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Trial to Evaluate the Efficacy and Safety of a New Full Length Recombinant Human FVIII for Hemophilia A (Leopold I)

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT01029340
First Posted: December 9, 2009
Last Update Posted: November 28, 2016
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.
Information provided by (Responsible Party):
Bayer
Results First Submitted: May 27, 2013  
Study Type: Interventional
Study Design: Allocation: Randomized;   Intervention Model: Crossover Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions: Blood Coagulation Disorders
Hemophilia A
Interventions: Biological: Recombinant Factor VIII (BAY81-8973)
Biological: Recombinant Factor VIII (Kogenate FS, BAY14-2222)

  Participant Flow
  Hide Participant Flow

Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
Participants were recruited from specialized hemophilia treatment centers.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
14 participants were enrolled in each of Arms 1 and 2 in Part A. Of these, 11 participants continued into each of Arms 3 and 4 in Part B. Arm 3 enrolled 20 and Arm 4 enrolled 21 additional participants who had not participated in Part A. Arm 5 enrolled 5 participants specifically for surgery in Part C who had not participated in Parts A or B.

Reporting Groups
  Description
Arm 1: Recombinant Factor VIII (BAY81-8973) Then Kogenate FS Part A - Arm 1: Participants first received one single intravenous (IV) injection of BAY81-8973 50 IU/kg, then 1 single IV injection of Kogenate FS (BAY14-2222) 50 IU/kg with a wash-out period of at least 2-3 days in between
Arm 2: Kogenate FS Then Recombinant Factor VIII (BAY81-8973) Part A - Arm 2: Participants first received one single intravenous (IV) injection of Kogenate FS (BAY14-2222) 50 IU/kg, then 1 single IV injection of BAY81-8973 50 IU/kg with a wash-out period of at least 2-3 days in between
Arm 3: Recombinant Factor VIII by CS/EP Then by CS/ADJ Part B - Arm 3: Participants received IV injection of BAY81-8973 at 20-50 IU/kg 2-3 times per week with BAY81-8973 measured by Chromogenic Substrate Assay Potency Per European Pharmacopeia (CS/EP) for 6 months and then crossed over to study drug measured by Chromogenic Substrate Assay/Adjusted (CS/ADJ) to Label Potency for 6 months
Arm 4: Recombinant Factor VIII by CS/ADJ Then by CS/EP Part B - Arm 4:. Participants received IV injection of BAY81-8973 at 20-50 IU/kg 2-3 times per week with BAY81-8973 measured by Chromogenic Substrate Assay/Adjusted (CS/ADJ) to Label Potency for 6 months and then crossed over to study drug measured by Chromogenic Substrate Assay Per European Pharmacopeia (CS/EP) for 6 months
Arm 5: Recombinant Factor VIII by CS/EP Part C - Arm 5: Participants received a loading dose of approximately 50 IU/kg of BAY81-8973 before the first surgical incision followed by further treatment with BAY81-8973 according to surgical requirements for up to 3 weeks
Arm 6: Recombinant Factor VIII (BAY81-8973) Part B + Extension Participants received IV injections of BAY81-8973 at 20-50 IU/kg 2-3 times per week with BAY81-8973 measured by Chromogenic Substrate Assay Potency Per European Pharmacopeia (CS/EP) for 6 months and CS/ADJ for 6 months sequence according to randomization and up to 12 months (CS/EP) during extension

Participant Flow for 7 periods

Period 1:   Part A Treatment Period
    Arm 1: Recombinant Factor VIII (BAY81-8973) Then Kogenate FS   Arm 2: Kogenate FS Then Recombinant Factor VIII (BAY81-8973)   Arm 3: Recombinant Factor VIII by CS/EP Then by CS/ADJ   Arm 4: Recombinant Factor VIII by CS/ADJ Then by CS/EP   Arm 5: Recombinant Factor VIII by CS/EP   Arm 6: Recombinant Factor VIII (BAY81-8973) Part B + Extension
STARTED   14   14   0   0   0   0 
Participants Received Treatment   14   14   0   0   0   0 
Safety Population   13 [1]   14   0   0   0   0 
COMPLETED   14   14   0   0   0   0 
NOT COMPLETED   0   0   0   0   0   0 
[1] One excluded because receiving Kogenate FS twice.

