Download PDF

Clinical Trial Results:
FEIBA NF: a prospective, open-label, randomized, parallel study to evaluate efficacy and safety of prophylactic versus on-demand treatment in subjects with hemophilia A or B and a high titer inhibitor

Summary
EudraCT number	2008-003855-65
Trial protocol	FR BG IT PL
Global end of trial date	17 Oct 2012

Results information
Results version number	v2(current)
This version publication date	05 Jun 2016
First version publication date	06 Aug 2015
Other versions	v1
Version creation reason	New data added to full data set Statistics added in description for endpoints on differences in mean transformed annualized bleeding rate as unable to add statistics to these endpoints in EudraCT due to EudraCT limitations of not currently accepting statistics for one analysis group. Pharmacoeconomics endpoints added.

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

Collapse all Expand all

Trial information

Top of page

Sponsor protocol code

090701

ISRCTN number

US NCT number

WHO universal trial number (UTN)

Sponsor organisation name

Baxalta US Inc.

Sponsor organisation address

One Baxter Way, Westlake Village CA, United States, 91362-3811

Public contact

Clinical Trial Registries and Results Disclosure, Baxalta US Inc., ClinicalTrialsDisclosure@baxalta.com

Scientific contact

Clinical Trial Registries and Results Disclosure, Baxalta US Inc., ClinicalTrialsDisclosure@baxalta.com

Sponsor organisation name

Baxalta Innovations GmbH

Sponsor organisation address

Industriestrasse 67, Vienna, Austria, 1221

Public contact

Clinical Trial Registries and Results Disclosure, Baxalta Innovations GmbH, ClinicalTrialsDisclosure@baxalta.com

Scientific contact

Clinical Trial Registries and Results Disclosure, Baxalta Innovations GmbH, ClinicalTrialsDisclosure@baxalta.com

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

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

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

Yes

Analysis stage

Final

Date of interim/final analysis

17 Oct 2012

Is this the analysis of the primary completion data?

Yes

Primary completion date

17 Oct 2012

Global end of trial reached?

Yes

Global end of trial date

17 Oct 2012

Was the trial ended prematurely?

Main objective of the trial

To demonstrate that the annualized rate of all types of bleeds in subjects on the prophylaxis arm is less than that of the subjects in the on-demand arm

Protection of trial subjects

This study was conducted in accordance with the protocol, the International Conference on Harmonisation Guideline for Good Clinical Practice (ICH GCP), Title 21 of the US Code of Federal Regulations (US CFR), the European Clinical Trial Directive (2001/20/EC and 2005/28/EC), and national and local requirements.

Background therapy

Evidence for comparator

Actual start date of recruitment

31 Mar 2009

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Yes

Number of subjects enrolled per country

Country: Number of subjects enrolled

United States: 2

Country: Number of subjects enrolled

Poland: 2

Country: Number of subjects enrolled

Brazil: 5

Country: Number of subjects enrolled

Ukraine: 8

Country: Number of subjects enrolled

Romania: 1

Country: Number of subjects enrolled

Croatia: 1

Country: Number of subjects enrolled

Russian Federation: 11

Country: Number of subjects enrolled

Bulgaria: 2

Country: Number of subjects enrolled

Japan: 2

Country: Number of subjects enrolled

New Zealand: 2

Worldwide total number of subjects

EEA total number of subjects

Number of subjects enrolled per age group

In utero

Preterm newborn - gestational age < 37 wk

Newborns (0-27 days)

Infants and toddlers (28 days-23 months)

Children (2-11 years)

Adolescents (12-17 years)

Adults (18-64 years)

From 65 to 84 years

85 years and over

Subject disposition

Top of page

Recruitment details

Enrollment was conducted in Europe, North America, Asia-Pacific, and South America at 17 clinical sites beginning in March 2009.

Screening details

52 participants were enrolled. Sixteen participants discontinued, (ten were screen failures and six were withdrawn before randomization (2 sponsor's decision- inhibitors, 3 withdrew consent, and 1 due to investigator decision to have participant on prophylaxis). Therefore 36 participants were randomized.

Period 1 title

Overall Study (overall period)

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Not blinded

Are arms mutually exclusive

On-demand arm

Arm description

Arm type

Experimental

Investigational medicinal product name

FEIBA NF

Investigational medicinal product code

Other name

Anti-Inhibitor Coagulant Complex (AICC), Nanofiltered

Pharmaceutical forms

Infusion

Routes of administration

Intravenous bolus use

Dosage and administration details

On demand: Subjects will be treated with the standard FEIBA NF dose and dosing interval prescribed by the treating physician throughout the 12-month study period. The recommended target dose of FEIBA NF for on-demand therapy will be based on the type of bleeding episode and the product will be infused as needed at the discretion of the investigator.

