Hemophilia A
Conditions
Keywords
Kogenate,, Children,, Factor VIII,, Hemophilia A,, Prophylactic
Brief summary
A prospective study to evaluate the effect of rFVIII-FS in different prophylactic regimens on bleeding events frequency and development of arthropathy in Previously Treated and Minimally treated Hemophilia A pediatric population.
Interventions
DRUGrFVIII-FS (Kogenate FS, BAY14-2222) 70 IU/kg, dosing once per week
rFVIII-FS (Octocog-alfa, antihemophilic factor \[recombinant\]) 70 IU/kg, dosing by injection once per week (weekly on Day 7 + 1 after previous injection) for 9 months. Dose escalation was permitted due to joint bleeding (escalation to 35 IU/kg twice a week or further escalation to 25 IU/kg three times a week)
DRUGrFVIII-FS (Kogenate FS, BAY14-2222), 70 IU/kg twice per week (30 IU/kg + 40 IU/kg)
rFVIII-FS (Octocog-alfa, antihemophilic factor \[recombinant\]) 70 IU/kg, dosing by injection twice per week (30 IU/kg \[day 1\] + 40 IU/kg \[day 4\]) for 9 months. Dose escalation was permitted due to joint bleeding (escalation to 25 IU/kg three times a week)
DRUGrFVIII-FS (Kogenate FS, BAY14-2222) 75 IU/kg, dosing three times per week (3 x 25 IU/kg)
rFVIII-FS (Octocog-alfa, antihemophilic factor \[recombinant\]) 75 IU/kg, dosing by injection three times per week (3 x 25 IU/kg \[day 1, 3, 5\]) for 9 months. No escalation opportunity for patients in this group
Sponsors
Bayer
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
1 Years to 12 Years
Healthy volunteers
No
Inclusion criteria
* Male * Severe hemophilia A or moderate hemophilia A * 1-12 years of age * Requiring treatment with FVIII
Exclusion criteria
* Current or prior inhibitor or familial antecedents of inhibitor * Surgery required during the study (9 months) * Positive for HIV
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Percentage of Participants With Less Than 2 Joint Bleeds During the 9-month Treatment Period | Up to 9 months |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Bleeding Events During the 9-month Treatment Period | Up to 9 months | — |
| Number of Participants With Joint Bleeds During the 9-month Treatment Period | Up to 9 months | — |
| Number of Participants in Each Group at the End of the Study | Up to 9 months | — |
| Number of Bleeds Per Participant During the 9-month Treatment Period | Up to 9 months | — |
| Change From Baseline in Stockholm Hemophilia Joint Score at 9 Months of Treatment | baseline and 9 months | The assessment of joint function using Stockholm Joint Score. The minimum value is 0 (the best condition), and the maximum value is 140 (the worst condition). |
| Haemo-QoL Standardized Total Score at 9 Months of Treatment (Completed by Participants in the Total Group) | 9 months | Quality of life (QoL) was measured by the Haemo-QoL standardized total Score, which ranged from 0 (the best condition) to 100 (the worst condition). |
| Haemo-QoL Standardized Total Score (Completed by Parents/Caregivers in the Total Group) at 9 Months of Treatment | 9 months | Quality of life (QoL) was measured by the Haemo-QoL standardized total Score, which ranged from 0 (the best condition) to 100 (the worst condition). |
| Actual Monthly rFVIII-FS Consumption | Up to 9 months | — |
Countries
Russia
Participant flow
Recruitment details
The recruitment period took from first patient first visit 28 Jun 2007 to last patient first visit 26 Dec 2008. The study period took from first patient first visit 28 Jun 2007 to last patient last visit 27 Sep 2009. All 4 sites were medical clinics. Assignment to a group was based on patients previous treatment schedule (non-randomized).
Pre-assignment details
There was an indefinite time period between screening and baseline. Study treatment started at visit 2 (baseline).
