Hemophilia A
Conditions
Brief summary
The purpose of this observational study is to describe the incidence of adverse events among patients treated with Refacto AF in usual health care settings in Germany and Austria.
Detailed description
Non-interventional study: subjects to be selected according to the usual clinical practice of their physician
Interventions
DRUGReFacto AF (Moroctocog alfa)
Patients will be treated with intravenous infusion of ReFacto AF per dosing and frequency as prescribed by the subjects' treating physician. ReFacto AF® will be prescribed in the context of routine clinical practice in Germany and Austria, respectively
Sponsors
Pfizer
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Healthy volunteers
No
Inclusion criteria
* Patients with hemophilia A of any severity already receiving or starting treatment with ReFacto AF.
Exclusion criteria
* Patients with Hemophilia A treated with a product other than Refacto AF.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Total Number of Bleeding Episodes in Participants | Baseline until last visit (up to 87 months) | Participants documented all bleeding episodes in a diary during the study. |
| Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | Baseline until last visit (up to 87 months) | An AE was any untoward medical occurrence in a participant who received study treatment without regard to possibility of causal relationship. SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability or incapacity; cancer; congenital anomaly. Treatment-emergent are events between first dose of study drug and up to last visit (up to 87 months) that were absent before treatment or that worsened relative to pretreatment state. AEs included both serious and non-serious adverse events. |
| Number of Participants With Treatment-Related Adverse Events (AEs) and Serious Adverse Events (SAEs) | Baseline until last visit (up to 87 months) | Treatment-related AE was any untoward medical occurrence attributed to study drug in a participant who received study drug. SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; cancer; congenital anomaly. AEs included both serious and non-serious adverse events. Relatedness of AEs with Refacto AF was assessed by the investigator. |
| Number of Participants With Factor VIII (FVIII) Inhibitor Development as Measured by the Nijmegen-Modified Bethesda Assay | Baseline until last visit (up to 87 months) | FVIII inhibitor development was defined as measured inhibitor titer of greater than (\>) 0.6 Bethesda Units (BU) using the Nijmegen-modified Bethesda assay. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean Total Number of Bleeding Episodes Per Year in Participants | Baseline until last visit (up to 87 months) | Participants documented all bleeding episodes in a diary during the study. Mean total number of bleeding episodes per year was calculated as: mean total number of bleeding episodes divided by duration of observation period (in years) for bleeding documentation. |
| Number of Participants With Change From Baseline Status in Days Missed From School or Work | Baseline until last visit (up to 87 months) | Change from baseline status in days missed from school or work was categorized in 3 categories: Improvement, unchanged and worsening. Improvement defined as a decrease in number of days missed by participants from school/work as compared to baseline; worsening was defined as an increase in number of days missed by participants from school/work as compared to baseline; unchanged was defined as no change in number of days missed by participants from school/work as compared to baseline. In this outcome measure, number of participants with change from baseline status (as improved, worsen, unchanged) in days missed from school/work were reported. |
| Participant Assessment of Satisfaction With Treatment Handling | End of study visit (any time up to 87 months) | Participants evaluated their satisfaction with handing (administration) of Refacto AF and rated it in 4 categories as: very satisfied, satisfied, unsatisfied and very unsatisfied. |
| Investigator Assessment of Treatment Satisfaction of Participants | End of study visit (any time up to 87 months) | Investigator assessed the treatment satisfaction of participants and categorized as very satisfied, satisfied, unsatisfied, or very unsatisfied. |
Countries
Austria, Germany
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| ReFacto AF: On Demand Treatment Participants were treated with intravenous (IV) injection of ReFacto AF whenever they had a bleeding episode, as a part of routine clinical practice at a dose and frequency prescribed by treating physician (with a mean recommended dose of 23.0 ± 8.0 international units per kilogram \[IU/kg\]). Participants were observed for up to a maximum duration of 87 months in this study. | 22 |
| ReFacto AF: Prophylaxis Treatment Participants were treated prophylactically with a regular IV injection of ReFacto AF to prevent any bleeding episode at a dose and frequency prescribed by treating physician (with a mean recommended dose of 26.7 ± 8.4 IU/kg). Participants were observed for up to a maximum duration of 87 months in this study. | 77 |
| ReFacto AF: Intermediate Prophylaxis Treatment Participants had intermediate prophylaxis (regular dosing with drug at a low dose than the defined prophylactic treatment) treatment with a regular IV injection of ReFacto AF to prevent any bleeding episode at a dose and frequency prescribed by treating physician (with a mean recommended dose of less than \[\>\] 26.7 ± 8.4 IU/kg). Participants were observed for up to a maximum duration of 87 months in this study. | 2 |
| Total | 101 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Death | 0 | 2 | 1 |
Baseline characteristics
| Characteristic | ReFacto AF: On Demand Treatment | ReFacto AF: Prophylaxis Treatment | ReFacto AF: Intermediate Prophylaxis Treatment | Total |
|---|---|---|---|---|
| Age, Continuous | 34.0 Years STANDARD_DEVIATION 20.2 | 18.5 Years STANDARD_DEVIATION 12.4 | 62.0 Years STANDARD_DEVIATION 7.1 | 22.7 Years STANDARD_DEVIATION 16.6 |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 22 Participants | 77 Participants | 2 Participants | 101 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 14 / 22 | 56 / 77 | 2 / 2 |
| serious Total, serious adverse events | 7 / 22 | 25 / 77 | 2 / 2 |
Outcome results
Primary
Mean Total Number of Bleeding Episodes in Participants
Participants documented all bleeding episodes in a diary during the study.
