A Trial Investigating Safety and Efficacy of Treatment Wi... | NCT01580293

ID	Type	Description	Link
2011-005210-11	EudraCT Number

Label	Type	Description	Intervention Names
Arm 1	Experimental	On-demand treatment of BAY94-9027 at individual dose and number of infusions based upon location and severity of bleeds	Biological: BAY94-9027
Arm 2	Experimental	Prophylaxis treatment of BAY94-9027; 2 infusions per week over 10 weeks followed by 2 infusions per week over 26 weeks in the main trial; and at least 1 day per week in the extension for at least 100 ED	Biological: BAY94-9027
Arm 3	Experimental	Prophylaxis treatment of BAY94-9027; 2 infusions per week over 10 weeks followed by infusion every 5 days over 26 weeks in the main trial; and at least 1 day per week in the extension for at least 100 ED	Biological: BAY94-9027
Arm 4	Experimental	Prophylaxis treatment of BAY94-9027; 2 infusions per week over 10 weeks followed by infusion every 7 days over 26 weeks in the main trial; and at least 1 day per week in the extension for at least 100 ED	Biological: BAY94-9027

Name	Type	Description	Arm Group Labels	Other Names
BAY94-9027	Biological	Intravenous infusion of BAY94-9027	Arm 1 Arm 2 Arm 3 Arm 4

Measure	Description	Time Frame
Annualized Number of Total Bleeds in On-demand Treatment Arm (Weeks 0 -36) and in Each Prophylaxis Arm (Weeks 10 - 36, Excluding Rescue Bleeds) - Part A, Main Trial	Annualized number of total bleeds was defined as the annualized sum of spontaneous bleeds and trauma bleeds. A participant who had the one-time increase in dose frequency was regarded as rescued. A rescue bleed was a bleed that occured after the dose frequency was increased. Rescue bleeds and periods were not considered for the annualized bleeding rate (ABR).	On-demand: Weeks 0 -36 and Prophylaxis: Weeks 10 - 36 during Part A

Measure	Description	Time Frame
Annualized Number of Joint Bleeds, Trauma, Spontaneous Bleeds in On-demand Treatment Arm (Weeks 0 -36) and in Each Prophylaxis Arm (Weeks 10 - 36, Excluding Rescue Bleeds) - Part A	A participant who had the one-time increase in dose frequency was regarded as rescued. A rescue bleed was a bleed that occured after the dose frequency was increased. Rescue bleeds and periods were not considered for the ABR.

Measure	Description	Time Frame
Change From Baseline in Overall Pain Severity and Interference Due to Pain at Week 36 - Part A	Brief Pain Inventory (BPI) - Short Form (BPI-SF) was a 15-item, self-administered, validated tool developed to assess pain used in the study for patient reported outcomes. Scores ranged from 0 to 10 and a higher score indicates a higher level of pain/interference.	Week 0 (baseline) and Week 36 during Part A

Name	Affiliation	Role
Bayer Study Director	Bayer	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
		Tucson	Arizona	85724-5024	United States

PubMed Identifier	Type	Citation	Retractions
30654111	Background	Baumann A, Piel I, Hucke F, Sandmann S, Hetzel T, Schwarz T. Pharmacokinetics, excretion, distribution, and metabolism of 60-kDa polyethylene glycol used in BAY 94-9027 in rats and its value for human prediction. Eur J Pharm Sci. 2019 Mar 15;130:11-20. doi: 10.1016/j.ejps.2019.01.015. Epub 2019 Jan 14.
31621991	Background

Label	URL
Click here to find information about studies related to Bayer Healthcare products conducted in Europe	View source

ID	Title	Description
FG000	BAY94-9027 On-demand Treatment, Part A	Participants received on-demand treatment with BAY94-9027 as an intravenous (IV) infusion at a dose as indicated based upon location and severity of bleeds (a maximum of 60 international units per kilogram [IU/kg]). Participants entering extension either continued their on-demand treatment or switched to one of the prophylaxis regimens.

Arm/Group Information

ID	Title	Description
BG000	BAY94-9027 On-demand Treatment, Main Trial	Participants received on-demand treatment with BAY94-9027 as an intravenous (IV)infusion at a dose as indicated based upon location and severity of bleeds (a maximum of 60 international units per kilogram [IU/kg]).
BG001	BAY94-9027 Prophylaxis Treatment, 2x/Week Dropped, Main Trial	4 participants dropped out during week 0-10
BG002	BAY94-9027 Prophylaxis Treatment, 2x/Week Failed, Main Trial	All participants started BAY94-9027 IV infusion with 2x/week at a dose of 25 IU/kg for 10 weeks. High bleeders (with 2 or more muscle or joint bleeds in the first 10 weeks) continued 2x/week infusion (2x/week 'failed') at a dose of 30 to 40 IU/kg.
BG003	BAY94-9027 Prophylaxis Treatment, 2x/Week Forced, Main Trial	All participants started BAY94-9027 IV infusion with 2x/week at a dose of 25 IU/kg for 10 weeks. Participants with < 2 spontaneous joint and/or muscle bleeds were randomized 1:1 to either every 5 or every 7 days dosing regimen. Participants enrolled after randomization arms were filled continued 2x/week treatment at a dose of 30-40 IU/kg (2x/week 'forced').
BG004	BAY94-9027 Prophylaxis Treatment, Every 5 Days, Main Trial	All participants started BAY94-9027 IV infusion with 2x/week at a dose of 25 IU/kg for 10 weeks. Participants with < 2 spontaneous joint and/or muscle bleeds were randomized 1:1 to either every 5 or every 7 days dosing regimen, participants randomized to the every 5 days treatment arm were to begin treatment with 45 IU/kg every 5 days with the option to increase dose up to 60 IU/kg/infusion.
BG005	BAY94-9027 Prophylaxis Treatment, Every 7 Days, Main Trial	All participants started BAY94-9027 IV infusion with 2x/week at a dose of 25 IU/kg for 10 weeks. Participants <2 spontaneous joint and/or muscle bleeds were randomized 1:1 to either every 5 or every 7 days dosing regimen, participants randomized to the every 7 days treatment arm were to administer a dose of 60 IU/kg (maximum 6000 IU) every 7 days.
BG006	BAY94-9027 Treatment in Major Surgery, Part B Only	Participants treated in Part B only were included. Participants treated in Part A and continued in Part B were excluded. Participants who underwent major surgery received study drug during their hospital stay and up until hospital discharge or 3 weeks post-surgery, whichever came first. Participants were treated according to the type of procedure, using tailored doses (a maximum of 60 IU/kg) expected to maintain acceptable therapeutic level of FVIII activity.
BG007	Total	Total of all reporting groups

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Annualized Number of Total Bleeds in On-demand Treatment Arm (Weeks 0 -36) and in Each Prophylaxis Arm (Weeks 10 - 36, Excluding Rescue Bleeds) - Part A, Main Trial

Annualized number of total bleeds was defined as the annualized sum of spontaneous bleeds and trauma bleeds. A participant who had the one-time increase in dose frequency was regarded as rescued. A rescue bleed was a bleed that occured after the dose frequency was increased. Rescue bleeds and periods were not considered for the annualized bleeding rate (ABR).

