Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

BAY81-8973 Pediatric Safety and Efficacy Trial

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01311648
Recruitment Status : Completed
First Posted : March 9, 2011
Results First Posted : November 3, 2020
Last Update Posted : November 23, 2020
Sponsor:
Information provided by (Responsible Party):
Bayer

Study Type Interventional
Study Design Allocation: N/A;   Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Haemophilia A
Intervention Biological: Recombinant Factor VIII (Kovaltry, BAY81-8973)
Enrollment 94
Recruitment Details Study Part A was conducted at multiple centers in 12 countries between 09-JUN-2011 (first participant first visit) and 02-JAN-2013 (last participant last visit); Study Part B was conducted at multiple centers in 15 countries between 19-SEP-2012 (first participant first visit) and 09-SEP-2019 (last participant last visit). Study extension phase is ongoing.
Pre-assignment Details Overall, 58 participants were screened in Part A, of which 7 participants were screening failures and 51 participants received at least one dose of the study drug; 52 participants were screened in Part B, of which 9 participants were screening failures and 43 participants received at least one dose of the study drug.
Arm/Group Title Part A: PTPs 0-<6 Years Part A: PTPs 6-12 Years Part B: PUPs/MTPs 0-<6 Years
Hide Arm/Group Description Previously treated patients (PTPs) aged below 6 years received BAY81-8973 25-50 IU/kg at least 2x/week for 6 months and at least 50 exposure days (ED) Previously treated patients (PTPs) aged 6 to 12 years received BAY81-8973 25-50 IU/kg at least 2x/week for 6 months and at least 50 exposure days (ED) Previously untreated patients (PUPs) or minimally treated patients (MTPs, patients who had no more than 3 exposure days [EDs] with any FVIII product) received BAY81-8973 15-50 IU/kg at least 1x/week for 50 EDs
Period Title: Overall Study
Started 25 26 43
Completed 25 26 22
Not Completed 0 0 21
Reason Not Completed
Protocol Violation             0             0             1
Adverse Event             0             0             1
Inhibitor management             0             0             17
Withdrawal by Subject             0             0             2
Arm/Group Title Part A: PTPs 0-<6 Years Part A: PTPs 6-12 Years Part B: PUPs/MTPs 0-<6 Years Total
Hide Arm/Group Description Previously treated patients (PTPs) aged below 6 years received BAY81-8973 25-50 IU/kg at least 2x/week for 6 months and at least 50 exposure days (ED) Previously treated patients (PTPs) aged 6 to 12 years received BAY81-8973 25-50 IU/kg at least 2x/week for 6 months and at least 50 exposure days (ED) Previously untreated patients (PUPs) or minimally treated patients (MTPs, patients who had no more than 3 exposure days [EDs] with any FVIII product) received BAY81-8973 15-50 IU/kg at least 1x/week for 50 EDs Total of all reporting groups
Overall Number of Baseline Participants 25 26 43 94
Hide Baseline Analysis Population Description
Safety analysis set (SAF): all subjects who entered Study Part A or Part B and received at least one infusion of study medication.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 25 participants 26 participants 43 participants 94 participants
3.8  (1.3) 8.8  (1.8) 1.1  (0.8) 3.9  (3.4)
Age, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 25 participants 26 participants 43 participants 94 participants
0- <6 years
25
 100.0%
0
   0.0%
43
 100.0%
68
  72.3%
6- 12 years
0
   0.0%
26
 100.0%
0
   0.0%
26
  27.7%
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 25 participants 26 participants 43 participants 94 participants
Female
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Male
25
 100.0%
26
 100.0%
43
 100.0%
94
 100.0%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 25 participants 26 participants 43 participants 94 participants
Hispanic or Latino
1
   4.0%
0
   0.0%
9
  20.9%
10
  10.6%
Not Hispanic or Latino
23
  92.0%
25
  96.2%
34
  79.1%
82
  87.2%
Unknown or Not Reported
1
   4.0%
1
   3.8%
0
   0.0%
2
   2.1%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 25 participants 26 participants 43 participants 94 participants
White
24
  96.0%
24
  92.3%
37
  86.0%
85
  90.4%
Black
1
   4.0%
2
   7.7%
1
   2.3%
4
   4.3%
American Indian or Alaska native
0
   0.0%
0
   0.0%
1
   2.3%
1
   1.1%
White, American Indian or Alaska native
0
   0.0%
0
   0.0%
1
   2.3%
1
   1.1%
Not reported
0
   0.0%
0
   0.0%
3
   7.0%
3
   3.2%
1.Primary Outcome
Title Annualized Number of Total Bleeds Within 48 h
Hide Description 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; Part B: 50 exposure days (approximately 8 months)] was summarized and reported. Total bleeds: sum of spontaneous bleeds, trauma bleeds, untreated bleeds and 'other' bleeds ('other' bleeds were infusions with reason given as 'other').
Time Frame Within 48 hours post infusion
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat (ITT) analysis set: all participants of the SAF who had infusion/bleeding data from the electronic patient diary (EPD).
