Prophylaxis Study of Recombinant Factor VIII Manufactured... | NCT00243386

Prophylaxis Study of Recombinant Factor VIII Manufactured... | NCT00243386 | Trialant

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
1	Active Comparator	Standard prophylaxis	Drug: Antihemophilic factor, recombinant, manufactured protein-free
2	Experimental	PK-driven prophylaxis	Drug: Antihemophilic factor, recombinant, manufactured protein-free

Interventions

Name	Type	Description	Arm Group Labels	Other Names
Antihemophilic factor, recombinant, manufactured protein-free	Drug	Standard prophylaxis: 20-40 IU/kg every 48+/-6 hours, actual dose determined by investigator	1

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Mean Transformed Annualized Bleed Rate Estimates From Each of the 1-year Prophylaxis Regimens	Participants were Randomized to Receive 1 of the 2 Following Prophylaxis Regimens (Study Part 2): 1. Standard prophylaxis (20-40 IU/kg (every 48 ±6 hour), exact regimen determined by investigator) 2. PK-driven prophylaxis (20-80 IU/kg (every 72 ±6 hour), exact regimen determined by sponsor) Annualized bleed rates were transformed using the square root of the number of bleeding episodes observed (X = bleeds/year), X' = √(X + 0.5). This transformation was performed to stabilize the variance and align the sample distribution with the assumption of normality inherent in using the t-test.	12 months ±2 weeks
Median Annualized Bleed Rate Estimates From Each of the 1 Year Prophylaxis Regimens	Participants were Randomized to Receive 1 of the 2 Following Prophylaxis Regimens (Part 2 of the study): 1. Standard prophylaxis- infusions every 48 ±6 hours, dosed at 20 to 40 IU/kg. 2. PK-driven prophylaxis- infusions every 72 ±6 hours dosed at 20 to 80 IU/kg.	12 months ±2 weeks

Secondary Outcomes

Measure	Description	Time Frame
Mean Difference of Transformed Annualized Bleeding Rate Between On-Demand and Standard Prophylaxis Treatment Regimens	Annualized bleed rates were transformed using the square root of the number of bleeding episodes observed (X bleeds/year), X' = √(X + 0.5). This transformation was performed to stabilize the variance and align the sample distribution with the assumption of normality inherent in using the paired t-test. Mean Difference of Transformed Annualized Bleeding Rate (TABR) = (On-Demand Treatment TABR) - (Standard Prophylaxis Treatment TABR). Participants from the On-Demand portion of the study were subsequently randomized to either Standard Prophylaxis or PK-Driven Prophylaxis, (i.e the same participants were analyzed across the two measurement time periods).

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

The subject has severe or moderately severe hemophilia A as defined by a baseline factor VIII level <= 2% of normal, as tested at screening
The subject has a documented history of at least 150 exposure days to factor VIII concentrates (either plasma-derived or recombinant)
The subject is within 7 to 65 years of age
The subject has a Karnofsky performance score > (greater than) 60
The subject is human immunodeficiency virus negative (HIV-) or is HIV+ with a CD4 count >= 400 cells/mm³ (CD4 count determined at screening, if necessary)
The subject has been on a documented on-demand treatment regimen for at least 12 months immediately prior to enrollment
The subject has a documented history (e.g. in medical charts or dispensing information, or signed investigator statement) of at least 8 joint hemorrhages in the 12 months immediately prior to enrollment
The subject resides within the coverage area of the mobile compliance device; coverage area will be determined at screening
The subject or the subject's legally authorized representative has provided written informed consent

Exclusion Criteria:

The subject has a known hypersensitivity to factor VIII concentrates or mouse or hamster proteins
The subject has a history of factor VIII inhibitors with a titer >= 0.6 BU (by Bethesda or Nijmegen assay) at any time prior to screening
The subject has a detectable factor VIII inhibitor at screening, with a titer >= 0.4 BU (by Nijmegen Assay) in the central laboratory
The subject has severe chronic liver disease as evidenced by, but not limited to, any of the following: International Normalized Ratio (INR) > 1.4, hypoalbuminemia, portal vein hypertension including presence of otherwise unexplained splenomegaly and history of esophageal varices.
The subject has been diagnosed with an inherited or acquired hemostatic defect other than hemophilia A (e.g., qualitative platelet defect or von Willebrand's Disease)
The subject has been treated during the last sixty (60) days prior to or is being treated at screening/enrollment with an immunomodulating drug.
The subject has participated in another investigational study within thirty (30) days of enrollment
The subject has previously participated in a clinical study with rAHF-PFM
The subject's clinical condition may require a major surgery (defined as moderate to critical risk and perioperative blood loss ≥ 500 mL) during the period of the subject's participation in the study
The subject is female of childbearing potential with a positive pregnancy test

Contacts/Locations Module

Name	Affiliation	Role
Study Director	Takeda	Study Director

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
22212248	Derived	Valentino LA, Mamonov V, Hellmann A, Quon DV, Chybicka A, Schroth P, Patrone L, Wong WY; Prophylaxis Study Group. A randomized comparison of two prophylaxis regimens and a paired comparison of on-demand and prophylaxis treatments in hemophilia A management. J Thromb Haemost. 2012 Mar;10(3):359-67. doi: 10.1111/j.1538-7836.2011.04611.x.

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	All Study Participants	Participants first underwent an open-label pharmacokinetic (PK) evaluation of rAHF-PFM. 48 hours after the initial PK study, a 6 month period of on-demand treatment was conducted (Part 1). After completing the on-demand treatment, participants were randomized to 1 of 2 prophylactic regimens for 12 months ±2 weeks (Part 2). The standard prophylactic regimen was dosed at 20 to 40 IU/kg every 48 ±6 hours, and the PK-driven prophylaxis regimen was dosed at 20 to 80 IU/kg every 72 ±6 hours.

