Download PDF

Clinical Trial Results:
A Phase II/III, multicenter, partially randomized, open label trial investigating safety and efficacy of on-demand and prophylactic treatment with BAY94-9027 in Severe Hemophilia A

Summary
EudraCT number	2011-005210-11
Trial protocol	GB BE NL NO AT DE DK PL FR IT Outside EU/EEA
Global end of trial date	21 Nov 2019

Results information
Results version number	v3(current)
This version publication date	31 May 2020
First version publication date	15 Apr 2016
Other versions	v1 , v2
Version creation reason

Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information

Collapse all Expand all

Trial information

Top of page

Sponsor protocol code

13024

ISRCTN number

US NCT number

NCT01580293

WHO universal trial number (UTN)

Sponsor organisation name

Bayer AG

Sponsor organisation address

Kaiser-Wilhelm-Allee, D-51368 Leverkusen, Germany,

Public contact

Therapeutic Area Head, Bayer AG, clinical-trials-contact@bayer.com

Scientific contact

Therapeutic Area Head, Bayer AG, clinical-trials-contact@bayer.com

Is trial part of an agreed paediatric investigation plan (PIP)

Yes

EMA paediatric investigation plan number(s)

EMEA-001229-PIP01-11

Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?

Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?

Yes

Analysis stage

Final

Date of interim/final analysis

10 Dec 2019

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

21 Nov 2019

Was the trial ended prematurely?

Main objective of the trial

1. Part A main study: To assess the efficacy of BAY94-9027 in prevention and treatment of bleeding at different infusion schedules 2. Part A Optional Extension: To assess the long term safety of BAY94-9027 over at least 100 accumulated exposure days (ED) (main study plus extension) 3. Part B main study and extension: To assess the safety and efficacy of BAY94-9027 in the prevention of bleeding during major surgical procedures

Protection of trial subjects

The conduct of this clinical study met all local legal and regulatory requirements. The study was conducted in accordance with the ethical principles that have their origin in the Declaration of Helsinki and the International Conference on Harmonization guideline E6: Good Clinical Practice. Before entering the study, the informed consent form was read by and explained to all subjects and/or their legally authorized representative. Participating subjects and/or their legally authorized representative signed informed consent form and could withdraw from the study at any time without any disadvantage and without having to provide a reason for this decision. Only investigators qualified by training and experience were selected as appropriate experts to investigate the study drug.

Background therapy

Evidence for comparator

Actual start date of recruitment

23 Apr 2012

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Yes

Number of subjects enrolled per country

Country: Number of subjects enrolled

Belgium: 2

Country: Number of subjects enrolled

Austria: 6

Country: Number of subjects enrolled

Canada: 1

Country: Number of subjects enrolled

Colombia: 5

Country: Number of subjects enrolled

Germany: 4

Country: Number of subjects enrolled

Denmark: 5

Country: Number of subjects enrolled

France: 6

Country: Number of subjects enrolled

United Kingdom: 8

Country: Number of subjects enrolled

Israel: 16

Country: Number of subjects enrolled

Italy: 8

Country: Number of subjects enrolled

Japan: 11

Country: Number of subjects enrolled

Korea, Republic of: 8

Country: Number of subjects enrolled

Netherlands: 8

Country: Number of subjects enrolled

Norway: 3

Country: Number of subjects enrolled

Poland: 3

Country: Number of subjects enrolled

Singapore: 9

Country: Number of subjects enrolled

Turkey: 5

Country: Number of subjects enrolled

Taiwan: 5

Country: Number of subjects enrolled

United States: 30

Country: Number of subjects enrolled

Romania: 2

Worldwide total number of subjects

145

EEA total number of subjects

Number of subjects enrolled per age group

In utero

Preterm newborn - gestational age < 37 wk

Newborns (0-27 days)

Infants and toddlers (28 days-23 months)

Children (2-11 years)

Adolescents (12-17 years)

Adults (18-64 years)

131

From 65 to 84 years

85 years and over

Subject disposition

Top of page

Recruitment details

The study was conducted in 2 parts: Part A (main study [36-week treatment period] and an optional extension [a minimum of 6 months and at least 100 total exposure days, or until marketing authorization of the drug]) and Part B (main study [up to 3 weeks] and extension [until the end of Part A extension]).

Screening details

Of 149 subjects screened in Part A, 134 were treated and the reasons for non-inclusion of 15 patients were screen failure, consent withdrawal, and non-adherence to protocol visit windows. A total of 16 subjects (including 5 subjects from Part A) were enrolled and treated in Part B.

Period 1 title

Part A_Main Trial

Is this the baseline period?

Allocation method

Not applicable

Blinding used

Not blinded

Are arms mutually exclusive

Yes

BAY94-9027 On-demand Treatment – Part A

Arm description

On-demand treatment with BAY94-9027 as an intravenous (IV) infusion over a period of 1 to 15 minutes at a dose as indicated based upon location and severity of bleeds (maximum of 60 international units per kilogram [IU/kg]).

Arm type

Experimental

Investigational medicinal product name

Damoctocog alfa pegol

Investigational medicinal product code

BAY94-9027

Other name

Pharmaceutical forms

Infusion

Routes of administration

Intravenous use

Dosage and administration details

On-demand treatment with BAY94-9027 as an IV infusion over a period of 1 to 15 minutes at a dose as indicated based upon location and severity of bleeds (maximum of 60 IU/kg).

BAY94-9027 Prophylaxis Treatment – Part A

Arm description

All subjects in the prophylaxis arms started BAY94-9027 IV infusion over a period of 1 to 15 minutes, with 2 times per week (2x/week) at a dose of 25-40 IU/kg for 10 weeks. Thereafter, only subjects with less than (<) 2 breakthrough (spontaneous, no identified trauma) joint and/or muscle bleeds qualified for random assignment to the less frequent dosing regimens. High bleeders continued 2x/week infusion. Subjects who qualified to be randomized, but enrolled after the every 5 day and every 7 day treatment arms were filled, remained on 2x/week treatment (2x/week ‘forced’ group).

Arm type

Experimental

Investigational medicinal product name

Damoctocog alfa pegol

Investigational medicinal product code

BAY94-9027

Other name

Pharmaceutical forms

Infusion

Routes of administration

Intravenous use

Dosage and administration details

All subjects in the prophylaxis arms started with BAY94-9027 IV infusion over a period of 1 to 15 minutes, 2x/week at a dose of 25-40 IU/kg for 10 weeks. Thereafter, only subjects with <2 breakthrough (spontaneous, no identified trauma) joint and/or muscle bleeds qualified for random assignment to the less frequent dosing regimens. High bleeders continued 2x/week infusion. Subjects who qualified to be randomized, but enrolled after the every 5 day and every 7 day treatment arms were filled, remained on 2x/week treatment (2x/week ‘forced’ group).

Number of subjects in period 1	BAY94-9027 On-demand Treatment – Part A	BAY94-9027 Prophylaxis Treatment – Part A
Started	20	114
Completed	18	108
Not completed	2	6
Consent withdrawn by subject	1	4
Adverse event, non-fatal	-	2
Unspecified	1	-

Period 2 title

Part A_Extension

Is this the baseline period?

Allocation method

Not applicable

Blinding used

Not blinded

Are arms mutually exclusive

Yes

BAY94-9027 On-demand Treatment – Extension

Arm description

Subjects entering extension either continued their on-demand treatment or switched to one of the prophylaxis regimens.

Arm type

Experimental

Investigational medicinal product name

Damoctocog alfa pegol

Investigational medicinal product code

BAY94-9027

Other name

Pharmaceutical forms

Infusion

Routes of administration

Intravenous use

Dosage and administration details

On-demand treatment with BAY94-9027 as an IV infusion over a period of 1 to 15 minutes at a dose as indicated based upon location and severity of bleeds (maximum of 60 IU/kg).

BAY94-9027 Prophylaxis Treatment – Extension

Arm description

Subjects entering extension either continued their prophylaxis regimen or switched to one of the other prophylaxis regimens.

Arm type

Experimental

Investigational medicinal product name

Damoctocog alfa pegol

Investigational medicinal product code

BAY94-9027

Other name

Pharmaceutical forms

Infusion

Routes of administration

Intravenous use

Dosage and administration details

Subjects received BAY 94-9027 IV infusion either 2x/week 25-40 IU/kg, or every 5 days 45-60 IU/kg or every 7 days 60 IU/kg.