Prophylaxis arm

Arm description

Arm type

Experimental

Investigational medicinal product name

FEIBA NF

Investigational medicinal product code

Other name

Anti-Inhibitor Coagulant Complex (AICC), Nanofiltered

Pharmaceutical forms

Infusion

Routes of administration

Intravenous bolus use

Dosage and administration details

Prophylaxis: 85 ± 15 U/kg (70-100 U/kg) every other day

On-demand arm versus Prophylaxis arm

Arm description

Please note that all uniquely titled arms defined in the results posted in ClinicalTrials.gov are imported into EU results as well. Period arm 'On-demand arm versus Prophylaxis arm' is used for some endpoints and in the statistical analysis section. Baseline characteristics for this period arm contain on-demand and prophylaxis subjects.

Arm type

Experimental

Investigational medicinal product name

FEIBA NF

Investigational medicinal product code

Other name

Anti-Inhibitor Coagulant Complex (AICC), Nanofiltered

Pharmaceutical forms

Infusion

Routes of administration

Intravenous bolus use

Dosage and administration details

Prophylaxis: 85 ± 15 U/kg (70-100 U/kg) every other day

Investigational medicinal product name

FEIBA NF

Investigational medicinal product code

Other name

Anti-Inhibitor Coagulant Complex (AICC), Nanofiltered

Pharmaceutical forms

Infusion

Routes of administration

Intravenous bolus use

Dosage and administration details

On-demand

Arm description

Please note that all uniquely titled arms defined in the results posted in ClinicalTrials.gov are imported into EU results as well. 'On-demand' is the same as 'On-demand arm'.

Arm type

Experimental

Investigational medicinal product name

FEIBA NF

Investigational medicinal product code

Other name

Anti-Inhibitor Coagulant Complex (AICC), Nanofiltered

Pharmaceutical forms

Infusion

Routes of administration

Intravenous bolus use

Dosage and administration details

Prophylaxis

Arm description

Please note that all uniquely titled arms defined in the results posted in ClinicalTrials.gov are imported into EU results as well. 'Prophylaxis' is the same as 'Prophylaxis arm'.

Arm type

Experimental

Investigational medicinal product name

FEIBA NF

Investigational medicinal product code

Other name

Anti-Inhibitor Coagulant Complex (AICC), Nanofiltered

Pharmaceutical forms

Infusion

Routes of administration

Intravenous bolus use

Dosage and administration details

Prophylaxis: 85 ± 15 U/kg (70-100 U/kg) every other day

Number of subjects in period 1	On-demand arm	Prophylaxis arm	On-demand arm versus Prophylaxis arm	On-demand	Prophylaxis
Started	19	17	36	19	17
Completed	17	16	33	17	16
Not completed	2	1	3	2	1
Adverse event, serious fatal	1	-	1	1	-
Adverse event, non-fatal	-	1	1	-	1
planned surgery	1	-	1	1	-

Baseline characteristics

Top of page

Reporting group title

On-demand arm

Reporting group description

Reporting group title

Prophylaxis arm

Reporting group description

Reporting group title

On-demand arm versus Prophylaxis arm

Reporting group description

Reporting group title

On-demand

Reporting group description

Please note that all uniquely titled arms defined in the results posted in ClinicalTrials.gov are imported into EU results as well. 'On-demand' is the same as 'On-demand arm'.

Reporting group title

Prophylaxis

Reporting group description

Please note that all uniquely titled arms defined in the results posted in ClinicalTrials.gov are imported into EU results as well. 'Prophylaxis' is the same as 'Prophylaxis arm'.

Reporting group values	On-demand arm	Prophylaxis arm	On-demand arm versus Prophylaxis arm	On-demand	Prophylaxis	Total
Number of subjects	19	17	36	19	17
Age categorical
Units: Subjects
Age continuous
Age continuous description
Units: years
arithmetic mean (standard deviation)	29.1 ± 15.2	25.6 ± 15.4	27.4 ± 15.2	29.1 ± 15.2	25.6 ± 15.4	-
Gender categorical
Gender categorical description
Units: Subjects
Female	0	0	0	0	0	0
Male	19	17	36	19	17	108
Region of Enrollment
Units: Subjects
United States	1	1	2	1	1	6
Poland	1	1	2	1	1	6
Brazil	3	2	5	3	2	15
Ukraine	4	4	8	4	4	24
Romania	0	1	1	0	1	3
Croatia	0	1	1	0	1	3
Russian Federation	8	3	11	8	3	33
Bulgaria	0	2	2	0	2	6
Japan	1	1	2	1	1	6
New Zealand	1	1	2	1	1	6

End points

Top of page

Reporting group title

On-demand arm

Reporting group description

Reporting group title

Prophylaxis arm

Reporting group description

Reporting group title

On-demand arm versus Prophylaxis arm

Reporting group description

Reporting group title

On-demand

Reporting group description

Please note that all uniquely titled arms defined in the results posted in ClinicalTrials.gov are imported into EU results as well. 'On-demand' is the same as 'On-demand arm'.

Reporting group title

Prophylaxis

Reporting group description

Please note that all uniquely titled arms defined in the results posted in ClinicalTrials.gov are imported into EU results as well. 'Prophylaxis' is the same as 'Prophylaxis arm'.