Arm/Group Title Part A: PTPs 0-<6 Years Part A: PTPs 6-12 Years Part B: PUPs/MTPs 0-<6 Years
Hide Arm/Group Description:
Previously treated patients (PTPs) aged below 6 years received BAY81-8973 25-50 IU/kg at least 2x/week for 6 months and at least 50 exposure days (ED)
Previously treated patients (PTPs) aged 6 to 12 years received BAY81-8973 25-50 IU/kg at least 2x/week for 6 months and at least 50 exposure days (ED)
Previously untreated patients (PUPs) or minimally treated patients (MTPs, patients who had no more than 3 exposure days [EDs] with any FVIII product) received BAY81-8973 15-50 IU/kg at least 1x/week for 50 EDs
Overall Number of Participants Analyzed 25 26 43
Mean (Standard Deviation)
Unit of Measure: Bleeds
2.23  (2.77) 1.86  (3.08) 1.9  (3.3)
2.Primary Outcome
Title Annualized Number of Total Bleeds Within 48 h
Hide Description 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; Part B: 50 exposure days (approximately 8 months)] was summarized and reported. Total bleeds: sum of spontaneous bleeds, trauma bleeds, untreated bleeds and 'other' bleeds ('other' bleeds were infusions with reason given as 'other').
Time Frame Within 48 hours post infusion
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat (ITT) analysis set: all participants of the SAF who had infusion/bleeding data from the electronic patient diary (EPD).
Arm/Group Title Part A: PTPs 0-<6 Years Part A: PTPs 6-12 Years Part B: PUPs/MTPs 0-<6 Years
Hide Arm/Group Description:
Previously treated patients (PTPs) aged below 6 years received BAY81-8973 25-50 IU/kg at least 2x/week for 6 months and at least 50 exposure days (ED)
Previously treated patients (PTPs) aged 6 to 12 years received BAY81-8973 25-50 IU/kg at least 2x/week for 6 months and at least 50 exposure days (ED)
Previously untreated patients (PUPs) or minimally treated patients (MTPs, patients who had no more than 3 exposure days [EDs] with any FVIII product) received BAY81-8973 15-50 IU/kg at least 1x/week for 50 EDs
Overall Number of Participants Analyzed 25 26 43
Median (Inter-Quartile Range)
Unit of Measure: Bleeds
1.88
(0.00 to 3.97)
0.00
(0.00 to 1.96)
0.0
(0.0 to 2.2)
3.Secondary Outcome
Title Annualized Number of Total Bleeds During Prophylaxis Treatment
Hide Description 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, 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; Part B: 50 exposure days (approximately 8 months)
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat (ITT) analysis set: all participants of the SAF who had infusion/bleeding data from the electronic patient diary (EPD).
Arm/Group Title Part A: PTPs 0-<6 Years Part A: PTPs 6-12 Years Part B: PUPs/MTPs 0-<6 Years
Hide Arm/Group Description:
Previously treated patients (PTPs) aged below 6 years received BAY81-8973 25-50 IU/kg at least 2x/week for 6 months and at least 50 exposure days (ED)
Previously treated patients (PTPs) aged 6 to 12 years received BAY81-8973 25-50 IU/kg at least 2x/week for 6 months and at least 50 exposure days (ED)
Previously untreated patients (PUPs) or minimally treated patients (MTPs, patients who had no more than 3 exposure days [EDs] with any FVIII product) received BAY81-8973 15-50 IU/kg at least 1x/week for 50 EDs
Overall Number of Participants Analyzed 25 26 43
Mean (Standard Deviation)
Unit of Measure: Bleeds
4.16  (5.02) 3.37  (5.01) 7.1  (8.6)
4.Secondary Outcome
Title Annualized Number of Total Bleeds During Prophylaxis Treatment
Hide Description 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, 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; Part B: 50 exposure days (approximately 8 months)
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat (ITT) analysis set: all participants of the SAF who had infusion/bleeding data from the electronic patient diary (EPD).