Intent to treat (ITT) population part A week 10-36, 4 participants dropped out during week 0-10.

Posted

Median

Inter-Quartile Range

bleeds

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

ID	Title	Description
OG000	BAY94-9027 On-demand Treatment, Main Trial	Participants received on-demand treatment with BAY94-9027 as an intravenous (IV)infusion at a dose as indicated based upon location and severity of bleeds (a maximum of 60 international units per kilogram [IU/kg]).
OG001	BAY94-9027 Prophylaxis Treatment, 2x/Week Failed, Main Trial	All participants started BAY94-9027 IV infusion with 2x/week at a dose of 25 IU/kg for 10 weeks. High bleeders (with 2 or more muscle or joint bleeds in the first 10 weeks) continued 2x/week infusion (2x/week 'failed') at a dose of 30 to 40 IU/kg.
OG002	BAY94-9027 Prophylaxis Treatment, 2x/Week Forced, Main Trial	All participants started BAY94-9027 IV infusion with 2x/week at a dose of 25 IU/kg for 10 weeks. Participants with < 2 spontaneous joint and/or muscle bleeds were randomized 1:1 to either every 5 or every 7 days dosing regimen. Participants enrolled after randomization arms were filled continued 2x/week treatment at a dose of 30-40 IU/kg (2x/week 'forced').
OG003	BAY94-9027 Prophylaxis Treatment, Every 5 Days, Main Trial	All participants started BAY94-9027 IV infusion with 2x/week at a dose of 25 IU/kg for 10 weeks. Participants with < 2 spontaneous joint and/or muscle bleeds were randomized 1:1 to either every 5 or every 7 days dosing regimen, participants randomized to the every 5 days treatment arm were to begin treatment with 45 IU/kg every 5 days with the option to increase dose up to 60 IU/kg/infusion.
OG004	BAY94-9027 Prophylaxis Treatment, Every 7 Days, Main Trial	All participants started BAY94-9027 IV infusion with 2x/week at a dose of 25 IU/kg for 10 weeks. Participants <2 spontaneous joint and/or muscle bleeds were randomized 1:1 to either every 5 or every 7 days dosing regimen, participants randomized to the every 7 days treatment arm were to administer a dose of 60 IU/kg (maximum 6000 IU) every 7 days.
OG005	BAY94-9027 Prophylaxis Treatment Total, Main Trial	All participants receiving an schedule of prophylaxis treatment, all prophylaxis arms combined.

Units	Counts
Participants	OG00020 OG00113 OG00211 OG003

Title

Denominators

Categories

Title	Measurements
	OG00023.42(17.84 to 37.25) OG0014.11(2.01 to 10.56) OG0021.93(0.00 to 5.24) OG003

Secondary

Annualized Number of Joint Bleeds, Trauma, Spontaneous Bleeds in On-demand Treatment Arm (Weeks 0 -36) and in Each Prophylaxis Arm (Weeks 10 - 36, Excluding Rescue Bleeds) - Part A

A participant who had the one-time increase in dose frequency was regarded as rescued. A rescue bleed was a bleed that occured after the dose frequency was increased. Rescue bleeds and periods were not considered for the ABR.

ITT population part A week 10-36, 4 participants dropped out during week 0-10.

Posted

Median

Inter-Quartile Range

bleeds

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

ID	Title	Description
OG000	BAY94-9027 On-demand Treatment, Main Trial	Participants received on-demand treatment with BAY94-9027 as an intravenous (IV)infusion at a dose as indicated based upon location and severity of bleeds (a maximum of 60 international units per kilogram [IU/kg]).
OG001	BAY94-9027 Prophylaxis Treatment, 2x/Week Failed, Main Trial	All participants started BAY94-9027 IV infusion with 2x/week at a dose of 25 IU/kg for 10 weeks. High bleeders (with 2 or more muscle or joint bleeds in the first 10 weeks) continued 2x/week infusion (2x/week 'failed') at a dose of 30 to 40 IU/kg.
OG002	BAY94-9027 Prophylaxis Treatment, 2x/Week Forced, Main Trial

Secondary

Annualized Number of Total Bleeds in On-demand Treatment Arm and in Each Prophylaxis Arm, Part A, Extension

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

ITT extension population. Participants in each regimen stayed on this regimen without switch. Participants who switched regimen were analyzed in the variable frequency arm.

Posted

Median

Inter-Quartile Range

bleeds

at least 100 total exposure days acquired, median time 3.9 years up to 7 years maximum

ID	Title	Description
OG000	BAY94-9027 On-demand Treatment, Extension	On-demand participants entering the Part A extension either continued their on-demand treatment or switched to one of the prophylaxis regimens.
OG001	BAY94-9027 Prophylaxis Treatment, 2x/Week, Extension	Prophylaxis participants entering the Part A extension were either to continue their prophylaxis regimen as it was at the conclusion of the main trial, or had the option of switching to one of the other prophylaxis regimens.
OG002	BAY94-9027 Prophylaxis Treatment, Every 5 Days, Extension	Prophylaxis participants entering the Part A extension were either to continue their prophylaxis regimen as it was at the conclusion of the main trial, or had the option of switching to one of the other prophylaxis regimens.

Secondary

Number of Participants Developed Human Coagulation Factor VIII (FVIII) Inhibitor - Part A

FVIII inhibitor testing was done according to the Nijmegen modified Bethesda assay. A positive inhibitor test was defined with a threshold of ≥0.6 Bethesda unit (BU) at the central laboratory.

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

Posted

Count of Participants

Participants

Weeks 0 to 36 during Part A

ID	Title	Description
OG000	BAY94-9027 On-demand Treatment, Main Trial	Participants received on-demand treatment with BAY94-9027 as an intravenous (IV)infusion at a dose as indicated based upon location and severity of bleeds (a maximum of 60 international units per kilogram [IU/kg]).
OG001	BAY94-9027 Prophylaxis Treatment, Week 0-36, Main Trial	All participants in the prophylaxis arms started BAY94-9027 IV infusion, with 2x/week at a dose of 25 IU/kg for 10 weeks. Thereafter, participants with less than 2 spontaneous joint and/or muscle bleeds were randomized 1:1 to either every 5 or every 7 days dosing regimen. High bleeders continued 2x/week infusion (2x/week 'failed'). Participants qualified to be randomized, but enrolled after randomized arms were filled, remained on 2x/week treatment (2x/week 'forced' group).

Secondary

Number of Bleeds Requiring 1, 2 or >= 3 Infusions to Control the Bleed - Part A

Number of bleeds requiring 1, 2 or >= 3 infusions to control the bleeding

Part A ITT population, analysis population includes participants who presented >=1 bleeding event.

