Have you or your loved ones been diagnosed with haemophilia a?
You may be eligible to participate in a haemophilia a clinical trial.
Have you or your loved ones been diagnosed with haemophilia a? You may be eligible to participate in a haemophilia a clinical trial.
What is a clinical trial? Is participating in a clinical trial right for you? Learn more
Have you or your loved ones been diagnosed with haemophilia a?
You may be eligible to participate in a haemophilia a clinical trial.
Have you or your loved ones been diagnosed with haemophilia a? You may be eligible to participate in a haemophilia a clinical trial.
Completed
Male
Up to 12
Years old
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).
Details for the study
Brief Title
BAY81-8973 Pediatric Safety and Efficacy Trial
Official Title
A Multicenter Phase III Uncontrolled Open-label Trial to Evaluate Safety and Efficacy of BAY81-8973 in Children With Severe Hemophilia A Under Prophylaxis Therapy
Brief Summary
The primary objective was to evaluate the safety and efficacy of the treatment with <br /> BAY81-8973 for prophylaxis and treatment of breakthrough bleeds in children with severe <br /> hemophilia A. <br /> <br /> The secondary objectives were <br /> <br /> - To assess the safety and efficacy of BAY81-8973 during surgeries. <br /> <br /> - To assess incremental recovery of BAY81-8973. <br /> <br /> - To assess pharmacokinetic (PK) parameters in a subset of children (Previously treated <br /> patients [PTPs] and previously untreated patients [PUPs] / minimally treated patients <br /> [MTPs] - participation in PK sampling was voluntary and required consent).
Treatments and/or Procedures
Recombinant Factor VIII (Kovaltry, BAY81 8973)
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
Recombinant Factor VIII (Kovaltry, BAY81 8973)
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.
Outcome Measures
Outcome measures are the tests that investigators perform to prove whether or not a treatment being tested in a clinical trial is having any effect.
Primary
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').
Primary
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').
Secondary
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.
Secondary
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).
Secondary
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.
Secondary
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').
Secondary
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.
Secondary
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).
Secondary
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.
Secondary
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.
Secondary
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.
Secondary
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').
Secondary
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.
Secondary
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.
Study Criteria
Inclusion Criteria:
- Male
- PTPs (previously treated patients): aged <= 12 years
- PUPs (previously untreated patients) / MTPs (minimally treated patients): aged < 6
years
- Severe hemophilia A defined as < 1% FVIII concentration (FVIII:C)
- PTPs: >= 50 exposure days (EDs) with any FVIII concentrate, no current evidence of
inhibitory antibody, and no history of FVIII inhibitor formation
- PUPs: no prior exposure to any FVIII product
- MTPs: having no more than 3 EDs with any FVIII product, no current evidence of
inhibitory antibody and no history of FVIII inhibitor formation
Exclusion Criteria:
- With another bleeding disorder that is different from Hemophilia A
- With thrombocytopenia (platelet count < 100 000/mm^3)
- Creatinine > 2x upper limit of normal or Aspartate aminotransferase (AST)/Alanine
aminotransferase (ALT) > 5x upper limit of normal
- Without a negative inhibitor testing at screening (except for PUPs)
- Receiving chemotherapy, immune modulatory drugs, has received another investigational
FVIII product within the last month, or received another experimental drug within the
last 3 months
- Requires any pre-medication to tolerate FVIII treatment
- Known hypersensitivity to active substance, mouse, or hamster protein