Arm/Group Title Part A: PTPs 0-<6 Years Part A: PTPs 6-12 Years Part B: PUPs/MTPs 0-<6 Years
Hide Arm/Group Description:
Previously treated patients (PTPs) aged below 6 years received BAY81-8973 25-50 IU/kg at least 2x/week for 6 months and at least 50 exposure days (ED)
Previously treated patients (PTPs) aged 6 to 12 years received BAY81-8973 25-50 IU/kg at least 2x/week for 6 months and at least 50 exposure days (ED)
Previously untreated patients (PUPs) or minimally treated patients (MTPs, patients who had no more than 3 exposure days [EDs] with any FVIII product) received BAY81-8973 15-50 IU/kg at least 1x/week for 50 EDs
Overall Number of Participants Analyzed 25 26 43
Median (Inter-Quartile Range)
Unit of Measure: Bleeds
2.03
(0.00 to 6.02)
0.93
(0.00 to 5.77)
4.7
(2.1 to 8.9)
5.Secondary Outcome
Title Hemostatic Control During Major and Minor Surgeries
Hide Description 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; Part B: 50 exposure days (approximately 8 months)
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in SAF who underwent major or minor surgeries during the study
Arm/Group Title Part A: PTPs 0-<6 Years Part A: PTPs 6-12 Years Part B: PUPs/MTPs 0-<6 Years
Hide Arm/Group Description:
Previously treated patients (PTPs) aged below 6 years received BAY81-8973 25-50 IU/kg at least 2x/week for 6 months and at least 50 exposure days (ED)
Previously treated patients (PTPs) aged 6 to 12 years received BAY81-8973 25-50 IU/kg at least 2x/week for 6 months and at least 50 exposure days (ED)
Previously untreated patients (PUPs) or minimally treated patients (MTPs, patients who had no more than 3 exposure days [EDs] with any FVIII product) received BAY81-8973 15-50 IU/kg at least 1x/week for 50 EDs
Overall Number of Participants Analyzed 0 1 6
Overall Number of Units Analyzed
Type of Units Analyzed: Surgeries
 0 1 6
Count of Units
Unit of Measure: Surgeries
Minor surgery Number Analyzed 0 Surgeries 0 Surgeries [1]  5 Surgeries [2] 
Excellent 0 0
3
  60.0%
Good 0 0
1
  20.0%
Moderate 0 0
0
   0.0%
Poor 0 0
0
   0.0%
Not available 0 0
1
  20.0%
Major surgery Number Analyzed 0 Surgeries 1 Surgeries 1 Surgeries [3] 
Excellent 0
0
   0.0%
0
   0.0%
Good 0
1
 100.0%
1
 100.0%
Moderate 0
0
   0.0%
0
   0.0%
Poor 0
0
   0.0%
0
   0.0%
Not available 0
0
   0.0%
0
   0.0%
[1]
0 participants
[2]
5 participants
[3]
1 participants
6.Secondary Outcome
Title Number of Participants With Inhibitor Development
Hide Description Number of participants with confirmed positive FVIII inhibitor titer (≥0.6 Bethesda unit [BU]) during the study was summarized and classified as participants developing low titer inhibitor (i.e. ≥0.6 to ≤ 5.0 BU) and participants developing high titer inhibitor (i.e. > 5.0 BU).
Time Frame Part A: 6 months and at least 50 exposure days; Part B: 50 exposure days (approximately 8 months)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety analysis set (SAF): all participants who entered Study Part A or Part B and received at least one infusion of study medication.
Arm/Group Title Part A: PTPs 0-<6 Years Part A: PTPs 6-12 Years Part B: PUPs/MTPs 0-<6 Years
Hide Arm/Group Description:
Previously treated patients (PTPs) aged below 6 years received BAY81-8973 25-50 IU/kg at least 2x/week for 6 months and at least 50 exposure days (ED)
Previously treated patients (PTPs) aged 6 to 12 years received BAY81-8973 25-50 IU/kg at least 2x/week for 6 months and at least 50 exposure days (ED)
Previously untreated patients (PUPs) or minimally treated patients (MTPs, patients who had no more than 3 exposure days [EDs] with any FVIII product) received BAY81-8973 15-50 IU/kg at least 1x/week for 50 EDs
Overall Number of Participants Analyzed 25 26 43
Measure Type: Count of Participants
Unit of Measure: Participants
Low titer inhibitor
0
   0.0%
0
   0.0%
6
  14.0%
High titer inhibitor
0
   0.0%
0
   0.0%
17
  39.5%
7.Secondary Outcome
Title Factor VIII Recovery Values
Hide Description 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; Part B: 50 exposure days (approximately 8 months)
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in ITT with valid FVIII recovery values
Arm/Group Title Part A: PTPs 0-<6 Years Part A: PTPs 6-12 Years Part B: PUPs/MTPs 0-<6 Years
Hide Arm/Group Description:
Previously treated patients (PTPs) aged below 6 years received BAY81-8973 25-50 IU/kg at least 2x/week for 6 months and at least 50 exposure days (ED)
Previously treated patients (PTPs) aged 6 to 12 years received BAY81-8973 25-50 IU/kg at least 2x/week for 6 months and at least 50 exposure days (ED)
Previously untreated patients (PUPs) or minimally treated patients (MTPs, patients who had no more than 3 exposure days [EDs] with any FVIII product) received BAY81-8973 15-50 IU/kg at least 1x/week for 50 EDs
Overall Number of Participants Analyzed 25 26 32
Mean (Standard Deviation)
Unit of Measure: kilograms/deciliter
1.63  (0.31) 1.72  (0.46) 1.17  (0.82)
8.Secondary Outcome
Title Consumption of Factor VIII in All Infusions
Hide Description 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; Part B: 50 exposure days (approximately 8 months)
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat (ITT) analysis set: all participants of the SAF who had infusion/bleeding data from the electronic patient diary (EPD)
Arm/Group Title Part A: PTPs 0-<6 Years Part A: PTPs 6-12 Years Part B: PUPs/MTPs 0-<6 Years
Hide Arm/Group Description:
Previously treated patients (PTPs) aged below 6 years received BAY81-8973 25-50 IU/kg at least 2x/week for 6 months and at least 50 exposure days (ED)
Previously treated patients (PTPs) aged 6 to 12 years received BAY81-8973 25-50 IU/kg at least 2x/week for 6 months and at least 50 exposure days (ED)
Previously untreated patients (PUPs) or minimally treated patients (MTPs, patients who had no more than 3 exposure days [EDs] with any FVIII product) received BAY81-8973 15-50 IU/kg at least 1x/week for 50 EDs
Overall Number of Participants Analyzed 25 26 43
Mean (Standard Deviation)
Unit of Measure: international units/kilogram/year
5499.1  (1996.2) 4679.1  (1688.7) 2195.8  (1903.6)
9.Secondary Outcome
Title Consumption of FVIII in Infusions for Prophylaxis
Hide Description 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; Part B: 50 exposure days (approximately 8 months)
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in ITT with at least one dose of prophylaxis treatment with study drug
Arm/Group Title Part A: PTPs 0-<6 Years Part A: PTPs 6-12 Years Part B: PUPs/MTPs 0-<6 Years
Hide Arm/Group Description:
Previously treated patients (PTPs) aged below 6 years received BAY81-8973 25-50 IU/kg at least 2x/week for 6 months and at least 50 exposure days (ED)
Previously treated patients (PTPs) aged 6 to 12 years received BAY81-8973 25-50 IU/kg at least 2x/week for 6 months and at least 50 exposure days (ED)
Previously untreated patients (PUPs) or minimally treated patients (MTPs, patients who had no more than 3 exposure days [EDs] with any FVIII product) received BAY81-8973 15-50 IU/kg at least 1x/week for 50 EDs
Overall Number of Participants Analyzed 25 26 42
Mean (Standard Deviation)
Unit of Measure: international units/kilogram/year
5224.8  (1760.2) 4492.7  (1667.6) 1486.6  (963.3)
10.Secondary Outcome
Title Consumption of FVIII in Infusions for the Treatment of Bleeds
Hide Description 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; Part B: 50 exposure days (approximately 8 months)
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in ITT with at least one bleed treated with study drug
Arm/Group Title Part A: PTPs 0-<6 Years Part A: PTPs 6-12 Years Part B: PUPs/MTPs 0-<6 Years
Hide Arm/Group Description:
Previously treated patients (PTPs) aged below 6 years received BAY81-8973 25-50 IU/kg at least 2x/week for 6 months and at least 50 exposure days (ED)
Previously treated patients (PTPs) aged 6 to 12 years received BAY81-8973 25-50 IU/kg at least 2x/week for 6 months and at least 50 exposure days (ED)
Previously untreated patients (PUPs) or minimally treated patients (MTPs, patients who had no more than 3 exposure days [EDs] with any FVIII product) received BAY81-8973 15-50 IU/kg at least 1x/week for 50 EDs
Overall Number of Participants Analyzed 15 11 35
Mean (Standard Deviation)
Unit of Measure: international units/kilogram/year
457.07  (526.87) 391.64  (219.61) 835.4  (1926.4)
11.Secondary Outcome
Title Number of Infusions Per Bleed
Hide Description 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; Part B: 50 exposure days (approximately 8 months)
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in ITT with at least one bleed
Arm/Group Title Part A: PTPs 0-<6 Years Part A: PTPs 6-12 Years Part B: PUPs/MTPs 0-<6 Years
Hide Arm/Group Description:
Previously treated patients (PTPs) aged below 6 years received BAY81-8973 25-50 IU/kg at least 2x/week for 6 months and at least 50 exposure days (ED)
Previously treated patients (PTPs) aged 6 to 12 years received BAY81-8973 25-50 IU/kg at least 2x/week for 6 months and at least 50 exposure days (ED)
Previously untreated patients (PUPs) or minimally treated patients (MTPs, patients who had no more than 3 exposure days [EDs] with any FVIII product) received BAY81-8973 15-50 IU/kg at least 1x/week for 50 EDs
Overall Number of Participants Analyzed 15 13 37
Mean (Standard Deviation)
Unit of Measure: Infusions
1.3  (1.8) 1.4  (1.7) 1.7  (8.7)
12.Secondary Outcome
Title Response to Treatment of Bleeds
Hide Description 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; Part B: 50 exposure days (approximately 8 months)
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in ITT with at least one bleed
Arm/Group Title Part A: PTPs 0-<6 Years Part A: PTPs 6-12 Years Part B: PUPs/MTPs 0-<6 Years
Hide Arm/Group Description:
Previously treated patients (PTPs) aged below 6 years received BAY81-8973 25-50 IU/kg at least 2x/week for 6 months and at least 50 exposure days (ED)
Previously treated patients (PTPs) aged 6 to 12 years received BAY81-8973 25-50 IU/kg at least 2x/week for 6 months and at least 50 exposure days (ED)
Previously untreated patients (PUPs) or minimally treated patients (MTPs, patients who had no more than 3 exposure days [EDs] with any FVIII product) received BAY81-8973 15-50 IU/kg at least 1x/week for 50 EDs
Overall Number of Participants Analyzed 15 13 37
Overall Number of Units Analyzed
Type of Units Analyzed: Bleeds assessed for the response
 44 37 105
Count of Units
Unit of Measure: Bleeds assessed for the response
Excellent
20
  45.5%
12
  32.4%
27
  25.7%
Good
23
  52.3%
18
  48.6%
56
  53.3%
Moderate
0
   0.0%
7
  18.9%
16
  15.2%
Poor
1
   2.3%
0
   0.0%
6
   5.7%
13.Secondary Outcome
Title Half-life (t1/2) of BAY81-8973 in Plasma
Hide Description Half-life (t1/2) of BAY81-8973 in plasma was measured. Geometric mean and percentage geometric coefficient of variation (%CV) were reported. Occurrence of "±" in relation with coefficient of variation is auto-generated by the database.