Number of subjects in period 2 ^[1]	BAY94-9027 On-demand Treatment – Extension	BAY94-9027 Prophylaxis Treatment – Extension
Started	14	107
Completed	14	95
Not completed	0	12
Consent withdrawn by subject	-	3
Completed (Japan only, no extension)	-	5
Adverse event, non-fatal	-	2
Unknown	-	1
Lost to follow-up	-	1

Notes
[1] - The number of subjects starting the period is not consistent with the number completing the preceding period. It is expected the number of subjects starting the subsequent period will be the same as the number completing the preceding period.
Justification: Not all subjects from main trial entered extension or remained in the same arm.

Period 3 title

Part B

Is this the baseline period?

Allocation method

Not applicable

Blinding used

Not blinded

BAY949027 Treatment in Major Surgery - Part B

Arm description

This reporting group included subjects who were treated in Part A and continued treatment in Part B, and subjects who were treated in Part B only. Subjects who underwent major surgery received BAY94-9027 IV infusion over a period of 1 to 15 minutes, for pre-surgical pharmacokinetic (PK) sampling, for surgery, and for the post-surgical period up to the time of discharge for a period not exceeding 3 weeks. Subjects were treated according to the type of procedure, using doses expected to maintain therapeutic levels of human coagulation factor VIII (FVIII) activity based upon pre-surgical PK measurements. The recommended maximum dose was 60 IU/kg. All treatments were administered as needed, and the dose was tailored to a subject’s individual response.

Arm type

Experimental

Investigational medicinal product name

Damoctocog alfa pegol

Investigational medicinal product code

BAY94-9027

Other name

Pharmaceutical forms

Infusion

Routes of administration

Intravenous use

Dosage and administration details

Subjects who underwent major surgery received BAY94-9027 IV infusion over a period of 1 to 15 minutes, for pre-surgical PK sampling, for surgery, and for the post-surgical period up to the time of discharge for a period not exceeding 3 weeks. Subjects were treated according to the type of procedure, using doses expected to maintain therapeutic levels of FVIII activity based upon pre-surgical PK measurements. The recommended maximum dose was 60 IU/kg. All treatments were administered as needed, and the dose was tailored to a subject’s individual response.

Number of subjects in period 3 ^[2]	BAY949027 Treatment in Major Surgery - Part B
Started	19
Completed	17
Not completed	2
Consent withdrawn by subject	1
Unknown	1

Notes
[2] - The number of subjects starting the period is not consistent with the number completing the preceding period. It is expected the number of subjects starting the subsequent period will be the same as the number completing the preceding period.
Justification: Not all the enrolled subjects were treated with study drugs. As baseline only included treated subjects, the worldwide number enrolled in the trial differs with the number of subjects reported in the baseline period.

Period 4 title

Baseline period

Is this the baseline period?

Yes ^[3]

Allocation method

Not applicable

Blinding used

Not blinded

Are arms mutually exclusive

BAY94-9027 Treatment - Part A

Arm description

This reporting group included both on-demand and prophylaxis arms treated with BAY94-9027 as an IV infusion over a period of 1 to 15 minutes in Part A, and included who continued treatment in Part B. On-demand arm: On-demand treatment at a dose as indicated based upon location and severity of bleeds (maximum of 60 IU/kg). Prophylaxis arm: All subjects in the prophylaxis arms started with 2x/week at a dose of 25-40 IU/kg for 10 weeks. Thereafter, only subjects with <2 breakthrough (spontaneous, no identified trauma) joint and/or muscle bleeds qualified for random assignment to the less frequent dosing regimens. High bleeders continued 2x/week infusion. Subjects who qualified to be randomized, but enrolled after the every 5 day and every 7 day treatment arms were filled, remained on 2x/week treatment (2x/week ‘forced’ group).

Arm type

Experimental

Investigational medicinal product name

Damoctocog alfa pegol

Investigational medicinal product code

BAY94-9027

Other name

Pharmaceutical forms

Infusion

Routes of administration

Intravenous use

Dosage and administration details

BAY94-9027 as an IV infusion over a period of 1 to 15 minutes, and the dosage schedule as follows: On-demand arm: On-demand treatment at a dose as indicated based upon location and severity of bleeds (maximum of 60 IU/kg). Prophylaxis arm: All subjects in the prophylaxis arms started with 2x/week at a dose of 25-40 IU/kg for 10 weeks. Thereafter, only subjects with <2 breakthrough (spontaneous, no identified trauma) joint and/or muscle bleeds qualified for random assignment to the less frequent dosing regimens. High bleeders continued 2x/week infusion. Subjects who qualified to be randomized, but enrolled after the every 5 day and every 7 day treatment arms were filled, remained on 2x/week treatment (2x/week ‘forced’ group).

BAY94-9027 Treatment in Major surgery - Part B Only

Arm description

This reporting group included subjects who were treated in Part B only, and excluded subjects who were treated in Part A and continued treatment in Part B. Subjects who underwent major surgery received BAY94-9027 IV infusion over a period of 1 to 15 minutes, for pre-surgical PK sampling, for surgery, and for the post-surgical period up to the time of discharge for a period not exceeding 3 weeks. Subjects were treated according to the type of procedure, using doses expected to maintain therapeutic levels of FVIII activity based upon pre-surgical PK measurements. The recommended maximum dose was 60 IU/kg. All treatments were administered as needed, and the dose was tailored to a subject’s individual response.

Arm type

Experimental

Investigational medicinal product name

Damoctocog alfa pegol

Investigational medicinal product code

BAY94-9027

Other name

Pharmaceutical forms

Infusion

Routes of administration

Intravenous use

Dosage and administration details

Notes
[3] - Period 1 is not the baseline period. It is expected that period 1 will be the baseline period.
Justification: This study was conducted in 2 parts, Part A and Part B. Hence, following periods (Parts A and B), a separate baseline period combining all the arms under Parts A and B, was created to report baseline characteristics.

Number of subjects in period 4	BAY94-9027 Treatment - Part A	BAY94-9027 Treatment in Major surgery - Part B Only
Started	134	11
Completed	126	10
Not completed	8	1
Consent withdrawn by subject	5	-
Adverse event, non-fatal	2	-
Unspecified	1	-
Dropped-out	-	1

Baseline characteristics

Top of page

Reporting group title

BAY94-9027 Treatment - Part A

Reporting group description

Reporting group title

BAY94-9027 Treatment in Major surgery - Part B Only

Reporting group description

Reporting group values	BAY94-9027 Treatment - Part A	BAY94-9027 Treatment in Major surgery - Part B Only	Total
Number of subjects	134	11
Age categorical
Units: Subjects
Age continuous
Units: years
arithmetic mean (standard deviation)	35.9 ( 13.5 )	37.9 ( 13.7 )	-
Gender categorical
Units: Subjects
Male	134	11	145

End points

Top of page

Reporting group title

BAY94-9027 On-demand Treatment – Part A

Reporting group description

Reporting group title

BAY94-9027 Prophylaxis Treatment – Part A

Reporting group description

Reporting group title

BAY94-9027 On-demand Treatment – Extension

Reporting group description

Subjects entering extension either continued their on-demand treatment or switched to one of the prophylaxis regimens.

Reporting group title

BAY94-9027 Prophylaxis Treatment – Extension

Reporting group description

Subjects entering extension either continued their prophylaxis regimen or switched to one of the other prophylaxis regimens.

Reporting group title

BAY949027 Treatment in Major Surgery - Part B

Reporting group description

Reporting group title

BAY94-9027 Treatment - Part A

Reporting group description

Reporting group title

BAY94-9027 Treatment in Major surgery - Part B Only

Reporting group description

Subject analysis set title

Part A Intent-To-Treat (ITT) Population

Subject analysis set type

Intention-to-treat

Subject analysis set description

Part A ITT population (N=132) included all the subjects who were enrolled into Part A of the study and received at least 1 dose of the study medication during Part A, and has subsequent infusion for either prophylaxis or bleed.

Subject analysis set title

Part B Intent-To-Treat (ITT) Population

Subject analysis set type

Intention-to-treat

Subject analysis set description

Part B ITT population (N=14) included all the subjects who were enrolled into Part B of the study, received at least 1 dose of the study medication during Part B, and had undergone surgery.