Primary: Reduction in annualized bleeding episode rate (ABR) among participants receiving prophylactic treatment as compared to those treated on-demand

Top of page

End point title

Reduction in annualized bleeding episode rate (ABR) among participants receiving prophylactic treatment as compared to those treated on-demand ^[1]

End point description

Participants were Randomized to Receive 1 of the 2 Following Treatment Regimens: 1.On-Demand: FEIBA NF dose & dosing interval as prescribed by treating physician 2.Prophylaxis: 85 ± 15 U/kg of FEIBA NF every other day during 12-month prophylactic period Annualized rate of bleeding episodes was calculated as: (Number of bleeding episodes/observed treatment period in days) * 365.25

End point type

Primary

End point timeframe

12 months ± 14 days

Notes
[1] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Baseline period arms are not mutually exclusive. Details see under description of period arms.

End point values	On-demand arm	Prophylaxis arm
Number of subjects analysed	19	17
Units: bleeds/year
median (inter-quartile range (Q1-Q3))	28.7 (17.7 to 50)	7.9 (2.9 to 11)

Statistical analysis 1

Statistical analysis description

H0: μ(on-demand) = μ(prophylaxis) Versus H1: μ(on-demand) ≠ μ(prophylaxis) (Where H0 implies no difference in mean bleeding episode rate between prophylaxis and on-demand treatment arms and H1 implies otherwise. This test was performed at a significance level of 5%, two-sided, two sample)

Comparison groups

On-demand arm v Prophylaxis arm

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.0003

Method

Two-sample, two-sided t-test

Confidence interval

level

95%

Secondary: Annualized Bleeding Rate by Treatment Regimen, Bleeding Etiology, and Bleed Type

Top of page

End point title

Annualized Bleeding Rate by Treatment Regimen, Bleeding Etiology, and Bleed Type ^[2]

End point description

Spontaneous includes unknown/undermined etiology

End point type

Secondary

End point timeframe

12 months ± 14 days

Notes
[2] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Baseline period arms are not mutually exclusive. Details see under description of period arms.

End point values	On-demand arm	Prophylaxis arm
Number of subjects analysed	19	17
Units: Bleeds per year
median (inter-quartile range (Q1-Q3))
Spontaneous	18.9 (10.9 to 43.5)	5.6 (2.9 to 8)
Traumatic	4.7 (1.9 to 10.7)	2.5 (0 to 3.1)
Joint	22.9 (14.1 to 46.9)	6 (2.9 to 10)
Non-Joint	2.9 (1 to 4.9)	0.5 (0 to 2)
Spontaneous Joint	16.6 (9.9 to 40.8)	4.5 (2.9 to 8)
Spontaneous Non-Joint	1 (1 to 2.9)	0 (0 to 1)
Traumatic Joint	4 (1 to 7.1)	1 (0 to 3.1)
Traumatic Non-Joint	0 (0 to 1.9)	0 (0 to 1)
All Bleeding Etiologies, and Bleed Types	28.7 (17.7 to 50)	7.9 (2.9 to 11)

No statistical analyses for this end point

Secondary: Differences in Mean Transformed Annualized Bleeding Rate Between On-Demand and Prophylaxis Treatment Regimens by Bleeding Etiology, and Bleeding Type

Top of page

End point title

Differences in Mean Transformed Annualized Bleeding Rate Between On-Demand and Prophylaxis Treatment Regimens by Bleeding Etiology, and Bleeding Type ^[3]

End point description

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 variance and align sample distribution with assumption of normality inherent in using t-test. Difference in mean transformed ABRs was used to perform statistical tests and generate p-values at a significance level of 5% Participants were Randomized to Receive 1 of the 2 Following Treatment Regimens: 1.On-Demand: FEIBA NF dose & dosing interval as prescribed by treating physician 2.Prophylaxis: 85 ± 15 U/kg of FEIBA NF every other day during 12-month prophylactic period. Statistical Analysis (on-demand vs prophylaxis arm, 2-sample, 2-sided t-test): Spontaneous bleeds: p=0.0008; traumatic bleeds: p=0.0199; joint bleeds: p=0.0006; non-joint bleeds: p=0.0227; spontaneous joint bleeds: p=0.0013; spontaneous non-joint bleeds: p=0.003; traumatic joint bleeds: p=0.0254; traumatic non-joint bleeds: p=0.9322.

End point type

Secondary

End point timeframe

12 months ± 14 days

Notes
[3] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Baseline period arms are not mutually exclusive. Details see under description of period arms.

End point values	On-demand arm versus Prophylaxis arm
Number of subjects analysed	36
Units: (bleeds/year)^(1/2)
arithmetic mean (standard deviation)
Spontaneous Bleeds	2.2 ± 1.8
Traumatic Bleeds	1 ± 1.2
Joint Bleeds	2.4 ± 1.9
Non-Joint Bleeds	0.8 ± 0.9
Spontaneous Joint Bleeds	2.1 ± 1.8
Spontaneous Non-Joint Bleeds	0.8 ± 0.8
Traumatic Joint Bleeds	0.9 ± 1.2
Traumatic Non-Joint Bleeds	0 ± 0.9

No statistical analyses for this end point

Secondary: Annualized Bleeding Rate for New Target Joints

Top of page

End point title

Annualized Bleeding Rate for New Target Joints ^[4]

End point description

Target joints are ≥4 bleeds/6 months in any one of the following joints: ankles, knees, elbows, and hips; a target joint bleeding episode refers to an individual anatomical location.