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Type	Comment	Reasons
Withdrawal by Subject		FG0001 subjects FG0010 subjects FG0020 subjects
Lost to Follow-up		FG0001 subjects FG0010 subjects FG0020 subjects
Screen Failures		FG0002 subjects FG0010 subjects FG0020 subjects

End of Part 1, But Prior to Prophylaxis

Type	Comment	Milestone Data
STARTED		FG00069 subjects FG0010 subjectsParticipants were randomized to PK-Driven or Standard Prophylaxis after Part 1 (On-Demand Regimen) FG0020 subjectsParticipants were randomized to PK-Driven or Standard Prophylaxis after Part 1 (On-Demand Regimen)
COMPLETED		FG00066 subjects FG0010 subjects FG0020 subjects
NOT COMPLETED		FG0003 subjects FG0010 subjects FG0020 subjects

Type	Comment	Reasons
Withdrawal by Subject		FG0001 subjects FG0010 subjects FG0020 subjects
Lost to Follow-up		FG000

PK-Driven or Standard Prophylaxis

Type	Comment	Milestone Data
STARTED		FG0000 subjectsParticipants were randomized to PK-Driven or Standard Prophylaxis after Part 1 (On-Demand Regimen) FG00134 subjects FG00232 subjects
COMPLETED		FG0000 subjects FG00131 subjects FG00232 subjects
NOT COMPLETED		FG0000 subjects FG0013 subjects FG0020 subjects

Type	Comment	Reasons
Withdrawn for Non-Compliance		FG0000 subjects FG0012 subjects FG0020 subjects
Lack of Efficacy		FG000

Arm/Group Information

ID	Title	Description
BG000	All Study Participants	Participants first underwent an open-label evaluation of rAHF-PFM PK. 48 hours after the initial PK study, a 6 month period of on-demand treatment was conducted (Part 1). After completing the on-demand treatment, participants were randomized to 1 of 2 prophylactic regimens for 12 months ±2 weeks (Part 2). The standard prophylactic regimen was dosed at 20 to 40 IU/kg every 48 ±6 hours, and the PK-driven prophylaxis regimen was dosed at 20 to 80 IU/kg every 72 ±6 hours.

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Continuous

Median

Full Range

years

Title

Denominators

Categories

Title	Measurements
	BG00026(7 to 59)

Sex: Female, Male

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG0000
Male	BG00073

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

Mean Transformed Annualized Bleed Rate Estimates From Each of the 1-year Prophylaxis Regimens

Participants were Randomized to Receive 1 of the 2 Following Prophylaxis Regimens (Study Part 2): 1. Standard prophylaxis (20-40 IU/kg (every 48 ±6 hour), exact regimen determined by investigator) 2. PK-driven prophylaxis (20-80 IU/kg (every 72 ±6 hour), exact regimen determined by sponsor) Annualized bleed rates were transformed using the square root of the number of bleeding episodes observed (X = bleeds/year), X' = √(X + 0.5). This transformation was performed to stabilize the variance and align the sample distribution with the assumption of normality inherent in using the t-test.

Per Protocol

Posted

Mean

Standard Deviation

(bleeds/year)^(1/2)

12 months ±2 weeks

ID	Title	Description
OG000	PK-Driven Prophylaxis	PK-driven prophylaxis regimen dosed at 20 to 80 IU/kg every 72 ±6 hours
OG001	Standard Prophylaxis	Standard prophylaxis regimen dosed at 20 to 40 IU/kg every 48 ±6 hours

Units	Counts
Participants	OG00023 OG00130

Title

Denominators

Categories

Title	Measurements
	OG0001.61± 1.10 OG0011.46± 0.98

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001	A t-test was used to compare the means of the transformed data. The null-hypothesis tested was H0: X'A(PK-driven prophylaxis) - X'B (standard prophylaxis) = 0 (i.e., no difference for treatment under the 2 prophylactic regimens. X' = (ABR+0.5)^(1/2)	t-test, 2 sided		0.6016							95							Superiority or Other (legacy)

Secondary

Mean Difference of Transformed Annualized Bleeding Rate Between On-Demand and Standard Prophylaxis Treatment Regimens

Annualized bleed rates were transformed using the square root of the number of bleeding episodes observed (X bleeds/year), X' = √(X + 0.5). This transformation was performed to stabilize the variance and align the sample distribution with the assumption of normality inherent in using the paired t-test. Mean Difference of Transformed Annualized Bleeding Rate (TABR) = (On-Demand Treatment TABR) - (Standard Prophylaxis Treatment TABR). Participants from the On-Demand portion of the study were subsequently randomized to either Standard Prophylaxis or PK-Driven Prophylaxis, (i.e the same participants were analyzed across the two measurement time periods).

Intent to treat

Posted

Mean

Standard Deviation

(bleeds/year)^(1/2)

On-demand 6 months (± 2 weeks); followed by Prophylaxis 12 months (± 2 weeks)

ID	Title	Description
OG000	On-Demand Versus Standard Prophylaxis	On-demand: rAHF-PFM was to be used for the treatment of bleeding episodes according to the severity and type of episode by the protocol-recommended dosing until the episode resolved: superficial (10-20 IU/kg every 12-14 hours), minor joint (20-40 IU/kg every 12-14 hours), deep muscle (30-60 IU/kg every 12-14 hours), major joint or life-threatening (60-100 IU/kg every 8-12 hours), genitourinary, Gastrointestinal (GI), and intracranial (60-100 IU/kg every 8-12 hours) Standard Prophylaxis: 20-40 IU/kg (every 48 ± 6 hours), exact regimen to be determined by the investigator

Secondary

Mean Difference of Transformed Annualized Bleeding Rate Between On-Demand and PK-Driven Prophylaxis Treatment Regimens

Annualized bleed rates were transformed using the square root of the number of bleeding episodes observed (X bleeds/year), X' = √(X + 0.5). This transformation was performed to stabilize the variance and align the sample distribution with the assumption of normality inherent in using the paired t-test. Mean Difference of Transformed Annualized Bleeding Rate (TABR) = (On-Demand Treatment TABR) - (PK-Driven Prophylaxis Treatment TABR) Participants from the On-Demand portion of the study were subsequently randomized to either Standard Prophylaxis or PK-Driven Prophylaxis, (i.e the same participants were analyzed across the two measurement time periods).

