Congenital Bleeding Disorder, Haemophilia A With Inhibitors, Haemophilia B With Inhibitors
Conditions
Brief summary
This study was conducted in Africa, Europe, the Middle-East and South America. The primary objective of this registry was to observe the use of single dose and multi-dose use of activated recombinant human factor VII and to compare short-term outcomes, including effectiveness, safety, quality of life and treatment satisfaction with the approved treatments.
Interventions
DRUGeptacog alfa (activated)
Treatment of patients experiencing bleeds at the discretion of the physician/caregiver
Sponsors
Novo Nordisk A/S
Study design
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
MALE
Healthy volunteers
No
Inclusion criteria
* Diagnosed with haemophilia A or B with inhibitors * Experience mild to moderate spontaneous bleeds which require on-demand treatment and who are currently prescribed activated recombinant human factor VII * Be able and willing to provide informed consent (or proxy consent by caregiver, if applicable), as required by local research ethics committee, governmental or regulatory authorities * Be willing to provide information on at least one alternate contact person in the event that the patient be somehow lost-to-follow-up over the course of registry participation (not applicable if patient is withdrawn)
Exclusion criteria
* Known hypersensitivity to the active substance or the excipients in the formulation of activated recombinant human factor VII, or to mouse, hamster or bovine protein
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Bleed Treatments Resulting in Effective Bleed Resolution (Spontaneous Bleed Episodes) | within 9 hours of first injection | The percentage of bleed treatments successfully resulting in bleed resolution. Analysis only considers the patient's opinion of effectiveness at 9 hours, with a rating of Effective considered as successful treatment. |
| Percentage of Bleed Treatments Resulting in Effective Pain Relief (Spontaneous Bleed Episodes) | within 9 hours of first injection | The percentage of participants with effective pain relief. Pain relief was a subjective assessment made by the patient during treatment of a bleed episode. |
| Percentage of Bleed Treatments Resulting in Effective Pain Relief (All Bleed Episodes) | within 9 hours of first injection | The percentage of participants with effective pain relief. Pain relief was a subjective assessment made by the patient during treatment of a bleed episode. |
| Percentage of Bleed Treatments Resulting in Effective Bleed Resolution (All Bleed Episodes) | within 9 hours of first injection | The percentage of bleed treatments successfully resulting in bleed resolution. Analysis only considers the patient's opinion of effectiveness at 9 hours, with a rating of Effective considered as successful treatment. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Bleed Treatments Resulting in Effective Pain Relief by Time Point (Spontaneous Bleed Episodes) | 1 hour, 3 hours and 6 hours, respectively, after first injection | Effective pain relief at 3 different time points for spontaneous bleeds. Patient reported outcomes are reported over 1 hour, 3 hours and 6 hours. |
| Total Number of Injections (All Bleed Episodes) | individual bleed episode | The median number of injections required to treat individual bleed episodes. |
| Total Number of Injections (Spontaneous Bleed Episodes) | individual bleed episode | The median number of injections required to treat individual bleed episodes. |
| Total Exposure (Cumulative Dose) to Activated Recombinant Human Factor VII (All Bleed Episodes) | individual bleed episode | The median total cumulative dose required to treat individual bleed episodes. |
| Total Exposure (Cumulative Dose) to Activated Recombinant Human Factor VII (Spontaneous Bleed Episodes) | individual bleed episode | The median total cumulative dose required to treat individual bleed episodes. |
| Percentage of Bleed Treatments Resulting in Patient Satisfaction With Symptom Relief (Spontaneous Bleed Episodes) | duration of bleed episode | Patient rate of satisfaction with symptom relief for the bleed episode overall on a 7-point Likert scale. Completion of questionnaire was voluntary. A Likert scale is an ordered, multiple choice questionnaire from which respondents choose one option that best aligns with their view of the particular outcome being measured. Scale answers ranged from extremely satisfied to extremely dissatisfied. The percentage of bleed episodes for which patients reported extremely satisfied, very satisfied or satisfied is presented. |
| Percentage of Bleed Treatments Resulting in Patient Satisfaction With Ease of Use (All Bleed Episodes) | duration of bleed episode | Rate of ease of use related to activated recombinant human factor VII on a 7-point Likert scale. Completion of questionnaire was voluntary. A Likert scale is an ordered, multiple choice questionnaire from which respondents choose one option that best aligns with their view of the particular outcome being measured. Scale answers ranged from extremely difficult to extremely easy. The percentage of bleed episodes for which patients reported extremely easy, very easy or easy is presented. |
| Percentage of Bleed Treatments Resulting in Patient Satisfaction With Ease of Use (Spontaneous Bleed Episodes) | duration of bleed episode | Rate of ease of use related to activated recombinant human factor VII on a 7-point Likert scale. Completion of questionnaire was voluntary. A Likert scale is an ordered, multiple choice questionnaire from which respondents choose one option that best aligns with their view of the particular outcome being measured. Scale answers ranged from extremely difficult to extremely easy. The percentage of bleed episodes for which patients reported extremely easy, very easy or easy is presented. |
| Overall Time to Cessation of Bleed/Achievement of Haemostasis (All Bleed Episodes) | duration of bleed episode | Median time to achievement of haemostasis/bleed cessation calculated using Kaplan Meier life table methods. If approximately 50% or less of bleeds achieved the endpoint in a given initial dose subgroup, the median cannot be calculated and it is reported as not applicable |
| Overall Time to Cessation of Bleed/Achievement of Haemostasis (Spontaneous Bleed Episodes) | duration of bleed episode | Median time to achievement of haemostasis/bleed cessation calculated using Kaplan Meier life table methods. If approximately 50% or less of bleeds achieved the endpoint in a given initial dose subgroup, the median cannot be calculated and it is reported as not applicable |
| Overall Time to Cessation/Achievement of Haemostasis (Spontaneous Bleed Episodes) | duration of bleed episode | Median time to achievement of haemostasis/bleed cessation calculated using Kaplan Meier life table methods. If approximately 50% or less of bleeds achieved the endpoint in a given initial dose subgroup, the median cannot be calculated and it is reported as not applicable. |
| Childrens' Health Related Quality of Life (Haemo-QoL): Overall Score | Baseline (week 0) and and registry discontinuation (up to 28 months) | The Haemo-QoL is a specific multidimensional validated and reliable questionnaire used to assess quality of life in patients with haemophilia. Scores are reported on a 0 to 100 scale-higher scores indicate more impairment. |
| Adults' Health Related Quality of Life (Haemo-QoL-A): Overall Score | Baseline (week 0) and and registry discontinuation (up to 28 months) | The adult Haemo-QoL-A is a specific multidimensional validated and reliable questionnaire used to assess quality of life in patients with haemophilia. Scores are reported on a 0 to 100 scale-higher scores indicate more impairment. |
| Percentage of Patients Reporting Satisfaction With Symptom Relief (All Bleed Episodes) | duration of bleed episode | Patient rate of satisfaction with symptom relief for the bleed episode overall on a 7-point Likert scale. Completion of questionnaire was voluntary. A Likert scale is an ordered, multiple choice questionnaire from which respondents choose one option that best aligns with their view of the particular outcome being measured. Scale answers ranged from extremely satisfied to extremely dissatisfied. The percentage of bleed episodes for which patients reported extremely satisfied, very satisfied or satisfied is presented. |
