HEMOPHILIA B
Conditions
Brief summary
The purpose of this post-approval study is to evaluate the safety and efficacy of Benefix in subjects with hemophilia B in usual care settings in China.
Detailed description
The purpose of this post-approval study is to provide supplementary information relating to the use of BeneFIX in Chinese subjects with hemophilia B, especially on the safety and efficacy in different populations of Chinese hemophilia B patients, in particular in pediatric patients \<6 years of age, pediatric patients ≥6 to ≤12 years of age, Previously Untreated Patients (PUPs) , subjects receiving prophylaxis treatment after enrollment in the study, and severe patients (FIX activity \<1%).
Interventions
DRUGBenefix
Subjects will be treated by the investigator according to usual care in China and in accord with the China BeneFIX Package Insert. The treatment duration is approximately 6 months (±7 days) or approximately 50 Exposure Days (EDs) (±5 EDs) (see protocol definition on EDs) whichever occurs first.
Sponsors
Pfizer
Study design
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Healthy volunteers
No
Inclusion criteria
* Male and/or female subjects with hemophilia B. * Subjects/parents/legal representatives must be able to comply with study procedures (informed consent/assent process, clinical visits, reporting of infusion and bleed data, reporting of adverse events, etc)
Exclusion criteria
* Presence of any other bleeding disorder in addition to hemophilia B. Subjects with a past history of, or current factor IX inhibitor. For laboratory-based assessments, any Bethesda inhibitor titer greater than the laboratory's normal range or ≥0.6 Bethesda Unit (BU)/mL. * Subjects with known hypersensitivity to the active substance or to any of the excipients of BeneFIX. * Subjects with a known hypersensitivity to Chinese Hamster Ovary cell proteins.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Who Developed Factor IX Inhibitor | Up to 6 months | Factor IX (FIX) inhibitor development was defined as any Bethesda inhibitor titer greater than the laboratory's normal range or Bethesda inhibitor titer \>=0.6 Bethesda Unit (BU)/mL. |
| Number of Participants With Allergic Reactions | Up to 6 months | FIX product allergy was defined as a hypersensitivity reaction to a FIX product with symptoms such as hives, urticaria, tightness of chest, wheezing, hypotension, and anaphylaxis based on investigator's judgments. |
| Number of Participants With Thrombotic Events | Up to 6 months | Thrombotic event was defined as any event associated with formation of a blood clot including catheter-associated thrombi and thrombotic complications. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Annualized Bleeding Rates (ABRs) in Participants Receiving On-demand Treatment With BeneFIX During Their On-demand Period | Up to 6 months or 50 exposure days whichever occurred first | For on-demand period, the annualized bleeding rate (ABR) was derived for each participant by the following formula: ABR = number of bleeds in on-demand period / (number of days in on-demand period/365.25). The on-demand period was defined as the entire time of enrollment in the study (ie, from the date of the enrollment visit through the day before the Final/Early Termination visit) except time in any prophylaxis period. The breaks in the prophylaxis period were considered on-demand periods. For an on-demand regimen to have been qualified to have ABR calculated, the sum of its periods needed to be \>= 14 days. |
| Number of Infusions Resulted in the Following Response to On-demand Treatment of Bleeds: Excellent, Good, Moderate, no Response | Up to 6 months or 50 exposure days whichever occurred first | Response was assessed using 4-point On-Demand Hemostasis Efficacy Rating Scale. Excellent means definite pain relief and/or improvement in signs of bleeding starting within 8 hours after an infusion, with no additional infusion administered; good means definite pain relief and/or improvement in signs of bleeding starting within 8 hours after an infusion, with at least one additional infusion administered for complete resolution of the bleeding episode, or definite pain relief and/or improvement in signs of bleeding starting after 8 hours following the infusion, with no additional infusion administered; moderate means probable or slight improvement starting after 8 hours following the infusion, with at least one additional infusion administered for complete resolution of the bleeding episode; no response means no improvement between infusions or during the 24 hour interval following an infusion, or condition worsens. Both first infusions and follow-up infusions were included. |
| Number of BeneFIX Infusions to Treat Each New Bleed | Up to 6 months or 50 exposure days whichever occurred first | The number of BeneFIX infusions administered to treat each new bleed was calculated by adding the on-demand initial treatment and any on-demand follow-up treatments for the same bleed. If there was more than one bleed location (eg, ankle and joint) with identical bleed start date and time, it was treated as one bleed occurrence. |
| Average Infusion Dose and Total Factor IX Consumption in On-demand Setting | Up to 6 months or 50 exposure days whichever occurred first | The total amount (international units \[IU\]) infused for each BeneFIX infusion was summed to calculate the total factor IX consumption for each participant. The average infusion dose for each participant was calculated as his total factor IX consumption (in IU) divided by the number of infusions administered. |
| Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Up to 7 months (28 calendar days after end of 6-month or 50-exposure day study treatment) | An adverse event (AE) was any untoward medical occurrence in a clinical investigation participant administered a product or medical device, regardless of the causality with the treatment or usage. A serious adverse event (SAE) was any untoward occurrence at any dose that resulted in death; was life threatening (immediate risk of death); required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity; resulted in congenital anomaly/birth defect. AEs included both serious and non-serious AEs. Treatment-emergent AEs were those with initial onset or increasing in severity after the first dose of study drug. |
| Average Infusion Dose and Total Factor IX Consumption in Recovery Setting | Up to 6 months or 50 exposure days whichever occurred first | The total amount (international units \[IU\]) infused for each BeneFIX infusion was summed to calculate the total factor IX consumption for each participant. The average infusion dose for each participant was calculated as his total factor IX consumption (in IU) divided by the number of infusions administered. |
| Percentage of Infusions With Less Than Expected Therapeutic Effects (LETEs) in On-demand Setting | Up to 6 months or 50 exposure days whichever occurred first | Less than expected therapeutic effect (LETE) in the on-demand setting was defined as 2 successive no response ratings recorded after 2 successive BeneFIX drug infusions, respectively. |
| Percentage of Infusions With Less Than Expected Therapeutic Effects (LETEs) in Prophylaxis Setting | Up to 6 months or 50 exposure days whichever occurred first | Less than expected therapeutic effect (LETE) in the prophylaxis setting was defined as occurrence of any spontaneous bleed within 48 hours after a regularly scheduled prophylactic dose of BeneFIX (which was not used to treat a bleed). |
| Average Infusion Dose and Total Factor IX Consumption in Prophylaxis Setting | Up to 6 months or 50 exposure days whichever occurred first | The total amount (international units \[IU\]) infused for each BeneFIX infusion was summed to calculate the total factor IX consumption for each participant. The average infusion dose for each participant was calculated as his total factor IX consumption (in IU) divided by the number of infusions administered. |
| Annualized Bleeding Rates (ABRs) in Participants Receiving Prophylaxis Treatment With BeneFIX During Their Prophylaxis Period | Up to 6 months or 50 exposure days whichever occurred first | For prophylaxis period, annualized bleeding rate (ABR) was derived for each participant by the following formula: ABR = number of bleeds in prophylaxis period / (number of days in prophylaxis period/365.25). A prophylaxis period was defined as time from first prophylaxis infusion through 6 calendar days after the day of last prophylaxis infusion, or the day of study conclusion visit, whichever was earlier. A break in the prophylaxis period was any period of 28 days or longer in which no prophylaxis infusions were given. For a prophylaxis regimen to have been qualified to have ABR calculated, the sum of its periods needed to be \>=14 days. |
| Number of Spontaneous/Non-traumatic Breakthrough Bleeds Within 48 Hours of a Prophylaxis Dose of BeneFIX | Up to 6 months or 50 exposure days whichever occurred first | The prophylaxis infusion time, bleed start time and bleed type (etiology) were used to determine the number of spontaneous, non-traumatic breakthrough bleeds that occurred \<=48 hours after a prophylaxis infusion. If there was more than 1 bleed location (eg, ankle and joint) with identical bleed start date and time, it was treated as 1 bleed occurrence. |
Countries
China
Participant flow
Recruitment details
This study enrolled 70 participants.
Participants by arm
| Arm | Count |
|---|---|
| BeneFIX Participants received intravenous (IV) infusions of BeneFIX for on-demand or prophylaxis treatment at a dose and frequency prescribed by the participant's treating physician in accordance with the China BeneFIX Package Insert for 6 months (±7 days) or 50 Exposure Days (EDs) (±5 EDs), whichever occurred first. | 70 |
| Total | 70 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Lost to Follow-up | 1 |
| Overall Study | Other | 1 |
| Overall Study | Protocol Violation | 1 |
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | BeneFIX |
|---|---|
| Age, Continuous | 7.8 years STANDARD_DEVIATION 7.2 |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 70 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 55 / 70 |
| serious Total, serious adverse events | 2 / 70 |
Outcome results
Primary
Number of Participants With Allergic Reactions
FIX product allergy was defined as a hypersensitivity reaction to a FIX product with symptoms such as hives, urticaria, tightness of chest, wheezing, hypotension, and anaphylaxis based on investigator's judgments.
Time frame: Up to 6 months
Population: All participants who received at least 1 dose of BeneFIX during the study. Participants in each arm were not mutually exclusive.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pediatric Participants <6 Years of Age | Number of Participants With Allergic Reactions | 0 participants |
| Pediatric Participants ≥6 to ≤12 Years of Age | Number of Participants With Allergic Reactions | 0 participants |
| Previously Untreated Participants (PUPs) | Number of Participants With Allergic Reactions | 0 participants |
| Participants Receiving Prophylaxis Treatment | Number of Participants With Allergic Reactions | 0 participants |
| Severe Participants (Factor IX Activity <1%) | Number of Participants With Allergic Reactions | 0 participants |
| Overall Participants | Number of Participants With Allergic Reactions | 0 participants |
Primary
Number of Participants With Thrombotic Events
Thrombotic event was defined as any event associated with formation of a blood clot including catheter-associated thrombi and thrombotic complications.