Intent to treat

Posted

Mean

Standard Deviation

(bleeds/year)^(1/2)

On-demand 6 months (± 2 weeks); followed by Prophylaxis 12 months (± 2 weeks)

ID	Title	Description
OG000	On-Demand Versus PK-Driven Prophylaxis	On-demand: rAHF-PFM was to be used for the treatment of bleeding episodes according to the severity and type of episode by the protocol-recommended dosing until the episode resolved: superficial (10-20 IU/kg every 12-14 hours), minor joint (20-40 IU/kg every 12-14 hours), deep muscle (30-60 IU/kg every 12-14 hours), major joint or life-threatening (60-100 IU/kg every 8-12 hours), genitourinary, GI, and intracranial (60-100 IU/kg every 8-12 hours) PK-driven prophylaxis: 20-80 IU/kg (every 72 ± 6 hours), exact regimen to be determined by the sponsor

Secondary

Mean Difference of Transformed Annualized Bleeding Rate Between On-Demand and Any Prophylaxis Treatment Regimens

Annualized bleed rates were transformed using the square root of the number of bleeding episodes observed (X bleeds/year), X' = √(X + 0.5). This transformation was performed to stabilize the variance and align the sample distribution with the assumption of normality inherent in using the paired t-test. Mean Difference of Transformed Annualized Bleeding Rate (TABR) = (On-Demand Treatment TABR) - (Any Prophylaxis Treatment TABR). Any Prophylaxis = Standard or PK-Driven Prophylaxis Participants from the On-Demand portion of the study were subsequently randomized to either Standard Prophylaxis or PK-Driven Prophylaxis, (i.e the same participants were analyzed across the two measurement time periods).

Intent to treat

Posted

Mean

Standard Deviation

(bleeds/year)^(1/2)

On-demand 6 months (± 2 weeks); Prophylaxis 12 months (± 2 weeks)

ID	Title	Description
OG000	On-Demand Versus Any Prophylaxis	On-demand: rAHF-PFM was to be used for the treatment of bleeding episodes according to the severity and type of episode by the protocol-recommended dosing until the episode resolved: superficial (10-20 IU/kg every 12-14 hours), minor joint (20-40 IU/kg every 12-14 hours), deep muscle (30-60 IU/kg every 12-14 hours), major joint or life-threatening (60-100 IU/kg every 8-12 hours), genitourinary, GI, and intracranial (60-100 IU/kg every 8-12 hours) Prophylaxis: •Standard prophylaxis: 20-40 IU/kg (every 48 ± 6 hours), exact regimen to be determined by the investigator •PK-driven prophylaxis: 20-80 IU/kg (every 72 ± 6 hours), exact regimen to be determined by the sponsor

Secondary

Total Weight-Adjusted Dose of rAHF-PFM Used Per Year for Each Prophylaxis Arm

Participants were Randomized to Receive 1 of the 2 Following Prophylaxis Regimens (Part 2 of the study): 1. Standard prophylaxis- infusions every 48 ±6 hours, dosed at 20 to 40 IU/kg. 2. PK-driven prophylaxis- infusions every 72 ±6 hours dosed at 20 to 80 IU/kg.

Intent to treat

Posted

Median

Inter-Quartile Range

IU/kg

12 months ±2 weeks

ID	Title	Description
OG000	PK-Driven Prophylaxis	PK-driven prophylaxis regimen dosed at 20 to 80 IU/kg every 72 ±6 hours
OG001	Standard Prophylaxis	Standard prophylaxis regimen dosed at 20 to 40 IU/kg every 48 ±6 hours

Units	Counts
Participants	OG000

Secondary

Bleeding Episodes Treated With 1 to ≥4 Infusions

The number of bleeding episodes treated with 1, 2, 3, or ≥4 infusions of rAHF-PFM to achieve adequate hemostasis

Intent to Treat Efficacy Set

Posted

Number

Bleeding episodes

Throughout the study period (4 years and 5 months)

ID	Title	Description
OG000	On-Demand Treatment	rAHF-PFM was to be used for the treatment of bleeding episodes according to the severity and type of episode by the protocol-recommended dosing until the episode resolved: superficial (10-20 IU/kg every 12-14 hours), minor joint (20-40 IU/kg every 12-14 hours), deep muscle (30-60 IU/kg every 12-14 hours), major joint or life-threatening (60-100 IU/kg every 8-12 hours), genitourinary, GI, and intracranial (60-100 IU/kg every 8-12 hours)
OG001	Standard Prophylaxis Treatment	20-40 IU/kg (every 48 ± 6 hours), exact regimen to be determined by the investigator
OG002	PK-Driven Prophylaxis	20-80 IU/kg (every 72 ± 6 hours), exact regimen to be determined by the sponsor

Secondary

Assessment of Hemostasis for Treatment of Bleeding Episodes

Number of rAHF-PFM-treated bleeding episodes with an assessment of hemostasis (4-point ordinal scale): Excellent: Full pain relief & bleeding cessation within ~8 hrs of 1 infusion. Additional infusions may have been given to maintain hemostasis; Good: Definite pain relief and/or improvement in bleeding within ~8 hrs after infusion. Possibly requires >1 infusion for complete resolution; Fair: Probable or slight relief of pain & slight improvement in bleeding within ~8 hrs after infusion. Requires >1 infusion for complete resolution; None: No improvement or condition worsens

Hemostatic Efficacy Rating Analysis Set (Participants with bleeding episodes that were rated)

Posted

Number

bleeding episodes

On-demand 6 months (± 2 weeks); Prophylaxis 12 months (± 2 weeks)

ID	Title	Description
OG000	On-Demand Regimen	rAHF-PFM was to be used for the treatment of bleeding episodes according to the severity and type of episode by the protocol-recommended dosing until the episode resolved: superficial (10-20 IU/kg every 12-14 hours), minor joint (20-40 IU/kg every 12-14 hours), deep muscle (30-60 IU/kg every 12-14 hours), major joint or life-threatening (60-100 IU/kg every 8-12 hours), genitourinary, GI, and intracranial (60-100 IU/kg every 8-12 hours)
OG001	Standard Prophylaxis	20-40 IU/kg (every 48 ± 6 hours), exact regimen to be determined by the investigator