Posted

Number

bleeds

Weeks 0 to 36

bleeds

ID	Title	Description
OG000	BAY94-9027 On-demand Treatment, Main Trial	Participants received on-demand treatment with BAY94-9027 as an intravenous (IV)infusion at a dose as indicated based upon location and severity of bleeds (a maximum of 60 international units per kilogram [IU/kg]).
OG001	BAY94-9027 Prophylaxis Treatment, Week 0-36, Main Trial	All participants in the prophylaxis arms started BAY94-9027 IV infusion, with 2x/week at a dose of 25 IU/kg for 10 weeks. Thereafter, participants with less than 2 spontaneous joint and/or muscle bleeds were randomized 1:1 to either every 5 or every 7 days dosing regimen. High bleeders continued 2x/week infusion (2x/week 'failed'). Participants qualified to be randomized, but enrolled after randomized arms were filled, remained on 2x/week treatment (2x/week 'forced' group).

Units	Counts

Secondary

Number of Bleeds According to Locations - Part A

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

Analysis population includes participants who presented >=1 bleeding event.

Posted

Number

bleeds

Weeks 0 -36

bleeds

ID	Title	Description
OG000	BAY94-9027 On-demand Treatment, Main Trial	Participants received on-demand treatment with BAY94-9027 as an intravenous (IV)infusion at a dose as indicated based upon location and severity of bleeds (a maximum of 60 international units per kilogram [IU/kg]).
OG001	BAY94-9027 Prophylaxis Treatment, Week 0-36, Main Trial	All participants in the prophylaxis arms started BAY94-9027 IV infusion, with 2x/week at a dose of 25 IU/kg for 10 weeks. Thereafter, participants with less than 2 spontaneous joint and/or muscle bleeds were randomized 1:1 to either every 5 or every 7 days dosing regimen. High bleeders continued 2x/week infusion (2x/week 'failed'). Participants qualified to be randomized, but enrolled after randomized arms were filled, remained on 2x/week treatment (2x/week 'forced' group).

Units	Counts
Participants

Secondary

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

Analysis population includes participants who presented >=1 bleeding event.

Posted

Number

bleeds

Weeks 0 to 36

bleeds

ID	Title	Description
OG000	BAY94-9027 On-demand Treatment, Main Trial	Participants received on-demand treatment with BAY94-9027 as an intravenous (IV)infusion at a dose as indicated based upon location and severity of bleeds (a maximum of 60 international units per kilogram [IU/kg]).
OG001	BAY94-9027 Prophylaxis Treatment, Week 0-36, Main Trial	All participants in the prophylaxis arms started BAY94-9027 IV infusion, with 2x/week at a dose of 25 IU/kg for 10 weeks. Thereafter, participants with less than 2 spontaneous joint and/or muscle bleeds were randomized 1:1 to either every 5 or every 7 days dosing regimen. High bleeders continued 2x/week infusion (2x/week 'failed'). Participants qualified to be randomized, but enrolled after randomized arms were filled, remained on 2x/week treatment (2x/week 'forced' group).

Units	Counts
Participants

Secondary

Number of Bleeds According to Participant's Assessment of Response to Treatment - Part A

Response to treatment was assessed by participant as excellent, good, moderate, poor or missing during Part A of the study.

Analysis population includes participants who presented >=1 bleeding event.

Posted

Number

bleeds

Weeks 0 to 36 during Part A

bleeds

ID	Title	Description
OG000	BAY94-9027 On-demand Treatment, Main Trial	Participants received on-demand treatment with BAY94-9027 as an intravenous (IV)infusion at a dose as indicated based upon location and severity of bleeds (a maximum of 60 international units per kilogram [IU/kg]).
OG001	BAY94-9027 Prophylaxis Treatment, Week 0-36, Main Trial	All participants in the prophylaxis arms started BAY94-9027 IV infusion, with 2x/week at a dose of 25 IU/kg for 10 weeks. Thereafter, participants with less than 2 spontaneous joint and/or muscle bleeds were randomized 1:1 to either every 5 or every 7 days dosing regimen. High bleeders continued 2x/week infusion (2x/week 'failed'). Participants qualified to be randomized, but enrolled after randomized arms were filled, remained on 2x/week treatment (2x/week 'forced' group).

Units

Secondary

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

For prophylaxis patients, the dose is related to all infusions.

ITT population part A week 10-36, 4 participants dropped out during week 0-10.

Posted

Median

Full Range

IU/kg/year

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

ID	Title	Description
OG000	BAY94-9027 On-demand Treatment, Main Trial	Participants received on-demand treatment with BAY94-9027 as an intravenous (IV)infusion at a dose as indicated based upon location and severity of bleeds (a maximum of 60 international units per kilogram [IU/kg]).
OG001	BAY94-9027 Prophylaxis Treatment, 2x/Week Failed, Main Trial	All participants started BAY94-9027 IV infusion with 2x/week at a dose of 25 IU/kg for 10 weeks. High bleeders (with 2 or more muscle or joint bleeds in the first 10 weeks) continued 2x/week infusion (2x/week 'failed') at a dose of 30 to 40 IU/kg.
OG002	BAY94-9027 Prophylaxis Treatment, 2x/Week Forced, Main Trial	All participants started BAY94-9027 IV infusion with 2x/week at a dose of 25 IU/kg for 10 weeks. Participants with < 2 spontaneous joint and/or muscle bleeds were randomized 1:1 to either every 5 or every 7 days dosing regimen. Participants enrolled after randomization arms were filled continued 2x/week treatment at a dose of 30-40 IU/kg (2x/week 'forced').

Secondary

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

For prophylaxis patients, the dose per infusion related to prophylaxis infusion.

ITT population part A week 10-36, 4 participants dropped out during week 0-10.

Posted

Median

Full Range

IU/kg/infusion

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

ID	Title	Description
OG000	BAY94-9027 On-demand Treatment, Main Trial	Participants received on-demand treatment with BAY94-9027 as an intravenous (IV)infusion at a dose as indicated based upon location and severity of bleeds (a maximum of 60 international units per kilogram [IU/kg]).
OG001	BAY94-9027 Prophylaxis Treatment, 2x/Week Failed, Main Trial	All participants started BAY94-9027 IV infusion with 2x/week at a dose of 25 IU/kg for 10 weeks. High bleeders (with 2 or more muscle or joint bleeds in the first 10 weeks) continued 2x/week infusion (2x/week 'failed') at a dose of 30 to 40 IU/kg.
OG002	BAY94-9027 Prophylaxis Treatment, 2x/Week Forced, Main Trial	All participants started BAY94-9027 IV infusion with 2x/week at a dose of 25 IU/kg for 10 weeks. Participants with < 2 spontaneous joint and/or muscle bleeds were randomized 1:1 to either every 5 or every 7 days dosing regimen. Participants enrolled after randomization arms were filled continued 2x/week treatment at a dose of 30-40 IU/kg (2x/week 'forced').

Secondary

Number of Participants Requiring an Increase in Dose Frequency, or Dose Increase, During Weeks 10 to 36 - Part A

ITT population part A week 10-36, 4 participants dropped out during week 0-10.