End point type

Secondary

End point timeframe

12 months ± 14 days

Notes
[4] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Baseline period arms are not mutually exclusive. Details see under description of period arms.

End point values	On-demand arm	Prophylaxis arm
Number of subjects analysed	19	17
Units: Bleeds per year
median (inter-quartile range (Q1-Q3))	5.9 (0 to 12.9)	0 (0 to 4.1)

No statistical analyses for this end point

Secondary: Differences in Mean Transformed Annualized Bleeding Rate Between On-Demand and Prophylaxis Treatment Regimens: New Target Joints

Top of page

End point title

Differences in Mean Transformed Annualized Bleeding Rate Between On-Demand and Prophylaxis Treatment Regimens: New Target Joints ^[5]

End point description

Annualized bleed rates (ABRs) 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 a two-sample, two-sided t-test. The difference in mean transformed ABRs was used to perform statistical tests and generate p-values at a significance level of 5%. Statistical Analysis (on-demand arm versus prophylaxis arm; two-sample, two-sided t-test): p=0.0271.

End point type

Secondary

End point timeframe

12 months ± 14 days

Notes
[5] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Baseline period arms are not mutually exclusive. Details see under description of period arms.

End point values	On-demand arm versus Prophylaxis arm
Number of subjects analysed	36
Units: (bleeds/year)^(1/2)
arithmetic mean (standard deviation)	1.6 ± 2.2

No statistical analyses for this end point

Secondary: Number of New Target Joints

Top of page

End point title

Number of New Target Joints ^[6]

End point description

Target Joints are defined as ≥4 bleeds/6 months in any one of the following joints: ankles, knees, elbows and hips

End point type

Secondary

End point timeframe

12 months ± 14 days

Notes
[6] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Baseline period arms are not mutually exclusive. Details see under description of period arms.

End point values	On-demand arm	Prophylaxis arm
Number of subjects analysed	19	17
Units: new target joints	23	7

No statistical analyses for this end point

Secondary: Assessment of Objective Clinical Symptoms- Visual Analog Scale (VAS): Pain in Adolescents and Adults (≥12 years old)

Top of page

End point title

Assessment of Objective Clinical Symptoms- Visual Analog Scale (VAS): Pain in Adolescents and Adults (≥12 years old) ^[7]

End point description

Pain caused by a bleeding episode in adolescents and adults (≥12 years old) was measured at pre-infusion (pre-inf) and at 6 ± 0.5 hours (h) and 24 ± 1 h post-infusion (post-inf) (after the last infusion given to treat a bleeding episode) on the VAS pain scale in millimeters from 0 (no pain) to 100 (worst possible pain). For analysis purposes, if short acting analgesics (duration of activity approximately 6 ± 0.5 h) were used, pain was assigned the highest possible score (100). Pain assessment occurred after each infusion related to single bleeding episodes. In case participants required an additional infusion within 24h, pain was assessed 6 ± 0.5 h and 24 ±1 h following the subsequent infusion. Change in VAS scores at 6 ± 0.5 h and 24 ±1 h post-infusion were also compared relative to pre-infusion VAS scores (ie, (pre-infusion VAS score) - (post-infusion VAS score)).

End point type

Secondary

End point timeframe

Throughout the study period, 12 months ± 14 days

Notes
[7] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Baseline period arms are not mutually exclusive. Details see under description of period arms.

End point values	On-demand arm	Prophylaxis arm
Number of subjects analysed	17	12
Units: Scores on a scale
median (inter-quartile range (Q1-Q3))
Pre-Infusion (N= 513, 130)	29 (12 to 55)	49.5 (34.7 to 81.6)
6 ± 0.5 hours post-infusion (N= 522, 158)	10 (4 to 37)	33.8 (8 to 52.6)
24 ± 1 hours post-infusion (N= 512,131)	3 (1 to 14)	6.2 (1 to 20)
Change (Pre-Inf to 6h post-inf) (N= 509, 129)	10 (4 to 21.8)	19.4 (5 to 41.6)
Change (Pre-Inf to 24h post-inf) (N= 489, 102)	18 (8 to 39.6)	37.8 (17 to 75.5)

No statistical analyses for this end point

Secondary: Assessment of Clinical Symptoms - Visual Analog Scale (VAS): Pain in Pediatrics (<12 years old)

Top of page

End point title

Assessment of Clinical Symptoms - Visual Analog Scale (VAS): Pain in Pediatrics (<12 years old) ^[8]

End point description

Pain caused by a bleeding episode (BE) in pediatric participants (<12 years old) was measured at pre-infusion (pre-inf) and at 6 ± 0.5 h and 24 ± 1 h post-infusion (post-inf) (after the last infusion given to treat a bleeding episode) using the children’s VAS pain scale (a facial expression scale with one end marked as no pain and the opposite end marked as the worst possible pain). For analysis purposes, if short acting analgesics (duration of activity approximately 6 ± 0.5 h) were used, pain was assigned the highest possible score (worst possible pain). Scores on the children's VAS scale are presented as: -No Pain -Mild Pain -Moderate pain -Severe pain -Very severe pain

End point type

Secondary

End point timeframe

12 months ± 14 days

Notes
[8] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Baseline period arms are not mutually exclusive. Details see under description of period arms.