Time frame: Up to 6 months
Population: All participants who received at least 1 dose of BeneFIX during the study. Participants in each arm were not mutually exclusive.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pediatric Participants <6 Years of Age | Number of Participants With Thrombotic Events | 0 participants |
| Pediatric Participants ≥6 to ≤12 Years of Age | Number of Participants With Thrombotic Events | 0 participants |
| Previously Untreated Participants (PUPs) | Number of Participants With Thrombotic Events | 0 participants |
| Participants Receiving Prophylaxis Treatment | Number of Participants With Thrombotic Events | 0 participants |
| Severe Participants (Factor IX Activity <1%) | Number of Participants With Thrombotic Events | 0 participants |
| Overall Participants | Number of Participants With Thrombotic Events | 0 participants |
Primary
Percentage of Participants Who Developed Factor IX Inhibitor
Factor IX (FIX) inhibitor development was defined as any Bethesda inhibitor titer greater than the laboratory's normal range or Bethesda inhibitor titer \>=0.6 Bethesda Unit (BU)/mL.
Time frame: Up to 6 months
Population: All participants who received at least 1 dose of BeneFIX during the study. Participants in each arm were not mutually exclusive.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pediatric Participants <6 Years of Age | Percentage of Participants Who Developed Factor IX Inhibitor | 3.3 percentage of participants |
| Pediatric Participants ≥6 to ≤12 Years of Age | Percentage of Participants Who Developed Factor IX Inhibitor | 0.0 percentage of participants |
| Previously Untreated Participants (PUPs) | Percentage of Participants Who Developed Factor IX Inhibitor | 0.0 percentage of participants |
| Participants Receiving Prophylaxis Treatment | Percentage of Participants Who Developed Factor IX Inhibitor | 1.8 percentage of participants |
| Severe Participants (Factor IX Activity <1%) | Percentage of Participants Who Developed Factor IX Inhibitor | 0.0 percentage of participants |
| Overall Participants | Percentage of Participants Who Developed Factor IX Inhibitor | 1.4 percentage of participants |
Secondary
Annualized Bleeding Rates (ABRs) in Participants Receiving On-demand Treatment With BeneFIX During Their On-demand Period
For on-demand period, the annualized bleeding rate (ABR) was derived for each participant by the following formula: ABR = number of bleeds in on-demand period / (number of days in on-demand period/365.25). The on-demand period was defined as the entire time of enrollment in the study (ie, from the date of the enrollment visit through the day before the Final/Early Termination visit) except time in any prophylaxis period. The breaks in the prophylaxis period were considered on-demand periods. For an on-demand regimen to have been qualified to have ABR calculated, the sum of its periods needed to be \>= 14 days.
Time frame: Up to 6 months or 50 exposure days whichever occurred first
Population: All participants who received on-demand treatment during on-demand period. Participants in each arm were not mutually exclusive.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pediatric Participants <6 Years of Age | Annualized Bleeding Rates (ABRs) in Participants Receiving On-demand Treatment With BeneFIX During Their On-demand Period | 14.8 episodes/year | Standard Deviation 15.59 |
| Pediatric Participants ≥6 to ≤12 Years of Age | Annualized Bleeding Rates (ABRs) in Participants Receiving On-demand Treatment With BeneFIX During Their On-demand Period | 28.2 episodes/year | Standard Deviation 26.16 |
| Previously Untreated Participants (PUPs) | Annualized Bleeding Rates (ABRs) in Participants Receiving On-demand Treatment With BeneFIX During Their On-demand Period | 6.2 episodes/year | Standard Deviation 2.4 |
| Participants Receiving Prophylaxis Treatment | Annualized Bleeding Rates (ABRs) in Participants Receiving On-demand Treatment With BeneFIX During Their On-demand Period | 29.3 episodes/year | Standard Deviation 25.95 |
| Severe Participants (Factor IX Activity <1%) | Annualized Bleeding Rates (ABRs) in Participants Receiving On-demand Treatment With BeneFIX During Their On-demand Period | 26.3 episodes/year | Standard Deviation 23.08 |
Secondary
Annualized Bleeding Rates (ABRs) in Participants Receiving Prophylaxis Treatment With BeneFIX During Their Prophylaxis Period
For prophylaxis period, annualized bleeding rate (ABR) was derived for each participant by the following formula: ABR = number of bleeds in prophylaxis period / (number of days in prophylaxis period/365.25). A prophylaxis period was defined as time from first prophylaxis infusion through 6 calendar days after the day of last prophylaxis infusion, or the day of study conclusion visit, whichever was earlier. A break in the prophylaxis period was any period of 28 days or longer in which no prophylaxis infusions were given. For a prophylaxis regimen to have been qualified to have ABR calculated, the sum of its periods needed to be \>=14 days.