Secondary

Total Area Under the Curve (AUC)

Total AUC estimated by AUC 0-48h plus an area extrapolated from the log-linear regression model

Intent to Treat Pharmacokinetic Analysis Set

Posted

Geometric Mean

Standard Deviation

IU*h/dL

Pharmacokinetic evaluations: 30 minutes pre-infusion up to 48 hours post-infusion

ID	Title	Description
OG000	≥14 Years of Age
OG001	<14 Years of Age

Units	Counts
Participants	OG000

Secondary

Area Under the Curve

Area under the factor VIII (FVIII) plasma concentration versus time curve (AUC) from 0 to 48 hours estimated using the linear trapezoidal method

Intent to Treat Pharmacokinetic Analysis Set

Posted

Geometric Mean

Standard Deviation

IU*h/dL

Pharmacokinetic evaluations: 30 minutes pre-infusion up to 48 hours post-infusion

ID	Title	Description
OG000	≥14 Years of Age
OG001	<14 Years of Age

Units	Counts
Participants	OG000

Secondary

Maximum Plasma Concentration (C-max)

Maximal Factor VIII Concentration After Infusion

Intent to Treat Pharmacokinetic Analysis Set

Posted

Geometric Mean

Standard Deviation

IU/dL

Within 1 hour post-infusion

ID	Title	Description
OG000	≥14 Years of Age
OG001	<14 Years of Age

Units	Counts
Participants	OG00065 OG001

Secondary

Adjusted Incremental Recovery (IR)

Change in factor VIII concentration from pre- to post-infusion at initial and termination study visits. Adjusted IR defined as: [Cmax (IU/dL) - pre-infusion FVIII (IU/dL)]/dose (IU/kg)

Intent to Treat Pharmacokinetic Analysis Set

Posted

Geometric Mean

Standard Deviation

IU/dL per IU/kg

30 minutes pre-infusion to 48 hours post-infusion

ID	Title	Description
OG000	≥14 Years of Age
OG001	<14 Years of Age

Units	Counts
Participants	OG000

Secondary

Terminal Half-life

Computed from the regression slope in the terminal phase of the model. Terminal half life is the time it takes for the plasma concentration or the amount of drug in the body to be reduced by 50%.

Intent to Treat Pharmacokinetic Analysis Set

Posted

Mean

Standard Deviation

hours

Pharmacokinetic evaluations: 30 minutes pre-infusion up to 48 hours post-infusion

ID	Title	Description
OG000	≥14 Years of Age
OG001	<14 Years of Age

Units	Counts
Participants	OG000

Secondary

Weight-Adjusted Clearance

Computed as the weight-adjusted dose divided by total AUC

Intent to Treat Pharmacokinetic Analysis Set

Posted

Mean

Standard Deviation

mL/(kg*h)

Pharmacokinetic evaluations: 30 minutes pre-infusion up to 48 hours post-infusion

ID	Title	Description
OG000	≥14 Years of Age
OG001	<14 Years of Age

Units	Counts
Participants	OG00065

Secondary

Mean Residence Time

Computed as total Area Under the Moment Curve (AUMC) divided by the total AUC

Intent to Treat Pharmacokinetic Analysis Set

Posted

Mean

Standard Deviation

hours

Pharmacokinetic evaluations: 30 minutes pre-infusion up to 48 hours post-infusion

ID	Title	Description
OG000	≥14 Years of Age
OG001	<14 Years of Age

Units	Counts
Participants	OG00065

Secondary

Volume of Distribution at Steady State

Computed as weight-adjusted clearance * mean residence time

Intent to Treat Pharmacokinetic Analysis Set

Posted

Mean

Standard Deviation

dL/kg

Pharmacokinetic evaluations: 30 minutes pre-infusion up to 48 hours post-infusion

ID	Title	Description
OG000	≥14 Years of Age
OG001	<14 Years of Age

Units	Counts
Participants	OG00065

Secondary

Factor VIII Inhibitor Development

Number of treated participants who developed factor VIII inhibitors

Safety Analysis Set

Posted

Number

Participants

Throughout study period (4 years and 5 months)

ID	Title	Description
OG000	All Study Participants	All participants who were exposed to Investigational Product (IP)

Units	Counts
Participants	OG00073

Secondary

Number of Participants With AEs Related to Investigational Product (IP)

Number of treated participants with AEs judged to be possibly or probably related to treatment with IP

Safety Analysis Set

Posted

Number

Participants

Throughout study period (4 years and 5 months)

ID	Title	Description
OG000	All Study Participants	All participants who were exposed to IP

Units	Counts
Participants	OG00073

Secondary

Number of Participants Who Reported ≥1 AE Regardless of Relatedness to Investigational Product (IP)

Number of treated participants with 1 or more AE regardless of relatedness to IP

Safety Analysis Set

Posted

Number

Participants

Throughout study period (4 years and 5 months)

ID	Title	Description
OG000	All Study Participants	All participants who were exposed to IP

Units	Counts
Participants	OG00073

Secondary

Number of Participants Who Reported ≥1 AE Regardless of Relatedness to IP by Treatment Regimen

Safety Analysis Set

Posted

Number

participants

Throughout the study period (4 years and 5 months)

ID	Title	Description
OG000	On-Demand	rAHF-PFM was to be used for the treatment of bleeding episodes according to the severity and type of episode by the protocol-recommended dosing until the episode resolved: superficial (10-20 IU/kg every 12-14 hours), minor joint (20-40 IU/kg every 12-14 hours), deep muscle (30-60 IU/kg every 12-14 hours), major joint or life-threatening (60-100 IU/kg every 8-12 hours), genitourinary, GI, and intracranial (60-100 IU/kg every 8-12 hours)
OG001	Standard Prophylaxis	20-40 IU/kg (every 48 ± 6 hours), exact regimen to be determined by the investigator
OG002	PK-Driven Prophylaxis	20-80 IU/kg (every 72 ± 6 hours), exact regimen to be determined by the sponsor