| Percentage of Bleed Treatments Resulting in Effective Haemostasis (Cessation of Bleeds) by Time Point (All Bleed Episodes) | 1 hour, 3 hours and 6 hours, respectively, after first injection | Effective haemostasis at 3 different time points for all bleeds. Patient reported outcomes are reported over 1 hour, 3 hours and 6 hours. |
| Percentage of Bleed Treatments Resulting in Effective Haemostasis (Cessation of Bleeds) by Time Point (Spontaneous Bleed Episodes) | 1 hour, 3 hours and 6 hours, respectively, after first injection | Effective haemostasis at 3 different time points for all bleeds. Patient reported outcomes are reported over 1 hour, 3 hours and 6 hours. |
| Percentage of Bleed Treatments Resulting in Effective Pain Relief by Time Point (All Bleed Episodes) | 1 hour, 3 hours and 6 hours, respectively, after first injection | Effective pain relief at 3 different time points for all bleeds. Patient reported outcomes are reported over 1 hour, 3 hours and 6 hours. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Bleed Treatments Resulting in Effective Haemostasis (Cessation of Bleed) by Dose Level (All Bleed Episodes) | within 9 hours after first injection | Percentage of bleeds with effective haemostasis within 9 hours of first injection of activated recombinant human factor VII. Patient reported assessments were sorted into 3 sub-categories: effective = bleed resolved or substantially improved; partially effective = bleed with some improvement; ineffective = bleed with no change or with worsening. |
| Percentage of Bleed Treatments Resulting in Effective Pain Relief by Initial Dose (Spontaneous Bleed Episodes) | within 9 hours after first injection | Percentage of bleeds with effective pain relief within 9 hours of first injection of activated recombinant human factor VII. Patient reported assessments were sorted into 3 sub-categories: Better = pain resolved or decreased substantially; Same = no change; Worsened = pain worsening. |
| Percentage of Bleed Treatments Resulting in Effective Pain Relief by Initial Dose (All Bleed Episodes) | within 9 hours after first injection | Percentage of bleeds with effective pain relief within 9 hours of first injection of activated recombinant human factor VII. Patient reported assessments were sorted into 3 sub-categories: Better = pain resolved or decreased substantially; Same = no change; Worsened = pain worsening. |
| Percentage of Bleed Treatments Resulting in Effective Haemostasis (Cessation of Bleed) by Dose Level (Spontaneous Bleed Episodes) | within 9 hours after first injection | Percentage of bleeds with effective haemostasis within 9 hours of first injection of activated recombinant human factor VII. Patient reported assessments were sorted into 3 sub-categories: effective = bleed resolved or substantially improved; partially effective = bleed with some improvement; ineffective = bleed with no change or with worsening. |
Countries
Algeria, Austria, Belgium, Czechia, France, Germany, Italy, Netherlands, Poland, Portugal, Saudi Arabia, South Africa, Sweden, Turkey (Türkiye), United Kingdom, Venezuela
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Activated Recombinant Human Factor VII Male patients above 2 years of age with haemophilia A or B who have developed inhibitors and have been prescribed on-demand treatment of activated recombinant human factor VII at any dose for treatment of mild to moderate spontaneous bleeds | 102 |
| Total | 102 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Death | 1 |
| Overall Study | Lost to Follow-up | 1 |
| Overall Study | Physician Decision | 6 |
| Overall Study | Withdrawal by Subject | 2 |
Baseline characteristics
| Characteristic | Activated Recombinant Human Factor VII |
|---|---|
| Age, Continuous | 23.3 years STANDARD_DEVIATION 16.37 |
| Age, Customized 18 years or above | 53 participants |
| Age, Customized 2 - 12 years | 35 participants |
| Age, Customized above 12 - 17 years | 14 participants |
| Estimated number of bleeds for the 6 months preceding enrolment in registry 12 - 18 (2 - 3 per month) | 12 participants |
| Estimated number of bleeds for the 6 months preceding enrolment in registry 1 - 6 (1 or less per month) | 65 participants |
| Estimated number of bleeds for the 6 months preceding enrolment in registry 18 (more than 3 per month) | 2 participants |
| Estimated number of bleeds for the 6 months preceding enrolment in registry 6 - 12 (1 - 2 per month) | 13 participants |
| Estimated number of bleeds for the 6 months preceding enrolment in registry Data missing | 1 participants |
| Estimated number of bleeds for the 6 months preceding enrolment in registry None | 9 participants |
| Gender Female | 0 Participants |
| Gender Male | 102 Participants |
| Outcome of immune tolerance induction (ITI) treatment None | 66 participants |
| Outcome of immune tolerance induction (ITI) treatment Ongoing ITI | 11 participants |
| Outcome of immune tolerance induction (ITI) treatment Successful, with inhibitor recurrence | 5 participants |
| Outcome of immune tolerance induction (ITI) treatment Unsuccessful | 20 participants |
| Peak inhibitor titre At least 5 Bethesda Units | 91 participants |
| Peak inhibitor titre Less than 5 Bethesda Units | 11 participants |
| Primary treatment pattern for the 6 months preceding enrolment in registry Data missing | 1 participants |
| Primary treatment pattern for the 6 months preceding enrolment in registry On-demand | 88 participants |
| Primary treatment pattern for the 6 months preceding enrolment in registry Prophylaxis | 13 participants |
| Primary treatment type and dose for the 6 months preceding enrolment in registry Multiple dose 90 mcg/kg NovoSeven® | 44 participants |
| Primary treatment type and dose for the 6 months preceding enrolment in registry Other bypassing agent (e.g., FEIBA) | 13 participants |
| Primary treatment type and dose for the 6 months preceding enrolment in registry Other dose regimen NovoSeven® | 17 participants |
| Primary treatment type and dose for the 6 months preceding enrolment in registry Single dose 270 mcg/kg NovoSeven® | 28 participants |
| Region of Enrollment Algeria | 17 participants |
| Region of Enrollment Austria | 3 participants |
| Region of Enrollment Belgium | 4 participants |
| Region of Enrollment Czech Republic | 1 participants |
| Region of Enrollment France | 16 participants |
| Region of Enrollment Germany | 4 participants |
| Region of Enrollment Italy | 16 participants |
| Region of Enrollment Netherlands | 1 participants |
| Region of Enrollment Poland | 9 participants |
| Region of Enrollment Portugal | 1 participants |
| Region of Enrollment Saudi Arabia | 2 participants |
| Region of Enrollment South Africa | 8 participants |
| Region of Enrollment Sweden | 1 participants |
| Region of Enrollment Turkey | 6 participants |
| Region of Enrollment United Kingdom | 7 participants |
| Region of Enrollment Venezuela | 6 participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 0 / 85 |
| serious Total, serious adverse events | 0 / 85 |
Outcome results
Primary
Percentage of Bleed Treatments Resulting in Effective Bleed Resolution (All Bleed Episodes)
The percentage of bleed treatments successfully resulting in bleed resolution. Analysis only considers the patient's opinion of effectiveness at 9 hours, with a rating of Effective considered as successful treatment.
Time frame: within 9 hours of first injection
Population: Analysis set is all bleed episodes, regardless of bleed type or initial dose level
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Activated Recombinant Human Factor VII | Percentage of Bleed Treatments Resulting in Effective Bleed Resolution (All Bleed Episodes) | Any initial dose, n=494 | 61.7 percentage of bleed episodes |
| Activated Recombinant Human Factor VII | Percentage of Bleed Treatments Resulting in Effective Bleed Resolution (All Bleed Episodes) | Low initial dose, n=156 | 67.9 percentage of bleed episodes |
| Activated Recombinant Human Factor VII | Percentage of Bleed Treatments Resulting in Effective Bleed Resolution (All Bleed Episodes) | Intermediate initial dose, n=127 | 62.2 percentage of bleed episodes |
| Activated Recombinant Human Factor VII | Percentage of Bleed Treatments Resulting in Effective Bleed Resolution (All Bleed Episodes) | High initial dose, n=211 | 56.9 percentage of bleed episodes |
Primary
Percentage of Bleed Treatments Resulting in Effective Bleed Resolution (Spontaneous Bleed Episodes)
The percentage of bleed treatments successfully resulting in bleed resolution. Analysis only considers the patient's opinion of effectiveness at 9 hours, with a rating of Effective considered as successful treatment.