Participants by arm
| Arm | Count |
|---|---|
| rFVIII-FS (Kogenate FS, BAY14-2222), 70 IU/kg qw rFVIII-FS (Octocog-alfa, antihemophilic factor \[recombinant\]) 70 IU/kg, dosing by injection once per week \[qw\] (weekly on Day 7 + 1 after previous injection) for 9 months. Dose escalation was permitted due to joint bleeding (escalation to 35 IU/kg twice a week or further escalation to 25 IU/kg three times a week) | 11 |
| rFVIII-FS (Kogenate FS, BAY14-2222), Biw (30 IU/kg + 40 IU/kg) rFVIII-FS (Octocog-alfa, antihemophilic factor \[recombinant\]) 70 IU/kg, dosing by injection twice per week \[biw\] (30 IU/kg \[day 1\] + 40 IU/kg \[day 4\]) for 9 months. Dose escalation was permitted due to joint bleeding (escalation to 25 IU/kg three times a week) | 13 |
| rFVIII-FS (Kogenate FS, BAY14-2222), Tiw (3 x 25 IU/kg) rFVIII-FS (Octocog-alfa, antihemophilic factor \[recombinant\]) 75 IU/kg, dosing by injection three times per week \[tiw\] (3 x 25 IU/kg \[day 1, 3, 5\]) for 9 months. No escalation opportunity for participants in this group | 8 |
| Total | 32 |
Baseline characteristics
| Characteristic | rFVIII-FS (Kogenate FS, BAY14-2222), 70 IU/kg qw | rFVIII-FS (Kogenate FS, BAY14-2222), Biw (30 IU/kg + 40 IU/kg) | rFVIII-FS (Kogenate FS, BAY14-2222), Tiw (3 x 25 IU/kg) | Total |
|---|---|---|---|---|
| Age, Continuous | 3.27 years STANDARD_DEVIATION 3.2 | 6.08 years STANDARD_DEVIATION 3.5 | 6.00 years STANDARD_DEVIATION 3.12 | 5.09 years STANDARD_DEVIATION 3.47 |
| Body Weight | 17.48 Kilograms STANDARD_DEVIATION 10.43 | 24.39 Kilograms STANDARD_DEVIATION 11.35 | 25.45 Kilograms STANDARD_DEVIATION 9.87 | 22.28 Kilograms STANDARD_DEVIATION 10.93 |
| Ethnicity Asian | 0 participants | 0 participants | 1 participants | 1 participants |
| Ethnicity Caucasian | 11 participants | 13 participants | 7 participants | 31 participants |
| FVIII trough level at Baseline | 1.43 Percentage of FVIII activity STANDARD_DEVIATION 0.7 | 1.62 Percentage of FVIII activity STANDARD_DEVIATION 1.79 | 0.77 Percentage of FVIII activity STANDARD_DEVIATION 0.24 | 1.34 Percentage of FVIII activity STANDARD_DEVIATION 1.24 |
| Height | 98.09 Centimeters STANDARD_DEVIATION 22.88 | 120.31 Centimeters STANDARD_DEVIATION 23.75 | 122.00 Centimeters STANDARD_DEVIATION 20.74 | 113.09 Centimeters STANDARD_DEVIATION 24.63 |
| Number of participants on Prophylaxis Prior to Screening On demand | 9 pariticipants | 6 pariticipants | 5 pariticipants | 20 pariticipants |
| Number of participants on Prophylaxis Prior to Screening Prophylaxis | 2 pariticipants | 7 pariticipants | 3 pariticipants | 12 pariticipants |
| Number of participants with bleeding rates in previous 6-9 Months Any bleedings | 10 participants | 11 participants | 8 participants | 29 participants |
| Number of participants with bleeding rates in previous 6-9 Months Any joint bleedings | 9 participants | 11 participants | 6 participants | 26 participants |
| Number of participants with bleeding rates in previous 6-9 Months No bleedings | 1 participants | 2 participants | 0 participants | 3 participants |
| Number of participants with different exposure days (ED) 0 ED | 1 participants | 0 participants | 0 participants | 1 participants |
| Number of participants with different exposure days (ED) >=100 ED | 5 participants | 11 participants | 4 participants | 20 participants |
| Number of participants with different exposure days (ED) 1 to <20 ED | 1 participants | 0 participants | 0 participants | 1 participants |
| Number of participants with different exposure days (ED) 20 to <100 ED | 4 participants | 2 participants | 4 participants | 10 participants |
| Percentage of participants with Target Joint Present | 36 Percentage of participants | 54 Percentage of participants | 88 Percentage of participants | 178 Percentage of participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 11 Participants | 13 Participants | 8 Participants | 32 Participants |
| Stockholm Joint Score | 3.9 scores on a scale STANDARD_DEVIATION 4.8 | 5.9 scores on a scale STANDARD_DEVIATION 5.8 | 7.1 scores on a scale STANDARD_DEVIATION 4.6 | 5.5 scores on a scale STANDARD_DEVIATION 5.2 |
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 | 4 / 11 | 3 / 13 | 3 / 8 |
| serious Total, serious adverse events | 1 / 11 | 2 / 13 | 0 / 8 |
Outcome results
Primary
Percentage of Participants With Less Than 2 Joint Bleeds During the 9-month Treatment Period
Time frame: Up to 9 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| rFVIII-FS (Kogenate FS, BAY14-2222), 70 IU/kg qw | Percentage of Participants With Less Than 2 Joint Bleeds During the 9-month Treatment Period | 72.7 Percentage of participants |
| rFVIII-FS (Kogenate FS, BAY14-2222), Biw (30 IU/kg + 40 IU/kg) | Percentage of Participants With Less Than 2 Joint Bleeds During the 9-month Treatment Period | 84.6 Percentage of participants |
| rFVIII-FS (Kogenate FS, BAY14-2222), Tiw (3 x 25 IU/kg) | Percentage of Participants With Less Than 2 Joint Bleeds During the 9-month Treatment Period | 75.0 Percentage of participants |
Secondary
Actual Monthly rFVIII-FS Consumption
Time frame: Up to 9 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| rFVIII-FS (Kogenate FS, BAY14-2222), 70 IU/kg qw | Actual Monthly rFVIII-FS Consumption | 390.8 IU/kg | Standard Deviation 106.9 |
| rFVIII-FS (Kogenate FS, BAY14-2222), Biw (30 IU/kg + 40 IU/kg) | Actual Monthly rFVIII-FS Consumption | 422.3 IU/kg | Standard Deviation 138.2 |
| rFVIII-FS (Kogenate FS, BAY14-2222), Tiw (3 x 25 IU/kg) | Actual Monthly rFVIII-FS Consumption | 501.4 IU/kg | Standard Deviation 241.2 |
Secondary
Change From Baseline in Stockholm Hemophilia Joint Score at 9 Months of Treatment
The assessment of joint function using Stockholm Joint Score. The minimum value is 0 (the best condition), and the maximum value is 140 (the worst condition).