Posted

Count of Participants

Participants

Weeks 10 to 36 during Part A

ID	Title	Description
OG000	BAY94-9027 Prophylaxis Treatment, 2x/Week Failed, Main Trial	All participants started BAY94-9027 IV infusion with 2x/week at a dose of 25 IU/kg for 10 weeks. High bleeders (with 2 or more muscle or joint bleeds in the first 10 weeks) continued 2x/week infusion (2x/week 'failed') at a dose of 30 to 40 IU/kg.
OG001	BAY94-9027 Prophylaxis Treatment, 2x/Week Forced, Main Trial	All participants started BAY94-9027 IV infusion with 2x/week at a dose of 25 IU/kg for 10 weeks. Participants with < 2 spontaneous joint and/or muscle bleeds were randomized 1:1 to either every 5 or every 7 days dosing regimen. Participants enrolled after randomization arms were filled continued 2x/week treatment at a dose of 30-40 IU/kg (2x/week 'forced').
OG002	BAY94-9027 Prophylaxis Treatment, Every 5 Days, Main Trial	All participants started BAY94-9027 IV infusion with 2x/week at a dose of 25 IU/kg for 10 weeks. Participants with < 2 spontaneous joint and/or muscle bleeds were randomized 1:1 to either every 5 or every 7 days dosing regimen, participants randomized to the every 5 days treatment arm were to begin treatment with 45 IU/kg every 5 days with the option to increase dose up to 60 IU/kg/infusion.

Secondary

Number of Surgeries According to Physician's Assessment of Adequacy of Hemostasis in Major Surgery - Part B

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. Adequacy of hemostasis was assessed as excellent, good, moderate or poor, by the surgeon or interventionalist during Part B of the study.

17 participants were included in the Part B ITT population.

Posted

Number

surgeries

Day of surgery

surgeries

ID	Title	Description
OG000	BAY949027 Treatment in Major Surgery, Part B	Participants who underwent major surgery received study drug during their hospital stay up to 3 weeks post surgery. Participants 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.

Units	Counts
Participants	OG000

Secondary

Recombinant Human Factor VIII (rFVIII) Usage Expressed as Dose Per Kilogram Per Infusion for Major Surgery - Part B

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. Total dose per kilogram per Infusion was expressed in international units per kilogram per infusion (IU/kg/infusion).

Part B ITT population

Posted

Median

Full Range

IU/kg/infusion

Up to 3 weeks post-surgery during Part B

surgeries

ID	Title	Description
OG000	BAY949027 Treatment in Major Surgery, Part B	Participants who underwent major surgery received study drug during their hospital stay up to 3 weeks post surgery. Participants 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.

Units	Counts
Participants	OG000

Secondary

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

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.rFVIII usage expressed as number of infusions and IU/kg per year, as well as IU/kg per event (surgery) was assessed by investigator.

Part B ITT population

Posted

Median

Full Range

infusions

Up to 3 weeks post-surgery during Part B

surgeries

ID	Title	Description
OG000	BAY949027 Treatment in Major Surgery, Part B	Participants who underwent major surgery received study drug during their hospital stay up to 3 weeks post surgery. Participants 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.

Units	Counts
Participants	OG000

Secondary

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

Cmax: Maximum observed drug concentration following an infusion of 60 IU/kg

Pharmacokinetic Analysis Set (PKS) with participants evaluable for this outcome, PKS included all participants with a valid profile of BAY94-9027 during Part A of the study.

Posted

Geometric Mean

Geometric Coefficient of Variation

IU/dL

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

ID	Title	Description
OG000	BAY94-9027 Treatment - Part A, Week 0	Part A, Week 0 included all PKS participants treated with a single (first) dose of BAY94-9027 as an IV infusion at Week 0.
OG001	BAY94-9027 Treatment - Part A, Week 36	Part A, Week 36 group included all PKS participants treated with multiple doses (last dose paired) of BAY94-9027 as an IV infusion at Week 36. Paired data were defined as the single dose data for the sub-set of participants who also had multiple dose PK data.

Units	Counts
Participants

Secondary

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

AUC: The total area under the plasma concentration versus time curve following an infusion of 60 IU/kg .

PKS with participants evaluable for this outcome

Posted

Geometric Mean

Geometric Coefficient of Variation

h*IU/dL

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

ID	Title	Description
OG000	BAY94-9027 Treatment - Part A, Week 0	Part A, Week 0 included all PKS participants treated with a single (first) dose of BAY94-9027 as an IV infusion at Week 0.
OG001	BAY94-9027 Treatment - Part A, Week 36	Part A, Week 36 group included all PKS participants treated with multiple doses (last dose paired) of BAY94-9027 as an IV infusion at Week 36. Paired data were defined as the single dose data for the sub-set of participants who also had multiple dose PK data.

Units	Counts
Participants

Secondary

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

t1/2: Terminal half-life is the time the plasma concentration during terminal phase is halved following an infusion of 60 IU/kg .

PKS with participants evaluable for this outcome

Posted

Geometric Mean

Geometric Coefficient of Variation

Hours

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

ID	Title	Description
OG000	BAY94-9027 Treatment - Part A, Week 0	Part A, Week 0 included all PKS participants treated with a single (first) dose of BAY94-9027 as an IV infusion at Week 0.
OG001	BAY94-9027 Treatment - Part A, Week 36	Part A, Week 36 group included all PKS participants treated with multiple doses (last dose paired) of BAY94-9027 as an IV infusion at Week 36. Paired data were defined as the single dose data for the sub-set of participants who also had multiple dose PK data.

Units	Counts
Participants

Secondary

Overall Human Coagulation Factor VIII (FVIII) Recovery Value by Chromogenic Assay - Part A

Recovery was calculated by the following formula: Recovery = (post-infusion FVIII activity - pre-infusion FVIII activity ) * weight / dose (in IU). Recovery is the increase of FVIII activity after the injection normalized by dose: IU/dl per IU/kg = kg/dL

Part A ITT population

Posted

Mean

Standard Deviation

Kilogram per deciliter

Weeks 0 to 36 during Part A

ID	Title	Description
OG000	BAY94-9027 On-demand Treatment, Main Trial	Participants received on-demand treatment with BAY94-9027 as an intravenous (IV)infusion at a dose as indicated based upon location and severity of bleeds (a maximum of 60 international units per kilogram [IU/kg]).
OG001	BAY94-9027 Prophylaxis Treatment, Week 0-36, Main Trial	All participants in the prophylaxis arms started BAY94-9027 IV infusion, with 2x/week at a dose of 25 IU/kg for 10 weeks. Thereafter, participants with less than 2 spontaneous joint and/or muscle bleeds were randomized 1:1 to either every 5 or every 7 days dosing regimen. High bleeders continued 2x/week infusion (2x/week 'failed'). Participants qualified to be randomized, but enrolled after randomized arms were filled, remained on 2x/week treatment (2x/week 'forced' group).