End point values	On-demand arm	Prophylaxis arm
Number of subjects analysed	2	2
Units: Bleeding episodes
Pre-Infusion (N= 54, 8) - No Pain	27	3
Pre-Infusion (N= 54, 8) - Mild Pain	3	1
Pre-Infusion (N= 54, 8) - Moderate Pain	12	3
Pre-Infusion (N= 54, 8) - Severe Pain	10	1
Pre-Infusion (N= 54, 8) - Very Severe Pain	2	0
6 ± 0.5 h post-infusion (N= 74, 8) - No Pain	47	3
± 0.5 h post-infusion (N= 74, 8) - Mild Pain	9	3
± 0.5 h post-infusion (N= 74, 8) - Moderate Pain	15	2
± 0.5 h post-infusion (N= 74, 8) - Severe Pain	3	0
± 0.5 h post-infusion (N= 74, 8)- Very Severe Pain	0	0
24 ± 1 h post-infusion (N= 77, 9) - No Pain	60	7
24 ± 1 h post-infusion (N= 77, 9) - Mild Pain	11	1
24 ± 1 h post-infusion (N= 77, 9) - Moderate Pain	6	1
24 ± 1 h post-infusion (N= 77, 9) - Severe Pain	0	0
24± 1h post-infusion (N = 77, 9) -Very Severe Pain	0	0

No statistical analyses for this end point

Secondary: Assessment of Clinical Symptoms - Range of Motion (ROM)

Top of page

End point title

Assessment of Clinical Symptoms - Range of Motion (ROM) ^[9]

End point description

ROM was measured using a goniometer for 3 key joints (ie, ankles, knees, and elbows) at screening, month 6, and termination (end of study visit)

End point type

Secondary

End point timeframe

12 months ± 14 days

Notes
[9] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Baseline period arms are not mutually exclusive. Details see under description of period arms.