Time frame: within 9 hours of first injection
Population: Analysis set is spontaneous bleed episodes treated with any initial dose
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Activated Recombinant Human Factor VII | Percentage of Bleed Treatments Resulting in Effective Bleed Resolution (Spontaneous Bleed Episodes) | Any initial dose, n=324 | 59.0 percentage of bleed episodes |
| Activated Recombinant Human Factor VII | Percentage of Bleed Treatments Resulting in Effective Bleed Resolution (Spontaneous Bleed Episodes) | Low initial dose, n=92 | 62.6 percentage of bleed episodes |
| Activated Recombinant Human Factor VII | Percentage of Bleed Treatments Resulting in Effective Bleed Resolution (Spontaneous Bleed Episodes) | Intermediate initial dose, n=91 | 60.4 percentage of bleed episodes |
| Activated Recombinant Human Factor VII | Percentage of Bleed Treatments Resulting in Effective Bleed Resolution (Spontaneous Bleed Episodes) | High initial dose, n=141 | 55.7 percentage of bleed episodes |
Primary
Percentage of Bleed Treatments Resulting in Effective Pain Relief (All Bleed Episodes)
The percentage of participants with effective pain relief. Pain relief was a subjective assessment made by the patient during treatment of a bleed episode.
Time frame: within 9 hours of first injection
Population: Analysis set is all bleed episodes, regardless of bleed type or initial dose level
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Activated Recombinant Human Factor VII | Percentage of Bleed Treatments Resulting in Effective Pain Relief (All Bleed Episodes) | Any initial dose, n=494 | 71.3 percentage of bleed episodes |
| Activated Recombinant Human Factor VII | Percentage of Bleed Treatments Resulting in Effective Pain Relief (All Bleed Episodes) | Low initial dose, n=156 | 82.1 percentage of bleed episodes |
| Activated Recombinant Human Factor VII | Percentage of Bleed Treatments Resulting in Effective Pain Relief (All Bleed Episodes) | Intermediate initial dose, n=127 | 60.6 percentage of bleed episodes |
| Activated Recombinant Human Factor VII | Percentage of Bleed Treatments Resulting in Effective Pain Relief (All Bleed Episodes) | High initial dose, n=211 | 69.7 percentage of bleed episodes |
Primary
Percentage of Bleed Treatments Resulting in Effective Pain Relief (Spontaneous Bleed Episodes)
The percentage of participants with effective pain relief. Pain relief was a subjective assessment made by the patient during treatment of a bleed episode.
Time frame: within 9 hours of first injection
Population: Analysis set is spontaneous bleed episodes treated with any initial dose
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Activated Recombinant Human Factor VII | Percentage of Bleed Treatments Resulting in Effective Pain Relief (Spontaneous Bleed Episodes) | Any initial dose, n=324 | 68.0 percentage of bleed episodes |
| Activated Recombinant Human Factor VII | Percentage of Bleed Treatments Resulting in Effective Pain Relief (Spontaneous Bleed Episodes) | Low initial dose, n=92 | 79.1 percentage of bleed episodes |
| Activated Recombinant Human Factor VII | Percentage of Bleed Treatments Resulting in Effective Pain Relief (Spontaneous Bleed Episodes) | Intermediate initial dose, n=91 | 58.2 percentage of bleed episodes |
| Activated Recombinant Human Factor VII | Percentage of Bleed Treatments Resulting in Effective Pain Relief (Spontaneous Bleed Episodes) | High initial dose, n=141 | 67.1 percentage of bleed episodes |
Secondary
Adults' Health Related Quality of Life (Haemo-QoL-A): Overall Score
The adult Haemo-QoL-A is a specific multidimensional validated and reliable questionnaire used to assess quality of life in patients with haemophilia. Scores are reported on a 0 to 100 scale-higher scores indicate more impairment.
Time frame: Baseline (week 0) and and registry discontinuation (up to 28 months)
Population: A subset of adult subjects above 16 years included in the study that completed the questionnaire at baseline and/or at discontinuation
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Activated Recombinant Human Factor VII | Adults' Health Related Quality of Life (Haemo-QoL-A): Overall Score | Baseline, n=11 | 35.31 scores on a scale | Standard Deviation 9.69 |
| Activated Recombinant Human Factor VII | Adults' Health Related Quality of Life (Haemo-QoL-A): Overall Score | Discontinuation, n=10 | 34.46 scores on a scale | Standard Deviation 12.14 |
Secondary
Childrens' Health Related Quality of Life (Haemo-QoL): Overall Score
The Haemo-QoL is a specific multidimensional validated and reliable questionnaire used to assess quality of life in patients with haemophilia. Scores are reported on a 0 to 100 scale-higher scores indicate more impairment.
Time frame: Baseline (week 0) and and registry discontinuation (up to 28 months)
Population: A subset of paediatric subjects age 4 to 16 (inclusive) included in the study that completed the questionnaire at baseline and/or at discontinuation
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Activated Recombinant Human Factor VII | Childrens' Health Related Quality of Life (Haemo-QoL): Overall Score | Baseline, n=7 | 47.49 scores on a scale | Standard Deviation 11.08 |
| Activated Recombinant Human Factor VII | Childrens' Health Related Quality of Life (Haemo-QoL): Overall Score | Discontinuation, n=7 | 54.12 scores on a scale | Standard Deviation 10.19 |
Secondary
Overall Time to Cessation/Achievement of Haemostasis (Spontaneous Bleed Episodes)
Median time to achievement of haemostasis/bleed cessation calculated using Kaplan Meier life table methods. If approximately 50% or less of bleeds achieved the endpoint in a given initial dose subgroup, the median cannot be calculated and it is reported as not applicable.
Time frame: duration of bleed episode
Population: Analysis set is spontaneous bleed episodes treated with any initial dose, excluding bleed episodes treated with more than one dose for which \> 24 hours between the 1st and 2nd dose was reported (bleed episodes with \> 24 hours between 1st and 2nd rFVIIa dose likely reflects treatment of re-bleeding or prophylactic/maintenance dosing)
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Activated Recombinant Human Factor VII | Overall Time to Cessation/Achievement of Haemostasis (Spontaneous Bleed Episodes) | Any dose, n=270 | 600 minutes |
| Activated Recombinant Human Factor VII | Overall Time to Cessation/Achievement of Haemostasis (Spontaneous Bleed Episodes) | Low dose, n=87 | 600 minutes |
| Activated Recombinant Human Factor VII | Overall Time to Cessation/Achievement of Haemostasis (Spontaneous Bleed Episodes) | Intermediate dose, n=80 | NA minutes |
| Activated Recombinant Human Factor VII | Overall Time to Cessation/Achievement of Haemostasis (Spontaneous Bleed Episodes) | High dose, n=103 | 480 minutes |
Secondary
Overall Time to Cessation of Bleed/Achievement of Haemostasis (All Bleed Episodes)
Median time to achievement of haemostasis/bleed cessation calculated using Kaplan Meier life table methods. If approximately 50% or less of bleeds achieved the endpoint in a given initial dose subgroup, the median cannot be calculated and it is reported as not applicable
Time frame: duration of bleed episode
Population: Analysis set is all bleed episodes, regardless of bleed type or initial dose level
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Activated Recombinant Human Factor VII | Overall Time to Cessation of Bleed/Achievement of Haemostasis (All Bleed Episodes) | Any dose, n=494 | 1200 minutes |
| Activated Recombinant Human Factor VII | Overall Time to Cessation of Bleed/Achievement of Haemostasis (All Bleed Episodes) | Low dose, n=156 | 720 minutes |
| Activated Recombinant Human Factor VII | Overall Time to Cessation of Bleed/Achievement of Haemostasis (All Bleed Episodes) | Intermediate dose, n=127 | NA minutes |
| Activated Recombinant Human Factor VII | Overall Time to Cessation of Bleed/Achievement of Haemostasis (All Bleed Episodes) | High dose, n=211 | 1200 minutes |
Secondary
Overall Time to Cessation of Bleed/Achievement of Haemostasis (Spontaneous Bleed Episodes)
Median time to achievement of haemostasis/bleed cessation calculated using Kaplan Meier life table methods. If approximately 50% or less of bleeds achieved the endpoint in a given initial dose subgroup, the median cannot be calculated and it is reported as not applicable
Time frame: duration of bleed episode
Population: Analysis set is spontaneous bleed episodes treated with any initial dose
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Activated Recombinant Human Factor VII | Overall Time to Cessation of Bleed/Achievement of Haemostasis (Spontaneous Bleed Episodes) | Any dose, n=324 | 1200 minutes |
| Activated Recombinant Human Factor VII | Overall Time to Cessation of Bleed/Achievement of Haemostasis (Spontaneous Bleed Episodes) | Low dose, n=92 | 600 minutes |
| Activated Recombinant Human Factor VII | Overall Time to Cessation of Bleed/Achievement of Haemostasis (Spontaneous Bleed Episodes) | Intermediate dose, n=91 | NA minutes |
| Activated Recombinant Human Factor VII | Overall Time to Cessation of Bleed/Achievement of Haemostasis (Spontaneous Bleed Episodes) | High dose, n=141 | 1200 minutes |
Secondary
Percentage of Bleed Treatments Resulting in Effective Haemostasis (Cessation of Bleeds) by Time Point (All Bleed Episodes)
Effective haemostasis at 3 different time points for all bleeds. Patient reported outcomes are reported over 1 hour, 3 hours and 6 hours.