Subject analysis set title

Part B Safety Population

Subject analysis set type

Safety analysis

Subject analysis set description

Part B Safety population (N=16) included all subjects who received at least 1 dose of study drug during Part B of the study.

Subject analysis set title

Pharmacokinetic Analysis Set (PKS)

Subject analysis set type

Sub-group analysis

Subject analysis set description

PKS (N=22) included all subjects with a valid profile of BAY94-9027 during Part A of the study.

Subject analysis set title

BAY94-9027 Treatment – Part A, Week 36

Subject analysis set type

Sub-group analysis

Subject analysis set description

This reporting group (N=15) included all PKS subjects treated with multiple doses (last dose paired) of BAY94-9027 as an IV infusion over 10 minutes at Week 36. Paired data were defined as the single dose data for the sub-set of subjects who also had multiple dose PK data.

Subject analysis set title

BAY94-9027 Treatment – Part A, Week 0

Subject analysis set type

Sub-group analysis

Subject analysis set description

This reporting group (N=22) included all PKS subjects treated with a single (first) dose of BAY94-9027 as an IV infusion over 10 minutes at Week 0.

Subject analysis set title

Part A Safety Population

Subject analysis set type

Safety analysis

Subject analysis set description

Part A Safety population (N=134) included all subjects who received at least 1 dose of study drug during Part A of the study.

Primary: Annualized Number of Total Bleeds in On-demand Treatment arm (Weeks 0 -36) and Prophylaxis arm (Weeks 10 - 36, excluding rescue bleeds) – Part A

Top of page

End point title

Annualized Number of Total Bleeds in On-demand Treatment arm (Weeks 0 -36) and Prophylaxis arm (Weeks 10 - 36, excluding rescue bleeds) – Part A ^[1]

End point description

Annualized number of total bleeds was defined as the annualized sum of spontaneous bleeds and trauma bleeds.

End point type

Primary

End point timeframe

On-demand: Weeks 0 -36 and Prophylaxis: Weeks 10 - 36 during Part A

Notes
[1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Descriptive statistics were done, no inferential statistical analyses were performed.

End point values	BAY94-9027 On-demand Treatment – Part A	BAY94-9027 Prophylaxis Treatment – Part A
Number of subjects analysed	20 ^[2]	110 ^[3]
Units: bleeds
median (full range (min-max))	23.42 (7.3 to 83.2)	2.09 (0 to 53.1)

Notes
[2] - Part A ITT population
[3] - Part A ITT population with evaluable subjects for this arm.

No statistical analyses for this end point

Secondary: Number of Bleeds Over Time Since Previous Prophylaxis Infusion - Part A

Top of page

End point title

Number of Bleeds Over Time Since Previous Prophylaxis Infusion - Part A

End point description

End point type

Secondary

End point timeframe

Weeks 0 to 36

End point values	BAY94-9027 Prophylaxis Treatment – Part A
Number of subjects analysed	110 ^[4]
Units: bleeds
<1 day	19
>=1 to <2 days	27
>=2 to <3 days	43
>=3 to <4 days	42
>=4 to <5 days	28
>=5 to <6 days	33
>=6 to <7 days	11
>=7 days	3

Notes
[4] - Part A ITT population with subjects evaluable for this ourcome

No statistical analyses for this end point

Secondary: Recombinant Human Factor VIII (rFVIII) Usage Expressed as Total Dose per Kilogram per Year – Part A

Top of page

End point title

Recombinant Human Factor VIII (rFVIII) Usage Expressed as Total Dose per Kilogram per Year – Part A

End point description

End point type

Secondary

End point timeframe

Weeks 0 to 36

End point values	BAY94-9027 On-demand Treatment – Part A	BAY94-9027 Prophylaxis Treatment – Part A
Number of subjects analysed	20 ^[5]	112 ^[6]
Units: IU/kg/year
median (full range (min-max))	1518.5 (390 to 3655)	3255.7 (893 to 5915)

Notes
[5] - Part A ITT population
[6] - Part A ITT population

No statistical analyses for this end point

Secondary: Recombinant Human Factor VIII (rFVIII) Usage Expressed as Number of Infusions for Major Surgery – Part B

Top of page

End point title

Recombinant Human Factor VIII (rFVIII) Usage Expressed as Number of Infusions for Major Surgery – Part B

End point description

Major surgery was defined as any surgical or invasive procedure (elective or emergent) in which the overall bleeding risk was excessive, required a general anesthetic in an individual without a bleeding disorder, penetrated or exposed a major body cavity, resulted in substantial impairment of physical or physiological functions, or required special anatomic knowledge or manipulative skill.

End point type

Secondary

End point timeframe

Baseline up to 6 weeks during Part B

End point values	BAY949027 Treatment in Major Surgery - Part B
Number of subjects analysed	14 ^[7]
Units: infusions
median (full range (min-max))	8 (2 to 37)

Notes
[7] - Part B ITT population

No statistical analyses for this end point

Secondary: Change From Baseline in Overall Pain Severity and Interference due to Pain at Week 36 – Part A

Top of page

End point title

Change From Baseline in Overall Pain Severity and Interference due to Pain at Week 36 – Part A

End point description

Brief Pain Inventor (BPI) – Short Form (BPI-SF) was a 15-item, self-administered, clinically valid, reliable and responsive measure developed to assess pain. BPI-SF was typically scored by averaging the pain severity score and overall pain interference score. Scores ranged from 0 to 10 and a higher score indicates a higher level of pain/interference. Mean change from baseline was reported in the below table. In the listed categories below, 'N' signifies the number of subjects evaluable for this outcome.

End point type

Secondary

End point timeframe

Week 0 (baseline) and Week 36 during Part A

End point values	BAY94-9027 On-demand Treatment – Part A	BAY94-9027 Prophylaxis Treatment – Part A
Number of subjects analysed	20 ^[8]	112 ^[9]
Units: scores on a scale
number (not applicable)
Pain severity subscale (N= 15, 83)	-0.8	0.1
Interference subscale (N=15, 85)	-0.99	-0.06

Notes
[8] - Part A ITT population
[9] - Part A ITT population with subjects evaluable for this outcome

No statistical analyses for this end point

Secondary: Change From Baseline in Work Productivity and Activity Impairment (WPAI) Questionnaire at Week 36 – Part A

Top of page

End point title

Change From Baseline in Work Productivity and Activity Impairment (WPAI) Questionnaire at Week 36 – Part A

End point description

The WPAI is a validated instrument to assess the effect of hemophilia on ability to work, attend classes, and perform regular daily activities in subjects aged 12 and above. The WPAI also contained classroom impairment questions (CIQ). The questionnaire was self-administered and comprised of nine questions that elicited information on work, classroom, and daily activity impairment during the previous seven days. WPAI outcomes that are overall work and activity impairment, transformed to impairment percentages (range from 0 to 100), with higher numbers indicating greater impairment and less productivity. In the listed categories below, 'N' signifies the number of subjects evaluable for this outcome.

End point type

Secondary

End point timeframe

Week 0 (baseline) and Week 36 during Part A

End point values	BAY94-9027 On-demand Treatment – Part A	BAY94-9027 Prophylaxis Treatment – Part A
Number of subjects analysed	20 ^[10]	112 ^[11]
Units: scores on a scale
arithmetic mean (standard deviation)
Activity impairment (N= 19,108)	4.74 ( 24.12 )	-7.13 ( 20 )
Overall work impairment (N= 12,62)	4.44 ( 21.94 )	-1.22 ( 21.94 )

Notes
[10] - Part A ITT population
[11] - Part A ITT population

No statistical analyses for this end point

Secondary: Recombinant Human Factor VIII (rFVIII) Usage Expressed as Number of Infusions– Part A

Top of page

End point title

Recombinant Human Factor VIII (rFVIII) Usage Expressed as Number of Infusions– Part A

End point description

End point type

Secondary

End point timeframe

Weeks 0 to 36

End point values	BAY94-9027 On-demand Treatment – Part A	BAY94-9027 Prophylaxis Treatment – Part A
Number of subjects analysed	20 ^[12]	112 ^[13]
Units: infusions
median (full range (min-max))	29 (9 to 76)	59 (4 to 101)

Notes
[12] - Part A ITT population
[13] - Part A ITT population

No statistical analyses for this end point

Secondary: Physician's Assessment of Adequacy of Hemostasis in Major Surgery – Part B