Time frame: Up to 6 months or 50 exposure days whichever occurred first
Population: All participants who participated in at least 1 day of a prophylaxis period (ie, had at least 1 prophylaxis dose). Participants in each arm were not mutually exclusive.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pediatric Participants <6 Years of Age | Annualized Bleeding Rates (ABRs) in Participants Receiving Prophylaxis Treatment With BeneFIX During Their Prophylaxis Period | 5.9 episodes/year | Standard Deviation 9.46 |
| Pediatric Participants ≥6 to ≤12 Years of Age | Annualized Bleeding Rates (ABRs) in Participants Receiving Prophylaxis Treatment With BeneFIX During Their Prophylaxis Period | 7.5 episodes/year | Standard Deviation 8.97 |
| Previously Untreated Participants (PUPs) | Annualized Bleeding Rates (ABRs) in Participants Receiving Prophylaxis Treatment With BeneFIX During Their Prophylaxis Period | 0.3 episodes/year | Standard Deviation 0.72 |
| Participants Receiving Prophylaxis Treatment | Annualized Bleeding Rates (ABRs) in Participants Receiving Prophylaxis Treatment With BeneFIX During Their Prophylaxis Period | 6.5 episodes/year | Standard Deviation 9.06 |
| Severe Participants (Factor IX Activity <1%) | Annualized Bleeding Rates (ABRs) in Participants Receiving Prophylaxis Treatment With BeneFIX During Their Prophylaxis Period | 5.5 episodes/year | Standard Deviation 7.94 |
| Overall Participants | Annualized Bleeding Rates (ABRs) in Participants Receiving Prophylaxis Treatment With BeneFIX During Their Prophylaxis Period | 6.5 episodes/year | Standard Deviation 9.06 |
Secondary
Average Infusion Dose and Total Factor IX Consumption in On-demand Setting
The total amount (international units \[IU\]) infused for each BeneFIX infusion was summed to calculate the total factor IX consumption for each participant. The average infusion dose for each participant was calculated as his total factor IX consumption (in IU) divided by the number of infusions administered.
Time frame: Up to 6 months or 50 exposure days whichever occurred first
Population: All participants who had a bleed during the study for which on-demand treatment with BeneFIX was administered. Participants in each arm were not mutually exclusive.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pediatric Participants <6 Years of Age | Average Infusion Dose and Total Factor IX Consumption in On-demand Setting | Total FIX consumption | 4277.8 IU | Standard Deviation 4659.47 |
| Pediatric Participants <6 Years of Age | Average Infusion Dose and Total Factor IX Consumption in On-demand Setting | Average infusion dose | 451.1 IU | Standard Deviation 161.44 |
| Pediatric Participants ≥6 to ≤12 Years of Age | Average Infusion Dose and Total Factor IX Consumption in On-demand Setting | Total FIX consumption | 6550.0 IU | Standard Deviation 6540.66 |
| Pediatric Participants ≥6 to ≤12 Years of Age | Average Infusion Dose and Total Factor IX Consumption in On-demand Setting | Average infusion dose | 658.5 IU | Standard Deviation 370.35 |
| Previously Untreated Participants (PUPs) | Average Infusion Dose and Total Factor IX Consumption in On-demand Setting | Total FIX consumption | 1770.0 IU | Standard Deviation 1173.46 |
| Previously Untreated Participants (PUPs) | Average Infusion Dose and Total Factor IX Consumption in On-demand Setting | Average infusion dose | 518.6 IU | Standard Deviation 295.7 |
| Participants Receiving Prophylaxis Treatment | Average Infusion Dose and Total Factor IX Consumption in On-demand Setting | Total FIX consumption | 4418.8 IU | Standard Deviation 3449.75 |
| Participants Receiving Prophylaxis Treatment | Average Infusion Dose and Total Factor IX Consumption in On-demand Setting | Average infusion dose | 607.7 IU | Standard Deviation 309.34 |
| Severe Participants (Factor IX Activity <1%) | Average Infusion Dose and Total Factor IX Consumption in On-demand Setting | Total FIX consumption | 11672.9 IU | Standard Deviation 16304.85 |
| Severe Participants (Factor IX Activity <1%) | Average Infusion Dose and Total Factor IX Consumption in On-demand Setting | Average infusion dose | 803.8 IU | Standard Deviation 549.75 |
| Overall Participants | Average Infusion Dose and Total Factor IX Consumption in On-demand Setting | Total FIX consumption | 9826.1 IU | Standard Deviation 14816.34 |
| Overall Participants | Average Infusion Dose and Total Factor IX Consumption in On-demand Setting | Average infusion dose | 731.6 IU | Standard Deviation 498.58 |
Secondary
Average Infusion Dose and Total Factor IX Consumption in Prophylaxis Setting
The total amount (international units \[IU\]) infused for each BeneFIX infusion was summed to calculate the total factor IX consumption for each participant. The average infusion dose for each participant was calculated as his total factor IX consumption (in IU) divided by the number of infusions administered.
