The primary objective was to evaluate the safety and efficacy of the treatment with BAY81-8973 for prophylaxis and treatment of breakthrough bleeds in children with severe hemophilia A. The secondary objectives were * To assess the safety and efficacy of BAY81-8973 during surgeries. * To assess incremental recovery of BAY81-8973. * To assess pharmacokinetic (PK) parameters in a subset of children (Previously treated patients \[PTPs\] and previously untreated patients \[PUPs\] / minimally treated patients \[MTPs\] - participation in PK sampling was voluntary and required consent).
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
94
Main study: 25-50 IU/kg at least 2x/week for 6 months and at least 50 EDs, IV infusion; Extension study: 25-50 IU/kg at least 2x/week for at least 100 cumulative EDs (main study - Part A and extension study), IV infusion. Exposure day (ED): An ED is a unit of time (1 day) in which replacement treatment of Hemophilia is given to a patient.
Main study: 15-50 IU/kg at least 1x/week for at least 50 EDs or until inhibitor development, IV infusion; Extension study: For participants having reached at least 50 EDs in main study - Part B: 25-50 IU/kg at least 2x/week for at least 100 cumulative EDs (main study - Part B and extension study), IV infusion. For participants who developed an inhibitor in main study - Part B: up to 200 IU/kg per day or 100 IU/kg twice a day at the discretion of the investigator and coordinating investigator until successful eradication of the inhibitor, or until failure, for up to18 months (treatment beyond 18 months required an agreement with the sponsor and coordinating investigator), IV infusion
Annualized Number of Total Bleeds Within 48 h
Annualized number (mean +/- standard deviation) of total bleeds that occurred within 48 hours after all prophylaxis infusions (Part A: 6 months and at least 50 exposure days \[EDs\]; Part B: at least 50 EDs or until inhibitor development) was summarized and reported. Total bleeds: sum of spontaneous bleeds, trauma bleeds (only treated bleeds were classified as spontaneous or trauma), untreated bleeds and 'other' bleeds ('other' bleeds were infusions with reason given as 'other').
Time frame: Within 48 hours post infusion
Annualized Number of Total Bleeds Within 48 h
Annualized number (median \[inter-quartile range (Q1-Q3)\]) of total bleeds that occurred within 48 hours after all prophylaxis infusions (Part A: 6 months and at least 50 exposure days \[EDs\]; Part B: at least 50 EDs or until inhibitor development) was summarized and reported. Total bleeds: sum of spontaneous bleeds, trauma bleeds (only treated bleeds were classified as spontaneous or trauma), untreated bleeds and 'other' bleeds ('other' bleeds were infusions with reason given as 'other').
Time frame: Within 48 hours post infusion
Annualized Number of Total Bleeds During Prophylaxis Treatment
Annualized number (mean +/- standard deviation) of total bleeds that occurred during prophylaxis treatment was summarized and reported. Total bleeds: sum of spontaneous bleeds, trauma bleeds (only treated bleeds were classified as spontaneous or trauma), untreated bleeds and 'other' bleeds ('other' bleeds were infusions with reason given as 'other').
Time frame: Part A: 6 months and at least 50 exposure days (EDs) (median 73 EDs; median 6 months); Part B: at least 50 EDs or until inhibitor development (median 46 EDs; median 8 months)
Annualized Number of Total Bleeds During Prophylaxis Treatment
Annualized number (median \[inter-quartile range (Q1-Q3)\]) of total bleeds that occurred during prophylaxis treatment was summarized and reported. Total bleeds: sum of spontaneous bleeds, trauma bleeds (only treated bleeds were classified as spontaneous or trauma), untreated bleeds and 'other' bleeds ('other' bleeds were infusions with reason given as 'other').
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
Unnamed facility
New Orleans, Louisiana, United States
Unnamed facility
Cincinnati, Ohio, United States
Unnamed facility
Cleveland, Ohio, United States
Unnamed facility
Columbus, Ohio, United States
Unnamed facility
Bahía Blanca, Buenos Aires, Argentina
Unnamed facility
Plovdiv, Bulgaria
Unnamed facility
Varna, Bulgaria
Unnamed facility
Edmonton, Alberta, Canada
Unnamed facility
Hamilton, Ontario, Canada
Unnamed facility
Toronto, Ontario, Canada
...and 33 more locations
Time frame: Part A: 6 months and at least 50 exposure days (EDs) (median 73 EDs; median 6 months); Part B: at least 50 EDs or until inhibitor development (median 46 EDs; median 8 months)
Hemostatic Control During Major and Minor Surgeries
For participants who underwent major or minor surgeries during the study, hemostasis during the surgeries was assessed as excellent, good, moderate or poor. Number of surgeries per assessment was summarized and reported.