Top of page

End point title

Physician's Assessment of Adequacy of Hemostasis in Major Surgery – Part B

End point description

End point type

Secondary

End point timeframe

Baseline up to 6 weeks during Part B

End point values	BAY949027 Treatment in Major Surgery - Part B
Number of subjects analysed	14 ^[14]
Units: Number of surgeries
Good	10
Excellent	7

Notes
[14] - Part B ITT population

No statistical analyses for this end point

Secondary: Recombinant Human Factor VIII (rFVIII) Usage Expressed as Total Dose per Kilogram per Infusion for Major Surgery – Part B

Top of page

End point title

Recombinant Human Factor VIII (rFVIII) Usage Expressed as Total Dose per Kilogram per Infusion for Major Surgery – Part B

End point description

End point type

Secondary

End point timeframe

Baseline up to 6 weeks during Part B

End point values	BAY949027 Treatment in Major Surgery - Part B
Number of subjects analysed	14 ^[15]
Units: IU/kg/infusion
median (full range (min-max))	34 (26 to 51)

Notes
[15] - Part B ITT population

No statistical analyses for this end point

Secondary: Investigator’s Assessment of Response to Treatment - Part B

Top of page

End point title

Investigator’s Assessment of Response to Treatment - Part B

End point description

Subject's response to treatment was assessed by Investigator as excellent, good, moderate, poor or missing during Part B of the study. No subjects were assessed as poor.

End point type

Secondary

End point timeframe

Baseline up to 6 weeks during Part B

End point values	BAY949027 Treatment in Major Surgery - Part B
Number of subjects analysed	14 ^[16]
Units: Number of surgeries
Excellent	8
Good	5
Moderate	3
Missing	1

Notes
[16] - Part B ITT population

No statistical analyses for this end point

Secondary: Subject's Assessment of Response to Treatment of a Bleed – Part A

Top of page

End point title

Subject's Assessment of Response to Treatment of a Bleed – Part A

End point description

Adequacy of hemostasis was assessed by subject as excellent, good, moderate, poor or missing during Part A of the study.

End point type

Secondary

End point timeframe

Weeks 0 to 36 during Part A

End point values	BAY94-9027 On-demand Treatment – Part A	BAY94-9027 Prophylaxis Treatment – Part A
Number of subjects analysed	20 ^[17]	112 ^[18]
Units: bleeds
Excellent or Good	252	256
Missing	3	6
Excellent	81	107
Good	171	149
Moderate	115	47
Poor	16	7

Notes
[17] - Part A ITT population
[18] - Part A ITT population

No statistical analyses for this end point

Secondary: Number of Subjects Developed Human Coagulation Factor VIII (FVIII) Inhibitor – Part A

Top of page

End point title

Number of Subjects Developed Human Coagulation Factor VIII (FVIII) Inhibitor – Part A

End point description

End point type

Secondary

End point timeframe

Weeks 0 to 36 during Part A

End point values	BAY94-9027 On-demand Treatment – Part A	BAY94-9027 Prophylaxis Treatment – Part A
Number of subjects analysed	20 ^[19]	114 ^[20]
Units: Subjects	0	0

Notes
[19] - Part A Safety population
[20] - Part A Safety population

No statistical analyses for this end point

Secondary: Change From Baseline in Quality of Life by Hemophilia Specific Quality of Life for Adults (Haemo-QoL-A) Overall Score at Week 36 – Part A

Top of page

End point title

Change From Baseline in Quality of Life by Hemophilia Specific Quality of Life for Adults (Haemo-QoL-A) Overall Score at Week 36 – Part A

End point description

Quality of life (QoL) was measured by the Haemo-QoL-A overall score, which ranged from 0 (the best condition) to 100 (the worst condition).

End point type

Secondary

End point timeframe

Week 0 (baseline) and Week 36 during Part A

End point values	BAY94-9027 On-demand Treatment – Part A	BAY94-9027 Prophylaxis Treatment – Part A
Number of subjects analysed	19 ^[21]	97 ^[22]
Units: scores on a scale
arithmetic mean (standard deviation)	-0.14 ( 9.7 )	2.59 ( 7.98 )

Notes
[21] - Part A ITT population with subjects evaluable for this outcome
[22] - Part A ITT population with subjects evaluable for this outcome

No statistical analyses for this end point

Secondary: Maximum Drug Plasma Concentration (Cmax) Following Single and Multiple Doses of BAY94-9027 – Part A

Top of page

End point title

Maximum Drug Plasma Concentration (Cmax) Following Single and Multiple Doses of BAY94-9027 – Part A

End point description

Maximum observed drug concentration, directly taken from analytical data. Geometric mean and percentage geometric coefficient of variation (%CV) were reported. Cmax was expressed in international Units per deciliter (IU/dL).

End point type

Secondary

End point timeframe

Weeks 0 and 36: pre-infusion (0 hours), post-infusion 15, 30 minutes, 1, 3, 6, 8, 24, 48, 72, 96 hours

End point values	BAY94-9027 Treatment – Part A, Week 36	BAY94-9027 Treatment – Part A, Week 0
Number of subjects analysed	15 ^[23]	22 ^[24]
Units: IU/dL
geometric mean (geometric coefficient of variation)	177.1 ( 20.98 )	162.8 ( 14.74 )

Notes
[23] - PKS with subjects evaluable for this outcome
[24] - PKS with subjects evaluable for this outcome

No statistical analyses for this end point

Secondary: Area Under the Plasma Concentration Versus Time Curve From Zero to Infinity (AUC) Following Single and Multiple Doses of BAY94-9027 – Part A

Top of page

End point title

Area Under the Plasma Concentration Versus Time Curve From Zero to Infinity (AUC) Following Single and Multiple Doses of BAY94-9027 – Part A

End point description

AUC=AUC(0-tlast)+Clast,calc/lambdaZ. AUC(0-tlast) is defined as AUC from time 0 to the last data point >lower limit of quantitation (LLOQ), calculated up by linear trapezoidal rule, down by logarithmic trapezoidal rule. Clast is the last concentration value above LLOQ, directly taken from analytical data. lambdaZ is the apparent terminal rate constant, calculated from the slope of a log-linear regression of the unweighted data considering the last concentration time points >LLOQ (3 IU/dL). AUC expressed in hour*IU/dL. Geometric mean and percentage geometric coefficient of variation (%CV) were reported.

End point type

Secondary

End point timeframe

Weeks 0 and 36: pre-infusion (0 hours), post-infusion 15, 30 minutes, 1, 3, 6, 8, 24, 48, 72, 96 hours

End point values	BAY94-9027 Treatment – Part A, Week 36	BAY94-9027 Treatment – Part A, Week 0
Number of subjects analysed	15 ^[25]	22 ^[26]
Units: h*IU/dL
geometric mean (geometric coefficient of variation)	4131 ( 28.8 )	3708 ( 33.77 )

Notes
[25] - PKS with subjects evaluable for this outcome
[26] - PKS with subjects evaluable for this outcome

No statistical analyses for this end point

Secondary: Terminal Elimination Half Life (t1/2) Following Single and Multiple Doses of BAY94-9027 – Part A

Top of page

End point title

Terminal Elimination Half Life (t1/2) Following Single and Multiple Doses of BAY94-9027 – Part A

End point description

t1/2=ln2/ lambdaZ. lambdaZ is the apparent terminal rate constant, calculated from the slope of a log-linear regression of the unweighted data considering the last concentration time points >LLOQ (3 IU/dL). Geometric mean and percentage geometric coefficient of variation (%CV) were reported.

End point type

Secondary

End point timeframe

Weeks 0 and 36: pre-infusion (0 hours), post-infusion 15, 30 minutes, 1, 3, 6, 8, 24, 48, 72, 96 hours

End point values	BAY94-9027 Treatment – Part A, Week 36	BAY94-9027 Treatment – Part A, Week 0
Number of subjects analysed	15 ^[27]	22 ^[28]
Units: Hours
geometric mean (geometric coefficient of variation)	19.6 ( 38.48 )	17.1 ( 27.05 )

Notes
[27] - PKS with subjects evaluable for this outcome
[28] - PKS with subjects evaluable for this outcome

No statistical analyses for this end point

Secondary: Overall Human Coagulation Factor VIII (FVIII) Recovery Value in Chromogenic Assay – Part A

Top of page

End point title

Overall Human Coagulation Factor VIII (FVIII) Recovery Value in Chromogenic Assay – Part A

End point description

Recovery was calculated by the following formula: Recovery = (post-infusion FVIII activity – pre-infusion FVIII activity ) * weight / dose (in IU).