Time Frame Pre-infusion and until 24 hours post infusion
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in PK analysis set (PKS) - A with evaluable data for this endpoint (PKS - A: all participants who entered Study Part A and received at least one infusion of study medication with evaluable pharmacokinetic data)
Arm/Group Title Part A: PTPs 0-<6 Years Part A: PTPs 6-12 Years
Hide Arm/Group Description:
Previously treated patients (PTPs) aged below 6 years received BAY81-8973 25-50 IU/kg at least 2x/week for 6 months and at least 50 exposure days (ED)
Previously treated patients (PTPs) aged 6 to 12 years received BAY81-8973 25-50 IU/kg at least 2x/week for 6 months and at least 50 exposure days (ED)
Overall Number of Participants Analyzed 2 9
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: Hours
13.2
(39.7% to N/A)
12.1
(16.3% to N/A)
Time Frame Part A: from the first BAY81-8973 infusion and up to 3 days after the last infusion (approximately 6 months); Part B: from the first BAY81-8973 infusion and up to 7 days after the last infusion (approximately 8 months)
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Part A: PTPs 0-<6 Years Part A: PTPs 6-12 Years Part B: PUPs/MTPs 0-<6 Years
Hide Arm/Group Description Previously treated patients (PTPs) aged below 6 years received BAY81-8973 25-50 IU/kg at least 2x/week for 6 months and at least 50 exposure days (ED). Previously treated patients (PTPs) aged 6 to 12 years received BAY81-8973 25-50 IU/kg at least 2x/week for 6 months and at least 50 exposure days (ED). Previously untreated patients (PUPs) or minimally treated patients (MTPs, patients who had no more than 3 exposure days [EDs] with any FVIII product) received BAY81-8973 15-50 IU/kg at least 1x/week for 50 EDs.
All-Cause Mortality
Part A: PTPs 0-<6 Years Part A: PTPs 6-12 Years Part B: PUPs/MTPs 0-<6 Years
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/25 (0.00%)      0/26 (0.00%)      0/43 (0.00%)    
Hide Serious Adverse Events
Part A: PTPs 0-<6 Years Part A: PTPs 6-12 Years Part B: PUPs/MTPs 0-<6 Years
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   0/25 (0.00%)      5/26 (19.23%)      26/43 (60.47%)    
Blood and lymphatic system disorders       
Blood loss anaemia * 1  0/25 (0.00%)  0 1/26 (3.85%)  1 0/43 (0.00%)  0
Factor VIII inhibition * 1  0/25 (0.00%)  0 0/26 (0.00%)  0 1/43 (2.33%)  1
Gastrointestinal disorders       
Vomiting * 1  0/25 (0.00%)  0 0/26 (0.00%)  0 1/43 (2.33%)  1
General disorders       
Catheter site haematoma * 1  0/25 (0.00%)  0 0/26 (0.00%)  0 1/43 (2.33%)  1
Decreased activity * 1  0/25 (0.00%)  0 0/26 (0.00%)  0 1/43 (2.33%)  1
Extravasation * 1  0/25 (0.00%)  0 0/26 (0.00%)  0 1/43 (2.33%)  1
Facial pain * 1  0/25 (0.00%)  0 0/26 (0.00%)  0 1/43 (2.33%)  1
Pyrexia * 1  0/25 (0.00%)  0 0/26 (0.00%)  0 1/43 (2.33%)  1
Infections and infestations       
Bacterial infection * 1  0/25 (0.00%)  0 1/26 (3.85%)  1 0/43 (0.00%)  0
Escherichia urinary tract infection * 1  0/25 (0.00%)  0 0/26 (0.00%)  0 1/43 (2.33%)  1
Gastroenteritis * 1  0/25 (0.00%)  0 1/26 (3.85%)  1 0/43 (0.00%)  0
Gastroenteritis staphylococcal * 1  0/25 (0.00%)  0 0/26 (0.00%)  0 1/43 (2.33%)  1
Gastroenteritis viral * 1  0/25 (0.00%)  0 0/26 (0.00%)  0 1/43 (2.33%)  1
Tooth abscess * 1  0/25 (0.00%)  0 1/26 (3.85%)  1 0/43 (0.00%)  0
Viral infection * 1  0/25 (0.00%)  0 1/26 (3.85%)  1 0/43 (0.00%)  0
Injury, poisoning and procedural complications       
Craniocerebral injury * 1  0/25 (0.00%)  0 0/26 (0.00%)  0 1/43 (2.33%)  1
Mouth injury * 1  0/25 (0.00%)  0 0/26 (0.00%)  0 1/43 (2.33%)  1
Investigations       