Time frame: Part A: 6 months and at least 50 exposure days (EDs) (median 73 EDs; median 6 months); Part B: at least 50 EDs or until inhibitor development (median 46 EDs; median 8 months)
Number of Participants With Inhibitor Development in Main Study
Number of participants with confirmed positive FVIII inhibitor titer (≥ 0.6 Bethesda unit \[BU/mL\]) during the main study was summarized and classified as participants developing low titer inhibitor (i.e. ≥ 0.6 to ≤ 5.0 BU/mL) and participants developing high titer inhibitor (i.e. \> 5.0 BU/mL).
Time frame: Part A: 6 months and at least 50 exposure days (EDs) (median 73 EDs; median 6 months); Part B: at least 50 EDs or until inhibitor development (median 46 EDs; median 8 months)
Number of Participants With New Inhibitor Development in Extension Study
Number of participants who had not developed an inhibitor during the main study but developed an inhibitor (confirmed positive FVIII inhibitor titer \[≥ 0.6 BU/mL\]) during the extension study was summarized and classified as participants developing low titer inhibitor (i.e. ≥ 0.6 to ≤ 5.0 BU/mL) and participants developing high titer inhibitor (i.e. \> 5.0 BU/mL).
Time frame: From start of extension study to at least 100 cumulative exposure days (EDs) (median 421 EDs; median 3.8 years)
Factor VIII Recovery Values
Incremental recovery of Factor VIII (FVIII) at 20-30 min after end of infusions was determined and mean recovery values were reported.
Time frame: Part A: 6 months and at least 50 exposure days (EDs) (median 73 EDs; median 6 months); Part B: at least 50 EDs or until inhibitor development (median 46 EDs; median 8 months)
Consumption of Factor VIII in All Infusions
Factor VIII (FVIII) usage/consumption was summarized for all infusions. Consumption per participant's body weight per year was calculated and reported.
Time frame: Part A: 6 months and at least 50 exposure days (EDs) (median 73 EDs; median 6 months); Part B: at least 50 EDs or until inhibitor development (median 46 EDs; median 8 months)
Consumption of FVIII in Infusions for Prophylaxis
Factor VIII (FVIII) usage/consumption was summarized for prophylaxis infusions. Consumption per participant's body weight per year was calculated and reported.
Time frame: Part A: 6 months and at least 50 exposure days (EDs) (median 73 EDs; median 6 months); Part B: at least 50 EDs or until inhibitor development (median 46 EDs; median 8 months)
Consumption of FVIII in Infusions for the Treatment of Bleeds
Factor VIII (FVIII) usage/consumption was summarized for infusions used to treat breakthrough bleeds. Consumption per participant's body weight per year was calculated and reported.
Time frame: Part A: 6 months and at least 50 exposure days (EDs) (median 73 EDs; median 6 months); Part B: at least 50 EDs or until inhibitor development (median 46 EDs; median 8 months)
Number of Infusions Per Bleed
The number of infusions used to treat a bleed was defined as the first infusion to treat the bleed plus all follow-up infusions to treat the same bleed, if any. The mean value of number of infusions for each bleed was calculated and reported.
Time frame: Part A: 6 months and at least 50 exposure days (EDs) (median 73 EDs; median 6 months); Part B: at least 50 EDs or until inhibitor development (median 46 EDs; median 8 months)
Response to Treatment of Bleeds
Participants or caregivers were asked to assess the response to treatment of bleeds as excellent, good, moderate or poor. Percentage of bleeds per assessment was summarized and reported.
Time frame: Part A: 6 months and at least 50 exposure days (EDs) (median 73 EDs; median 6 months); Part B: at least 50 EDs or until inhibitor development (median 46 EDs; median 8 months)
Half-life (t1/2) of BAY81-8973 in Plasma
Half-life (t1/2) of BAY81-8973 in plasma was measured. Geometric mean and percentage geometric coefficient of variation (%CV) were reported.
Time frame: Pre-infusion and until 24 hours post infusion