End point type

Secondary

End point timeframe

Weeks 0 to 36 during Part A

End point values	BAY94-9027 On-demand Treatment – Part A	BAY94-9027 Prophylaxis Treatment – Part A
Number of subjects analysed	20 ^[29]	112 ^[30]
Units: Kilogram per deciliter
arithmetic mean (full range (min-max))	2.671 (1.87 to 3.85)	2.675 (1.32 to 4.48)

Notes
[29] - Part A ITT population
[30] - Part A ITT population

No statistical analyses for this end point

Secondary: Bleed Location – Part A

Top of page

End point title

Bleed Location – Part A

End point description

Bleed locations were categorised as joint, muscle, skin/mucosa, internal, others and missing.

End point type

Secondary

End point timeframe

Weeks 0 to 36 during Part A

End point values	BAY94-9027 On-demand Treatment – Part A	BAY94-9027 Prophylaxis Treatment – Part A
Number of subjects analysed	20 ^[31]	112 ^[32]
Units: bleeds
Missing	0	0
Joint	303	235
Muscle	54	59
Skin/Mucosa	12	12
Internal	7	7
Other	26	16

Notes
[31] - Part A ITT population
[32] - Part A ITT population with subjects evaluable for this outcome

No statistical analyses for this end point

Secondary: Annualized Number of Joint Bleeds, Trauma, Spontaneous Bleeds for Subjects in Prophylaxis arm- Part A

Top of page

End point title

Annualized Number of Joint Bleeds, Trauma, Spontaneous Bleeds for Subjects in Prophylaxis arm- Part A

End point description

End point type

Secondary

End point timeframe

Weeks 10 to 36

End point values	BAY94-9027 Prophylaxis Treatment – Part A
Number of subjects analysed	110 ^[33]
Units: bleeds
median (full range (min-max))
Joint Bleeds	1.93 (0 to 53.1)
Trauma Bleeds	0 (0 to 14.4)
Spontaneous Bleeds	0 (0 to 53.1)

Notes
[33] - Part A ITT population with subjects evaluable for this outcome

No statistical analyses for this end point

Secondary: Recombinant Human Factor VIII (rFVIII) Usage Expressed as Total Dose per Kilogram per Infusion - Part A

Top of page

End point title

Recombinant Human Factor VIII (rFVIII) Usage Expressed as Total Dose per Kilogram per Infusion - Part A

End point description

End point type

Secondary

End point timeframe

Weeks 0 to 36 during Part A

End point values	BAY94-9027 On-demand Treatment – Part A	BAY94-9027 Prophylaxis Treatment – Part A
Number of subjects analysed	20 ^[34]	112 ^[35]
Units: IU/kg/infusion
median (full range (min-max))	32.8 (23 to 58)	38.7 (25 to 48)

Notes
[34] - Part A ITT population
[35] - Part A ITT population

No statistical analyses for this end point

Secondary: Recombinant Human Factor VIII(rFVIII) Usage Expressed as Total Dose per Kilogram In Subjects with Prophylaxis Treatment – Part A

Top of page

End point title

Recombinant Human Factor VIII(rFVIII) Usage Expressed as Total Dose per Kilogram In Subjects with Prophylaxis Treatment – Part A

End point description

End point type

Secondary

End point timeframe

Weeks 0 to 36 during Part A

End point values	BAY94-9027 Prophylaxis Treatment – Part A
Number of subjects analysed	112 ^[36]
Units: IU/kg
median (full range (min-max))	2203.1 (100 to 2819)

Notes
[36] - Part A ITT population treated for prophylaxis

No statistical analyses for this end point

Secondary: Number of Infusions to Control the Bleed – Part A

Top of page

End point title

Number of Infusions to Control the Bleed – Part A

End point description

End point type

Secondary

End point timeframe

Weeks 0 to 36

End point values	BAY94-9027 On-demand Treatment – Part A	BAY94-9027 Prophylaxis Treatment – Part A
Number of subjects analysed	20 ^[37]	112 ^[38]
Units: bleeds
1 infusion	307	262
2 infusions	45	22
Greater than or equal to (>=) 3 infusions	34	32

Notes
[37] - Part A ITT population
[38] - Part A ITT population

No statistical analyses for this end point

Secondary: Number of Subjects Requiring Dose Escalation or Dose Increase During Weeks 10 to 36 – Part A

Top of page

End point title

Number of Subjects Requiring Dose Escalation or Dose Increase During Weeks 10 to 36 – Part A ^[39]

End point description

End point type

Secondary

End point timeframe

Weeks 10 to 36 during Part A

Notes
[39] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint was analysed during Part A only and reported as planned.

End point values	BAY94-9027 Treatment - Part A
Number of subjects analysed	110 ^[40]
Units: Subjects
Dose frequency increased	11
Dose increased	9

Notes
[40] - Part A ITT population with subjects evaluable for this outcome

No statistical analyses for this end point

Secondary: Physician's Assessment of Adequacy of Hemostasis During Minor Surgery – Part A

Top of page

End point title

Physician's Assessment of Adequacy of Hemostasis During Minor Surgery – Part A ^[41]

End point description

Minor surgery was defined as any surgical procedure that did not meet the definition of major, and included simple dental extractions, incision and drainage of abscesses, or simple excisions. A total of 17 minor surgeries performed in 10 subjects were reported during Part A of the study. Adequacy of hemostasis was assessed as excellent or good by the Physician during Part A of the study. The maximum blood loss during surgery was 100 mL during the draining of an abscess. No subjects required blood transfusions.

End point type

Secondary

End point timeframe

Weeks 0 to 36 during Part A

Notes
[41] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint was analysed during Part A and Part B, however, Physician's Assessment of Adequacy of Hemostasis during Part B was reported as a separate endpoint.

End point values	BAY94-9027 Treatment - Part A
Number of subjects analysed	10 ^[42]
Units: Number of surgeries
Excellent	9
Good	6
Missing	2

Notes
[42] - Part A ITT population

No statistical analyses for this end point

Other pre-specified: Number of Subjects With Change/Drop in Hemoglobin/Hematocrit Laboratory Assessments – Part B

Top of page

End point title

Number of Subjects With Change/Drop in Hemoglobin/Hematocrit Laboratory Assessments – Part B

End point description

Hematocrit is defined as the volume percentage (%) of red blood cells in blood. In the listed categories below, 'N' signifies the number of subjects evaluable for this outcome.

End point type

Other pre-specified

End point timeframe

Baseline up to 6 weeks during Part B

End point values	BAY949027 Treatment in Major Surgery - Part B
Number of subjects analysed	16 ^[43]
Units: Subjects
Hematocrit (N=11)	3
Hemoglobin (N=11)	2

Notes
[43] - Part B Safety population

No statistical analyses for this end point

Other pre-specified: Maximum Blood Loss in Major Surgery – Part B

Top of page

End point title

Maximum Blood Loss in Major Surgery – Part B

End point description

End point type

Other pre-specified

End point timeframe

Baseline up to 6 weeks during Part B

End point values	BAY949027 Treatment in Major Surgery - Part B
Number of subjects analysed	14 ^[44]
Units: milliliter
number (not applicable)
During surgery	1000

Notes
[44] - Part B ITT population with subjects treated for major surgery

No statistical analyses for this end point

Other pre-specified: Number of Subjects who Took Anti-fibrinolytic Medications During Major Surgery – Part B

Top of page

End point title

Number of Subjects who Took Anti-fibrinolytic Medications During Major Surgery – Part B

End point description

End point type

Other pre-specified

End point timeframe

Baseline up to 6 weeks during Part B

End point values	BAY949027 Treatment in Major Surgery - Part B
Number of subjects analysed	14 ^[45]
Units: Subjects	6

Notes
[45] - Part B ITT population with subjects treated for major surgery

No statistical analyses for this end point

Other pre-specified: Units of Blood Transfused in Major Surgery – Part B

Top of page

End point title

Units of Blood Transfused in Major Surgery – Part B

End point description

End point type

Other pre-specified

End point timeframe

Baseline up to 6 weeks during Part B

End point values	BAY949027 Treatment in Major Surgery - Part B
Number of subjects analysed	4 ^[46]
Units: Milliliter
median (full range (min-max))	865 (600 to 1381.2)

Notes
[46] - Part B ITT population who had blood transfusions during major surgery

No statistical analyses for this end point

Adverse events

Top of page

Timeframe for reporting adverse events

Adverse event data were collected after the first dose of study drug and up to 7 days after the last dose over a period of approximately 5 years

Assessment type

Non-systematic

Dictionary name

MedDRA

Dictionary version

22.1

Reporting group title

BAY94-9027 Treatment, Part A, Main Trial

Reporting group description

Subjects entering Part A main trial were treated with BAY 94-9027 for either on-demand or prophylactic treatment.