Time frame: Baseline until last visit (up to 87 months)
Population: Effectiveness analysis set =participants registered in study and had at least 1 dose of ReFacto AF documented by participants diary entries. Participant's registration included confirmation of obtained participant's informed consent from the physician. Here, 'N' (number of participants analyzed) = participants evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| ReFacto AF: On Demand Treatment | Mean Total Number of Bleeding Episodes in Participants | 71.2 bleeding episodes | Standard Deviation 73.3 |
| ReFacto AF: Prophylaxis Treatment | Mean Total Number of Bleeding Episodes in Participants | 15.4 bleeding episodes | Standard Deviation 14.7 |
| ReFacto AF: Intermediate Prophylaxis Treatment | Mean Total Number of Bleeding Episodes in Participants | 68.5 bleeding episodes | Standard Deviation 31.8 |
Primary
Number of Participants With Factor VIII (FVIII) Inhibitor Development as Measured by the Nijmegen-Modified Bethesda Assay
FVIII inhibitor development was defined as measured inhibitor titer of greater than (\>) 0.6 Bethesda Units (BU) using the Nijmegen-modified Bethesda assay.
Time frame: Baseline until last visit (up to 87 months)
Population: Safety analysis set included all participants with informed consent and treated with at least 1 dose of ReFacto AF.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| ReFacto AF: On Demand Treatment | Number of Participants With Factor VIII (FVIII) Inhibitor Development as Measured by the Nijmegen-Modified Bethesda Assay | 1 participants |
| ReFacto AF: Prophylaxis Treatment | Number of Participants With Factor VIII (FVIII) Inhibitor Development as Measured by the Nijmegen-Modified Bethesda Assay | 2 participants |
| ReFacto AF: Intermediate Prophylaxis Treatment | Number of Participants With Factor VIII (FVIII) Inhibitor Development as Measured by the Nijmegen-Modified Bethesda Assay | 0 participants |
Primary
Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
An AE was any untoward medical occurrence in a participant who received study treatment without regard to possibility of causal relationship. SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability or incapacity; cancer; congenital anomaly. Treatment-emergent are events between first dose of study drug and up to last visit (up to 87 months) that were absent before treatment or that worsened relative to pretreatment state. AEs included both serious and non-serious adverse events.
Time frame: Baseline until last visit (up to 87 months)
Population: Safety analysis set included all participants with informed consent and treated with at least 1 dose of ReFacto AF.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| ReFacto AF: On Demand Treatment | Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | AEs | 15 participants |
| ReFacto AF: On Demand Treatment | Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | SAEs | 7 participants |
| ReFacto AF: Prophylaxis Treatment | Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | AEs | 59 participants |
| ReFacto AF: Prophylaxis Treatment | Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | SAEs | 25 participants |
| ReFacto AF: Intermediate Prophylaxis Treatment | Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | AEs | 2 participants |
| ReFacto AF: Intermediate Prophylaxis Treatment | Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | SAEs | 2 participants |
Primary
Number of Participants With Treatment-Related Adverse Events (AEs) and Serious Adverse Events (SAEs)
Treatment-related AE was any untoward medical occurrence attributed to study drug in a participant who received study drug. SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; cancer; congenital anomaly. AEs included both serious and non-serious adverse events. Relatedness of AEs with Refacto AF was assessed by the investigator.