Time frame: Up to 6 months or 50 exposure days whichever occurred first
Population: All participants who received at least 1 dose of prophylaxis BeneFIX treatment during the study. Participants in each arm were not mutually exclusive.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pediatric Participants <6 Years of Age | Average Infusion Dose and Total Factor IX Consumption in Prophylaxis Setting | Total FIX consumption | 14709.3 IU | Standard Deviation 8910.57 |
| Pediatric Participants <6 Years of Age | Average Infusion Dose and Total Factor IX Consumption in Prophylaxis Setting | Average infusion dose | 429.3 IU | Standard Deviation 193.52 |
| Pediatric Participants ≥6 to ≤12 Years of Age | Average Infusion Dose and Total Factor IX Consumption in Prophylaxis Setting | Total FIX consumption | 22102.7 IU | Standard Deviation 18860.51 |
| Pediatric Participants ≥6 to ≤12 Years of Age | Average Infusion Dose and Total Factor IX Consumption in Prophylaxis Setting | Average infusion dose | 623.1 IU | Standard Deviation 377.99 |
| Previously Untreated Participants (PUPs) | Average Infusion Dose and Total Factor IX Consumption in Prophylaxis Setting | Total FIX consumption | 13846.4 IU | Standard Deviation 5868.21 |
| Previously Untreated Participants (PUPs) | Average Infusion Dose and Total Factor IX Consumption in Prophylaxis Setting | Average infusion dose | 351.9 IU | Standard Deviation 194.48 |
| Participants Receiving Prophylaxis Treatment | Average Infusion Dose and Total Factor IX Consumption in Prophylaxis Setting | Total FIX consumption | 19224.1 IU | Standard Deviation 15424.7 |
| Participants Receiving Prophylaxis Treatment | Average Infusion Dose and Total Factor IX Consumption in Prophylaxis Setting | Average infusion dose | 540.1 IU | Standard Deviation 316.56 |
| Severe Participants (Factor IX Activity <1%) | Average Infusion Dose and Total Factor IX Consumption in Prophylaxis Setting | Total FIX consumption | 20628.4 IU | Standard Deviation 19894 |
| Severe Participants (Factor IX Activity <1%) | Average Infusion Dose and Total Factor IX Consumption in Prophylaxis Setting | Average infusion dose | 557.0 IU | Standard Deviation 407.05 |
| Overall Participants | Average Infusion Dose and Total Factor IX Consumption in Prophylaxis Setting | Total FIX consumption | 19224.1 IU | Standard Deviation 15424.7 |
| Overall Participants | Average Infusion Dose and Total Factor IX Consumption in Prophylaxis Setting | Average infusion dose | 540.1 IU | Standard Deviation 316.56 |
Secondary
Average Infusion Dose and Total Factor IX Consumption in Recovery Setting
The total amount (international units \[IU\]) infused for each BeneFIX infusion was summed to calculate the total factor IX consumption for each participant. The average infusion dose for each participant was calculated as his total factor IX consumption (in IU) divided by the number of infusions administered.
Time frame: Up to 6 months or 50 exposure days whichever occurred first
Population: All participants who received at least 1 recovery infusion with BeneFIX during the study. Participants in each arm were not mutually exclusive.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pediatric Participants <6 Years of Age | Average Infusion Dose and Total Factor IX Consumption in Recovery Setting | Total FIX consumption | 1156.3 IU | Standard Deviation 1341.14 |
| Pediatric Participants <6 Years of Age | Average Infusion Dose and Total Factor IX Consumption in Recovery Setting | Average infusion dose | 773.4 IU | Standard Deviation 371.46 |
| Pediatric Participants ≥6 to ≤12 Years of Age | Average Infusion Dose and Total Factor IX Consumption in Recovery Setting | Total FIX consumption | 1688.9 IU | Standard Deviation 1123.27 |
| Pediatric Participants ≥6 to ≤12 Years of Age | Average Infusion Dose and Total Factor IX Consumption in Recovery Setting | Average infusion dose | 890.7 IU | Standard Deviation 270.46 |
| Previously Untreated Participants (PUPs) | Average Infusion Dose and Total Factor IX Consumption in Recovery Setting | Total FIX consumption | 250.0 IU | — |
| Previously Untreated Participants (PUPs) | Average Infusion Dose and Total Factor IX Consumption in Recovery Setting | Average infusion dose | 250.0 IU | — |
| Participants Receiving Prophylaxis Treatment | Average Infusion Dose and Total Factor IX Consumption in Recovery Setting | Total FIX consumption | 1378.8 IU | Standard Deviation 1291.66 |
| Participants Receiving Prophylaxis Treatment | Average Infusion Dose and Total Factor IX Consumption in Recovery Setting | Average infusion dose | 889.9 IU | Standard Deviation 502.77 |
| Severe Participants (Factor IX Activity <1%) | Average Infusion Dose and Total Factor IX Consumption in Recovery Setting | Total FIX consumption | 1467.3 IU | Standard Deviation 1318.28 |
| Severe Participants (Factor IX Activity <1%) | Average Infusion Dose and Total Factor IX Consumption in Recovery Setting | Average infusion dose | 962.0 IU | Standard Deviation 556.45 |
| Overall Participants | Average Infusion Dose and Total Factor IX Consumption in Recovery Setting | Total FIX consumption | 1419.8 IU | Standard Deviation 1192.62 |
| Overall Participants | Average Infusion Dose and Total Factor IX Consumption in Recovery Setting | Average infusion dose | 929.1 IU | Standard Deviation 475.75 |
Secondary
Number of BeneFIX Infusions to Treat Each New Bleed
The number of BeneFIX infusions administered to treat each new bleed was calculated by adding the on-demand initial treatment and any on-demand follow-up treatments for the same bleed. If there was more than one bleed location (eg, ankle and joint) with identical bleed start date and time, it was treated as one bleed occurrence.