Secondary

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

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

Part A ITT population with participants evaluable for this outcome

Posted

Mean

Standard Deviation

scores on a scale

Week 0 (baseline) and Week 36 during Part A

ID	Title	Description
OG000	BAY94-9027 On-demand Treatment, Main Trial	Participants received on-demand treatment with BAY94-9027 as an intravenous (IV)infusion at a dose as indicated based upon location and severity of bleeds (a maximum of 60 international units per kilogram [IU/kg]).
OG001	BAY94-9027 Prophylaxis Treatment, Week 0-36, Main Trial	All participants in the prophylaxis arms started BAY94-9027 IV infusion, with 2x/week at a dose of 25 IU/kg for 10 weeks. Thereafter, participants with less than 2 spontaneous joint and/or muscle bleeds were randomized 1:1 to either every 5 or every 7 days dosing regimen. High bleeders continued 2x/week infusion (2x/week 'failed'). Participants qualified to be randomized, but enrolled after randomized arms were filled, remained on 2x/week treatment (2x/week 'forced' group).

Other Pre-specified

Change From Baseline in Overall Pain Severity and Interference Due to Pain at Week 36 - Part A

Brief Pain Inventory (BPI) - Short Form (BPI-SF) was a 15-item, self-administered, validated tool developed to assess pain used in the study for patient reported outcomes. Scores ranged from 0 to 10 and a higher score indicates a higher level of pain/interference.

Analysis population includes participants evaluable in each category for this outcome.

Posted

Mean

Standard Deviation

scores on a scale

Week 0 (baseline) and Week 36 during Part A

ID	Title	Description
OG000	BAY94-9027 On-demand Treatment, Main Trial	Participants received on-demand treatment with BAY94-9027 as an intravenous (IV)infusion at a dose as indicated based upon location and severity of bleeds (a maximum of 60 international units per kilogram [IU/kg]).
OG001	BAY94-9027 Prophylaxis Treatment, Week 0-36, Main Trial	All participants in the prophylaxis arms started BAY94-9027 IV infusion, with 2x/week at a dose of 25 IU/kg for 10 weeks. Thereafter, participants with less than 2 spontaneous joint and/or muscle bleeds were randomized 1:1 to either every 5 or every 7 days dosing regimen. High bleeders continued 2x/week infusion (2x/week 'failed'). Participants qualified to be randomized, but enrolled after randomized arms were filled, remained on 2x/week treatment (2x/week 'forced' group).

Other Pre-specified

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

The WPAI is a validated instrument to assess the effect of hemophilia on ability to work, attend classes, and perform regular daily activities in participants 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.

Analysis population includes participants evaluable in each category for this outcome.

Posted

Mean

Standard Deviation

scores on a scale

Week 0 (baseline) and Week 36 during Part A

ID	Title	Description
OG000	BAY94-9027 On-demand Treatment, Main Trial	Participants received on-demand treatment with BAY94-9027 as an intravenous (IV)infusion at a dose as indicated based upon location and severity of bleeds (a maximum of 60 international units per kilogram [IU/kg]).
OG001	BAY94-9027 Prophylaxis Treatment Total, Main Trial	All participants receiving an schedule of prophylaxis treatment, all prophylaxis arms combined.

Other Pre-specified

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

For prophylaxis patients, the dose is related to all infusions.

ITT population part A week 10-36, 4 participants dropped out during week 0-10.

Posted

Median

Full Range

infusions

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

ID	Title	Description
OG000	BAY94-9027 On-demand Treatment, Main Trial	Participants received on-demand treatment with BAY94-9027 as an intravenous (IV)infusion at a dose as indicated based upon location and severity of bleeds (a maximum of 60 international units per kilogram [IU/kg]).
OG001	BAY94-9027 Prophylaxis Treatment, 2x/Week Failed, Main Trial	All participants started BAY94-9027 IV infusion with 2x/week at a dose of 25 IU/kg for 10 weeks. High bleeders (with 2 or more muscle or joint bleeds in the first 10 weeks) continued 2x/week infusion (2x/week 'failed') at a dose of 30 to 40 IU/kg.
OG002	BAY94-9027 Prophylaxis Treatment, 2x/Week Forced, Main Trial	All participants started BAY94-9027 IV infusion with 2x/week at a dose of 25 IU/kg for 10 weeks. Participants with < 2 spontaneous joint and/or muscle bleeds were randomized 1:1 to either every 5 or every 7 days dosing regimen. Participants enrolled after randomization arms were filled continued 2x/week treatment at a dose of 30-40 IU/kg (2x/week 'forced').

Other Pre-specified

Recombinant Human Factor VIII (rFVIII) Usage Expressed as Dose Per Kilogram With Prophylaxis Treatment - Part A

For prophylaxis patients, the dose per kilogram is related to prophylaxis infusions.

ITT population part A week 10-36, 4 participants dropped out during week 0-10.

Posted

Median

Full Range

IU/kg

Weeks 10 - 36 during Part A

ID	Title	Description
OG000	BAY94-9027 Prophylaxis Treatment, 2x/Week Failed, Main Trial	All participants started BAY94-9027 IV infusion with 2x/week at a dose of 25 IU/kg for 10 weeks. High bleeders (with 2 or more muscle or joint bleeds in the first 10 weeks) continued 2x/week infusion (2x/week 'failed') at a dose of 30 to 40 IU/kg.
OG001	BAY94-9027 Prophylaxis Treatment, 2x/Week Forced, Main Trial	All participants started BAY94-9027 IV infusion with 2x/week at a dose of 25 IU/kg for 10 weeks. Participants with < 2 spontaneous joint and/or muscle bleeds were randomized 1:1 to either every 5 or every 7 days dosing regimen. Participants enrolled after randomization arms were filled continued 2x/week treatment at a dose of 30-40 IU/kg (2x/week 'forced').
OG002	BAY94-9027 Prophylaxis Treatment, Every 5 Days, Main Trial	All participants started BAY94-9027 IV infusion with 2x/week at a dose of 25 IU/kg for 10 weeks. Participants with < 2 spontaneous joint and/or muscle bleeds were randomized 1:1 to either every 5 or every 7 days dosing regimen, participants randomized to the every 5 days treatment arm were to begin treatment with 45 IU/kg every 5 days with the option to increase dose up to 60 IU/kg/infusion.

Other Pre-specified

Number of Minor Surgeries According to Physician's Assessment of Adequacy of Hemostasis - Part A

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.

Part A ITT population

Posted

Number

minor surgeries

Weeks 0 to 36 during Part A

minor surgeries

ID	Title	Description
OG000	BAY94-9027 Treatment - Part A	This group included both on-demand and prophylaxis arms in Part A.

Units	Counts
Participants	OG000

Other Pre-specified

Number of Surgeries According to Physician's Assessment of Response to Hemostasis, Post-surgery - Part B Main Trial

Response to treatment during surgery was assessed by investigator/surgeon as excellent, good, moderate, poor or missing during Part B of the study.

Part B ITT population

Posted

Number

surgeries

Up to 3 weeks post-surgery during Part B

surgeries

ID	Title	Description
OG000	BAY949027 Treatment in Major Surgery, Part B	Participants who underwent major surgery received study drug during their hospital stay up to 3 weeks post surgery. Participants 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.

