Hemophilia A With Inhibitors
Conditions
Brief summary
The objective of this study is to assess whether prophylactic therapy with an activated prothrombin complex concentrate (FEIBA)will result in a significant reduction in the number of bleeds in patients with hemophilia and persistent high responding inhibitors.
Interventions
DRUGactivated prothrombin complex concentrate (FEIBA)
FEIBA for prophylaxis therapy dosed at 85 U/Kg +/- 15% on three non-consecutive days each week for 6 months FEIBA for on-demand therapy dosed at 85 U/Kg +/- 15% for bleeding episodes for 6 months
Sponsors
Tulane University School of Medicine
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
24 Months to No maximum
Healthy volunteers
No
Inclusion criteria
* hemophilia A, any severity, with documented history of high-titer inhibitor (\>5BU); current use of bypassing agents (PCCs, aPCCs or rFVIIa) for treatment of bleeds; \>/= 6 bleeds requiring bypassing therapy in the previous 6 months
Exclusion criteria
* concomitant immune tolerance therapy; clinically symptomatic liver disease, platelet count less than 100,000
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Number of Bleeds During 6 Month Treatment Period | 6 months |
Countries
United States
Participant flow
Recruitment details
The study was conducted at 16 hemophilia treatment centers in Europe and the United States.
Pre-assignment details
Patients were randomized to one of two 6 month treatment periods. Following the initial treatment period each subject had a 3 month wash-out period during which time they used on-demand therapy to treat bleeding. Following the 3 month wash-out period each patient was crossed-over to the other 6 month treatment period.
Participants by arm
| Arm | Count |
|---|---|
| On-demand First Patients receive 6 months of on-demand therapy with study drug followed by 6 months of prophylaxis therapy with study drug | 17 |
| Prophylaxis First Patients receive 6 months of prophylaxis therapy with study drug followed by 6 months on-demand therapy with study drug | 17 |
| Total | 34 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Therapy 1 (Months 1-6) | Lost to Follow-up | 0 | 1 |
| Therapy 1 (Months 1-6) | Withdrawal by Subject | 3 | 1 |
| Therapy 2 (Months 10-15) | Adverse Event | 1 | 0 |
| Therapy 2 (Months 10-15) | Death | 1 | 0 |
| Washout Period (Months 7-9) | Death | 0 | 1 |
Baseline characteristics
| Characteristic | On-demand First | Prophylaxis First | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 4 Participants | 7 Participants | 11 Participants |
| Age, Categorical >=65 years | 0 Participants | 1 Participants | 1 Participants |
| Age, Categorical Between 18 and 65 years | 13 Participants | 9 Participants | 22 Participants |
| Age, Continuous | 29.3 years STANDARD_DEVIATION 13.4 | 24.9 years STANDARD_DEVIATION 20.6 | 27.1 years STANDARD_DEVIATION 17.3 |
| Region of Enrollment Europe | 14 participants | 14 participants | 28 participants |
| Region of Enrollment United States | 3 participants | 3 participants | 6 participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 17 Participants | 17 Participants | 34 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 | 16 / 31 | 17 / 31 | 14 / 29 |
| serious Total, serious adverse events | 3 / 31 | 4 / 31 | 4 / 29 |
Outcome results
Primary
Number of Bleeds During 6 Month Treatment Period
Time frame: 6 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Bleeds During the On-demand Period | Number of Bleeds During 6 Month Treatment Period | 13.1 bleeds | Standard Deviation 7.1 |
| Bleeds During the Prophylaxis Period | Number of Bleeds During 6 Month Treatment Period | 5.0 bleeds | Standard Deviation 5 |
Comparison: The Wilcoxin signed-rank test was used to compare the frequency of bleeds between the prophylaxis and on-demand periods.p-value: <0.001Wilcoxon (Mann-Whitney)