Units	Counts
Participants

Secondary

Number of Participants With SAEs by Preferred MedDRA Term and Treatment Regimen

Safety Analysis Set

Posted

Number

participants

Throughout the study period (4 years and 5 months)

ID	Title	Description
OG000	On-Demand
OG001	Standard Prophylaxis	20-40 IU/kg (every 48 ± 6 hours), exact regimen to be determined by the investigator
OG002	PK-Driven Prophylaxis	20-80 IU/kg (every 72 ± 6 hours), exact regimen to be determined by the sponsor
OG003	SAEs Outside of the 3 Treatment Arms	Participants with SAEs that occurred after exposure to investigational product, but outside of the three treatment arms

Units	Counts
Participants

Secondary

AEs With Onset ≤1 Hour Following the End of an Infusion, Regardless of Relatedness

Safety Analysis Set

Posted

Number

Events

Throughout study period (4 years and 5 months)

ID	Title	Description
OG000	All Study Participants	All participants who were exposed to investigational product (IP)

Units	Counts
Participants	OG00073

Title	Denominators	Categories

Secondary

Number of Participants With Severe SAEs and Severe Non-SAEs by Preferred MedDRA Term and Treatment Regimen

This outcome is focused only on SEVERE SAEs and SEVERE non-SAEs

Safety Analysis Set

Posted

Number

participants

Throughout the study period (4 years and 5 months)

ID	Title	Description
OG000	On-Demand	rAHF-PFM was to be used for the treatment of bleeding episodes according to the severity and type of episode by the protocol-recommended dosing until the episode resolved: superficial (10-20 IU/kg every 12-14 hours), minor joint (20-40 IU/kg every 12-14 hours), deep muscle (30-60 IU/kg every 12-14 hours), major joint or life-threatening (60-100 IU/kg every 8-12 hours), genitourinary, GI, and intracranial (60-100 IU/kg every 8-12 hours
OG001	Standard Prophylaxis	20-40 IU/kg (every 48 ± 6 hours), exact regimen to be determined by the investigator
OG002	PK-Driven Prophylaxis	20-80 IU/kg (every 72 ± 6 hours), exact regimen to be determined by the sponsor

Secondary

Baseline Health-related Quality of Life (HRQoL) Scores: PF, RP, BP, GH, VT, SF, RE, MH, PCS, and MCS

Physical Functioning (PF); Role Limitation Due to Physical Health (RP); Bodily Pain (BP); General Health (GH); Vitality (VT); Social Functioning (SF); Role Limitation Due to Emotional Problems (RE); Mental Health (MH), Physical Component Score (PCS); Mental Component Score (MCS). Baseline SF-36v1 Scores, where data available. Scores range 0-100, higher scores represent better health. There is no total overall score; scoring is done for subscores and summary scores. The raw data from the SF-36 items were transformed to norm based scores for each of the 8 HRQoL/SF-36 health domain scores.

Safety Analysis Set

Posted

Median

Full Range

Scores on a scale

Baseline

ID	Title	Description
OG000	Assessed Before Treatment

Units	Counts
Participants	OG000

Secondary

Health-related Quality of Life (HRQoL) Scores: PF, RP, BP, GH, VT, SF, RE, MH, PCS, and MCS at the End of Treatment Regimens

Pharmacoeconomic Analysis Set

Posted

Median

Full Range

Scores on a scale

End of on-demand treatment period (6 months) and at study termination (approximately 18 months)

ID	Title	Description
OG000	On-Demand Treatment	rAHF-PFM was to be used for the treatment of bleeding episodes according to the severity and type of episode by the protocol-recommended dosing until the episode resolved: superficial (10-20 IU/kg every 12-14 hours), minor joint (20-40 IU/kg every 12-14 hours), deep muscle (30-60 IU/kg every 12-14 hours), major joint or life-threatening (60-100 IU/kg every 8-12 hours), genitourinary, GI, and intracranial (60-100 IU/kg every 8-12 hours
OG001	Standard Prophylaxis	20-40 IU/kg (every 48 ± 6 hours), exact regimen to be determined by the investigator

Secondary

HRQoL Scores Change From On-Demand Treatment Regimen Period Through Prophylaxis Period

Differences in health domain scores = (End of on-demand treatment) - (End of prophylaxis regimen). A negative value for the median difference equates to a larger domain score for the prophylaxis regimen Physical Functioning (PF); Role Limitation Due to Physical Health (RP); Bodily Pain (BP); General Health (GH); Vitality (VT); Social Functioning (SF); Role Limitation Due to Emotional Problems (RE); Mental Health (MH), Physical Component Score (PCS); Mental Component Score (MCS). Scores range 0-100, higher scores represent better health. There is no total overall score; scoring is done for subscores and summary scores. The raw data from the SF-36 items were transformed to norm based scores for each of the 8 HRQoL/SF-36 health domain scores.

Pharmacoeconomic Analysis Set ≥14 Years and Older

Posted

Median

Full Range

Scores on a scale

End of on-demand treatment period (6 months) and at study termination (approximately 18 months)

ID	Title	Description
OG000	On-Demand to Standard Prophylaxis
OG001	On-Demand to PK-Driven Prophylaxis
OG002	On-Demand to Any Prophylaxis Treatment

Primary

Median Annualized Bleed Rate Estimates From Each of the 1 Year Prophylaxis Regimens

Intent to treat

Posted

Median

Full Range

Bleeds per year

12 months ±2 weeks

ID	Title	Description
OG000	PK-Driven Prophylaxis	PK-driven prophylaxis regimen dosed at 20 to 80 IU/kg every 72 ±6 hours
OG001	Standard Prophylaxis	Standard prophylaxis regimen dosed at 20 to 40 IU/kg every 48 ±6 hours

Units	Counts
Participants	OG000

Secondary

Bodily Pain HRQoL Scores Change From On-Demand Period Through Prophylaxis Period

Change = (End of on-demand treatment) - (End of prophylaxis regimen). A negative value for the median difference equates to a larger domain score for the prophylaxis regimen. Scores range 0-100, higher scores represent better health. There is no total overall score; scoring is done for subscores and summary scores. The raw data from the SF-36 items were transformed to norm based scores.