Time frame: 1 hour, 3 hours and 6 hours, respectively, after first injection
Population: Analysis set is all bleed episodes, regardless of bleed type or initial dose level
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Activated Recombinant Human Factor VII | Percentage of Bleed Treatments Resulting in Effective Haemostasis (Cessation of Bleeds) by Time Point (All Bleed Episodes) | Any initial dose (1 hour), n=494 | 21.1 percentage of bleed episodes |
| Activated Recombinant Human Factor VII | Percentage of Bleed Treatments Resulting in Effective Haemostasis (Cessation of Bleeds) by Time Point (All Bleed Episodes) | Low initial dose (1 hour), n=156 | 16.8 percentage of bleed episodes |
| Activated Recombinant Human Factor VII | Percentage of Bleed Treatments Resulting in Effective Haemostasis (Cessation of Bleeds) by Time Point (All Bleed Episodes) | Intermediate initial dose (1 hr), n=127 | 25.8 percentage of bleed episodes |
| Activated Recombinant Human Factor VII | Percentage of Bleed Treatments Resulting in Effective Haemostasis (Cessation of Bleeds) by Time Point (All Bleed Episodes) | High initial dose (1 hour), n=211 | 21.5 percentage of bleed episodes |
| Activated Recombinant Human Factor VII | Percentage of Bleed Treatments Resulting in Effective Haemostasis (Cessation of Bleeds) by Time Point (All Bleed Episodes) | Any initial dose (3 hours), n=494 | 36.9 percentage of bleed episodes |
| Activated Recombinant Human Factor VII | Percentage of Bleed Treatments Resulting in Effective Haemostasis (Cessation of Bleeds) by Time Point (All Bleed Episodes) | Low initial dose (3 hours), n=156 | 32.5 percentage of bleed episodes |
| Activated Recombinant Human Factor VII | Percentage of Bleed Treatments Resulting in Effective Haemostasis (Cessation of Bleeds) by Time Point (All Bleed Episodes) | Intermediate initial dose (3 hrs), n=127 | 41.1 percentage of bleed episodes |
| Activated Recombinant Human Factor VII | Percentage of Bleed Treatments Resulting in Effective Haemostasis (Cessation of Bleeds) by Time Point (All Bleed Episodes) | High initial dose (3 hours), n=211 | 37.6 percentage of bleed episodes |
| Activated Recombinant Human Factor VII | Percentage of Bleed Treatments Resulting in Effective Haemostasis (Cessation of Bleeds) by Time Point (All Bleed Episodes) | Any initial dose (6 hours), n=494 | 50.8 percentage of bleed episodes |
| Activated Recombinant Human Factor VII | Percentage of Bleed Treatments Resulting in Effective Haemostasis (Cessation of Bleeds) by Time Point (All Bleed Episodes) | Low initial dose (6 hours), n=156 | 51.3 percentage of bleed episodes |
| Activated Recombinant Human Factor VII | Percentage of Bleed Treatments Resulting in Effective Haemostasis (Cessation of Bleeds) by Time Point (All Bleed Episodes) | Intermediate initial dose (6 hrs), n=127 | 51.2 percentage of bleed episodes |
| Activated Recombinant Human Factor VII | Percentage of Bleed Treatments Resulting in Effective Haemostasis (Cessation of Bleeds) by Time Point (All Bleed Episodes) | High initial dose (6 hours), n=211 | 50.2 percentage of bleed episodes |
Secondary
Percentage of Bleed Treatments Resulting in Effective Haemostasis (Cessation of Bleeds) by Time Point (Spontaneous Bleed Episodes)
Effective haemostasis at 3 different time points for all bleeds. Patient reported outcomes are reported over 1 hour, 3 hours and 6 hours.
Time frame: 1 hour, 3 hours and 6 hours, respectively, after first injection
Population: Analysis set is spontaneous bleed episodes treated with any initial dose
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Activated Recombinant Human Factor VII | Percentage of Bleed Treatments Resulting in Effective Haemostasis (Cessation of Bleeds) by Time Point (Spontaneous Bleed Episodes) | Any initial dose (1 hour), n=324 | 19.3 percentage of bleed episodes |
| Activated Recombinant Human Factor VII | Percentage of Bleed Treatments Resulting in Effective Haemostasis (Cessation of Bleeds) by Time Point (Spontaneous Bleed Episodes) | Low initial dose (1 hour), n=92 | 7.7 percentage of bleed episodes |
| Activated Recombinant Human Factor VII | Percentage of Bleed Treatments Resulting in Effective Haemostasis (Cessation of Bleeds) by Time Point (Spontaneous Bleed Episodes) | Intermediate initial dose (1 hr), n=91 | 24.4 percentage of bleed episodes |
| Activated Recombinant Human Factor VII | Percentage of Bleed Treatments Resulting in Effective Haemostasis (Cessation of Bleeds) by Time Point (Spontaneous Bleed Episodes) | High initial dose (1 hour), n=141 | 23.6 percentage of bleed episodes |
| Activated Recombinant Human Factor VII | Percentage of Bleed Treatments Resulting in Effective Haemostasis (Cessation of Bleeds) by Time Point (Spontaneous Bleed Episodes) | Any initial dose (3 hours), n=324 | 36.9 percentage of bleed episodes |
| Activated Recombinant Human Factor VII | Percentage of Bleed Treatments Resulting in Effective Haemostasis (Cessation of Bleeds) by Time Point (Spontaneous Bleed Episodes) | Low initial dose (3 hours), n=92 | 27.8 percentage of bleed episodes |
| Activated Recombinant Human Factor VII | Percentage of Bleed Treatments Resulting in Effective Haemostasis (Cessation of Bleeds) by Time Point (Spontaneous Bleed Episodes) | Intermediate initial dose (3 hrs), n=91 | 40.7 percentage of bleed episodes |
| Activated Recombinant Human Factor VII | Percentage of Bleed Treatments Resulting in Effective Haemostasis (Cessation of Bleeds) by Time Point (Spontaneous Bleed Episodes) | High initial dose (3 hours), n=141 | 40.3 percentage of bleed episodes |
| Activated Recombinant Human Factor VII | Percentage of Bleed Treatments Resulting in Effective Haemostasis (Cessation of Bleeds) by Time Point (Spontaneous Bleed Episodes) | Any initial dose (6 hours), n=324 | 48.1 percentage of bleed episodes |
| Activated Recombinant Human Factor VII | Percentage of Bleed Treatments Resulting in Effective Haemostasis (Cessation of Bleeds) by Time Point (Spontaneous Bleed Episodes) | Low initial dose (6 hours), n=92 | 43.3 percentage of bleed episodes |
| Activated Recombinant Human Factor VII | Percentage of Bleed Treatments Resulting in Effective Haemostasis (Cessation of Bleeds) by Time Point (Spontaneous Bleed Episodes) | Intermediate initial dose (6 hrs), n=91 | 50.5 percentage of bleed episodes |
| Activated Recombinant Human Factor VII | Percentage of Bleed Treatments Resulting in Effective Haemostasis (Cessation of Bleeds) by Time Point (Spontaneous Bleed Episodes) | High initial dose (6 hours), n=141 | 49.6 percentage of bleed episodes |
Secondary
Percentage of Bleed Treatments Resulting in Effective Pain Relief by Time Point (All Bleed Episodes)
Effective pain relief at 3 different time points for all bleeds. Patient reported outcomes are reported over 1 hour, 3 hours and 6 hours.