Reporting group title

BAY94-9027 Treatment in Major Surgery, Part B

Reporting group description

Subjects, either Part B subjects only or subjects from Part A/Part A Extension, who underwent major surgery received study drug during their hospital stay up to 3 weeks post-surgery. Subjects were treated according to the type of procedure, using tailored doses (a maximum of 60 IU/kg/infusion) expected to maintain acceptable therapeutic level of FVIII activity.

Reporting group title

BAY94-9027 Treatment, Part A, Extension

Reporting group description

Subjects in Part A extension either continued their regimen from main trial or switched to one of the other regimens at any time.

Serious adverse events	BAY94-9027 Treatment, Part A, Main Trial	BAY94-9027 Treatment in Major Surgery, Part B	BAY94-9027 Treatment, Part A, Extension
Total subjects affected by serious adverse events
subjects affected / exposed	13 / 134 (9.70%)	2 / 22 (9.09%)	36 / 121 (29.75%)
number of deaths (all causes)	0	0	0
number of deaths resulting from adverse events	0	0	0
Vascular disorders
Haematoma
subjects affected / exposed	0 / 134 (0.00%)	1 / 22 (4.55%)	2 / 121 (1.65%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Surgical and medical procedures
Joint arthroplasty
subjects affected / exposed	0 / 134 (0.00%)	0 / 22 (0.00%)	1 / 121 (0.83%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Knee arthroplasty
subjects affected / exposed	1 / 134 (0.75%)	0 / 22 (0.00%)	0 / 121 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Renal stone removal
subjects affected / exposed	0 / 134 (0.00%)	0 / 22 (0.00%)	1 / 121 (0.83%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Ureteral stent insertion
subjects affected / exposed	0 / 134 (0.00%)	0 / 22 (0.00%)	1 / 121 (0.83%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Immune system disorders
Drug hypersensitivity
subjects affected / exposed	1 / 134 (0.75%)	0 / 22 (0.00%)	0 / 121 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Psychiatric disorders
Depression
subjects affected / exposed	0 / 134 (0.00%)	0 / 22 (0.00%)	1 / 121 (0.83%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Product issues
Device malfunction
subjects affected / exposed	1 / 134 (0.75%)	0 / 22 (0.00%)	0 / 121 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Investigations
Anti factor VIII antibody positive
subjects affected / exposed	0 / 134 (0.00%)	2 / 22 (9.09%)	0 / 121 (0.00%)
occurrences causally related to treatment / all	0 / 0	2 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Colonoscopy
subjects affected / exposed	1 / 134 (0.75%)	0 / 22 (0.00%)	0 / 121 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Liver function test increased
subjects affected / exposed	0 / 134 (0.00%)	0 / 22 (0.00%)	1 / 121 (0.83%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Injury, poisoning and procedural complications
Alcohol poisoning
subjects affected / exposed	1 / 134 (0.75%)	0 / 22 (0.00%)	0 / 121 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Contusion
subjects affected / exposed	0 / 134 (0.00%)	0 / 22 (0.00%)	1 / 121 (0.83%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Fall
subjects affected / exposed	0 / 134 (0.00%)	0 / 22 (0.00%)	1 / 121 (0.83%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Fibula fracture
subjects affected / exposed	0 / 134 (0.00%)	0 / 22 (0.00%)	1 / 121 (0.83%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Hand fracture
subjects affected / exposed	0 / 134 (0.00%)	0 / 22 (0.00%)	1 / 121 (0.83%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Head injury
subjects affected / exposed	0 / 134 (0.00%)	0 / 22 (0.00%)	2 / 121 (1.65%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Humerus fracture
subjects affected / exposed	0 / 134 (0.00%)	0 / 22 (0.00%)	1 / 121 (0.83%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Injury
subjects affected / exposed	1 / 134 (0.75%)	0 / 22 (0.00%)	0 / 121 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Ligament rupture
subjects affected / exposed	0 / 134 (0.00%)	0 / 22 (0.00%)	1 / 121 (0.83%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Overdose
subjects affected / exposed	1 / 134 (0.75%)	0 / 22 (0.00%)	0 / 121 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Periprosthetic fracture
subjects affected / exposed	0 / 134 (0.00%)	0 / 22 (0.00%)	1 / 121 (0.83%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Tendon rupture
subjects affected / exposed	1 / 134 (0.75%)	0 / 22 (0.00%)	0 / 121 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Tibia fracture
subjects affected / exposed	0 / 134 (0.00%)	0 / 22 (0.00%)	1 / 121 (0.83%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Cardiac disorders
Angina unstable
subjects affected / exposed	0 / 134 (0.00%)	0 / 22 (0.00%)	1 / 121 (0.83%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Nervous system disorders
Epilepsy
subjects affected / exposed	0 / 134 (0.00%)	0 / 22 (0.00%)	1 / 121 (0.83%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Blood and lymphatic system disorders
Anaemia
subjects affected / exposed	0 / 134 (0.00%)	0 / 22 (0.00%)	1 / 121 (0.83%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Eye disorders
Macular fibrosis
subjects affected / exposed	0 / 134 (0.00%)	0 / 22 (0.00%)	1 / 121 (0.83%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Gastrointestinal disorders
Anal fistula
subjects affected / exposed	0 / 134 (0.00%)	0 / 22 (0.00%)	1 / 121 (0.83%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Enterocolitis
subjects affected / exposed	0 / 134 (0.00%)	0 / 22 (0.00%)	1 / 121 (0.83%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Gastrointestinal haemorrhage
subjects affected / exposed	0 / 134 (0.00%)	0 / 22 (0.00%)	1 / 121 (0.83%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Inguinal hernia
subjects affected / exposed	0 / 134 (0.00%)	0 / 22 (0.00%)	2 / 121 (1.65%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Intestinal obstruction
subjects affected / exposed	0 / 134 (0.00%)	0 / 22 (0.00%)	1 / 121 (0.83%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Mouth haemorrhage
subjects affected / exposed	0 / 134 (0.00%)	0 / 22 (0.00%)	1 / 121 (0.83%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Pancreatitis acute
subjects affected / exposed	1 / 134 (0.75%)	0 / 22 (0.00%)	0 / 121 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Retroperitoneal haematoma
subjects affected / exposed	0 / 134 (0.00%)	0 / 22 (0.00%)	1 / 121 (0.83%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Tooth impacted
subjects affected / exposed	0 / 134 (0.00%)	0 / 22 (0.00%)	2 / 121 (1.65%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Hepatobiliary disorders
Bile duct stone
subjects affected / exposed	1 / 134 (0.75%)	0 / 22 (0.00%)	0 / 121 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Hepatic cirrhosis
subjects affected / exposed	0 / 134 (0.00%)	0 / 22 (0.00%)	1 / 121 (0.83%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Skin and subcutaneous tissue disorders
Dermatitis exfoliative generalised
subjects affected / exposed	0 / 134 (0.00%)	0 / 22 (0.00%)	1 / 121 (0.83%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Renal and urinary disorders
Hydronephrosis
subjects affected / exposed	0 / 134 (0.00%)	0 / 22 (0.00%)	1 / 121 (0.83%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Nephrolithiasis
subjects affected / exposed	0 / 134 (0.00%)	0 / 22 (0.00%)	1 / 121 (0.83%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Renal colic
subjects affected / exposed	0 / 134 (0.00%)	0 / 22 (0.00%)	1 / 121 (0.83%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Ureterolithiasis
subjects affected / exposed	0 / 134 (0.00%)	0 / 22 (0.00%)	1 / 121 (0.83%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Musculoskeletal and connective tissue disorders
Arthralgia
subjects affected / exposed	0 / 134 (0.00%)	0 / 22 (0.00%)	1 / 121 (0.83%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Arthropathy
subjects affected / exposed	1 / 134 (0.75%)	0 / 22 (0.00%)	1 / 121 (0.83%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Back pain
subjects affected / exposed	0 / 134 (0.00%)	0 / 22 (0.00%)	2 / 121 (1.65%)
occurrences causally related to treatment / all	0 / 0	0 / 0	2 / 3
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Chondrocalcinosis pyrophosphate
subjects affected / exposed	0 / 134 (0.00%)	0 / 22 (0.00%)	1 / 121 (0.83%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Haemarthrosis
subjects affected / exposed	1 / 134 (0.75%)	0 / 22 (0.00%)	1 / 121 (0.83%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Haemophilic arthropathy
subjects affected / exposed	1 / 134 (0.75%)	0 / 22 (0.00%)	4 / 121 (3.31%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 5
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Osteoarthritis
subjects affected / exposed	0 / 134 (0.00%)	0 / 22 (0.00%)	1 / 121 (0.83%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Rotator cuff syndrome
subjects affected / exposed	0 / 134 (0.00%)	0 / 22 (0.00%)	1 / 121 (0.83%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Synovitis
subjects affected / exposed	0 / 134 (0.00%)	0 / 22 (0.00%)	1 / 121 (0.83%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Infections and infestations
Anal abscess
subjects affected / exposed	0 / 134 (0.00%)	0 / 22 (0.00%)	1 / 121 (0.83%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Arthritis bacterial
subjects affected / exposed	0 / 134 (0.00%)	0 / 22 (0.00%)	1 / 121 (0.83%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Cellulitis
subjects affected / exposed	0 / 134 (0.00%)	0 / 22 (0.00%)	1 / 121 (0.83%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Device related infection
subjects affected / exposed	1 / 134 (0.75%)	0 / 22 (0.00%)	0 / 121 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Gastroenteritis
subjects affected / exposed	1 / 134 (0.75%)	0 / 22 (0.00%)	0 / 121 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Medical device site joint infection
subjects affected / exposed	0 / 134 (0.00%)	0 / 22 (0.00%)	1 / 121 (0.83%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Nasal vestibulitis
subjects affected / exposed	0 / 134 (0.00%)	0 / 22 (0.00%)	1 / 121 (0.83%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Pneumonia
subjects affected / exposed	1 / 134 (0.75%)	0 / 22 (0.00%)	0 / 121 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0