Period 2:   Part A Follow up Period
    Arm 1: Recombinant Factor VIII (BAY81-8973) Then Kogenate FS   Arm 2: Kogenate FS Then Recombinant Factor VIII (BAY81-8973)   Arm 3: Recombinant Factor VIII by CS/EP Then by CS/ADJ   Arm 4: Recombinant Factor VIII by CS/ADJ Then by CS/EP   Arm 5: Recombinant Factor VIII by CS/EP   Arm 6: Recombinant Factor VIII (BAY81-8973) Part B + Extension
STARTED   14   14   0   0   0   0 
COMPLETED   14   14   0   0   0   0 
NOT COMPLETED   0   0   0   0   0   0 

Period 3:   Part B Treatment Period
    Arm 1: Recombinant Factor VIII (BAY81-8973) Then Kogenate FS   Arm 2: Kogenate FS Then Recombinant Factor VIII (BAY81-8973)   Arm 3: Recombinant Factor VIII by CS/EP Then by CS/ADJ   Arm 4: Recombinant Factor VIII by CS/ADJ Then by CS/EP   Arm 5: Recombinant Factor VIII by CS/EP   Arm 6: Recombinant Factor VIII (BAY81-8973) Part B + Extension
STARTED   0   0   31 [1]   32 [2]   0   0 
Participants Received Treatment   0   0   30   32   0   0 
COMPLETED   0   0   29   32   0   0 
NOT COMPLETED   0   0   2   0   0   0 
Withdrawal by Subject                0                0                1                0                0                0 
Protocol Violation                0                0                1                0                0                0 
[1] Enrolled 4 participants from Arm 1 and 7 participants from Arm 2
[2] Enrolled 7 participants from Arm 1 and 4 participants from Arm 2

Period 4:   Part B Follow up Period
    Arm 1: Recombinant Factor VIII (BAY81-8973) Then Kogenate FS   Arm 2: Kogenate FS Then Recombinant Factor VIII (BAY81-8973)   Arm 3: Recombinant Factor VIII by CS/EP Then by CS/ADJ   Arm 4: Recombinant Factor VIII by CS/ADJ Then by CS/EP   Arm 5: Recombinant Factor VIII by CS/EP   Arm 6: Recombinant Factor VIII (BAY81-8973) Part B + Extension
STARTED   0   0   29   32   0   0 
COMPLETED   0   0   29   32   0   0 
NOT COMPLETED   0   0   0   0   0   0 

Period 5:   Extension Period
    Arm 1: Recombinant Factor VIII (BAY81-8973) Then Kogenate FS   Arm 2: Kogenate FS Then Recombinant Factor VIII (BAY81-8973)   Arm 3: Recombinant Factor VIII by CS/EP Then by CS/ADJ   Arm 4: Recombinant Factor VIII by CS/ADJ Then by CS/EP   Arm 5: Recombinant Factor VIII by CS/EP   Arm 6: Recombinant Factor VIII (BAY81-8973) Part B + Extension
STARTED   0   0   0   0   0   55 
COMPLETED   0   0   0   0   0   43 
NOT COMPLETED   0   0   0   0   0   12 
Adverse Event                0                0                0                0                0                1 
starting another study                0                0                0                0                0                8 
non-compliance                0                0                0                0                0                1 
Withdrawal by Subject                0                0                0                0                0                1 
Physician Decision                0                0                0                0                0                1 

Period 6:   Part C Treatment Period
    Arm 1: Recombinant Factor VIII (BAY81-8973) Then Kogenate FS   Arm 2: Kogenate FS Then Recombinant Factor VIII (BAY81-8973)   Arm 3: Recombinant Factor VIII by CS/EP Then by CS/ADJ   Arm 4: Recombinant Factor VIII by CS/ADJ Then by CS/EP   Arm 5: Recombinant Factor VIII by CS/EP   Arm 6: Recombinant Factor VIII (BAY81-8973) Part B + Extension
STARTED   0   0   0   0   5   0 
Participants Received Treatment   0   0   0   0   5   0 
COMPLETED   0   0   0   0   5   0 
NOT COMPLETED   0   0   0   0   0   0 

Period 7:   Part C Follow up Period
    Arm 1: Recombinant Factor VIII (BAY81-8973) Then Kogenate FS   Arm 2: Kogenate FS Then Recombinant Factor VIII (BAY81-8973)   Arm 3: Recombinant Factor VIII by CS/EP Then by CS/ADJ   Arm 4: Recombinant Factor VIII by CS/ADJ Then by CS/EP   Arm 5: Recombinant Factor VIII by CS/EP   Arm 6: Recombinant Factor VIII (BAY81-8973) Part B + Extension
STARTED   0   0   0   0   5   0 
COMPLETED   0   0   0   0   5   0 
NOT COMPLETED   0   0   0   0   0   0 