Anti factor VIII antibody positive * 1  0/25 (0.00%)  0 0/26 (0.00%)  0 22/43 (51.16%)  24
Musculoskeletal and connective tissue disorders       
Haemarthrosis * 1  0/25 (0.00%)  0 0/26 (0.00%)  0 3/43 (6.98%)  5
Haematoma muscle * 1  0/25 (0.00%)  0 0/26 (0.00%)  0 1/43 (2.33%)  1
Soft tissue haemorrhage * 1  0/25 (0.00%)  0 0/26 (0.00%)  0 2/43 (4.65%)  2
Nervous system disorders       
Cerebral haemorrhage * 1  0/25 (0.00%)  0 0/26 (0.00%)  0 1/43 (2.33%)  1
Encephalomalacia * 1  0/25 (0.00%)  0 1/26 (3.85%)  1 0/43 (0.00%)  0
Surgical and medical procedures       
Central venous catheterisation * 1  0/25 (0.00%)  0 0/26 (0.00%)  0 1/43 (2.33%)  1
Dental cleaning * 1  0/25 (0.00%)  0 1/26 (3.85%)  1 0/43 (0.00%)  0
Vascular disorders       
Haematoma * 1  0/25 (0.00%)  0 0/26 (0.00%)  0 1/43 (2.33%)  1
1
Term from vocabulary, MedDRA 22.0
*
Indicates events were collected by non-systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 3%
Part A: PTPs 0-<6 Years Part A: PTPs 6-12 Years Part B: PUPs/MTPs 0-<6 Years
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   16/25 (64.00%)      19/26 (73.08%)      27/43 (62.79%)    
Blood and lymphatic system disorders       
Anaemia * 1  0/25 (0.00%)  0 1/26 (3.85%)  3 3/43 (6.98%)  3
Blood loss anaemia * 1  0/25 (0.00%)  0 0/26 (0.00%)  0 2/43 (4.65%)  2
Ear and labyrinth disorders       
Ear pain * 1  0/25 (0.00%)  0 1/26 (3.85%)  1 1/43 (2.33%)  1
Eye disorders       
Conjunctivitis allergic * 1  0/25 (0.00%)  0 1/26 (3.85%)  1 0/43 (0.00%)  0
Photophobia * 1  0/25 (0.00%)  0 1/26 (3.85%)  1 0/43 (0.00%)  0
Strabismus * 1  0/25 (0.00%)  0 1/26 (3.85%)  3 0/43 (0.00%)  0
Gastrointestinal disorders       
Abdominal pain * 1  0/25 (0.00%)  0 1/26 (3.85%)  1 0/43 (0.00%)  0
Abdominal pain upper * 1  1/25 (4.00%)  1 0/26 (0.00%)  0 0/43 (0.00%)  0
Constipation * 1  0/25 (0.00%)  0 1/26 (3.85%)  1 1/43 (2.33%)  1
Dental caries * 1  0/25 (0.00%)  0 1/26 (3.85%)  1 0/43 (0.00%)  0
Diarrhoea * 1  2/25 (8.00%)  3 1/26 (3.85%)  2 6/43 (13.95%)  8
Functional gastrointestinal disorder * 1  0/25 (0.00%)  0 1/26 (3.85%)  2 1/43 (2.33%)  1
Glossodynia * 1  1/25 (4.00%)  1 0/26 (0.00%)  0 0/43 (0.00%)  0
Haematochezia * 1  0/25 (0.00%)  0 1/26 (3.85%)  1 0/43 (0.00%)  0
Stomatitis * 1  0/25 (0.00%)  0 1/26 (3.85%)  1 0/43 (0.00%)  0
Teething * 1  0/25 (0.00%)  0 0/26 (0.00%)  0 2/43 (4.65%)  3
Toothache * 1  0/25 (0.00%)  0 1/26 (3.85%)  1 0/43 (0.00%)  0
Vomiting * 1  1/25 (4.00%)  1 1/26 (3.85%)  1 4/43 (9.30%)  8
General disorders       
Fatigue * 1  0/25 (0.00%)  0 1/26 (3.85%)  1 0/43 (0.00%)  0
Hyperthermia * 1  0/25 (0.00%)  0 1/26 (3.85%)  1 0/43 (0.00%)  0
Infusion site swelling * 1  0/25 (0.00%)  0 1/26 (3.85%)  1 0/43 (0.00%)  0
Injection site bruising * 1  0/25 (0.00%)  0 1/26 (3.85%)  1 0/43 (0.00%)  0
Peripheral swelling * 1  0/25 (0.00%)  0 1/26 (3.85%)  1 0/43 (0.00%)  0
Pyrexia * 1  5/25 (20.00%)  10 2/26 (7.69%)  2 12/43 (27.91%)  19
Immune system disorders       
Hypersensitivity * 1  0/25 (0.00%)  0 1/26 (3.85%)  1 0/43 (0.00%)  0
Infections and infestations       
Bronchiolitis * 1  0/25 (0.00%)  0 0/26 (0.00%)  0 2/43 (4.65%)  4
Bronchitis * 1  1/25 (4.00%)  1 0/26 (0.00%)  0 0/43 (0.00%)  0
Conjunctivitis * 1  2/25 (8.00%)  2 0/26 (0.00%)  0 3/43 (6.98%)  3
Cystitis * 1  1/25 (4.00%)  1 0/26 (0.00%)  0 1/43 (2.33%)  1
Ear infection * 1  1/25 (4.00%)  1 0/26 (0.00%)  0 2/43 (4.65%)  2
Gastroenteritis * 1  0/25 (0.00%)  0 1/26 (3.85%)  1 1/43 (2.33%)  1
Gastroenteritis viral * 1  0/25 (0.00%)  0 0/26 (0.00%)  0 3/43 (6.98%)  3
Gastrointestinal viral infection * 1  0/25 (0.00%)  0 1/26 (3.85%)  1 0/43 (0.00%)  0