Frequency threshold for reporting non-serious adverse events: 5%

Non-serious adverse events	BAY94-9027 Treatment, Part A, Main Trial	BAY94-9027 Treatment in Major Surgery, Part B	BAY94-9027 Treatment, Part A, Extension
Total subjects affected by non serious adverse events
subjects affected / exposed	67 / 134 (50.00%)	16 / 22 (72.73%)	74 / 121 (61.16%)
Investigations
Haemoglobin decreased
subjects affected / exposed	0 / 134 (0.00%)	3 / 22 (13.64%)	2 / 121 (1.65%)
occurrences all number	0	3	2
Injury, poisoning and procedural complications
Limb injury
subjects affected / exposed	3 / 134 (2.24%)	0 / 22 (0.00%)	8 / 121 (6.61%)
occurrences all number	3	0	8
Procedural haemorrhage
subjects affected / exposed	0 / 134 (0.00%)	3 / 22 (13.64%)	0 / 121 (0.00%)
occurrences all number	0	3	0
Procedural hypotension
subjects affected / exposed	0 / 134 (0.00%)	2 / 22 (9.09%)	0 / 121 (0.00%)
occurrences all number	0	2	0
Procedural pain
subjects affected / exposed	2 / 134 (1.49%)	9 / 22 (40.91%)	7 / 121 (5.79%)
occurrences all number	2	10	8
Vascular disorders
Haematoma
subjects affected / exposed	0 / 134 (0.00%)	2 / 22 (9.09%)	3 / 121 (2.48%)
occurrences all number	0	2	3
Nervous system disorders
Headache
subjects affected / exposed	16 / 134 (11.94%)	0 / 22 (0.00%)	14 / 121 (11.57%)
occurrences all number	28	0	21
General disorders and administration site conditions
Pyrexia
subjects affected / exposed	1 / 134 (0.75%)	3 / 22 (13.64%)	10 / 121 (8.26%)
occurrences all number	1	3	13
Gastrointestinal disorders
Nausea
subjects affected / exposed	5 / 134 (3.73%)	2 / 22 (9.09%)	5 / 121 (4.13%)
occurrences all number	6	2	7
Respiratory, thoracic and mediastinal disorders
Cough
subjects affected / exposed	8 / 134 (5.97%)	0 / 22 (0.00%)	9 / 121 (7.44%)
occurrences all number	11	0	11
Epistaxis
subjects affected / exposed	8 / 134 (5.97%)	0 / 22 (0.00%)	6 / 121 (4.96%)
occurrences all number	10	0	6
Skin and subcutaneous tissue disorders
Rash
subjects affected / exposed	1 / 134 (0.75%)	2 / 22 (9.09%)	3 / 121 (2.48%)
occurrences all number	1	2	6
Psychiatric disorders
Insomnia
subjects affected / exposed	3 / 134 (2.24%)	2 / 22 (9.09%)	1 / 121 (0.83%)
occurrences all number	3	2	1
Musculoskeletal and connective tissue disorders
Arthralgia
subjects affected / exposed	11 / 134 (8.21%)	2 / 22 (9.09%)	26 / 121 (21.49%)
occurrences all number	13	2	40
Back pain
subjects affected / exposed	8 / 134 (5.97%)	0 / 22 (0.00%)	14 / 121 (11.57%)
occurrences all number	10	0	17
Haemarthrosis
subjects affected / exposed	2 / 134 (1.49%)	1 / 22 (4.55%)	8 / 121 (6.61%)
occurrences all number	2	1	8
Musculoskeletal pain
subjects affected / exposed	4 / 134 (2.99%)	0 / 22 (0.00%)	7 / 121 (5.79%)
occurrences all number	4	0	10
Osteoarthritis
subjects affected / exposed	0 / 134 (0.00%)	0 / 22 (0.00%)	7 / 121 (5.79%)
occurrences all number	0	0	12
Pain in extremity
subjects affected / exposed	5 / 134 (3.73%)	0 / 22 (0.00%)	8 / 121 (6.61%)
occurrences all number	6	0	11
Infections and infestations
Influenza
subjects affected / exposed	5 / 134 (3.73%)	0 / 22 (0.00%)	8 / 121 (6.61%)
occurrences all number	9	0	12
Nasopharyngitis
subjects affected / exposed	24 / 134 (17.91%)	1 / 22 (4.55%)	25 / 121 (20.66%)
occurrences all number	34	1	55
Pharyngitis
subjects affected / exposed	1 / 134 (0.75%)	0 / 22 (0.00%)	7 / 121 (5.79%)
occurrences all number	1	0	9
Upper respiratory tract infection
subjects affected / exposed	3 / 134 (2.24%)	0 / 22 (0.00%)	12 / 121 (9.92%)
occurrences all number	3	0	14

More information

Top of page

Were there any global substantial amendments to the protocol? Yes

27 Mar 2012

Implemented changes and clarifications secondary to the recommendations of regulatory agencies and in response to specific questions and comments received from pediatric specialists and investigators. The primary revision was a prolongation of the total treatment period from 32 to 36 weeks allowing for a longer observation period after subjects in the prophylaxis treatment arm had been randomized to a less frequent infusion schedule. Stopping rules in the event of inhibitor development were defined and a scheduled data monitoring committee review of the efficacy and safety of BAY94-9027 in the prophylaxis arms was added to occur after approximately 20 subjects had completed 2 months of treatment following randomization. The objectives were modified to clarify that inhibitor development was a specific important safety outcome and an additional laboratory assessment was added to measure possible peak antibody response following the first dose of BAY94-9027. Minor changes included clarification of the time points for PK assessments, the duration of wash-outs required for specific observations, and definition of objective criteria to assess efficacy of surgical interventions. The efficacy variables for Part A were categorized to aid understanding of the outcomes being assessed.

13 Dec 2012

Added an optional extension to allow subjects to continue treatment with BAY94-9027 after completion of Part A of the main study. Text was added to more fully define for investigators the effects of the longer half-life of BAY94-9027 on the intervals required for repeat and follow-up infusions for the treatment of bleeds, and additional information for situations when local monitoring of FVIII may have been obtained, including clarification of the reagents that may have been used. Information regarding the available vial sizes, storage, and use of BAY94-9027 was updated.