End point values	On-demand arm	Prophylaxis arm
Number of subjects analysed	19	17
Units: degrees
median (inter-quartile range (Q1-Q3))
Left Elbow - Extension: Screening	15 (0 to 45)	10 (0 to 25)
Left Elbow - Extension: Month 6 (n = 18,16)	10 (0 to 41)	8 (0 to 42.5)
Left Elbow - Extension: Termination (n = 17,16)	20 (0 to 41)	15.5 (0 to 40)
Left Elbow - Flexion: Screening (n = 19,17)	125 (90 to 140)	115 (80 to 140)
Left Elbow - Flexion: Month 6 (n = 18,16)	130 (90 to 140)	125 (72.5 to 143)
Left Elbow - Flexion: Termination (n = 17,16)	110 (90 to 140)	125 (75 to 145)
Left Elbow - Pronation: Screening (n = 18,16)	64 (55 to 90)	55 (22.5 to 77.5)
Left Elbow - Pronation: Month 6 (n = 17,14)	80 (60 to 90)	67.5 (35 to 80)
Left Elbow - Pronation: Termination (n = 17,15)	68 (60 to 90)	65 (30 to 80)
Left Elbow - Supination: Screening (n = 18,16)	75 (50 to 90)	42.5 (17.5 to 77.5)
Left Elbow - Supination: Month 6 (n = 17,14)	80 (50 to 90)	60 (35 to 80)
Left Elbow - Supination: Termination (n = 17,15)	70 (50 to 90)	70 (35 to 80)
Right Elbow - Extension: Screening (n = 19,17)	20 (0 to 50)	10 (0 to 50)
Right Elbow - Extension: Month 6 (n = 18,16)	17.5 (0 to 50)	10 (0 to 42.5)
Right Elbow - Extension: Termination (n = 18,16)	22.5 (0 to 45)	20 (0 to 62.5)
Right Elbow - Flexion: Screening (n = 19,17)	120 (105 to 140)	100 (80 to 130)
Right Elbow - Flexion: Month 6 (n = 18,16)	122.5 (110 to 140)	100 (85 to 136)
Right Elbow - Flexion: Termination (n = 18,16)	121 (110 to 140)	99 (70 to 127.5)
Right Elbow - Pronation: Screening (n = 18,16)	75 (55 to 90)	57.5 (27.5 to 80)
Right Elbow - Pronation: Month 6 (n = 17,14)	80 (55 to 90)	72.5 (40 to 80)
Right Elbow - Pronation: Termination (n = 18,15)	67.5 (55 to 90)	70 (40 to 80)
Right Elbow - Supination: Screening (n = 18,16)	75 (45 to 90)	52.5 (20 to 80)
Right Elbow - Supination: Month 6 (n = 17,14)	70 (45 to 90)	72.5 (30 to 80)
Right Elbow - Supination: Termination (n = 18,15)	75 (45 to 90)	70 (30 to 80)
Left Knee - Extension: Screening (n = 18,16)	15 (5 to 90)	1.5 (0 to 55.5)
Left Knee - Extension: Month 6 (n = 17,14)	15 (5 to 70)	0 (0 to 20)
Left Knee - Extension: Termination (n = 18,15)	15 (5 to 90)	0 (0 to 70)
Left Knee - Flexion: Screening (n = 19,17)	100 (80 to 130)	90 (65 to 115)
Left Knee - Flexion: Month 6 (n = 18,16)	112.5 (80 to 130)	97.5 (65 to 125)
Left Knee - Flexion: Termination (n = 18,16)	105 (60 to 130)	92.5 (70 to 125)
Right Knee - Extension: Screening (n = 18,16)	35 (10 to 90)	5 (0 to 30)
Right Knee - Extension: Month 6 (n = 17,14)	20 (10 to 90)	10 (2 to 30)
Right Knee - Extension: Termination (n = 18,15)	17.5 (10 to 90)	5 (0 to 30)
Right Knee - Flexion: Screening (n = 19,17)	90 (20 to 122)	80 (60 to 125)
Right Knee - Flexion: Month 6 (n = 18,16)	90 (20 to 130)	82.5 (56 to 127.5)
Right Knee - Flexion: Termination (n = 18,16)	85 (20 to 120)	87.5 (56 to 127.5)
Left Ankle - Dorsiflexion: Screening (n = 18,16)	20 (15 to 30)	17.5 (9 to 37.5)
Left Ankle - Dorsiflexion: Month 6 (n = 17,14)	20 (11 to 35)	17.5 (8 to 50)
Left Ankle - Dorsiflexion: Termination (n = 17,15)	15 (11 to 25)	20 (5 to 50)
Left Ankle - Plantarflexion: Screening (n = 18,16)	34.5 (30 to 40)	30 (10 to 35)
Left Ankle - Plantarflexion: Month 6 (n = 17,14)	34 (25 to 35)	30 (15 to 40)
Left Ankle - Plantarflexion: Termination (n=17,15)	35 (30 to 40)	30 (15 to 35)
Left Ankle - Pronation: Screening (n = 19,17)	14 (10 to 20)	15 (10 to 15)
Left Ankle - Pronation: Month 6 (n = 18,15)	15 (10 to 20)	15 (10 to 16)
Left Ankle - Pronation: Termination (n = 18,16)	15 (10 to 20)	12.5 (10 to 15.5)
Left Ankle - Supination: Screening (n = 19,17)	25 (10 to 30)	15 (10 to 27)
Left Ankle - Supination: Month 6 (n = 18,15)	25 (20 to 30)	25 (10 to 30)
Left Ankle - Supination: Termination (n = 18,16)	25 (16 to 30)	20 (10 to 27.5)
Right Ankle - Dorsiflexion: Screening (n = 18,16)	15 (10 to 20)	20 (7.5 to 35)
Right Ankle - Dorsiflexion: Month 6 (n = 17,14)	15 (15 to 20)	25 (6 to 40)
Right Ankle - Dorsiflexion: Termination (n= 17,15)	15 (14 to 20)	20 (10 to 40)
Right Ankle - Plantarflexion: Screening (n= 18,16)	35 (30 to 40)	20 (9 to 39)
Right Ankle - Plantarflexion: Month 6 (n= 17,14)	30 (25 to 40)	23 (10 to 40)
Right Ankle - Plantarflexion: Termination(n=17,15)	30 (25 to 40)	21 (10 to 40)
Right Ankle - Pronation: Screening (n = 19,17)	10 (10 to 15)	10 (10 to 20)
Right Ankle - Pronation: Month 6 (n= 18,15)	10 (10 to 20)	10 (10 to 20)
Right Ankle - Pronation: Termination (n= 18,16)	10 (10 to 17)	11 (10 to 17.5)
Right Ankle - Supination: Screening (n = 19,17)	17 (10 to 30)	20 (10 to 30)
Right Ankle - Supination: Month 6 (n= 18,15)	20 (10 to 30)	20 (10 to 30)
Right Ankle - Supination: Termination (n= 18,16)	20 (10 to 30)	20 (10 to 30)

No statistical analyses for this end point

Secondary: Assessment of Hemostasis for Treatment of Bleeding Episodes- Overall Efficacy Rating at 6 hours

Top of page

End point title

Assessment of Hemostasis for Treatment of Bleeding Episodes- Overall Efficacy Rating at 6 hours ^[10]

End point description

Number of rAHF-PFM-treated bleeding episodes with an assessment of hemostasis (4-point ordinal scale): Excellent: Full pain relief & bleeding cessation within ~6 hours of 1 infusion. Additional infusions may have been given to maintain hemostasis; Good: Definite pain relief and/or improvement in bleeding within ~6 hours after infusion. Possibly requires >1 infusion for complete resolution; Fair: Probable or slight relief of pain & slight improvement in bleeding within ~6 hours after infusion. Requires >1 infusion for complete resolution; None: No improvement or condition worsens

End point type

Secondary

End point timeframe

6 h ± 30 min post-infusion

Notes
[10] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Baseline period arms are not mutually exclusive. Details see under description of period arms.