Time frame: baseline and 9 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| rFVIII-FS (Kogenate FS, BAY14-2222), 70 IU/kg qw | Change From Baseline in Stockholm Hemophilia Joint Score at 9 Months of Treatment | -1.4 Scores on a scale | Standard Deviation 2.4 |
| rFVIII-FS (Kogenate FS, BAY14-2222), Biw (30 IU/kg + 40 IU/kg) | Change From Baseline in Stockholm Hemophilia Joint Score at 9 Months of Treatment | -2.0 Scores on a scale | Standard Deviation 4.5 |
| rFVIII-FS (Kogenate FS, BAY14-2222), Tiw (3 x 25 IU/kg) | Change From Baseline in Stockholm Hemophilia Joint Score at 9 Months of Treatment | -1.8 Scores on a scale | Standard Deviation 2.2 |
Secondary
Haemo-QoL Standardized Total Score at 9 Months of Treatment (Completed by Participants in the Total Group)
Quality of life (QoL) was measured by the Haemo-QoL standardized total Score, which ranged from 0 (the best condition) to 100 (the worst condition).
Time frame: 9 months
Population: Participants who completed the questionnaire.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| rFVIII-FS (Kogenate FS, BAY14-2222), 70 IU/kg qw | Haemo-QoL Standardized Total Score at 9 Months of Treatment (Completed by Participants in the Total Group) | 30.28 Scores on a scale | Standard Deviation 13.09 |
| rFVIII-FS (Kogenate FS, BAY14-2222), Biw (30 IU/kg + 40 IU/kg) | Haemo-QoL Standardized Total Score at 9 Months of Treatment (Completed by Participants in the Total Group) | 39.07 Scores on a scale | Standard Deviation 23.5 |
| rFVIII-FS (Kogenate FS, BAY14-2222), Tiw (3 x 25 IU/kg) | Haemo-QoL Standardized Total Score at 9 Months of Treatment (Completed by Participants in the Total Group) | 30.27 Scores on a scale | Standard Deviation 11.95 |
Secondary
Haemo-QoL Standardized Total Score (Completed by Parents/Caregivers in the Total Group) at 9 Months of Treatment
Quality of life (QoL) was measured by the Haemo-QoL standardized total Score, which ranged from 0 (the best condition) to 100 (the worst condition).