Time frame: 1 hour, 3 hours and 6 hours, respectively, after first injection
Population: Analysis set is all bleed episodes, regardless of bleed type or initial dose level
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Activated Recombinant Human Factor VII | Percentage of Bleed Treatments Resulting in Effective Pain Relief by Time Point (All Bleed Episodes) | Any initial dose (1 hour), n=494 | 27.7 percentage of bleed episodes |
| Activated Recombinant Human Factor VII | Percentage of Bleed Treatments Resulting in Effective Pain Relief by Time Point (All Bleed Episodes) | Low initial dose (1 hour), n=156 | 29.9 percentage of bleed episodes |
| Activated Recombinant Human Factor VII | Percentage of Bleed Treatments Resulting in Effective Pain Relief by Time Point (All Bleed Episodes) | Intermediate initial dose (1 hr), n=127 | 19.8 percentage of bleed episodes |
| Activated Recombinant Human Factor VII | Percentage of Bleed Treatments Resulting in Effective Pain Relief by Time Point (All Bleed Episodes) | High initial dose (1 hour), n=211 | 30.8 percentage of bleed episodes |
| Activated Recombinant Human Factor VII | Percentage of Bleed Treatments Resulting in Effective Pain Relief by Time Point (All Bleed Episodes) | Any initial dose (3 hours), n=494 | 53.1 percentage of bleed episodes |
| Activated Recombinant Human Factor VII | Percentage of Bleed Treatments Resulting in Effective Pain Relief by Time Point (All Bleed Episodes) | Low initial dose (3 hours), n=156 | 59.7 percentage of bleed episodes |
| Activated Recombinant Human Factor VII | Percentage of Bleed Treatments Resulting in Effective Pain Relief by Time Point (All Bleed Episodes) | Intermediate initial dose (3 hrs), n=127 | 47.2 percentage of bleed episodes |
| Activated Recombinant Human Factor VII | Percentage of Bleed Treatments Resulting in Effective Pain Relief by Time Point (All Bleed Episodes) | High initial dose (3 hours), n=211 | 51.7 percentage of bleed episodes |
| Activated Recombinant Human Factor VII | Percentage of Bleed Treatments Resulting in Effective Pain Relief by Time Point (All Bleed Episodes) | Any initial dose (6 hours), n=494 | 66.0 percentage of bleed episodes |
| Activated Recombinant Human Factor VII | Percentage of Bleed Treatments Resulting in Effective Pain Relief by Time Point (All Bleed Episodes) | Low initial dose (6 hours), n=156 | 77.8 percentage of bleed episodes |
| Activated Recombinant Human Factor VII | Percentage of Bleed Treatments Resulting in Effective Pain Relief by Time Point (All Bleed Episodes) | Intermediate initial dose (6 hrs), n=127 | 57.7 percentage of bleed episodes |
| Activated Recombinant Human Factor VII | Percentage of Bleed Treatments Resulting in Effective Pain Relief by Time Point (All Bleed Episodes) | High initial dose (6 hours), n=211 | 62.3 percentage of bleed episodes |
Secondary
Percentage of Bleed Treatments Resulting in Effective Pain Relief by Time Point (Spontaneous Bleed Episodes)
Effective pain relief at 3 different time points for spontaneous bleeds. Patient reported outcomes are reported over 1 hour, 3 hours and 6 hours.
Time frame: 1 hour, 3 hours and 6 hours, respectively, after first injection
Population: Analysis set is spontaneous bleed episodes treated with any initial dose
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Activated Recombinant Human Factor VII | Percentage of Bleed Treatments Resulting in Effective Pain Relief by Time Point (Spontaneous Bleed Episodes) | Any initial dose (1 hour), n=324 | 24.7 percentage of bleed episodes |
| Activated Recombinant Human Factor VII | Percentage of Bleed Treatments Resulting in Effective Pain Relief by Time Point (Spontaneous Bleed Episodes) | Low initial dose (1 hour), n=92 | 24.4 percentage of bleed episodes |
| Activated Recombinant Human Factor VII | Percentage of Bleed Treatments Resulting in Effective Pain Relief by Time Point (Spontaneous Bleed Episodes) | Intermediate initial dose (1 hr), n=91 | 18.7 percentage of bleed episodes |
| Activated Recombinant Human Factor VII | Percentage of Bleed Treatments Resulting in Effective Pain Relief by Time Point (Spontaneous Bleed Episodes) | High initial dose (1 hour), n=141 | 28.8 percentage of bleed episodes |
| Activated Recombinant Human Factor VII | Percentage of Bleed Treatments Resulting in Effective Pain Relief by Time Point (Spontaneous Bleed Episodes) | Any initial dose (3 hours), n=324 | 49.1 percentage of bleed episodes |
| Activated Recombinant Human Factor VII | Percentage of Bleed Treatments Resulting in Effective Pain Relief by Time Point (Spontaneous Bleed Episodes) | Low initial dose (3 hours), n=92 | 55.6 percentage of bleed episodes |
| Activated Recombinant Human Factor VII | Percentage of Bleed Treatments Resulting in Effective Pain Relief by Time Point (Spontaneous Bleed Episodes) | Intermediate initial dose (3 hrs), n=91 | 44.0 percentage of bleed episodes |
| Activated Recombinant Human Factor VII | Percentage of Bleed Treatments Resulting in Effective Pain Relief by Time Point (Spontaneous Bleed Episodes) | High initial dose (3 hours), n=141 | 48.2 percentage of bleed episodes |
| Activated Recombinant Human Factor VII | Percentage of Bleed Treatments Resulting in Effective Pain Relief by Time Point (Spontaneous Bleed Episodes) | Any initial dose (6 hours), n=324 | 62.8 percentage of bleed episodes |
| Activated Recombinant Human Factor VII | Percentage of Bleed Treatments Resulting in Effective Pain Relief by Time Point (Spontaneous Bleed Episodes) | Low initial dose (6 hours), n=92 | 77.5 percentage of bleed episodes |
| Activated Recombinant Human Factor VII | Percentage of Bleed Treatments Resulting in Effective Pain Relief by Time Point (Spontaneous Bleed Episodes) | Intermediate initial dose (6 hrs), n=91 | 55.6 percentage of bleed episodes |
| Activated Recombinant Human Factor VII | Percentage of Bleed Treatments Resulting in Effective Pain Relief by Time Point (Spontaneous Bleed Episodes) | High initial dose (6 hours), n=141 | 58.0 percentage of bleed episodes |
Secondary
Percentage of Bleed Treatments Resulting in Patient Satisfaction With Ease of Use (All Bleed Episodes)
Rate of ease of use related to activated recombinant human factor VII on a 7-point Likert scale. Completion of questionnaire was voluntary. A Likert scale is an ordered, multiple choice questionnaire from which respondents choose one option that best aligns with their view of the particular outcome being measured. Scale answers ranged from extremely difficult to extremely easy. The percentage of bleed episodes for which patients reported extremely easy, very easy or easy is presented.