End point values	On-demand arm	Prophylaxis arm
Number of subjects analysed	19	14
Units: bleeding episodes
Excellent (n = 16, 5)	109	16
Good (n = 19, 14)	355	106
Fair (n = 15, 6)	142	42
None (n = 6, 2)	14	5
Rating Not Done (n = 3, 2)	3	2
Not Available (n = 0, 1)	0	2

No statistical analyses for this end point

Secondary: Assessment of Hemostasis for Treatment of Bleeding Episodes- Overall Efficacy Rating at 24 hours

Top of page

End point title

Assessment of Hemostasis for Treatment of Bleeding Episodes- Overall Efficacy Rating at 24 hours ^[11]

End point description

Number of rAHF-PFM-treated bleeding episodes with an assessment of hemostasis (4-point ordinal scale): Excellent: Full pain relief & bleeding cessation within ~24 hours of 1 infusion. Additional infusions may have been given to maintain hemostasis; Good: Definite pain relief and/or improvement in bleeding within ~24 hours after infusion. Possibly requires >1 infusion for complete resolution; Fair: Probable or slight relief of pain & slight improvement in bleeding within ~24 hours after infusion. Requires >1 infusion for complete resolution; None: No improvement or condition worsens

End point type

Secondary

End point timeframe

24 ± 1 h post-infusion

Notes
[11] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Baseline period arms are not mutually exclusive. Details see under description of period arms.

End point values	On-demand arm	Prophylaxis arm
Number of subjects analysed	19	14
Units: bleeding episodes
Excellent (n = 16, 6)	282	42
Good (n = 19, 14)	280	89
Fair (n = 9, 3)	36	12
None (n = 1,0)	1	0
Rating Not Done (n = 8, 3)	24	28
Not Available (n = 0, 1)	0	2

No statistical analyses for this end point

Secondary: Total Weight Adjusted Dose to Control a Bleeding Episode

Top of page

End point title

Total Weight Adjusted Dose to Control a Bleeding Episode ^[12]

End point description

End point type

Secondary

End point timeframe

12 months ± 14 days

Notes
[12] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Baseline period arms are not mutually exclusive. Details see under description of period arms.

End point values	On-demand arm	Prophylaxis arm
Number of subjects analysed	19	14
Units: Units/kg
median (inter-quartile range (Q1-Q3))	4049.7 (2324.5 to 7408.4)	1524.9 (293.2 to 2883.5)

Statistical analysis 1

Comparison groups

Prophylaxis arm v On-demand arm

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.0067

Method

Mann-Whitney tests (Wilcoxon-Rank Sum)

Confidence interval

level

95%

Secondary: The Number of Bleeding Episode (BE) Which Required 1, 2, 3, or ≥4 Infusions to Control Bleeding

Top of page

End point title

The Number of Bleeding Episode (BE) Which Required 1, 2, 3, or ≥4 Infusions to Control Bleeding ^[13]

End point description

End point type

Secondary

End point timeframe

12 months ± 14 days

Notes
[13] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Baseline period arms are not mutually exclusive. Details see under description of period arms.

End point values	On-demand arm	Prophylaxis arm
Number of subjects analysed	19	14
Units: Bleeding Episodes (BEs)
1 infusion	352	98
2 infusions	134	41
3 infusions	62	13
≥4 infusions	75	21

No statistical analyses for this end point

Secondary: Abnormal Activated Partial Thromboplastin Time (aPTT) Assay Results

Top of page

End point title

Abnormal Activated Partial Thromboplastin Time (aPTT) Assay Results ^[14]

End point description

The normal reference range of values for aPTT is 22.8 – 31 seconds.

End point type

Secondary

End point timeframe

Screening visit, Month 3, Month 6, Month 9, and Termination visit

Notes
[14] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Baseline period arms are not mutually exclusive. Details see under description of period arms.

End point values	On-demand arm	Prophylaxis arm
Number of subjects analysed	19	16
Units: seconds
median (inter-quartile range (Q1-Q3))
Screening visit (n= 19, 16)	67.3 (63.1 to 75.1)	68.5 (61 to 73.1)
Month 3 (n= 14, 15)	68 (62.7 to 76.2)	62.7 (57.5 to 67.2)
Month 6 (n= 17, 15)	68.2 (64.6 to 72.1)	65.6 (62.6 to 69.5)
Month 9 (n= 17, 15)	70 (64.6 to 77.9)	68.1 (58.1 to 73.9)
Termination visit (n= 18, 16)	69.8 (63.4 to 75.6)	69.4 (60.5 to 77.1)

No statistical analyses for this end point

Secondary: Abnormal D-Dimer Assay Results

Top of page

End point title

Abnormal D-Dimer Assay Results ^[15]

End point description

The normal reference range of values for D-dimers is <500 ng/mL.