Units	Counts
Participants	OG000

Other Pre-specified

Number of Participants With Change/Drop in Hemoglobin/Hematocrit Laboratory Assessments - Part B

Hematocrit is defined as the volume percentage (%) of red blood cells in blood.

Part B Safety population (N=17) included all participants who received at least 1 dose of study drug during Part B of the study.

Posted

Count of Participants

Participants

Up to 3 weeks post-surgery during Part B

ID	Title	Description
OG000	BAY949027 Treatment in Major Surgery, Part B	Participants who underwent major surgery received study drug during their hospital stay up to 3 weeks post surgery. Participants 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.

Units	Counts
Participants	OG000

Other Pre-specified

Maximum Blood Loss During Major Surgery - Part B

Part B ITT population with participants treated for major surgery

Posted

Number

milliliter

day of surgery

surgeries

ID	Title	Description
OG000	BAY949027 Treatment in Major Surgery, Part B	Participants who underwent major surgery received study drug during their hospital stay up to 3 weeks post surgery. Participants 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.

Units	Counts
Participants	OG000

Other Pre-specified

Number of Participants Who Took Anti-fibrinolytic Medications During Major Surgery - Part B

Part B ITT population with participants treated for major surgery

Posted

Count of Participants

Participants

Up to 3 weeks post-surgery during Part B

ID	Title	Description
OG000	BAY949027 Treatment in Major Surgery, Part B	Participants who underwent major surgery received study drug during their hospital stay up to 3 weeks post surgery. Participants 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.

Units	Counts
Participants	OG000

Other Pre-specified

Volume of Blood Transfused in Major Surgery - Part B

Part B ITT population who had blood transfusions during major surgery

Posted

Median

Full Range

milliliter

Up to 3 weeks post-surgery during Part B

surgeries

ID	Title	Description
OG000	BAY949027 Treatment in Major Surgery, Part B	Participants who underwent major surgery received study drug during their hospital stay up to 3 weeks post surgery. Participants 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.