Time frame: Baseline until last visit (up to 87 months)
Population: Safety analysis set included all participants with informed consent and treated with at least 1 dose of ReFacto AF.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| ReFacto AF: On Demand Treatment | Number of Participants With Treatment-Related Adverse Events (AEs) and Serious Adverse Events (SAEs) | AEs | 2 participants |
| ReFacto AF: On Demand Treatment | Number of Participants With Treatment-Related Adverse Events (AEs) and Serious Adverse Events (SAEs) | SAEs | 0 participants |
| ReFacto AF: Prophylaxis Treatment | Number of Participants With Treatment-Related Adverse Events (AEs) and Serious Adverse Events (SAEs) | AEs | 7 participants |
| ReFacto AF: Prophylaxis Treatment | Number of Participants With Treatment-Related Adverse Events (AEs) and Serious Adverse Events (SAEs) | SAEs | 0 participants |
| ReFacto AF: Intermediate Prophylaxis Treatment | Number of Participants With Treatment-Related Adverse Events (AEs) and Serious Adverse Events (SAEs) | AEs | 0 participants |
| ReFacto AF: Intermediate Prophylaxis Treatment | Number of Participants With Treatment-Related Adverse Events (AEs) and Serious Adverse Events (SAEs) | SAEs | 0 participants |
Secondary
Investigator Assessment of Treatment Satisfaction of Participants
Investigator assessed the treatment satisfaction of participants and categorized as very satisfied, satisfied, unsatisfied, or very unsatisfied.
Time frame: End of study visit (any time up to 87 months)
Population: Effectiveness analysis set =participants registered in study and had at least 1 dose of ReFacto AF documented by participants diary entries. Participant's registration included confirmation of obtained participant's informed consent from the physician. Here, 'N' =participants evaluable for this outcome measure.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| ReFacto AF: On Demand Treatment | Investigator Assessment of Treatment Satisfaction of Participants | Unsatisfied | 0 participants |
| ReFacto AF: On Demand Treatment | Investigator Assessment of Treatment Satisfaction of Participants | Very satisfied | 13 participants |
| ReFacto AF: On Demand Treatment | Investigator Assessment of Treatment Satisfaction of Participants | Very unsatisfied | 0 participants |
| ReFacto AF: On Demand Treatment | Investigator Assessment of Treatment Satisfaction of Participants | Satisfied | 4 participants |
| ReFacto AF: Prophylaxis Treatment | Investigator Assessment of Treatment Satisfaction of Participants | Unsatisfied | 1 participants |
| ReFacto AF: Prophylaxis Treatment | Investigator Assessment of Treatment Satisfaction of Participants | Satisfied | 29 participants |
| ReFacto AF: Prophylaxis Treatment | Investigator Assessment of Treatment Satisfaction of Participants | Very unsatisfied | 0 participants |
| ReFacto AF: Prophylaxis Treatment | Investigator Assessment of Treatment Satisfaction of Participants | Very satisfied | 44 participants |
| ReFacto AF: Intermediate Prophylaxis Treatment | Investigator Assessment of Treatment Satisfaction of Participants | Very unsatisfied | 0 participants |
| ReFacto AF: Intermediate Prophylaxis Treatment | Investigator Assessment of Treatment Satisfaction of Participants | Very satisfied | 0 participants |
| ReFacto AF: Intermediate Prophylaxis Treatment | Investigator Assessment of Treatment Satisfaction of Participants | Satisfied | 2 participants |
| ReFacto AF: Intermediate Prophylaxis Treatment | Investigator Assessment of Treatment Satisfaction of Participants | Unsatisfied | 0 participants |
Secondary
Mean Total Number of Bleeding Episodes Per Year in Participants
Participants documented all bleeding episodes in a diary during the study. Mean total number of bleeding episodes per year was calculated as: mean total number of bleeding episodes divided by duration of observation period (in years) for bleeding documentation.