Pharmacoeconomic analysis set for participants ≥14 years of age

Posted

Median

Full Range

Scores on a scale

End of on-demand treatment period (6 months) and at study termination (approximately 18 months)

ID	Title	Description
OG000	≥14 Years of Age	After an on-demand treatment period, participants were randomized to 1 of 2 prophylactic regimens for 12 months. The standard prophylactic regimen was dosed at 20 to 40 IU/kg every 48 ±6 hours, and the PK-driven prophylaxis regimen was dosed at 20 to 80 IU/kg every 72 ±6 hours.

Units	Counts
Participants	OG000

Secondary

Physical Component Scores (PCS) HRQoL Scores Change From On-Demand Period Through Prophylaxis Period

Change = (End of on-demand treatment) - (End of prophylaxis regimen) A negative value for the median difference equates to a larger domain score for the prophylaxis regimen. Scores range 0-100, higher scores represent better health. There is no total overall score; scoring is done for subscores and summary scores. The raw data from the SF-36 items were transformed to norm based scores.

Pharmacoeconomic analysis set for participants ≥14 years of age

Posted

Median

Full Range

Scores on a scale

End of on-demand treatment period (6 months) and at study termination (approximately 18 months)

ID	Title	Description
OG000	≥14 Years of Age	After an on-demand treatment period, participants were randomized to 1 of 2 prophylactic regimens for 12 months. The standard prophylactic regimen was dosed at 20 to 40 IU/kg every 48 ±6 hours, and the PK-driven prophylaxis regimen was dosed at 20 to 80 IU/kg every 72 ±6 hours.

Units	Counts
Participants	OG000

Post-Hoc

Median (IQR) Annualized Bleed Rates

Bleed rates (number of bleeding episodes per subject) were annualized to account for the varying number of days a subject may have actually been on each regimen.

Per-Protocol Efficacy Analysis Set

Posted

Median

Inter-Quartile Range

Bleeding episodes

On-demand 6 months (± 2 weeks); Prophylaxis 12 months (± 2 weeks)

ID	Title	Description
OG000	On-Demand Regimen	After the initial PK study, a 6 month period of on-demand treatment was conducted (Part 1)
OG001	Standard Prophylaxis	Dosed at 20 to 40 IU/kg every 48 ±6 hours for 12 months (Part 2)
OG002	PK-driven Prophylaxis	Dosed at 20 to 80 IU/kg every 72 ±6 hours for 12 months (Part 2)
OG003	Any Prophylaxis	Either Standard or PK-driven Prophylaxis

Arm/Groups

ID	Title	Description	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	On-Demand	On-demand: rAHF-PFM was to be used for the treatment of bleeding episodes according to the severity and type of episode by the protocol-recommended dosing until the episode resolved: superficial (10-20 IU/kg every 12-14 hours), minor joint (20-40 IU/kg every 12-14 hours), deep muscle (30-60 IU/kg every 12-14 hours), major joint or life-threatening (60-100 IU/kg every 8-12 hours), genitourinary, GI, and intracranial (60-100 IU/kg every 8-12 hours)	7	73	18	73
EG001	Standard Prophylaxis	Standard prophylaxis regimen dosed at 20 to 40 IU/kg (every 48 ±6 hours), exact regimen to be determined by the investigator	2	32	4	32
EG002	PK-Driven Prophylaxis	PK-driven prophylaxis regimen dosed at 20 to 80 IU/kg (every 72 ±6 hours) exact regimen to be determined by the sponsor	3	34	7	34
EG003	SAEs Outside of the 3 Treatment Arms	Participants with SAEs that occurred after exposure to investigational product, but outside of the three treatment arms	1	1	0	1

Serious Adverse Events

Term	Organ System	Source Vocabulary	Notes	Statistical Information
ABDOMINAL PAIN	Gastrointestinal disorders	MedDRA (Unspecified)		EG0001 events1 affected73 at risk EG0010 events0 affected32 at risk EG0020 events0 affected34 at risk EG0030 events0 affected1 at risk
NAUSEA	Gastrointestinal disorders	MedDRA (Unspecified)		EG0001 events1 affected73 at risk EG0010 events0 affected32 at risk EG0020 events0 affected34 at risk EG003
TOOTH ABSCESS	Infections and infestations	MedDRA (Unspecified)		EG0001 events1 affected73 at risk EG0010 events0 affected32 at risk EG0020 events0 affected34 at risk EG003
JOINT DISLOCATION	Injury, poisoning and procedural complications	MedDRA (Unspecified)		EG0001 events1 affected73 at risk EG0010 events0 affected32 at risk EG0020 events0 affected34 at risk EG003
HAEMOPHILIC ARTHROPATHY	Musculoskeletal and connective tissue disorders	MedDRA (Unspecified)		EG0001 events1 affected73 at risk EG0010 events0 affected32 at risk EG0021 events1 affected34 at risk EG003
SYNOVITIS	Musculoskeletal and connective tissue disorders	MedDRA (Unspecified)		EG0001 events1 affected73 at risk EG0010 events0 affected32 at risk EG0020 events0 affected34 at risk EG003
CALCULUS URINARY	Renal and urinary disorders	MedDRA (Unspecified)		EG0001 events1 affected73 at risk EG0010 events0 affected32 at risk EG0020 events0 affected34 at risk EG003
HOSPITALIZATION	Surgical and medical procedures	MedDRA (Unspecified)		EG0001 events1 affected73 at risk EG0010 events0 affected32 at risk EG0020 events0 affected34 at risk EG003
PULPITIS DENTAL	Infections and infestations	MedDRA (Unspecified)		EG0000 events0 affected73 at risk EG0011 events1 affected32 at risk EG0020 events0 affected34 at risk EG003
SOMNAMBULISM	Psychiatric disorders	MedDRA (Unspecified)		EG0000 events0 affected73 at risk EG0011 events1 affected32 at risk EG0020 events0 affected34 at risk EG003
FACTOR VIII INHIBITION	Blood and lymphatic system disorders	MedDRA (Unspecified)	This event was unconfirmed and therefore did not meet protocol definition for a Factor VIII inhibitor.	EG0000 events0 affected73 at risk EG0010 events0 affected32 at risk EG0021 events1 affected34 at risk EG003
APPENDICITIS	Infections and infestations	MedDRA (Unspecified)		EG0000 events0 affected73 at risk EG0010 events0 affected32 at risk EG0021 events1 affected34 at risk EG003
PAIN IN EXTREMITY	Musculoskeletal and connective tissue disorders	MedDRA (Unspecified)		EG0000 events0 affected73 at risk EG0010 events0 affected32 at risk EG0020 events0 affected34 at risk EG003