Time frame: duration of bleed episode
Population: Analysis set is all bleed episodes, regardless of bleed type or initial dose level
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Activated Recombinant Human Factor VII | Percentage of Bleed Treatments Resulting in Patient Satisfaction With Ease of Use (All Bleed Episodes) | Any dose, n=494 | 74.9 percentage of bleed episodes |
| Activated Recombinant Human Factor VII | Percentage of Bleed Treatments Resulting in Patient Satisfaction With Ease of Use (All Bleed Episodes) | Low dose, n=156 | 84.6 percentage of bleed episodes |
| Activated Recombinant Human Factor VII | Percentage of Bleed Treatments Resulting in Patient Satisfaction With Ease of Use (All Bleed Episodes) | Intermediate dose, n=127 | 74.8 percentage of bleed episodes |
| Activated Recombinant Human Factor VII | Percentage of Bleed Treatments Resulting in Patient Satisfaction With Ease of Use (All Bleed Episodes) | High dose, n=211 | 67.8 percentage of bleed episodes |
Secondary
Percentage of Bleed Treatments Resulting in Patient Satisfaction With Ease of Use (Spontaneous Bleed Episodes)
Rate of ease of use related to activated recombinant human factor VII on a 7-point Likert scale. Completion of questionnaire was voluntary. A Likert scale is an ordered, multiple choice questionnaire from which respondents choose one option that best aligns with their view of the particular outcome being measured. Scale answers ranged from extremely difficult to extremely easy. The percentage of bleed episodes for which patients reported extremely easy, very easy or easy is presented.
Time frame: duration of bleed episode
Population: Analysis set is spontaneous bleed episodes treated with any initial dose
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Activated Recombinant Human Factor VII | Percentage of Bleed Treatments Resulting in Patient Satisfaction With Ease of Use (Spontaneous Bleed Episodes) | Any dose, n=324 | 69.1 percentage of bleed episodes |
| Activated Recombinant Human Factor VII | Percentage of Bleed Treatments Resulting in Patient Satisfaction With Ease of Use (Spontaneous Bleed Episodes) | Low dose, n=92 | 81.5 percentage of bleed episodes |
| Activated Recombinant Human Factor VII | Percentage of Bleed Treatments Resulting in Patient Satisfaction With Ease of Use (Spontaneous Bleed Episodes) | Intermediate dose, n=91 | 69.2 percentage of bleed episodes |
| Activated Recombinant Human Factor VII | Percentage of Bleed Treatments Resulting in Patient Satisfaction With Ease of Use (Spontaneous Bleed Episodes) | High dose, n=141 | 61.0 percentage of bleed episodes |
Secondary
Percentage of Bleed Treatments Resulting in Patient Satisfaction With Symptom Relief (Spontaneous Bleed Episodes)
Patient rate of satisfaction with symptom relief for the bleed episode overall on a 7-point Likert scale. Completion of questionnaire was voluntary. A Likert scale is an ordered, multiple choice questionnaire from which respondents choose one option that best aligns with their view of the particular outcome being measured. Scale answers ranged from extremely satisfied to extremely dissatisfied. The percentage of bleed episodes for which patients reported extremely satisfied, very satisfied or satisfied is presented.
Time frame: duration of bleed episode
Population: Analysis set is spontaneous bleed episodes treated with any initial dose
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Activated Recombinant Human Factor VII | Percentage of Bleed Treatments Resulting in Patient Satisfaction With Symptom Relief (Spontaneous Bleed Episodes) | Any dose, n=324 | 68.2 percentage of bleed episodes |
| Activated Recombinant Human Factor VII | Percentage of Bleed Treatments Resulting in Patient Satisfaction With Symptom Relief (Spontaneous Bleed Episodes) | Low dose, n=92 | 75.0 percentage of bleed episodes |
| Activated Recombinant Human Factor VII | Percentage of Bleed Treatments Resulting in Patient Satisfaction With Symptom Relief (Spontaneous Bleed Episodes) | Intermediate dose, n=91 | 69.2 percentage of bleed episodes |
| Activated Recombinant Human Factor VII | Percentage of Bleed Treatments Resulting in Patient Satisfaction With Symptom Relief (Spontaneous Bleed Episodes) | High dose, n=141 | 63.1 percentage of bleed episodes |
Secondary
Percentage of Patients Reporting Satisfaction With Symptom Relief (All Bleed Episodes)
Patient rate of satisfaction with symptom relief for the bleed episode overall on a 7-point Likert scale. Completion of questionnaire was voluntary. A Likert scale is an ordered, multiple choice questionnaire from which respondents choose one option that best aligns with their view of the particular outcome being measured. Scale answers ranged from extremely satisfied to extremely dissatisfied. The percentage of bleed episodes for which patients reported extremely satisfied, very satisfied or satisfied is presented.
Time frame: duration of bleed episode
Population: Analysis set is all bleed episodes, regardless of bleed type or initial dose level
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Activated Recombinant Human Factor VII | Percentage of Patients Reporting Satisfaction With Symptom Relief (All Bleed Episodes) | Any dose, n=494 | 72.7 percentage of bleed episodes |
| Activated Recombinant Human Factor VII | Percentage of Patients Reporting Satisfaction With Symptom Relief (All Bleed Episodes) | Low dose, n=156 | 82.1 percentage of bleed episodes |
| Activated Recombinant Human Factor VII | Percentage of Patients Reporting Satisfaction With Symptom Relief (All Bleed Episodes) | Intermediate dose, n=127 | 69.3 percentage of bleed episodes |
| Activated Recombinant Human Factor VII | Percentage of Patients Reporting Satisfaction With Symptom Relief (All Bleed Episodes) | High dose, n=211 | 67.8 percentage of bleed episodes |
Secondary
Total Exposure (Cumulative Dose) to Activated Recombinant Human Factor VII (All Bleed Episodes)
The median total cumulative dose required to treat individual bleed episodes.
Time frame: individual bleed episode
Population: Analysis set is all bleed episodes, regardless of bleed type or initial dose level. Excludes bleeds episodes with greater than 24 hours between 1st and 2nd rFVII dose where total cumulative dose recorded likely reflects treatment of re-bleeding or prophylactic/maintenance dosing
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Activated Recombinant Human Factor VII | Total Exposure (Cumulative Dose) to Activated Recombinant Human Factor VII (All Bleed Episodes) | Any initial dose, n=494 | 270 mcg/kg |
| Activated Recombinant Human Factor VII | Total Exposure (Cumulative Dose) to Activated Recombinant Human Factor VII (All Bleed Episodes) | Low dose, n=156 | 267 mcg/kg |
| Activated Recombinant Human Factor VII | Total Exposure (Cumulative Dose) to Activated Recombinant Human Factor VII (All Bleed Episodes) | Intermediate dose, n=127 | 256 mcg/kg |
| Activated Recombinant Human Factor VII | Total Exposure (Cumulative Dose) to Activated Recombinant Human Factor VII (All Bleed Episodes) | High dose, n=211 | 270 mcg/kg |
Secondary
Total Exposure (Cumulative Dose) to Activated Recombinant Human Factor VII (Spontaneous Bleed Episodes)
The median total cumulative dose required to treat individual bleed episodes.
