | Title | Description |
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| OG000 | Safety Population | The Safety population consisted of subjects who received at least 1 dose of rIX-FP during the study. |
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| Secondary | The Frequency of Related Adverse Events | The percentage of participants experiencing treatment-related adverse-events (TEAEs). | | Posted | | Number | | Percentage of participants | | For the duration of the study; median 20.27 months. | | | | ID | Title | Description |
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| OG000 | Prophylaxis | 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. | | OG001 | On-demand | Episodic treatment for bleeding episodes for up to 26 weeks then switch to routine weekly prophylaxis for the remainder of the study. Subjects may participate in a surgical 'sub-study' in which rIX-FP may be administered prior to, during and after surgical intervention. | | OG002 | Safety Population | The Safety population consisted of subjects who received at least 1 dose of rIX-FP during the study. |
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| Secondary | Number of Subjects Developing Antibodies Against rIX-FP | | | Posted | | Number | | participants | | For the duration of the study; median 20.27 months. | | | | ID | Title | Description |
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| OG000 | Safety Population | The Safety population consisted of subjects who received at least 1 dose of rIX-FP during the study. |
| | | Title | Denominators | Categories |
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| Secondary | 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. | | Posted | | Number | | percentage of bleeding episodes treated | | For the duration of the study; median 20.27 months. | bleeding episodes requiring treatment | Participants | | ID | Title | Description |
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| OG000 | Prophylaxis | 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. | | OG001 | On-demand Arm, On-demand Regimen | Participants in the On-demand Arm, when receiving episodic treatment for bleeding episodes (on-demand regimen). | | OG002 | On-demand Arm, Prophylaxis Regimen | Participants in the On-demand Arm, when receiving routine weekly prophylaxis (prophylaxis regimen). |
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| Secondary | 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. | | Posted | | Number | | percentage of bleeding episodes | | For the duration of the study; median 20.27 months | bleeding episodes requiring treatment | Participants | | ID | Title | Description |
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| OG000 | Prophylaxis | 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. | | OG001 | On-demand | Episodic treatment for bleeding episodes for up to 26 weeks then switch to routine weekly prophylaxis for the remainder of the study. Subjects may participate in a surgical 'sub-study' in which rIX-FP may be administered prior to, during and after surgical intervention. |
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| Secondary | 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. | | Posted | | Mean | Standard Deviation | IU/kg/month | | Median 269, 240, 386 and 316 days, respectively (see Description) | | | | ID | Title | Description |
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| OG000 | On-demand Arm, Prophylaxis Regimen | Participants in the On-demand Arm, when receiving routine weekly prophylaxis (prophylaxis regimen). | | OG001 | Prophylaxis Arm, 7-day Regimen | Subjects received prophylactic rIX-FP on a weekly basis. | | OG002 | Prophylaxis Arm, 10-day Regimen | Subjects received prophylactic rIX-FP every 10 days. | | OG003 | Prophylaxis Arm, 14-day Regimen | Subjects received prophylactic rIX-FP every 14 days. |
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| Secondary | Incremental Recovery of rIX-FP | Pharmacokinetic (PK) data are presented for a single 50 IU/kg dose of rIX-FP. | The PK population comprised 46 subjects who received at least 1 dose of rIX-FP at 50 IU/kg. Data are presented for subjects from the PK population who had a sufficient number of analyzable PK samples for evaluation of the PK profile of rIX-FP. | Posted | | Mean | Standard Deviation | (IU/dL)/(IU/kg) | | 336 hours | | | | ID | Title | Description |
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| OG000 | Prophylaxis | 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. | | OG001 | On-demand | Episodic treatment for bleeding episodes for up to 26 weeks then switch to routine weekly prophylaxis for the remainder of the study. Subjects may participate in a surgical 'sub-study' in which rIX-FP may be administered prior to, during and after surgical intervention. |
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| Secondary | 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. | The PK population comprised 46 subjects who received at least 1 dose of rIX-FP at 50 IU/kg. Data are presented for subjects from the PK population who had a sufficient number of analyzable PK samples for evaluation of the PK profile of rIX-FP. | Posted | | Mean | Standard Deviation | hour | | 336 hours | | | | ID | Title | Description |
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| OG000 | Prophylaxis | 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. | | OG001 | On-demand | Episodic treatment for bleeding episodes up to 26 weeks then switch to routine weekly prophylaxis for the remainder of the study. Subjects may participate in a surgical 'sub-study' in which rIX-FP may be administered prior to, during and after surgical intervention. |
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| Secondary | 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. | The PK population comprised 46 subjects who received at least 1 dose of rIX-FP at 50 IU/kg. Data are presented for subjects from the PK population who had a sufficient number of analyzable PK samples for evaluation of the PK profile of rIX-FP. | Posted | | Mean | Standard Deviation | IU*hr/dL | | 336 hours | | | | ID | Title | Description |
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| OG000 | Prophylaxis | 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. | | OG001 | On-demand | Episodic treatment for bleeding episodes for up to 26 weeks then switch to routine weekly prophylaxis for the remainder of the study. Subjects may participate in a surgical 'sub-study' in which rIX-FP may be administered prior to, during and after surgical intervention. |
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| Secondary | Clearance of a Single Dose of rIX-FP | PK data are presented for a single 50 IU/kg dose of rIX-FP. | The PK population comprised 46 subjects who received at least 1 dose of rIX-FP at 50 IU/kg. Data are presented for subjects from the PK population who had a sufficient number of analyzable PK samples for evaluation of the PK profile of rIX-FP. | Posted | | Mean | Standard Deviation | mL/hr | | 336 hours | | | | ID | Title | Description |
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| OG000 | Prophylaxis | 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. | | OG001 | On-demand | Episodic treatment for bleeding episodes for up to 26 weeks then switch to routine weekly prophylaxis for the remainder of the study. Subjects may participate in a surgical 'sub-study' in which rIX-FP may be administered prior to, during and after surgical intervention. |
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| Secondary | 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. | | Posted | | Number | | events | | Up to 14 days after surgery | events | Participants | | ID | Title | Description |
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| OG000 | Surgical Population | The Surgical population consisted of 3 subjects in the prophylaxis arm and 1 subject in the on demand arm who received at least 1 dose of rIX FP for a major or minor surgical procedure. |
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| Secondary | 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. | | Posted | | Median | Inter-Quartile Range | bleeds/year/subject | | During treatment, between median 240 and 386 days per subject. | | | | ID | Title | Description |
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| OG000 | Prophylaxis Arm, 7-day Regimen | Subjects received prophylactic rIX-FP on a weekly basis. | | OG001 | Prophylaxis Arm, 10-day Regimen | Subjects received prophylactic rIX-FP every 10 days. | | OG002 | Prophylaxis Arm, 14-day Regimen | Subjects received prophylactic rIX-FP every 14 days. |
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