25 Mar 2014

The purpose of the amendment was to add to the protocol an optional extension of Part B to allow subjects to continue to undergo major surgeries using BAY94-9027 during the Part A extension and after ten Part B subjects had completed major surgery.

Were there any global interruptions to the trial? No

Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.

"±" in relation with geometric CV is auto-generated.Decimal places automatically truncated.Patient satisfaction & burden were not reported due to concerns regarding instrument development & validation, and translation error in 2 questionnaire items.

http://www.ncbi.nlm.nih.gov/pubmed/30654111
http://www.ncbi.nlm.nih.gov/pubmed/31621991
http://www.ncbi.nlm.nih.gov/pubmed/27992112

Select Country:	Select Age Range:
Select Trial Status:	Select Trial Phase:
Select Gender:
Select Date Range: to
Select Rare Disease:
IMP with orphan designation in the indication
Orphan Designation Number:
Results Status:
Clear advanced search filters

Austria
Belgium
Bulgaria
Croatia
Cyprus
Czechia
Denmark
Estonia
Finland
France
Germany
Greece
Hungary
Iceland
Ireland
Italy
Latvia
Liechtenstein
Lithuania
Luxembourg
Malta
Netherlands
Norway
Poland
Portugal
Romania
Slovakia
Slovenia
Spain
Sweden
United Kingdom
Outside EU/EEA

Clinical trials

Clinical Trial Results: A Phase II/III, multicenter, partially randomized, open label trial investigating safety and efficacy of on-demand and prophylactic treatment with BAY94-9027 in Severe Hemophilia A

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Annualized Number of Total Bleeds in On-demand Treatment arm (Weeks 0 -36) and Prophylaxis arm (Weeks 10 - 36, excluding rescue bleeds) – Part A

Primary: Annualized Number of Total Bleeds in On-demand Treatment arm (Weeks 0 -36) and Prophylaxis arm (Weeks 10 - 36, excluding rescue bleeds) – Part A

Secondary: Number of Bleeds Over Time Since Previous Prophylaxis Infusion - Part A

Secondary: Number of Bleeds Over Time Since Previous Prophylaxis Infusion - Part A

Secondary: Recombinant Human Factor VIII (rFVIII) Usage Expressed as Total Dose per Kilogram per Year – Part A

Secondary: Recombinant Human Factor VIII (rFVIII) Usage Expressed as Total Dose per Kilogram per Year – Part A

Secondary: Recombinant Human Factor VIII (rFVIII) Usage Expressed as Number of Infusions for Major Surgery – Part B

Secondary: Recombinant Human Factor VIII (rFVIII) Usage Expressed as Number of Infusions for Major Surgery – Part B

Secondary: Change From Baseline in Overall Pain Severity and Interference due to Pain at Week 36 – Part A

Secondary: Change From Baseline in Overall Pain Severity and Interference due to Pain at Week 36 – Part A

Secondary: Change From Baseline in Work Productivity and Activity Impairment (WPAI) Questionnaire at Week 36 – Part A

Secondary: Change From Baseline in Work Productivity and Activity Impairment (WPAI) Questionnaire at Week 36 – Part A

Secondary: Recombinant Human Factor VIII (rFVIII) Usage Expressed as Number of Infusions– Part A

Secondary: Recombinant Human Factor VIII (rFVIII) Usage Expressed as Number of Infusions– Part A

Secondary: Physician's Assessment of Adequacy of Hemostasis in Major Surgery – Part B

Secondary: Physician's Assessment of Adequacy of Hemostasis in Major Surgery – Part B

Secondary: Recombinant Human Factor VIII (rFVIII) Usage Expressed as Total Dose per Kilogram per Infusion for Major Surgery – Part B

Secondary: Recombinant Human Factor VIII (rFVIII) Usage Expressed as Total Dose per Kilogram per Infusion for Major Surgery – Part B

Secondary: Investigator’s Assessment of Response to Treatment - Part B

Secondary: Investigator’s Assessment of Response to Treatment - Part B

Secondary: Subject's Assessment of Response to Treatment of a Bleed – Part A

Secondary: Subject's Assessment of Response to Treatment of a Bleed – Part A

Secondary: Number of Subjects Developed Human Coagulation Factor VIII (FVIII) Inhibitor – Part A

Secondary: Number of Subjects Developed Human Coagulation Factor VIII (FVIII) Inhibitor – Part A

Secondary: Change From Baseline in Quality of Life by Hemophilia Specific Quality of Life for Adults (Haemo-QoL-A) Overall Score at Week 36 – Part A

Secondary: Change From Baseline in Quality of Life by Hemophilia Specific Quality of Life for Adults (Haemo-QoL-A) Overall Score at Week 36 – Part A

Secondary: Maximum Drug Plasma Concentration (Cmax) Following Single and Multiple Doses of BAY94-9027 – Part A

Secondary: Maximum Drug Plasma Concentration (Cmax) Following Single and Multiple Doses of BAY94-9027 – Part A

Secondary: Area Under the Plasma Concentration Versus Time Curve From Zero to Infinity (AUC) Following Single and Multiple Doses of BAY94-9027 – Part A

Secondary: Area Under the Plasma Concentration Versus Time Curve From Zero to Infinity (AUC) Following Single and Multiple Doses of BAY94-9027 – Part A

Secondary: Terminal Elimination Half Life (t1/2) Following Single and Multiple Doses of BAY94-9027 – Part A

Secondary: Terminal Elimination Half Life (t1/2) Following Single and Multiple Doses of BAY94-9027 – Part A

Secondary: Overall Human Coagulation Factor VIII (FVIII) Recovery Value in Chromogenic Assay – Part A

Secondary: Overall Human Coagulation Factor VIII (FVIII) Recovery Value in Chromogenic Assay – Part A

Secondary: Bleed Location – Part A

Secondary: Bleed Location – Part A

Secondary: Annualized Number of Joint Bleeds, Trauma, Spontaneous Bleeds for Subjects in Prophylaxis arm- Part A

Secondary: Annualized Number of Joint Bleeds, Trauma, Spontaneous Bleeds for Subjects in Prophylaxis arm- Part A

Secondary: Recombinant Human Factor VIII (rFVIII) Usage Expressed as Total Dose per Kilogram per Infusion - Part A

Secondary: Recombinant Human Factor VIII (rFVIII) Usage Expressed as Total Dose per Kilogram per Infusion - Part A

Secondary: Recombinant Human Factor VIII(rFVIII) Usage Expressed as Total Dose per Kilogram In Subjects with Prophylaxis Treatment – Part A

Secondary: Recombinant Human Factor VIII(rFVIII) Usage Expressed as Total Dose per Kilogram In Subjects with Prophylaxis Treatment – Part A

Secondary: Number of Infusions to Control the Bleed – Part A

Secondary: Number of Infusions to Control the Bleed – Part A

Secondary: Number of Subjects Requiring Dose Escalation or Dose Increase During Weeks 10 to 36 – Part A

Secondary: Number of Subjects Requiring Dose Escalation or Dose Increase During Weeks 10 to 36 – Part A

Secondary: Physician's Assessment of Adequacy of Hemostasis During Minor Surgery – Part A

Secondary: Physician's Assessment of Adequacy of Hemostasis During Minor Surgery – Part A

Other pre-specified: Number of Subjects With Change/Drop in Hemoglobin/Hematocrit Laboratory Assessments – Part B

Other pre-specified: Number of Subjects With Change/Drop in Hemoglobin/Hematocrit Laboratory Assessments – Part B

Other pre-specified: Maximum Blood Loss in Major Surgery – Part B

Other pre-specified: Maximum Blood Loss in Major Surgery – Part B

Other pre-specified: Number of Subjects who Took Anti-fibrinolytic Medications During Major Surgery – Part B

Other pre-specified: Number of Subjects who Took Anti-fibrinolytic Medications During Major Surgery – Part B

Other pre-specified: Units of Blood Transfused in Major Surgery – Part B

Other pre-specified: Units of Blood Transfused in Major Surgery – Part B

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

Online references

More information

Clinical Trial Results:
A Phase II/III, multicenter, partially randomized, open label trial investigating safety and efficacy of on-demand and prophylactic treatment with BAY94-9027 in Severe Hemophilia A