Time frame: individual bleed episode
Population: Analysis set is spontaneous bleed episodes. Excludes bleeds episodes with \> 24 hours between 1st and 2nd rFVII dose where total cumulative dose recorded likely reflects treatment of re-bleeding or prophylactic/maintenance dosing, and 2 bleed episodes categorised as CNS that would not meet criteria of mild to moderate spontaneous bleed episodes
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Activated Recombinant Human Factor VII | Total Exposure (Cumulative Dose) to Activated Recombinant Human Factor VII (Spontaneous Bleed Episodes) | Any initial dose, n=324 | 184 mcg/kg |
| Activated Recombinant Human Factor VII | Total Exposure (Cumulative Dose) to Activated Recombinant Human Factor VII (Spontaneous Bleed Episodes) | Low dose, n=92 | 284 mcg/kg |
| Activated Recombinant Human Factor VII | Total Exposure (Cumulative Dose) to Activated Recombinant Human Factor VII (Spontaneous Bleed Episodes) | Intermediate dose, n=91 | 270 mcg/kg |
| Activated Recombinant Human Factor VII | Total Exposure (Cumulative Dose) to Activated Recombinant Human Factor VII (Spontaneous Bleed Episodes) | High dose, n=141 | 270 mcg/kg |
Secondary
Total Number of Injections (All Bleed Episodes)
The median number of injections required to treat individual bleed episodes.
Time frame: individual bleed episode
Population: Analysis set is all bleed episodes, regardless of bleed type or initial dose level
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Activated Recombinant Human Factor VII | Total Number of Injections (All Bleed Episodes) | Any initial dose, n=494 | 2 injections |
| Activated Recombinant Human Factor VII | Total Number of Injections (All Bleed Episodes) | Low dose, n=156 | 2 injections |
| Activated Recombinant Human Factor VII | Total Number of Injections (All Bleed Episodes) | Intermediate dose, n=127 | 2 injections |
| Activated Recombinant Human Factor VII | Total Number of Injections (All Bleed Episodes) | High dose, n=211 | 1 injections |
Secondary
Total Number of Injections (Spontaneous Bleed Episodes)
The median number of injections required to treat individual bleed episodes.
Time frame: individual bleed episode
Population: Analysis set is spontaneous bleed episodes treated with any initial dose
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Activated Recombinant Human Factor VII | Total Number of Injections (Spontaneous Bleed Episodes) | Any initial dose, n=324 | 2 injections |
| Activated Recombinant Human Factor VII | Total Number of Injections (Spontaneous Bleed Episodes) | Low dose, n=92 | 2 injections |
| Activated Recombinant Human Factor VII | Total Number of Injections (Spontaneous Bleed Episodes) | Intermediate dose, n=91 | 2 injections |
| Activated Recombinant Human Factor VII | Total Number of Injections (Spontaneous Bleed Episodes) | High dose, n=141 | 1 injections |
Other Pre-specified
Percentage of Bleed Treatments Resulting in Effective Haemostasis (Cessation of Bleed) by Dose Level (All Bleed Episodes)
Percentage of bleeds with effective haemostasis within 9 hours of first injection of activated recombinant human factor VII. Patient reported assessments were sorted into 3 sub-categories: effective = bleed resolved or substantially improved; partially effective = bleed with some improvement; ineffective = bleed with no change or with worsening.
Time frame: within 9 hours after first injection
Population: Analysis set is all bleed episodes, regardless of bleed type or initial dose level
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Activated Recombinant Human Factor VII | Percentage of Bleed Treatments Resulting in Effective Haemostasis (Cessation of Bleed) by Dose Level (All Bleed Episodes) | Any, effective | 61.7 percentage of bleed episodes |
| Activated Recombinant Human Factor VII | Percentage of Bleed Treatments Resulting in Effective Haemostasis (Cessation of Bleed) by Dose Level (All Bleed Episodes) | Any, partially effective | 26.7 percentage of bleed episodes |
| Activated Recombinant Human Factor VII | Percentage of Bleed Treatments Resulting in Effective Haemostasis (Cessation of Bleed) by Dose Level (All Bleed Episodes) | Any, ineffective | 11.7 percentage of bleed episodes |
| Activated Recombinant Human Factor VII | Percentage of Bleed Treatments Resulting in Effective Haemostasis (Cessation of Bleed) by Dose Level (All Bleed Episodes) | Low, effective | 67.5 percentage of bleed episodes |
| Activated Recombinant Human Factor VII | Percentage of Bleed Treatments Resulting in Effective Haemostasis (Cessation of Bleed) by Dose Level (All Bleed Episodes) | Low, partially effective | 21.2 percentage of bleed episodes |
| Activated Recombinant Human Factor VII | Percentage of Bleed Treatments Resulting in Effective Haemostasis (Cessation of Bleed) by Dose Level (All Bleed Episodes) | Low, ineffective | 11.3 percentage of bleed episodes |
| Activated Recombinant Human Factor VII | Percentage of Bleed Treatments Resulting in Effective Haemostasis (Cessation of Bleed) by Dose Level (All Bleed Episodes) | Intermediate, effective | 62.1 percentage of bleed episodes |
| Activated Recombinant Human Factor VII | Percentage of Bleed Treatments Resulting in Effective Haemostasis (Cessation of Bleed) by Dose Level (All Bleed Episodes) | Intermediate, partially effective | 31.5 percentage of bleed episodes |
| Activated Recombinant Human Factor VII | Percentage of Bleed Treatments Resulting in Effective Haemostasis (Cessation of Bleed) by Dose Level (All Bleed Episodes) | Intermediate, ineffective | 6.5 percentage of bleed episodes |
| Activated Recombinant Human Factor VII | Percentage of Bleed Treatments Resulting in Effective Haemostasis (Cessation of Bleed) by Dose Level (All Bleed Episodes) | High, effective | 57.1 percentage of bleed episodes |
| Activated Recombinant Human Factor VII | Percentage of Bleed Treatments Resulting in Effective Haemostasis (Cessation of Bleed) by Dose Level (All Bleed Episodes) | High, partially effective | 27.8 percentage of bleed episodes |
| Activated Recombinant Human Factor VII | Percentage of Bleed Treatments Resulting in Effective Haemostasis (Cessation of Bleed) by Dose Level (All Bleed Episodes) | High, ineffective | 15.1 percentage of bleed episodes |
Other Pre-specified
Percentage of Bleed Treatments Resulting in Effective Haemostasis (Cessation of Bleed) by Dose Level (Spontaneous Bleed Episodes)
Percentage of bleeds with effective haemostasis within 9 hours of first injection of activated recombinant human factor VII. Patient reported assessments were sorted into 3 sub-categories: effective = bleed resolved or substantially improved; partially effective = bleed with some improvement; ineffective = bleed with no change or with worsening.