Time frame: 9 months
Population: Participants who completed the questionnaire.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| rFVIII-FS (Kogenate FS, BAY14-2222), 70 IU/kg qw | Haemo-QoL Standardized Total Score (Completed by Parents/Caregivers in the Total Group) at 9 Months of Treatment | 29.13 Scores on a scale | Standard Deviation 17.4 |
| rFVIII-FS (Kogenate FS, BAY14-2222), Biw (30 IU/kg + 40 IU/kg) | Haemo-QoL Standardized Total Score (Completed by Parents/Caregivers in the Total Group) at 9 Months of Treatment | 28.43 Scores on a scale | Standard Deviation 10.27 |
| rFVIII-FS (Kogenate FS, BAY14-2222), Tiw (3 x 25 IU/kg) | Haemo-QoL Standardized Total Score (Completed by Parents/Caregivers in the Total Group) at 9 Months of Treatment | 31.38 Scores on a scale | Standard Deviation 13.06 |
Secondary
Number of Bleeds Per Participant During the 9-month Treatment Period
Time frame: Up to 9 months
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| rFVIII-FS (Kogenate FS, BAY14-2222), 70 IU/kg qw | Number of Bleeds Per Participant During the 9-month Treatment Period | All bleeds | 3.0 bleeds per participant |
| rFVIII-FS (Kogenate FS, BAY14-2222), 70 IU/kg qw | Number of Bleeds Per Participant During the 9-month Treatment Period | Joint bleeds | 0 bleeds per participant |
| rFVIII-FS (Kogenate FS, BAY14-2222), Biw (30 IU/kg + 40 IU/kg) | Number of Bleeds Per Participant During the 9-month Treatment Period | All bleeds | 2.0 bleeds per participant |
| rFVIII-FS (Kogenate FS, BAY14-2222), Biw (30 IU/kg + 40 IU/kg) | Number of Bleeds Per Participant During the 9-month Treatment Period | Joint bleeds | 0 bleeds per participant |
| rFVIII-FS (Kogenate FS, BAY14-2222), Tiw (3 x 25 IU/kg) | Number of Bleeds Per Participant During the 9-month Treatment Period | All bleeds | 1.5 bleeds per participant |
| rFVIII-FS (Kogenate FS, BAY14-2222), Tiw (3 x 25 IU/kg) | Number of Bleeds Per Participant During the 9-month Treatment Period | Joint bleeds | 0 bleeds per participant |
Secondary
Number of Participants in Each Group at the End of the Study
Time frame: Up to 9 months
Population: Participants were allowed to switch treatment groups upon occurrence of joint bleed. Therefore the number of participants per group at the end of the study is different from the number of participants per group at baseline.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| rFVIII-FS (Kogenate FS, BAY14-2222), 70 IU/kg qw | Number of Participants in Each Group at the End of the Study | 8 Participants |
| rFVIII-FS (Kogenate FS, BAY14-2222), Biw (30 IU/kg + 40 IU/kg) | Number of Participants in Each Group at the End of the Study | 14 Participants |
| rFVIII-FS (Kogenate FS, BAY14-2222), Tiw (3 x 25 IU/kg) | Number of Participants in Each Group at the End of the Study | 10 Participants |
Secondary
Number of Participants With Bleeding Events During the 9-month Treatment Period
Time frame: Up to 9 months
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| rFVIII-FS (Kogenate FS, BAY14-2222), 70 IU/kg qw | Number of Participants With Bleeding Events During the 9-month Treatment Period | no bleeds | 3 Participants |
| rFVIII-FS (Kogenate FS, BAY14-2222), 70 IU/kg qw | Number of Participants With Bleeding Events During the 9-month Treatment Period | bleeds at all | 8 Participants |
| rFVIII-FS (Kogenate FS, BAY14-2222), Biw (30 IU/kg + 40 IU/kg) | Number of Participants With Bleeding Events During the 9-month Treatment Period | no bleeds | 4 Participants |
| rFVIII-FS (Kogenate FS, BAY14-2222), Biw (30 IU/kg + 40 IU/kg) | Number of Participants With Bleeding Events During the 9-month Treatment Period | bleeds at all | 9 Participants |
| rFVIII-FS (Kogenate FS, BAY14-2222), Tiw (3 x 25 IU/kg) | Number of Participants With Bleeding Events During the 9-month Treatment Period | no bleeds | 4 Participants |
| rFVIII-FS (Kogenate FS, BAY14-2222), Tiw (3 x 25 IU/kg) | Number of Participants With Bleeding Events During the 9-month Treatment Period | bleeds at all | 4 Participants |
Secondary
Number of Participants With Joint Bleeds During the 9-month Treatment Period
Time frame: Up to 9 months
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| rFVIII-FS (Kogenate FS, BAY14-2222), 70 IU/kg qw | Number of Participants With Joint Bleeds During the 9-month Treatment Period | no bleeds | 8 Participants |
| rFVIII-FS (Kogenate FS, BAY14-2222), 70 IU/kg qw | Number of Participants With Joint Bleeds During the 9-month Treatment Period | bleeds at all | 3 Participants |
| rFVIII-FS (Kogenate FS, BAY14-2222), Biw (30 IU/kg + 40 IU/kg) | Number of Participants With Joint Bleeds During the 9-month Treatment Period | no bleeds | 9 Participants |
| rFVIII-FS (Kogenate FS, BAY14-2222), Biw (30 IU/kg + 40 IU/kg) | Number of Participants With Joint Bleeds During the 9-month Treatment Period | bleeds at all | 4 Participants |
| rFVIII-FS (Kogenate FS, BAY14-2222), Tiw (3 x 25 IU/kg) | Number of Participants With Joint Bleeds During the 9-month Treatment Period | no bleeds | 6 Participants |
| rFVIII-FS (Kogenate FS, BAY14-2222), Tiw (3 x 25 IU/kg) | Number of Participants With Joint Bleeds During the 9-month Treatment Period | bleeds at all | 2 Participants |