Hand-foot-and-mouth disease * 1  1/25 (4.00%)  1 0/26 (0.00%)  0 1/43 (2.33%)  1
Hookworm infection * 1  1/25 (4.00%)  1 0/26 (0.00%)  0 0/43 (0.00%)  0
Influenza * 1  0/25 (0.00%)  0 1/26 (3.85%)  1 4/43 (9.30%)  4
Nasopharyngitis * 1  2/25 (8.00%)  3 2/26 (7.69%)  2 6/43 (13.95%)  16
Oral herpes * 1  0/25 (0.00%)  0 1/26 (3.85%)  1 1/43 (2.33%)  1
Otitis media * 1  1/25 (4.00%)  1 0/26 (0.00%)  0 1/43 (2.33%)  3
Otitis media acute * 1  0/25 (0.00%)  0 1/26 (3.85%)  1 1/43 (2.33%)  1
Pneumonia * 1  1/25 (4.00%)  1 0/26 (0.00%)  0 1/43 (2.33%)  1
Rhinitis * 1  1/25 (4.00%)  1 1/26 (3.85%)  1 3/43 (6.98%)  4
Tonsillitis * 1  1/25 (4.00%)  2 1/26 (3.85%)  1 1/43 (2.33%)  1
Tooth abscess * 1  1/25 (4.00%)  1 1/26 (3.85%)  2 0/43 (0.00%)  0
Tracheitis * 1  0/25 (0.00%)  0 1/26 (3.85%)  1 1/43 (2.33%)  1
Upper respiratory tract infection * 1  1/25 (4.00%)  1 1/26 (3.85%)  2 3/43 (6.98%)  3
Varicella * 1  0/25 (0.00%)  0 1/26 (3.85%)  1 1/43 (2.33%)  1
Vascular device infection * 1  1/25 (4.00%)  1 0/26 (0.00%)  0 0/43 (0.00%)  0
Viral infection * 1  3/25 (12.00%)  3 2/26 (7.69%)  2 1/43 (2.33%)  1
Viral upper respiratory tract infection * 1  0/25 (0.00%)  0 1/26 (3.85%)  1 0/43 (0.00%)  0
Injury, poisoning and procedural complications       
Contusion * 1  2/25 (8.00%)  3 0/26 (0.00%)  0 1/43 (2.33%)  1
Face injury * 1  0/25 (0.00%)  0 0/26 (0.00%)  0 2/43 (4.65%)  2
Fall * 1  0/25 (0.00%)  0 0/26 (0.00%)  0 2/43 (4.65%)  2
Genital contusion * 1  1/25 (4.00%)  1 0/26 (0.00%)  0 0/43 (0.00%)  0
Head injury * 1  1/25 (4.00%)  1 0/26 (0.00%)  0 1/43 (2.33%)  1
Limb injury * 1  0/25 (0.00%)  0 1/26 (3.85%)  1 0/43 (0.00%)  0
Lip injury * 1  1/25 (4.00%)  1 0/26 (0.00%)  0 0/43 (0.00%)  0
Road traffic accident * 1  0/25 (0.00%)  0 1/26 (3.85%)  1 0/43 (0.00%)  0
Skin abrasion * 1  0/25 (0.00%)  0 1/26 (3.85%)  1 0/43 (0.00%)  0
Skin injury * 1  1/25 (4.00%)  1 0/26 (0.00%)  0 0/43 (0.00%)  0
Skin laceration * 1  1/25 (4.00%)  1 0/26 (0.00%)  0 1/43 (2.33%)  1
Subcutaneous haematoma * 1  1/25 (4.00%)  1 0/26 (0.00%)  0 0/43 (0.00%)  0
Tongue injury * 1  1/25 (4.00%)  1 0/26 (0.00%)  0 0/43 (0.00%)  0
Investigations       
Haemoglobin decreased * 1  1/25 (4.00%)  1 0/26 (0.00%)  0 0/43 (0.00%)  0
neutrophil count increased * 1  0/25 (0.00%)  0 1/26 (3.85%)  1 0/43 (0.00%)  0
White blood cell count increased * 1  0/25 (0.00%)  0 1/26 (3.85%)  1 0/43 (0.00%)  0
Metabolism and nutrition disorders       
Dehydration * 1  0/25 (0.00%)  0 1/26 (3.85%)  1 0/43 (0.00%)  0
Musculoskeletal and connective tissue disorders       
Arthralgia * 1  0/25 (0.00%)  0 1/26 (3.85%)  1 0/43 (0.00%)  0
Joint swelling * 1  0/25 (0.00%)  0 1/26 (3.85%)  1 0/43 (0.00%)  0
Musculoskeletal pain * 1  0/25 (0.00%)  0 1/26 (3.85%)  1 0/43 (0.00%)  0
Pain in extremity * 1  0/25 (0.00%)  0 1/26 (3.85%)  1 1/43 (2.33%)  1
Synovitis * 1  1/25 (4.00%)  1 0/26 (0.00%)  0 0/43 (0.00%)  0
Nervous system disorders       
Headache * 1  2/25 (8.00%)  3 4/26 (15.38%)  4 0/43 (0.00%)  0
Reproductive system and breast disorders       
Perineal pain * 1  0/25 (0.00%)  0 1/26 (3.85%)  1 0/43 (0.00%)  0
Respiratory, thoracic and mediastinal disorders       
Cough * 1  2/25 (8.00%)  4 4/26 (15.38%)  4 1/43 (2.33%)  1
Oropharyngeal pain * 1  0/25 (0.00%)  0 2/26 (7.69%)  3 0/43 (0.00%)  0
Productive cough * 1  2/25 (8.00%)  3 0/26 (0.00%)  0 0/43 (0.00%)  0
Rhinitis allergic * 1  1/25 (4.00%)  1 0/26 (0.00%)  0 0/43 (0.00%)  0
Tonsillar hypertrophy * 1  1/25 (4.00%)  1 0/26 (0.00%)  0 0/43 (0.00%)  0
Increased upper airway secretion * 1  1/25 (4.00%)  1 0/26 (0.00%)  0 0/43 (0.00%)  0