Units	Counts
Participants	OG000

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA (22.1)	Non-systematic Assessment	EG0000 events0 affected134 at risk EG0011 events1 affected121 at risk EG0020 events0 affected22 at risk
Angina unstable	Cardiac disorders	MedDRA (22.1)	Non-systematic Assessment	EG0000 events0 affected134 at risk EG0011 events1 affected121 at risk EG0020 events0 affected22 at risk
Macular fibrosis	Eye disorders	MedDRA (22.1)	Non-systematic Assessment	EG0000 events0 affected134 at risk EG0011 events1 affected121 at risk EG0020 events0 affected22 at risk
Anal fistula	Gastrointestinal disorders	MedDRA (22.1)	Non-systematic Assessment	EG0000 events0 affected134 at risk EG0012 events1 affected121 at risk EG0020 events0 affected22 at risk
Enterocolitis	Gastrointestinal disorders	MedDRA (22.1)	Non-systematic Assessment	EG0000 events0 affected134 at risk EG0011 events1 affected121 at risk EG0020 events0 affected22 at risk
Gastrointestinal haemorrhage	Gastrointestinal disorders	MedDRA (22.1)	Non-systematic Assessment	EG0000 events0 affected134 at risk EG0011 events1 affected121 at risk EG0020 events0 affected22 at risk
Inguinal hernia	Gastrointestinal disorders	MedDRA (22.1)	Non-systematic Assessment	EG0000 events0 affected134 at risk EG0013 events2 affected121 at risk EG0020 events0 affected22 at risk
Intestinal obstruction	Gastrointestinal disorders	MedDRA (22.1)	Non-systematic Assessment	EG0000 events0 affected134 at risk EG0011 events1 affected121 at risk EG0020 events0 affected22 at risk
Mouth haemorrhage	Gastrointestinal disorders	MedDRA (22.1)	Non-systematic Assessment	EG0000 events0 affected134 at risk EG0011 events1 affected121 at risk EG0020 events0 affected22 at risk
Pancreatitis acute	Gastrointestinal disorders	MedDRA (22.1)	Non-systematic Assessment	EG0001 events1 affected134 at risk EG0010 events0 affected121 at risk EG0020 events0 affected22 at risk
Retroperitoneal haematoma	Gastrointestinal disorders	MedDRA (22.1)	Non-systematic Assessment	EG0000 events0 affected134 at risk EG0011 events1 affected121 at risk EG0020 events0 affected22 at risk
Tooth impacted	Gastrointestinal disorders	MedDRA (22.1)	Non-systematic Assessment	EG0000 events0 affected134 at risk EG0012 events2 affected121 at risk EG0020 events0 affected22 at risk
Bile duct stone	Hepatobiliary disorders	MedDRA (22.1)	Non-systematic Assessment	EG0001 events1 affected134 at risk EG0010 events0 affected121 at risk EG0020 events0 affected22 at risk
Hepatic cirrhosis	Hepatobiliary disorders	MedDRA (22.1)	Non-systematic Assessment	EG0000 events0 affected134 at risk EG0011 events1 affected121 at risk EG0020 events0 affected22 at risk
Drug hypersensitivity	Immune system disorders	MedDRA (22.1)	Non-systematic Assessment	EG0001 events1 affected134 at risk EG0010 events0 affected121 at risk EG0020 events0 affected22 at risk
Anal abscess	Infections and infestations	MedDRA (22.1)	Non-systematic Assessment	EG0000 events0 affected134 at risk EG0013 events1 affected121 at risk EG0020 events0 affected22 at risk
Arthritis bacterial	Infections and infestations	MedDRA (22.1)	Non-systematic Assessment	EG0000 events0 affected134 at risk EG0011 events1 affected121 at risk EG0020 events0 affected22 at risk
Cellulitis	Infections and infestations	MedDRA (22.1)	Non-systematic Assessment	EG0000 events0 affected134 at risk EG0011 events1 affected121 at risk EG0020 events0 affected22 at risk
Device related infection	Infections and infestations	MedDRA (22.1)	Non-systematic Assessment	EG0001 events1 affected134 at risk EG0010 events0 affected121 at risk EG0020 events0 affected22 at risk
Gastroenteritis	Infections and infestations	MedDRA (22.1)	Non-systematic Assessment	EG0001 events1 affected134 at risk EG0010 events0 affected121 at risk EG0020 events0 affected22 at risk
Medical device site joint infection	Infections and infestations	MedDRA (22.1)	Non-systematic Assessment	EG0000 events0 affected134 at risk EG0011 events1 affected121 at risk EG0020 events0 affected22 at risk
Nasal vestibulitis	Infections and infestations	MedDRA (22.1)	Non-systematic Assessment	EG0000 events0 affected134 at risk EG0011 events1 affected121 at risk EG0020 events0 affected22 at risk
Pneumonia	Infections and infestations	MedDRA (22.1)	Non-systematic Assessment	EG0001 events1 affected134 at risk EG0010 events0 affected121 at risk EG0020 events0 affected22 at risk
Alcohol poisoning	Injury, poisoning and procedural complications	MedDRA (22.1)	Non-systematic Assessment	EG0001 events1 affected134 at risk EG0010 events0 affected121 at risk EG0020 events0 affected22 at risk
Contusion	Injury, poisoning and procedural complications	MedDRA (22.1)	Non-systematic Assessment	EG0000 events0 affected134 at risk EG0011 events1 affected121 at risk EG0020 events0 affected22 at risk
Fall	Injury, poisoning and procedural complications	MedDRA (22.1)	Non-systematic Assessment	EG0000 events0 affected134 at risk EG0011 events1 affected121 at risk EG0020 events0 affected22 at risk
Fibula fracture	Injury, poisoning and procedural complications	MedDRA (22.1)	Non-systematic Assessment	EG0000 events0 affected134 at risk EG0011 events1 affected121 at risk EG0020 events0 affected22 at risk
Hand fracture	Injury, poisoning and procedural complications	MedDRA (22.1)	Non-systematic Assessment	EG0000 events0 affected134 at risk EG0011 events1 affected121 at risk EG0020 events0 affected22 at risk
Head injury	Injury, poisoning and procedural complications	MedDRA (22.1)	Non-systematic Assessment	EG0000 events0 affected134 at risk EG0012 events2 affected121 at risk EG0020 events0 affected22 at risk
Humerus fracture	Injury, poisoning and procedural complications	MedDRA (22.1)	Non-systematic Assessment	EG0000 events0 affected134 at risk EG0011 events1 affected121 at risk EG0020 events0 affected22 at risk
Injury	Injury, poisoning and procedural complications	MedDRA (22.1)	Non-systematic Assessment	EG0001 events1 affected134 at risk EG0010 events0 affected121 at risk EG0020 events0 affected22 at risk
Ligament rupture	Injury, poisoning and procedural complications	MedDRA (22.1)	Non-systematic Assessment	EG0000 events0 affected134 at risk EG0011 events1 affected121 at risk EG0020 events0 affected22 at risk
Overdose	Injury, poisoning and procedural complications	MedDRA (22.1)	Non-systematic Assessment	EG0001 events1 affected134 at risk EG0010 events0 affected121 at risk EG0020 events0 affected22 at risk
Periprosthetic fracture	Injury, poisoning and procedural complications	MedDRA (22.1)	Non-systematic Assessment	EG0000 events0 affected134 at risk EG0011 events1 affected121 at risk EG0020 events0 affected22 at risk
Tendon rupture	Injury, poisoning and procedural complications	MedDRA (22.1)	Non-systematic Assessment	EG0001 events1 affected134 at risk EG0010 events0 affected121 at risk EG0020 events0 affected22 at risk
Tibia fracture	Injury, poisoning and procedural complications	MedDRA (22.1)	Non-systematic Assessment	EG0000 events0 affected134 at risk EG0011 events1 affected121 at risk EG0020 events0 affected22 at risk
Anti factor VIII antibody positive	Investigations	MedDRA (22.1)	Non-systematic Assessment	EG0000 events0 affected134 at risk EG0010 events0 affected121 at risk EG0022 events2 affected22 at risk
Colonoscopy	Investigations	MedDRA (22.1)	Non-systematic Assessment	EG0001 events1 affected134 at risk EG0010 events0 affected121 at risk EG0020 events0 affected22 at risk
Liver function test increased	Investigations	MedDRA (22.1)	Non-systematic Assessment	EG0000 events0 affected134 at risk EG0012 events1 affected121 at risk EG0020 events0 affected22 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA (22.1)	Non-systematic Assessment	EG0000 events0 affected134 at risk EG0011 events1 affected121 at risk EG0020 events0 affected22 at risk
Arthropathy	Musculoskeletal and connective tissue disorders	MedDRA (22.1)	Non-systematic Assessment	EG0001 events1 affected134 at risk EG0012 events1 affected121 at risk EG0020 events0 affected22 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA (22.1)	Non-systematic Assessment	EG0000 events0 affected134 at risk EG0013 events2 affected121 at risk EG0020 events0 affected22 at risk
Chondrocalcinosis pyrophosphate	Musculoskeletal and connective tissue disorders	MedDRA (22.1)	Non-systematic Assessment	EG0000 events0 affected134 at risk EG0011 events1 affected121 at risk EG0020 events0 affected22 at risk
Haemarthrosis	Musculoskeletal and connective tissue disorders	MedDRA (22.1)	Non-systematic Assessment	EG0001 events1 affected134 at risk EG0011 events1 affected121 at risk EG0020 events0 affected22 at risk
Haemophilic arthropathy	Musculoskeletal and connective tissue disorders	MedDRA (22.1)	Non-systematic Assessment	EG0001 events1 affected134 at risk EG0015 events4 affected121 at risk EG0020 events0 affected22 at risk