Time frame: within 9 hours after first injection
Population: Analysis set is spontaneous bleed episodes treated with any initial dose
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Activated Recombinant Human Factor VII | Percentage of Bleed Treatments Resulting in Effective Haemostasis (Cessation of Bleed) by Dose Level (Spontaneous Bleed Episodes) | Any, effective | 59.0 percentage of bleed episodes |
| Activated Recombinant Human Factor VII | Percentage of Bleed Treatments Resulting in Effective Haemostasis (Cessation of Bleed) by Dose Level (Spontaneous Bleed Episodes) | Any, partially effective | 29.3 percentage of bleed episodes |
| Activated Recombinant Human Factor VII | Percentage of Bleed Treatments Resulting in Effective Haemostasis (Cessation of Bleed) by Dose Level (Spontaneous Bleed Episodes) | Any, ineffective | 11.7 percentage of bleed episodes |
| Activated Recombinant Human Factor VII | Percentage of Bleed Treatments Resulting in Effective Haemostasis (Cessation of Bleed) by Dose Level (Spontaneous Bleed Episodes) | Low, effective | 62.1 percentage of bleed episodes |
| Activated Recombinant Human Factor VII | Percentage of Bleed Treatments Resulting in Effective Haemostasis (Cessation of Bleed) by Dose Level (Spontaneous Bleed Episodes) | Low, partially effective | 21.8 percentage of bleed episodes |
| Activated Recombinant Human Factor VII | Percentage of Bleed Treatments Resulting in Effective Haemostasis (Cessation of Bleed) by Dose Level (Spontaneous Bleed Episodes) | Low, ineffective | 16.1 percentage of bleed episodes |
| Activated Recombinant Human Factor VII | Percentage of Bleed Treatments Resulting in Effective Haemostasis (Cessation of Bleed) by Dose Level (Spontaneous Bleed Episodes) | Intermediate, effective | 60.4 percentage of bleed episodes |
| Activated Recombinant Human Factor VII | Percentage of Bleed Treatments Resulting in Effective Haemostasis (Cessation of Bleed) by Dose Level (Spontaneous Bleed Episodes) | Intermediate, partially effective | 36.3 percentage of bleed episodes |
| Activated Recombinant Human Factor VII | Percentage of Bleed Treatments Resulting in Effective Haemostasis (Cessation of Bleed) by Dose Level (Spontaneous Bleed Episodes) | Intermediate, ineffective | 3.3 percentage of bleed episodes |
| Activated Recombinant Human Factor VII | Percentage of Bleed Treatments Resulting in Effective Haemostasis (Cessation of Bleed) by Dose Level (Spontaneous Bleed Episodes) | High, effective | 56.1 percentage of bleed episodes |
| Activated Recombinant Human Factor VII | Percentage of Bleed Treatments Resulting in Effective Haemostasis (Cessation of Bleed) by Dose Level (Spontaneous Bleed Episodes) | High, partially effective | 29.5 percentage of bleed episodes |
| Activated Recombinant Human Factor VII | Percentage of Bleed Treatments Resulting in Effective Haemostasis (Cessation of Bleed) by Dose Level (Spontaneous Bleed Episodes) | High, ineffective | 14.4 percentage of bleed episodes |
Other Pre-specified
Percentage of Bleed Treatments Resulting in Effective Pain Relief by Initial Dose (All Bleed Episodes)
Percentage of bleeds with effective pain relief within 9 hours of first injection of activated recombinant human factor VII. Patient reported assessments were sorted into 3 sub-categories: Better = pain resolved or decreased substantially; Same = no change; Worsened = pain worsening.
Time frame: within 9 hours after first injection
Population: Analysis set is all bleed episodes, regardless of bleed type or initial dose level
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Activated Recombinant Human Factor VII | Percentage of Bleed Treatments Resulting in Effective Pain Relief by Initial Dose (All Bleed Episodes) | Any, better | 71.3 percentage of bleed episodes |
| Activated Recombinant Human Factor VII | Percentage of Bleed Treatments Resulting in Effective Pain Relief by Initial Dose (All Bleed Episodes) | Any, same | 25.6 percentage of bleed episodes |
| Activated Recombinant Human Factor VII | Percentage of Bleed Treatments Resulting in Effective Pain Relief by Initial Dose (All Bleed Episodes) | Any, worsened | 3.1 percentage of bleed episodes |
| Activated Recombinant Human Factor VII | Percentage of Bleed Treatments Resulting in Effective Pain Relief by Initial Dose (All Bleed Episodes) | Low, better | 60.0 percentage of bleed episodes |
| Activated Recombinant Human Factor VII | Percentage of Bleed Treatments Resulting in Effective Pain Relief by Initial Dose (All Bleed Episodes) | Low, same | 39.2 percentage of bleed episodes |
| Activated Recombinant Human Factor VII | Percentage of Bleed Treatments Resulting in Effective Pain Relief by Initial Dose (All Bleed Episodes) | Low, worsened | 0.8 percentage of bleed episodes |
| Activated Recombinant Human Factor VII | Percentage of Bleed Treatments Resulting in Effective Pain Relief by Initial Dose (All Bleed Episodes) | Intermediate, better | 82.4 percentage of bleed episodes |
| Activated Recombinant Human Factor VII | Percentage of Bleed Treatments Resulting in Effective Pain Relief by Initial Dose (All Bleed Episodes) | Intermediate, same | 15.0 percentage of bleed episodes |
| Activated Recombinant Human Factor VII | Percentage of Bleed Treatments Resulting in Effective Pain Relief by Initial Dose (All Bleed Episodes) | Intermediate, worsened | 2.6 percentage of bleed episodes |
| Activated Recombinant Human Factor VII | Percentage of Bleed Treatments Resulting in Effective Pain Relief by Initial Dose (All Bleed Episodes) | High, better | 69.9 percentage of bleed episodes |
| Activated Recombinant Human Factor VII | Percentage of Bleed Treatments Resulting in Effective Pain Relief by Initial Dose (All Bleed Episodes) | High, same | 25.2 percentage of bleed episodes |
| Activated Recombinant Human Factor VII | Percentage of Bleed Treatments Resulting in Effective Pain Relief by Initial Dose (All Bleed Episodes) | High, worsened | 4.9 percentage of bleed episodes |
Other Pre-specified
Percentage of Bleed Treatments Resulting in Effective Pain Relief by Initial Dose (Spontaneous Bleed Episodes)
Percentage of bleeds with effective pain relief within 9 hours of first injection of activated recombinant human factor VII. Patient reported assessments were sorted into 3 sub-categories: Better = pain resolved or decreased substantially; Same = no change; Worsened = pain worsening.
Time frame: within 9 hours after first injection
Population: Analysis set is spontaneous bleed episodes treated with any initial dose
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Activated Recombinant Human Factor VII | Percentage of Bleed Treatments Resulting in Effective Pain Relief by Initial Dose (Spontaneous Bleed Episodes) | Any, better | 68.1 percentage of bleed episodes |
| Activated Recombinant Human Factor VII | Percentage of Bleed Treatments Resulting in Effective Pain Relief by Initial Dose (Spontaneous Bleed Episodes) | Any, same | 28.7 percentage of bleed episodes |
| Activated Recombinant Human Factor VII | Percentage of Bleed Treatments Resulting in Effective Pain Relief by Initial Dose (Spontaneous Bleed Episodes) | Any, worsened | 3.2 percentage of bleed episodes |
| Activated Recombinant Human Factor VII | Percentage of Bleed Treatments Resulting in Effective Pain Relief by Initial Dose (Spontaneous Bleed Episodes) | Low, better | 79.8 percentage of bleed episodes |
| Activated Recombinant Human Factor VII | Percentage of Bleed Treatments Resulting in Effective Pain Relief by Initial Dose (Spontaneous Bleed Episodes) | Low, same | 16.9 percentage of bleed episodes |
| Activated Recombinant Human Factor VII | Percentage of Bleed Treatments Resulting in Effective Pain Relief by Initial Dose (Spontaneous Bleed Episodes) | Low, worsened | 3.4 percentage of bleed episodes |
| Activated Recombinant Human Factor VII | Percentage of Bleed Treatments Resulting in Effective Pain Relief by Initial Dose (Spontaneous Bleed Episodes) | Intermediate, better | 58.2 percentage of bleed episodes |
| Activated Recombinant Human Factor VII | Percentage of Bleed Treatments Resulting in Effective Pain Relief by Initial Dose (Spontaneous Bleed Episodes) | Intermediate, same | 40.7 percentage of bleed episodes |
| Activated Recombinant Human Factor VII | Percentage of Bleed Treatments Resulting in Effective Pain Relief by Initial Dose (Spontaneous Bleed Episodes) | Intermediate, worsened | 1.1 percentage of bleed episodes |
| Activated Recombinant Human Factor VII | Percentage of Bleed Treatments Resulting in Effective Pain Relief by Initial Dose (Spontaneous Bleed Episodes) | High, better | 67.2 percentage of bleed episodes |
| Activated Recombinant Human Factor VII | Percentage of Bleed Treatments Resulting in Effective Pain Relief by Initial Dose (Spontaneous Bleed Episodes) | High, same | 28.5 percentage of bleed episodes |
| Activated Recombinant Human Factor VII | Percentage of Bleed Treatments Resulting in Effective Pain Relief by Initial Dose (Spontaneous Bleed Episodes) | High, worsened | 4.4 percentage of bleed episodes |