Skin and subcutaneous tissue disorders       
Pruritus * 1  3/25 (12.00%)  3 0/26 (0.00%)  0 0/43 (0.00%)  0
Rash * 1  0/25 (0.00%)  0 2/26 (7.69%)  3 3/43 (6.98%)  3
Surgical and medical procedures       
Tooth extraction * 1  0/25 (0.00%)  0 2/26 (7.69%)  3 0/43 (0.00%)  0
1
Term from vocabulary, MedDRA 22.0
*
Indicates events were collected by non-systematic assessment
Due to the small number of subject per reporting group, all presented summary measures (e.g. mean and proportion) have to be evaluated with caution. If displayed standard deviation should be taken into account.
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The sponsor can review results communications prior to public release and can embargo communications regarding trial results within 60 days. The sponsor can require changes to the communication for any patentable subject matter or termed confidential information. The PI cannot publish the results prior the first multicenter publication. If there is no multicenter publication within 18 months after the trial completion the PI has the right to publish the results from the PI site
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Therapeutic Area Head
Organization: Bayer
Phone: 1-888-8422937
EMail: clinical-trials-contact@bayer.com
Publications of Results:
Oldenburg J, Windyga J, Hampton K, Lalezari S, Tseneklidou-Stoeter D, Beckmann H, Maas Enriquez M. Safety and efficacy of BAY 81-8973 for surgery in previously treated patients with haemophilia A: results of the LEOPOLD clinical trial programme. Haemophilia. 2016 May;22(3):349-53. doi: 10.1111/hae.12839. Epub 2016 Mar 1.
Ljung R, Kenet G, Mancuso ME, Kaleva V, Rusen L, Tseneklidou-Stoeter D, Michaels LA, Shah A, Hong W, Maas Enriquez M; investigators of the LEOPOLD Kids Trial. BAY 81-8973 safety and efficacy for prophylaxis and treatment of bleeds in previously treated children with severe haemophilia A: results of the LEOPOLD Kids Trial. Haemophilia. 2016 May;22(3):354-60. doi: 10.1111/hae.12866. Epub 2015 Dec 9.
Keating GM. BAY 81-8973 (Octocog Alfa; Kovaltry(®)): A Review in Haemophilia A. BioDrugs. 2016 Oct;30(5):453-459. Review.
Shah A, Delesen H, Garger S, Lalezari S. Pharmacokinetic properties of BAY 81-8973, a full-length recombinant factor VIII. Haemophilia. 2015 Nov;21(6):766-71. doi: 10.1111/hae.12691. Epub 2015 May 8.
Maas Enriquez M, Thrift J, Garger S, Katterle Y. BAY 81-8973, a full-length recombinant factor VIII: Human heat shock protein 70 improves the manufacturing process without affecting clinical safety. Protein Expr Purif. 2016 Nov;127:111-115. doi: 10.1016/j.pep.2016.07.009. Epub 2016 Jul 18. Review.
Garmann D, McLeay S, Shah A, Vis P, Maas Enriquez M, Ploeger BA. Population pharmacokinetic characterization of BAY 81-8973, a full-length recombinant factor VIII: lessons learned - importance of including samples with factor VIII levels below the quantitation limit. Haemophilia. 2017 Jul;23(4):528-537. doi: 10.1111/hae.13192. Epub 2017 Feb 20.
Mahlangu JN, Ahuja SP, Windyga J, Church N, Shah A, Schwartz L. BAY 81-8973, a full-length recombinant factor VIII for the treatment of hemophilia A: product review. Ther Adv Hematol. 2018 Jul;9(7):191-205. doi: 10.1177/2040620718777903. Epub 2018 Jun 12. Review.
Layout table for additonal information
Responsible Party: Bayer
ClinicalTrials.gov Identifier: NCT01311648    
Other Study ID Numbers: 13400
2010-021781-29 ( EudraCT Number )
First Submitted: February 18, 2011
First Posted: March 9, 2011
Results First Submitted: September 1, 2020
Results First Posted: November 3, 2020
Last Update Posted: November 23, 2020