Time frame: Up to 6 months or 50 exposure days whichever occurred first
Population: All participants who had a bleed during the study for which on-demand treatment with BeneFIX was administered. Participants in each arm were not mutually exclusive.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pediatric Participants <6 Years of Age | Number of BeneFIX Infusions to Treat Each New Bleed | 1.7 infusions | Standard Deviation 1.72 |
| Pediatric Participants ≥6 to ≤12 Years of Age | Number of BeneFIX Infusions to Treat Each New Bleed | 1.5 infusions | Standard Deviation 2.03 |
| Previously Untreated Participants (PUPs) | Number of BeneFIX Infusions to Treat Each New Bleed | 1.1 infusions | Standard Deviation 0.34 |
| Participants Receiving Prophylaxis Treatment | Number of BeneFIX Infusions to Treat Each New Bleed | 1.5 infusions | Standard Deviation 1.23 |
| Severe Participants (Factor IX Activity <1%) | Number of BeneFIX Infusions to Treat Each New Bleed | 1.5 infusions | Standard Deviation 2.01 |
| Overall Participants | Number of BeneFIX Infusions to Treat Each New Bleed | 1.5 infusions | Standard Deviation 1.71 |
Secondary
Number of Infusions Resulted in the Following Response to On-demand Treatment of Bleeds: Excellent, Good, Moderate, no Response
Response was assessed using 4-point On-Demand Hemostasis Efficacy Rating Scale. Excellent means definite pain relief and/or improvement in signs of bleeding starting within 8 hours after an infusion, with no additional infusion administered; good means definite pain relief and/or improvement in signs of bleeding starting within 8 hours after an infusion, with at least one additional infusion administered for complete resolution of the bleeding episode, or definite pain relief and/or improvement in signs of bleeding starting after 8 hours following the infusion, with no additional infusion administered; moderate means probable or slight improvement starting after 8 hours following the infusion, with at least one additional infusion administered for complete resolution of the bleeding episode; no response means no improvement between infusions or during the 24 hour interval following an infusion, or condition worsens. Both first infusions and follow-up infusions were included.
Time frame: Up to 6 months or 50 exposure days whichever occurred first
Population: All participants who had a bleed during the study for which on-demand treatment with BeneFIX was administered. Participants in each arm were not mutually exclusive.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Pediatric Participants <6 Years of Age | Number of Infusions Resulted in the Following Response to On-demand Treatment of Bleeds: Excellent, Good, Moderate, no Response | Excellent | 77 infusions |
| Pediatric Participants <6 Years of Age | Number of Infusions Resulted in the Following Response to On-demand Treatment of Bleeds: Excellent, Good, Moderate, no Response | Good | 60 infusions |
| Pediatric Participants <6 Years of Age | Number of Infusions Resulted in the Following Response to On-demand Treatment of Bleeds: Excellent, Good, Moderate, no Response | Moderate | 22 infusions |
| Pediatric Participants <6 Years of Age | Number of Infusions Resulted in the Following Response to On-demand Treatment of Bleeds: Excellent, Good, Moderate, no Response | No response | 5 infusions |
| Pediatric Participants ≥6 to ≤12 Years of Age | Number of Infusions Resulted in the Following Response to On-demand Treatment of Bleeds: Excellent, Good, Moderate, no Response | Moderate | 23 infusions |
| Pediatric Participants ≥6 to ≤12 Years of Age | Number of Infusions Resulted in the Following Response to On-demand Treatment of Bleeds: Excellent, Good, Moderate, no Response | Good | 91 infusions |
| Pediatric Participants ≥6 to ≤12 Years of Age | Number of Infusions Resulted in the Following Response to On-demand Treatment of Bleeds: Excellent, Good, Moderate, no Response | Excellent | 94 infusions |
| Pediatric Participants ≥6 to ≤12 Years of Age | Number of Infusions Resulted in the Following Response to On-demand Treatment of Bleeds: Excellent, Good, Moderate, no Response | No response | 3 infusions |
| Previously Untreated Participants (PUPs) | Number of Infusions Resulted in the Following Response to On-demand Treatment of Bleeds: Excellent, Good, Moderate, no Response | No response | 0 infusions |
| Previously Untreated Participants (PUPs) | Number of Infusions Resulted in the Following Response to On-demand Treatment of Bleeds: Excellent, Good, Moderate, no Response | Moderate | 0 infusions |
| Previously Untreated Participants (PUPs) | Number of Infusions Resulted in the Following Response to On-demand Treatment of Bleeds: Excellent, Good, Moderate, no Response | Good | 9 infusions |
| Previously Untreated Participants (PUPs) | Number of Infusions Resulted in the Following Response to On-demand Treatment of Bleeds: Excellent, Good, Moderate, no Response | Excellent | 9 infusions |
| Participants Receiving Prophylaxis Treatment | Number of Infusions Resulted in the Following Response to On-demand Treatment of Bleeds: Excellent, Good, Moderate, no Response | Excellent | 133 infusions |