  Baseline Characteristics
  Hide Baseline Characteristics

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
Arm 1: Recombinant Factor VIII (BAY81-8973) Then Kogenate FS Part A - Arm 1: Participants first received one single intravenous (IV) injection of BAY81-8973 50 IU/kg, then 1 single IV injection of Kogenate FS (BAY14-2222) 50 IU/kg with a wash-out period of at least 2-3 days in between
Arm 2: Kogenate FS Then Recombinant Factor VIII (BAY81-8973) Part A - Arm 2: Participants first received one single intravenous (IV) injection of Kogenate FS (BAY14-2222) 50 IU/kg, then 1 single IV injection of BAY81-8973 50 IU/kg with a wash-out period of at least 2-3 days in between
Arm 3: Recombinant Factor VIII by CS/EP Then by CS/ADJ Part B - Arm 3: Participants received IV injection of BAY81-8973 at 20-50 IU/kg 2-3 times per week with BAY81-8973 measured by Chromogenic Substrate Assay Potency Per European Pharmacopeia for 6 months and then crossed over to study drug measured by Chromogenic Substrate Assay/Adjusted to Label Potency for 6 months
Arm 4: Recombinant Factor VIII by CS/ADJ Then by CS/EP Part B - Arm 4:. Participants received IV injection of BAY81-8973 at 20-50 IU/kg 2-3 times per week with BAY81-8973 measured by Chromogenic Substrate Assay/Adjusted to Label Potency for 6 months and then crossed over to study drug measured by Chromogenic Substrate Assay Per European Pharmacopeia for 6 months
Arm 5: Recombinant Factor VIII (BAY81-8973) by CS/EP - Part C Participants received a loading dose of approximately 50 IU/kg of BAY81-8973 before the first surgical incision, followed by further treatment with BAY81-8973 according to surgical requirements for up to 3 weeks
Total Total of all reporting groups

Baseline Measures
   Arm 1: Recombinant Factor VIII (BAY81-8973) Then Kogenate FS   Arm 2: Kogenate FS Then Recombinant Factor VIII (BAY81-8973)   Arm 3: Recombinant Factor VIII by CS/EP Then by CS/ADJ   Arm 4: Recombinant Factor VIII by CS/ADJ Then by CS/EP   Arm 5: Recombinant Factor VIII (BAY81-8973) by CS/EP - Part C   Total 
Overall Participants Analyzed 
[Units: Participants]
 14   14   20   21   5   74 
Age, Customized [1] [2] [3] 
[Units: Participants]
           
Part A < 18 years   1   4   NA [2]   NA [2]   NA [2]   NA [3] 
Part A =/> 18 years   12   9   NA [2]   NA [2]   NA [2]   NA [3] 
Part B < 18 years   NA [2]   NA [2]   5   5   NA [2]   NA [3] 
Part B =/> 18 years   NA [2]   NA [2]   25   27   NA [2]   NA [3] 
Part C < 18 years   NA [2]   NA [2]   NA [2]   NA [2]   0   NA [3] 
Part C =/> 18 years   NA [2]   NA [2]   NA [2]   NA [2]   5   NA [3] 
[1] Part A based on pharmacokinetic (PK) analysis set; Parts B and C based on safety analysis set
[2] Data is not available because participants did not participate in this phase.
[3] Total not calculated because data are not available (NA) in one or more arms.
Gender, Customized [1] [2] [3] 
[Units: Participants]
           
Part A - Female   0   0   NA [2]   NA [2]   NA [2]   NA [3] 
Part A - Male   13   13   NA [2]   NA [2]   NA [2]   NA [3] 
Part B - Female   NA [2]   NA [2]   0   0   NA [2]   NA [3] 
Part B - Male   NA [2]   NA [2]   30   32   NA [2]   NA [3] 
Part C - Female   NA [2]   NA [2]   NA [2]   NA [2]   0   NA [3] 
Part C - Male   NA [2]   NA [2]   NA [2]   NA [2]   5   NA [3] 
[1] Part A based on PK analysis set; Parts B and C based on safety analysis set
[2] Data is not available because participants did not participate in this phase.
[3] Total not calculated because data are not available (NA) in one or more arms.
Most recent treatment before enrolment in the study [1] [2] [3] 
[Units: Participants]
           
On-demand   4   3   4   8   NA [2]   NA [3] 
Prophylaxis   10   11   26   24   NA [2]   NA [3] 
[1] Parts A, B and C all based on safety analysis set
[2] Data is not available because participants did not participate in this phase.
[3] Total not calculated because data are not available (NA) in one or more arms.