Other Adverse Events

Term	Organ System	Source Vocabulary	Statistical Information
DIARRHOEA	Gastrointestinal disorders	MedDRA (Unspecified)	EG0004 events4 affected73 at risk EG0010 events0 affected32 at risk EG0020 events0 affected34 at risk EG0030 events0 affected1 at risk
IRRITABLE BOWEL SYNDROME	Gastrointestinal disorders	MedDRA (Unspecified)	EG0000 events0 affected73 at risk EG0010 events0 affected32 at risk EG0024 events2 affected34 at risk EG003
NASOPHARYNGITIS	Infections and infestations	MedDRA (Unspecified)	EG0007 events6 affected73 at risk EG0010 events0 affected32 at risk EG0020 events0 affected34 at risk EG003
UPPER RESPIRATORY TRACT INFECTION	Infections and infestations	MedDRA (Unspecified)	EG0004 events4 affected73 at risk EG0010 events0 affected32 at risk EG0022 events2 affected34 at risk EG003
ARTHRALGIA	Musculoskeletal and connective tissue disorders	MedDRA (Unspecified)	EG0000 events0 affected73 at risk EG0013 events2 affected32 at risk EG0020 events0 affected34 at risk EG003
HEADACHE	Nervous system disorders	MedDRA (Unspecified)	EG0006 events4 affected73 at risk EG0010 events0 affected32 at risk EG0025 events3 affected34 at risk EG003
COUGH	Respiratory, thoracic and mediastinal disorders	MedDRA (Unspecified)	EG0000 events0 affected73 at risk EG0012 events2 affected32 at risk EG0020 events0 affected34 at risk EG003

Ancestor Terms

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

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000		Paired t-Test		<0.0001	2-sided paired T-tests were done comparing transformed annualized bleeding rates between On-Demand and Prophylaxis regimens.						95							Superiority or Other (legacy)

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000		Paired t-test		<0.0001	2-sided paired T-tests were done comparing transformed annualized bleeding rates between On-Demand and Prophylaxis regimens.						95							Superiority or Other (legacy)

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000		Paired t-test		<0.0001	2-sided paired T-tests were done comparing transformed annualized bleeding rates between On-Demand and Prophylaxis regimens.						95							Superiority or Other (legacy)

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001		Wilcoxon-Rank Sum (Mann-Whitney)		0.4924							95							Superiority or Other (legacy)

Title

Denominators

Categories

1 infusion (n = 62, 13, 22)

Title	Measurements
	OG0001168 OG00168 OG00290

2 infusions (n = 51, 6, 9)

Title	Measurements
	OG000277 OG00112 OG00237

3 infusions (n = 27, 2, 4)

Title	Measurements
	OG000128 OG0014 OG0025

4 or more infusions (n = 21, 5, 5)

Title	Measurements
	OG00050 OG0019 OG0027

Title

Denominators

Categories

Excellent

Title	Measurements
	OG000547 OG00139 OG00233

Good

Title	Measurements
	OG000943 OG00138 OG00275

Fair

Title	Measurements
	OG000167 OG00116 OG00211

None

Title	Measurements
	OG0003 OG0010 OG00220

Unknown

Title	Measurements
	OG00013 OG0010 OG0020

Title

Denominators

Categories

ABDOMINAL PAIN

Title	Measurements
	OG0001 OG0010 OG0020 OG0030

NAUSEA

Title	Measurements
	OG0001 OG0010 OG0020 OG003

TOOTH ABSCESS

Title	Measurements
	OG0001 OG0010 OG0020 OG003

JOINT DISLOCATION

Title	Measurements
	OG0001 OG0010 OG0020 OG003

HAEMOPHILIC ARTHROPATHY

Title	Measurements
	OG0001 OG0010 OG0021 OG003

SYNOVITIS

Title	Measurements
	OG0001 OG0010 OG0020 OG003

CALCULUS URINARY

Title	Measurements
	OG0001 OG0010 OG0020 OG003

HOSPITALIZATION

Title	Measurements
	OG0001 OG0010 OG0020 OG003

PULPITIS DENTAL

Title	Measurements
	OG0000 OG0011 OG0020 OG003

SOMNAMBULISM

Title	Measurements
	OG0000 OG0011 OG0020 OG003

FACTOR VIII INHIBITION (UNCONFIRMED)

Title	Measurements
	OG0000 OG0010 OG0021 OG003

APPENDICITIS

Title	Measurements
	OG0000 OG0010 OG0021 OG003

PAIN IN EXTREMITY

Title	Measurements
	OG0000 OG0010 OG0020 OG003

Title

Denominators

Categories

TOOTH ABSCESS (SAE)

Title	Measurements
	OG0001 OG0010 OG0020

HAEMOPHILIC ARTHROPATHY (SAE)

Title	Measurements
	OG0000 OG0010 OG0021

HAEMOPHILIC ARTHROPATHY (non-SAE)

Title	Measurements
	OG0001 OG0010 OG0021

ABDOMINAL PAIN (non-SAE)