| Participants Receiving Prophylaxis Treatment | Number of Infusions Resulted in the Following Response to On-demand Treatment of Bleeds: Excellent, Good, Moderate, no Response | No response | 1 infusions |
| Participants Receiving Prophylaxis Treatment | Number of Infusions Resulted in the Following Response to On-demand Treatment of Bleeds: Excellent, Good, Moderate, no Response | Good | 96 infusions |
| Participants Receiving Prophylaxis Treatment | Number of Infusions Resulted in the Following Response to On-demand Treatment of Bleeds: Excellent, Good, Moderate, no Response | Moderate | 19 infusions |
| Severe Participants (Factor IX Activity <1%) | Number of Infusions Resulted in the Following Response to On-demand Treatment of Bleeds: Excellent, Good, Moderate, no Response | Moderate | 33 infusions |
| Severe Participants (Factor IX Activity <1%) | Number of Infusions Resulted in the Following Response to On-demand Treatment of Bleeds: Excellent, Good, Moderate, no Response | No response | 2 infusions |
| Severe Participants (Factor IX Activity <1%) | Number of Infusions Resulted in the Following Response to On-demand Treatment of Bleeds: Excellent, Good, Moderate, no Response | Good | 145 infusions |
| Severe Participants (Factor IX Activity <1%) | Number of Infusions Resulted in the Following Response to On-demand Treatment of Bleeds: Excellent, Good, Moderate, no Response | Excellent | 122 infusions |
| Overall Participants | Number of Infusions Resulted in the Following Response to On-demand Treatment of Bleeds: Excellent, Good, Moderate, no Response | Good | 204 infusions |
| Overall Participants | Number of Infusions Resulted in the Following Response to On-demand Treatment of Bleeds: Excellent, Good, Moderate, no Response | Moderate | 54 infusions |
| Overall Participants | Number of Infusions Resulted in the Following Response to On-demand Treatment of Bleeds: Excellent, Good, Moderate, no Response | No response | 8 infusions |
| Overall Participants | Number of Infusions Resulted in the Following Response to On-demand Treatment of Bleeds: Excellent, Good, Moderate, no Response | Excellent | 254 infusions |
Secondary
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
An adverse event (AE) was any untoward medical occurrence in a clinical investigation participant administered a product or medical device, regardless of the causality with the treatment or usage. A serious adverse event (SAE) was any untoward occurrence at any dose that resulted in death; was life threatening (immediate risk of death); required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity; resulted in congenital anomaly/birth defect. AEs included both serious and non-serious AEs. Treatment-emergent AEs were those with initial onset or increasing in severity after the first dose of study drug.
Time frame: Up to 7 months (28 calendar days after end of 6-month or 50-exposure day study treatment)
Population: All participants who received at least 1 dose of BeneFIX during the study. Participants in each arm were not mutually exclusive.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Pediatric Participants <6 Years of Age | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | AEs | 28 participants |
| Pediatric Participants <6 Years of Age | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | SAEs | 2 participants |
| Pediatric Participants ≥6 to ≤12 Years of Age | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | AEs | 26 participants |
| Pediatric Participants ≥6 to ≤12 Years of Age | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | SAEs | 0 participants |
| Previously Untreated Participants (PUPs) | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | AEs | 10 participants |
| Previously Untreated Participants (PUPs) | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | SAEs | 0 participants |
| Participants Receiving Prophylaxis Treatment | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | AEs | 46 participants |
| Participants Receiving Prophylaxis Treatment | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | SAEs | 2 participants |
| Severe Participants (Factor IX Activity <1%) | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | AEs | 30 participants |
| Severe Participants (Factor IX Activity <1%) | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | SAEs | 0 participants |
| Overall Participants | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | AEs | 62 participants |
| Overall Participants | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | SAEs | 2 participants |
Secondary
Number of Spontaneous/Non-traumatic Breakthrough Bleeds Within 48 Hours of a Prophylaxis Dose of BeneFIX
The prophylaxis infusion time, bleed start time and bleed type (etiology) were used to determine the number of spontaneous, non-traumatic breakthrough bleeds that occurred \<=48 hours after a prophylaxis infusion. If there was more than 1 bleed location (eg, ankle and joint) with identical bleed start date and time, it was treated as 1 bleed occurrence.
