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

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.
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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.

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 ]

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
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