Title	Measurements
	OG0001 OG0010 OG0020

ARTHRALGIA (non-SAE)

Title	Measurements
	OG0001 OG0010 OG0020

Title

Denominators

Categories

Physical Functioning (PF)

Title	Measurements
	OG00044.56(17.29 to 57.14)

Role-Physical (RP)

Title	Measurements
	OG00042.10(27.95 to 56.24)

Bodily Pain (BP)

Title	Measurements
	OG00046.48(25.07 to 62.75)

General Health (GH)

Title	Measurements
	OG00043.87(19.52 to 64.00)

Vitality (VT)

Title	Measurements
	OG00051.42(25.39 to 67.20)

Social Functioning (SF)

Title	Measurements
	OG00046.28(19.14 to 57.14)

Role-Emotional (RE)

Title	Measurements
	OG00055.34(23.74 to 55.34)

Mental Health (MH)

Title	Measurements
	OG00050.44(20.91 to 64.07)

Physical Component Score (PCS)

Title	Measurements
	OG00042.32(20.10 to 67.67)

Mental Component Score (MCS)

Title	Measurements
	OG00052.65(22.56 to 68.10)

Title

Denominators

Categories

Bodily Pain (BP)

Title	Measurements
	OG00046.5(29.4 to 62.8) OG00151.6(19.9 to 62.8) OG00251.6(29.4 to 62.8) OG00351.6(19.9 to 62.8)

General Health (GH)

Title	Measurements
	OG00043.9(19.5 to 64.0) OG00148.6(19.5 to 64.0) OG00246.2(29.8 to 60.3) OG003

Mental Component Score (MCS), On-Demand n=62

Title	Measurements
	OG00054.9(22.8 to 69.9) OG00156.1(13.3 to 69.6) OG00254.5(11.4 to 62.5) OG003

Mental Health (MH), On-Demand n=62

Title	Measurements
	OG00051.6(14.1 to 64.1) OG00150.4(20.9 to 64.1) OG00252.7(7.3 to 64.1) OG003

Physical Component Score (PCS), On-Demand n=62

Title	Measurements
	OG00044.0(16.1 to 61.2) OG00150.2(17.6 to 68.8) OG00247.3(25.3 to 62.3) OG003

Physical Functioning (PF), On-Demand n=62

Title	Measurements
	OG00048.8(17.3 to 57.1) OG00146.7(21.5 to 57.1) OG00246.7(17.3 to 57.1) OG003

Role Emotional (RE)

Title	Measurements
	OG00055.3(23.7 to 55.3) OG00155.3(23.7 to 55.3) OG00255.3(23.7 to 55.3) OG003

Role Physical (RP)

Title	Measurements
	OG00049.2(28.0 to 56.2) OG00156.2(28.0 to 56.2) OG00256.2(28.0 to 56.2) OG003

Social Functioning (SF)

Title	Measurements
	OG00046.3(30.0 to 57.1) OG00151.7(24.6 to 57.1) OG00251.7(13.7 to 57.1) OG003

Vitality (VT)

Title	Measurements
	OG00053.8(32.5 to 70.4) OG00156.2(27.8 to 70.4) OG00256.2(23.0 to 68.0) OG003

Title

Denominators

Categories

Physical Functioning (PF)

Title	Measurements
	OG0000.00(-10.48 to 14.68) OG001-2.10(-18.88 to 20.97) OG002-2.10(-18.88 to 20.97)

Role Physical (RP)

Title	Measurements
	OG0000.00(-28.29 to 21.21) OG0010.00(-28.29 to 28.29) OG0020.00(-28.29 to 28.29)

Bodily Pain (BP)

Title	Measurements
	OG0000.00(-29.55 to 17.55) OG001-4.29(-25.27 to 13.28) OG0020.00(-29.55 to 17.55)

General Health (GH)

Title	Measurements
	OG000-3.74(-29.55 to 17.55) OG001-2.34(-21.07 to 18.73) OG002-2.34(-20.13 to 17.79)

Vitality (VT)

Title	Measurements
	OG0000.00(-9.47 to 23.67) OG0010.00(-16.57 to 30.77) OG0020.00(-16.57 to 30.77)

Social Functioning (SF)

Title	Measurements
	OG0000.00(-21.72 to 16.29) OG0010.00(-16.29 to 16.29) OG0020.00(-21.72 to 16.29)

Role Emotional (RE)

Title	Measurements
	OG0000.00(-10.53 to 31.60) OG0010.00(-31.60 to 21.07) OG0020.00(-31.60 to 31.60)

Mental Health (MH)

Title	Measurements
	OG0000.00(-13.63 to 15.90) OG001-1.13(-40.90 to 34.08) OG0020.00(-40.90 to 34.08)

Physical Component Score (PCS)

Title	Measurements
	OG000-2.55(-20.22 to 8.69) OG001-3.14(-16.78 to 19.70) OG002-2.76(-20.22 to 19.70)

Mental Component Score (MCS)

Title	Measurements
	OG0001.52(-8.31 to 21.64) OG0010.79(-35.25 to 24.56) OG0021.30(-35.25 to 24.56)

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001		Wilcoxon-Rank Sum (Mann-Whitney)		0.1467							95							Superiority or Other (legacy)

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000		Wilcoxon signed-rank test		0.0007	Due to multiple hypotheses testing results, adjusted alpha values are set to α=0.005 (0.05/10). Adjustments take into account 10 hypotheses tests between On-Demand and any Prophylaxis. Statistically significant results are considered p-values < α						95							Superiority or Other (legacy)

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000		Wilcoxon signed-rank test		0.0002	Due to multiple hypotheses testing results, adjusted alpha values are set to α=0.005 (0.05/10). Adjustments take into account 10 hypotheses tests between On-Demand and any Prophylaxis. Statistically significant results are considered p-values < α						95							Superiority or Other (legacy)

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG003		Wilcoxon Signed-Rank Test		<0.0001							95							Superiority or Other (legacy)

Facility	Status	City	State	ZIP	Country	Contacts
		Los Angeles	California		United States

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