Time frame: Up to 6 months or 50 exposure days whichever occurred first
Population: All participants with any spontaneous/non-traumatic breakthrough bleeds within 48 hours of a prophylaxis dose. Participants in each arm were not mutually exclusive.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pediatric Participants <6 Years of Age | Number of Spontaneous/Non-traumatic Breakthrough Bleeds Within 48 Hours of a Prophylaxis Dose of BeneFIX | 1.3 breakthrough bleeds | Standard Deviation 0.5 |
| Pediatric Participants ≥6 to ≤12 Years of Age | Number of Spontaneous/Non-traumatic Breakthrough Bleeds Within 48 Hours of a Prophylaxis Dose of BeneFIX | 2.6 breakthrough bleeds | Standard Deviation 2.3 |
| Participants Receiving Prophylaxis Treatment | Number of Spontaneous/Non-traumatic Breakthrough Bleeds Within 48 Hours of a Prophylaxis Dose of BeneFIX | 2.1 breakthrough bleeds | Standard Deviation 1.92 |
| Severe Participants (Factor IX Activity <1%) | Number of Spontaneous/Non-traumatic Breakthrough Bleeds Within 48 Hours of a Prophylaxis Dose of BeneFIX | 2.6 breakthrough bleeds | Standard Deviation 2.3 |
| Overall Participants | Number of Spontaneous/Non-traumatic Breakthrough Bleeds Within 48 Hours of a Prophylaxis Dose of BeneFIX | 2.1 breakthrough bleeds | Standard Deviation 1.92 |
Secondary
Percentage of Infusions With Less Than Expected Therapeutic Effects (LETEs) in On-demand Setting
Less than expected therapeutic effect (LETE) in the on-demand setting was defined as 2 successive no response ratings recorded after 2 successive BeneFIX drug infusions, respectively.
Time frame: Up to 6 months or 50 exposure days whichever occurred first
Population: All participants who had a bleed during the study for which on-demand treatment with BeneFIX was administered. Participants in each arm were not mutually exclusive.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pediatric Participants <6 Years of Age | Percentage of Infusions With Less Than Expected Therapeutic Effects (LETEs) in On-demand Setting | 0 percentage of infusions |
| Pediatric Participants ≥6 to ≤12 Years of Age | Percentage of Infusions With Less Than Expected Therapeutic Effects (LETEs) in On-demand Setting | 0 percentage of infusions |
| Previously Untreated Participants (PUPs) | Percentage of Infusions With Less Than Expected Therapeutic Effects (LETEs) in On-demand Setting | 0 percentage of infusions |
| Participants Receiving Prophylaxis Treatment | Percentage of Infusions With Less Than Expected Therapeutic Effects (LETEs) in On-demand Setting | 0 percentage of infusions |
| Severe Participants (Factor IX Activity <1%) | Percentage of Infusions With Less Than Expected Therapeutic Effects (LETEs) in On-demand Setting | 0 percentage of infusions |
| Overall Participants | Percentage of Infusions With Less Than Expected Therapeutic Effects (LETEs) in On-demand Setting | 0 percentage of infusions |
Secondary
Percentage of Infusions With Less Than Expected Therapeutic Effects (LETEs) in Prophylaxis Setting
Less than expected therapeutic effect (LETE) in the prophylaxis setting was defined as occurrence of any spontaneous bleed within 48 hours after a regularly scheduled prophylactic dose of BeneFIX (which was not used to treat a bleed).
Time frame: Up to 6 months or 50 exposure days whichever occurred first
Population: All participants who received at least 1 dose of prophylaxis BeneFIX treatment during the study. Participants in each arm were not mutually exclusive.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pediatric Participants <6 Years of Age | Percentage of Infusions With Less Than Expected Therapeutic Effects (LETEs) in Prophylaxis Setting | 0.1 percentage of infusions |
| Pediatric Participants ≥6 to ≤12 Years of Age | Percentage of Infusions With Less Than Expected Therapeutic Effects (LETEs) in Prophylaxis Setting | 0.1 percentage of infusions |
| Previously Untreated Participants (PUPs) | Percentage of Infusions With Less Than Expected Therapeutic Effects (LETEs) in Prophylaxis Setting | 0 percentage of infusions |
| Participants Receiving Prophylaxis Treatment | Percentage of Infusions With Less Than Expected Therapeutic Effects (LETEs) in Prophylaxis Setting | 0.1 percentage of infusions |
| Severe Participants (Factor IX Activity <1%) | Percentage of Infusions With Less Than Expected Therapeutic Effects (LETEs) in Prophylaxis Setting | 0.2 percentage of infusions |
| Overall Participants | Percentage of Infusions With Less Than Expected Therapeutic Effects (LETEs) in Prophylaxis Setting | 0.1 percentage of infusions |