Time frame: Baseline until last visit (up to 87 months)
Population: Effectiveness analysis set =participants registered in study and had at least 1 dose of ReFacto AF documented by participants diary entries. Participant's registration included confirmation of obtained participant's informed consent from the physician. Here, 'N' =participants evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| ReFacto AF: On Demand Treatment | Mean Total Number of Bleeding Episodes Per Year in Participants | 18.6 bleeding episodes per year | Standard Deviation 19.6 |
| ReFacto AF: Prophylaxis Treatment | Mean Total Number of Bleeding Episodes Per Year in Participants | 5.1 bleeding episodes per year | Standard Deviation 5.8 |
| ReFacto AF: Intermediate Prophylaxis Treatment | Mean Total Number of Bleeding Episodes Per Year in Participants | 13.4 bleeding episodes per year | Standard Deviation 0.5 |
Secondary
Number of Participants With Change From Baseline Status in Days Missed From School or Work
Change from baseline status in days missed from school or work was categorized in 3 categories: Improvement, unchanged and worsening. Improvement defined as a decrease in number of days missed by participants from school/work as compared to baseline; worsening was defined as an increase in number of days missed by participants from school/work as compared to baseline; unchanged was defined as no change in number of days missed by participants from school/work as compared to baseline. In this outcome measure, number of participants with change from baseline status (as improved, worsen, unchanged) in days missed from school/work were reported.
Time frame: Baseline until last visit (up to 87 months)
Population: Analysis was performed on effectiveness analysis set. Here, 'N' signifies those participants who were evaluable for this outcome measure. For this outcome measure, data for Refacto AF: intermediate prophylaxis treatment arm could not be analyzed since all participants of this arm were neither working nor school going.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| ReFacto AF: On Demand Treatment | Number of Participants With Change From Baseline Status in Days Missed From School or Work | Improvement | 4 participants |
| ReFacto AF: On Demand Treatment | Number of Participants With Change From Baseline Status in Days Missed From School or Work | Unchanged | 4 participants |
| ReFacto AF: On Demand Treatment | Number of Participants With Change From Baseline Status in Days Missed From School or Work | Worsening | 3 participants |
| ReFacto AF: Prophylaxis Treatment | Number of Participants With Change From Baseline Status in Days Missed From School or Work | Improvement | 25 participants |
| ReFacto AF: Prophylaxis Treatment | Number of Participants With Change From Baseline Status in Days Missed From School or Work | Unchanged | 29 participants |
| ReFacto AF: Prophylaxis Treatment | Number of Participants With Change From Baseline Status in Days Missed From School or Work | Worsening | 6 participants |
Secondary
Participant Assessment of Satisfaction With Treatment Handling
Participants evaluated their satisfaction with handing (administration) of Refacto AF and rated it in 4 categories as: very satisfied, satisfied, unsatisfied and very unsatisfied.
Time frame: End of study visit (any time up to 87 months)
Population: Effectiveness analysis set =participants registered in study and had at least 1 dose of ReFacto AF documented by participants diary entries. Participant's registration included confirmation of obtained participant's informed consent from the physician. Here, 'N' =participants evaluable for this outcome measure.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| ReFacto AF: On Demand Treatment | Participant Assessment of Satisfaction With Treatment Handling | Very satisfied | 13 participants |
| ReFacto AF: On Demand Treatment | Participant Assessment of Satisfaction With Treatment Handling | Satisfied | 5 participants |
| ReFacto AF: On Demand Treatment | Participant Assessment of Satisfaction With Treatment Handling | Unsatisfied | 0 participants |
| ReFacto AF: On Demand Treatment | Participant Assessment of Satisfaction With Treatment Handling | Very unsatisfied | 0 participants |
| ReFacto AF: Prophylaxis Treatment | Participant Assessment of Satisfaction With Treatment Handling | Very unsatisfied | 0 participants |
| ReFacto AF: Prophylaxis Treatment | Participant Assessment of Satisfaction With Treatment Handling | Very satisfied | 42 participants |
| ReFacto AF: Prophylaxis Treatment | Participant Assessment of Satisfaction With Treatment Handling | Unsatisfied | 4 participants |
| ReFacto AF: Prophylaxis Treatment | Participant Assessment of Satisfaction With Treatment Handling | Satisfied | 28 participants |
| ReFacto AF: Intermediate Prophylaxis Treatment | Participant Assessment of Satisfaction With Treatment Handling | Very unsatisfied | 0 participants |
| ReFacto AF: Intermediate Prophylaxis Treatment | Participant Assessment of Satisfaction With Treatment Handling | Satisfied | 2 participants |
| ReFacto AF: Intermediate Prophylaxis Treatment | Participant Assessment of Satisfaction With Treatment Handling | Unsatisfied | 0 participants |
| ReFacto AF: Intermediate Prophylaxis Treatment | Participant Assessment of Satisfaction With Treatment Handling | Very satisfied | 0 participants |