  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Part A - Area Under the Drug Concentration-time Curve (AUC)   [ Time Frame: Samples taken at pre-injection, and at 0.25, 0.5, 1, 3, 6, 8, 24, 30 and 48 hours post injection. AUC calculated from time of injection to infinity. ]

2.  Primary:   Part A - Half-life (t 1/2)   [ Time Frame: Samples taken at pre-injection, and at 0.25, 0.5, 1, 3, 6, 8, 24, 30 and 48 hours post injection. ]

3.  Primary:   Part B - Annualized Number of Total Bleeds   [ Time Frame: 12 months after randomization ]

4.  Secondary:   Part B - The in Vivo Recovery Values of Human Factor VIII (FVIII)   [ Time Frame: 15-30 minutes after the injection ]

5.  Secondary:   Part B - Annualized Number of Bleeds in Each 6-month Potency Assignment Period   [ Time Frame: 6 months on each potency ]

6.  Secondary:   Part B - Control of Bleeding as Measured by the Number of Injections Required to Treat a Bleed   [ Time Frame: 6 months on each potency ]

7.  Secondary:   Part B - Changes From Baseline at 12 Months in Quality of Life (QoL) as Measured by Transformed Total Score of Haemo-QoL Questionnaire   [ Time Frame: Baseline and 12 months ]

8.  Secondary:   Part B - Changes From Baseline at 12 Months in Utility Index as Measured by EQ–5D Questionaire   [ Time Frame: Baseline and 12 months ]

9.  Secondary:   Part A - Number of Participants With Inhibitory Antibody Formation   [ Time Frame: Up to 6 weeks after first injection of study drug ]

10.  Secondary:   Part B - Number of Participants With Incidence of Inhibitory Antibody Formation   [ Time Frame: Up to 12 months after drug administration ]

11.  Secondary:   Part C - Number of Participants With Incidence of Inhibitory Antibody Formation   [ Time Frame: before and 3 weeks after surgery ]

12.  Secondary:   Part A - Number of Participants With Incidence of Antibody Formation to Heat-shock Protein (HSP-70)   [ Time Frame: Up to 6 weeks after drug administration ]

13.  Secondary:   Part B - Number of Participants With Incidence of Antibody Formation to Heat-shock Protein (HSP-70)   [ Time Frame: Up to 12 months after drug administration ]

14.  Secondary:   Part C - Number of Participants With Incidence of Antibody Formation to Heat-shock Protein (HSP-70)   [ Time Frame: before and 3 weeks after surgery ]

15.  Secondary:   Part A - Number of Participants With Incidence of Antibody Formation to Host Cell Proteins (HCP)   [ Time Frame: Up to 4 weeks after drug administration ]

16.  Secondary:   Part B - Number of Participants With Incidence of Antibody Formation to Host Cell Proteins (HCP)   [ Time Frame: Up to 12 months after drug administration ]

17.  Secondary:   Part C - Number of Participants With Incidence of Antibody Formation to Host Cell Proteins (HCP)   [ Time Frame: before and 3 weeks after surgery ]

18.  Secondary:   Part B - Number of Participants With Assessment of the Hemostasis During Major Surgery   [ Time Frame: An average of 1 month after start of treatment ]

19.  Secondary:   Part C - Number of Participants With Assessment of the Hemostasis During Major Surgery   [ Time Frame: at the time of surgery ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
  Hide Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
No text entered.


  More Information
  Hide More Information

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 agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed.


Results Point of Contact:  
Name/Title: Therapeutic Area Head
Organization: BAYER
e-mail: clinical-trial-contact@bayerhealthcare.com


Publications of Results:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Responsible Party: Bayer
ClinicalTrials.gov Identifier: NCT01029340     History of Changes
Other Study ID Numbers: 12954
2009-012149-43 ( EudraCT Number )
First Submitted: December 8, 2009
First Posted: December 9, 2009
Results First Submitted: May 27, 2013
Results First Posted: November 18, 2013
Last Update Posted: November 28, 2016