Osteoarthritis	Musculoskeletal and connective tissue disorders	MedDRA (22.1)	Non-systematic Assessment	EG0000 events0 affected134 at risk EG0011 events1 affected121 at risk EG0020 events0 affected22 at risk
Rotator cuff syndrome	Musculoskeletal and connective tissue disorders	MedDRA (22.1)	Non-systematic Assessment	EG0000 events0 affected134 at risk EG0011 events1 affected121 at risk EG0020 events0 affected22 at risk
Synovitis	Musculoskeletal and connective tissue disorders	MedDRA (22.1)	Non-systematic Assessment	EG0000 events0 affected134 at risk EG0011 events1 affected121 at risk EG0020 events0 affected22 at risk
Epilepsy	Nervous system disorders	MedDRA (22.1)	Non-systematic Assessment	EG0000 events0 affected134 at risk EG0011 events1 affected121 at risk EG0020 events0 affected22 at risk
Device malfunction	Product Issues	MedDRA (22.1)	Non-systematic Assessment	EG0001 events1 affected134 at risk EG0010 events0 affected121 at risk EG0020 events0 affected22 at risk
Depression	Psychiatric disorders	MedDRA (22.1)	Non-systematic Assessment	EG0000 events0 affected134 at risk EG0011 events1 affected121 at risk EG0020 events0 affected22 at risk
Hydronephrosis	Renal and urinary disorders	MedDRA (22.1)	Non-systematic Assessment	EG0000 events0 affected134 at risk EG0011 events1 affected121 at risk EG0020 events0 affected22 at risk
Nephrolithiasis	Renal and urinary disorders	MedDRA (22.1)	Non-systematic Assessment	EG0000 events0 affected134 at risk EG0011 events1 affected121 at risk EG0020 events0 affected22 at risk
Renal colic	Renal and urinary disorders	MedDRA (22.1)	Non-systematic Assessment	EG0000 events0 affected134 at risk EG0011 events1 affected121 at risk EG0020 events0 affected22 at risk
Ureterolithiasis	Renal and urinary disorders	MedDRA (22.1)	Non-systematic Assessment	EG0000 events0 affected134 at risk EG0011 events1 affected121 at risk EG0020 events0 affected22 at risk
Dermatitis exfoliative generalised	Skin and subcutaneous tissue disorders	MedDRA (22.1)	Non-systematic Assessment	EG0000 events0 affected134 at risk EG0011 events1 affected121 at risk EG0020 events0 affected22 at risk
Joint arthroplasty	Surgical and medical procedures	MedDRA (22.1)	Non-systematic Assessment	EG0000 events0 affected134 at risk EG0011 events1 affected121 at risk EG0020 events0 affected22 at risk
Knee arthroplasty	Surgical and medical procedures	MedDRA (22.1)	Non-systematic Assessment	EG0001 events1 affected134 at risk EG0010 events0 affected121 at risk EG0020 events0 affected22 at risk
Renal stone removal	Surgical and medical procedures	MedDRA (22.1)	Non-systematic Assessment	EG0000 events0 affected134 at risk EG0012 events1 affected121 at risk EG0020 events0 affected22 at risk
Ureteral stent insertion	Surgical and medical procedures	MedDRA (22.1)	Non-systematic Assessment	EG0000 events0 affected134 at risk EG0011 events1 affected121 at risk EG0020 events0 affected22 at risk
Haematoma	Vascular disorders	MedDRA (22.1)	Non-systematic Assessment	EG0000 events0 affected134 at risk EG0012 events2 affected121 at risk EG0021 events1 affected22 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Nausea	Gastrointestinal disorders	MedDRA (22.1)	Non-systematic Assessment	EG0006 events5 affected134 at risk EG0017 events5 affected121 at risk EG0022 events2 affected22 at risk
Pyrexia	General disorders	MedDRA (22.1)	Non-systematic Assessment	EG0001 events1 affected134 at risk EG00113 events10 affected121 at risk EG0023 events3 affected22 at risk
Influenza	Infections and infestations	MedDRA (22.1)	Non-systematic Assessment	EG0009 events5 affected134 at risk EG00112 events8 affected121 at risk EG0020 events0 affected22 at risk
Nasopharyngitis	Infections and infestations	MedDRA (22.1)	Non-systematic Assessment	EG00034 events24 affected134 at risk EG00155 events25 affected121 at risk EG0021 events1 affected22 at risk
Pharyngitis	Infections and infestations	MedDRA (22.1)	Non-systematic Assessment	EG0001 events1 affected134 at risk EG0019 events7 affected121 at risk EG0020 events0 affected22 at risk
Upper respiratory tract infection	Infections and infestations	MedDRA (22.1)	Non-systematic Assessment	EG0003 events3 affected134 at risk EG00114 events12 affected121 at risk EG0020 events0 affected22 at risk
Limb injury	Injury, poisoning and procedural complications	MedDRA (22.1)	Non-systematic Assessment	EG0003 events3 affected134 at risk EG0018 events8 affected121 at risk EG0020 events0 affected22 at risk
Procedural haemorrhage	Injury, poisoning and procedural complications	MedDRA (22.1)	Non-systematic Assessment	EG0000 events0 affected134 at risk EG0010 events0 affected121 at risk EG0023 events3 affected22 at risk
Procedural hypotension	Injury, poisoning and procedural complications	MedDRA (22.1)	Non-systematic Assessment	EG0000 events0 affected134 at risk EG0010 events0 affected121 at risk EG0022 events2 affected22 at risk
Procedural pain	Injury, poisoning and procedural complications	MedDRA (22.1)	Non-systematic Assessment	EG0002 events2 affected134 at risk EG0018 events7 affected121 at risk EG00210 events9 affected22 at risk
Haemoglobin decreased	Investigations	MedDRA (22.1)	Non-systematic Assessment	EG0000 events0 affected134 at risk EG0012 events2 affected121 at risk EG0023 events3 affected22 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA (22.1)	Non-systematic Assessment	EG00013 events11 affected134 at risk EG00140 events26 affected121 at risk EG0022 events2 affected22 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA (22.1)	Non-systematic Assessment	EG00010 events8 affected134 at risk EG00117 events14 affected121 at risk EG0020 events0 affected22 at risk
Haemarthrosis	Musculoskeletal and connective tissue disorders	MedDRA (22.1)	Non-systematic Assessment	EG0002 events2 affected134 at risk EG0018 events8 affected121 at risk EG0021 events1 affected22 at risk
Musculoskeletal pain	Musculoskeletal and connective tissue disorders	MedDRA (22.1)	Non-systematic Assessment	EG0004 events4 affected134 at risk EG00110 events7 affected121 at risk EG0020 events0 affected22 at risk
Osteoarthritis	Musculoskeletal and connective tissue disorders	MedDRA (22.1)	Non-systematic Assessment	EG0000 events0 affected134 at risk EG00112 events7 affected121 at risk EG0020 events0 affected22 at risk
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA (22.1)	Non-systematic Assessment	EG0006 events5 affected134 at risk EG00111 events8 affected121 at risk EG0020 events0 affected22 at risk
Headache	Nervous system disorders	MedDRA (22.1)	Non-systematic Assessment	EG00028 events16 affected134 at risk EG00121 events14 affected121 at risk EG0020 events0 affected22 at risk
Insomnia	Psychiatric disorders	MedDRA (22.1)	Non-systematic Assessment	EG0003 events3 affected134 at risk EG0011 events1 affected121 at risk EG0022 events2 affected22 at risk
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA (22.1)	Non-systematic Assessment	EG00011 events8 affected134 at risk EG00111 events9 affected121 at risk EG0020 events0 affected22 at risk
Epistaxis	Respiratory, thoracic and mediastinal disorders	MedDRA (22.1)	Non-systematic Assessment	EG00010 events8 affected134 at risk EG0016 events6 affected121 at risk EG0020 events0 affected22 at risk
Rash	Skin and subcutaneous tissue disorders	MedDRA (22.1)	Non-systematic Assessment	EG0001 events1 affected134 at risk EG0016 events3 affected121 at risk EG0022 events2 affected22 at risk
Haematoma	Vascular disorders	MedDRA (22.1)	Non-systematic Assessment	EG0000 events0 affected134 at risk EG0013 events3 affected121 at risk EG0022 events2 affected22 at risk

ID	Term
D025861	Blood Coagulation Disorders, Inherited
D001778	Blood Coagulation Disorders
D006402	Hematologic Diseases
D006425	Hemic and Lymphatic Diseases
D020147	Coagulation Protein Disorders
D006474	Hemorrhagic Disorders
D030342	Genetic Diseases, Inborn
D009358	Congenital, Hereditary, and Neonatal Diseases and Abnormalities

ID	Term
D001779	Blood Coagulation Factors
D001798	Blood Proteins
D011506	Proteins
D000602	Amino Acids, Peptides, and Proteins
D011498	Protein Precursors
D001685	Biological Factors

ID	Title	Description	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	BAY94-9027 Treatment, Part A, Main Trial	Subjects entering Part A main trial were treated with BAY 94-9027 for either on-demand or prophylactic treatment.	134	13	134	67	134
EG001	BAY94-9027 Treatment, Part A, Extension	Subjects in Part A extension either continued their regimen from main trial or switched to one of the other regimens at any time.	121	36	121	74	121
EG002	BAY94-9027 Treatment in Major Surgery, Part B	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.	22	2	22	16	22