End point type

Secondary

End point timeframe

Screening visit, Month 3, Month 6, Month 9, and Termination visit

Notes
[15] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Baseline period arms are not mutually exclusive. Details see under description of period arms.

End point values	On-demand arm	Prophylaxis arm
Number of subjects analysed	9	9
Units: ng/mL
median (inter-quartile range (Q1-Q3))
Screening visit (n= 7, 6)	862 (647 to 1035)	833.5 (644 to 1164)
Month 3 (n= 7, 8)	690 (561 to 830)	1021.5 (730 to 1633.5)
Month 6 (n= 9, 8)	969 (753 to 1103)	1032 (652 to 1442.5)
Month 9 (n= 6, 8)	731.5 (592 to 1398)	1121 (942.5 to 1448.5)
Termination visit (n= 5, 9)	813 (695 to 1386)	1031 (872 to 1258)

No statistical analyses for this end point

Secondary: Abnormal Fibrinogen Assay Results

Top of page

End point title

Abnormal Fibrinogen Assay Results ^[16]

End point description

The normal reference range of values for fibrinogen is 200-400 mg/dL. Note: 99999 entered where there were no abnormal fibrinogen assay results for this arm/group at this time point.

End point type

Secondary

End point timeframe

Screening visit, Month 3, Month 6, Month 9, and Termination visit

Notes
[16] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Baseline period arms are not mutually exclusive. Details see under description of period arms.

End point values	On-demand arm	Prophylaxis arm
Number of subjects analysed	4	6
Units: mg/dL
median (inter-quartile range (Q1-Q3))
Screening visit (n= 4, 6)	428 (414 to 478.5)	422 (411 to 428)
Month 3 (n= 0, 2)	99999 (99999 to 99999)	402 (199 to 605)
Month 6 (n= 3, 1)	415 (412 to 418)	759 (759 to 759)
Month 9 (n= 1, 4)	508 (508 to 508)	326.5 (183.5 to 635.5)
Termination visit (n= 2, 2)	456.5 (425 to 488)	522.5 (414 to 631)

No statistical analyses for this end point

Secondary: Abnormal Fibrin Degradation Products (FDP) Assay Results

Top of page

End point title

Abnormal Fibrin Degradation Products (FDP) Assay Results ^[17]

End point description

The normal reference range of values for FDP is 0-5 ug/mL. Note: 99999 entered where there were no abnormal fibrin degradation products assay results for this arm/group at this time point

End point type

Secondary

End point timeframe

Screening visit, Month 3, Month 6, Month 9, and Termination visit

Notes
[17] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Baseline period arms are not mutually exclusive. Details see under description of period arms.

End point values	On-demand arm	Prophylaxis arm
Number of subjects analysed	3	2
Units: ug/mL
median (inter-quartile range (Q1-Q3))
Screening visit (n= 1, 2)	16 (16 to 16)	12 (8 to 16)
Month 3 (n= 0, 2)	99999 (99999 to 99999)	8 (8 to 8)
Month 6 (n= 1, 1)	8 (8 to 8)	8 (8 to 8)
Month 9 (n= 1, 2)	8 (8 to 8)	8 (8 to 8)
Termination visit (n= 3, 1)	8 (8 to 8)	8 (8 to 8)

No statistical analyses for this end point

Secondary: Abnormal Prothrombin Fragment F 1.2 Assay Results

Top of page

End point title

Abnormal Prothrombin Fragment F 1.2 Assay Results ^[18]

End point description

The normal reference range of values for prothrombin fragment F 1.2 is 69-229 pmol/L.

End point type

Secondary

End point timeframe

Screening visit, Month 3, Month 6, Month 9, and Termination visit

Notes
[18] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Baseline period arms are not mutually exclusive. Details see under description of period arms.

End point values	On-demand arm	Prophylaxis arm
Number of subjects analysed	6	9
Units: pmol/L
median (inter-quartile range (Q1-Q3))
Screening visit (n= 2, 1)	284 (278 to 290)	308 (308 to 308)
Month 3 (n= 6, 7)	336.5 (267 to 414)	579 (354 to 972)
Month 6 (n= 3, 9)	448 (272 to 714)	430 (366 to 504)
Month 9 (n= 4, 9)	382 (313 to 405.5)	415 (272 to 472)
Termination visit (n= 4, 7)	252.5 (250 to 265)	643 (376 to 1679)

No statistical analyses for this end point

Secondary: Abnormal Prothrombin Time Assay Results

Top of page

End point title

Abnormal Prothrombin Time Assay Results ^[19]

End point description

The normal reference range of values for PT is 9.7-12.3 sec. Note: 99999 entered where there were no abnormal prothrombin time assay results for this arm/group at this time point

End point type

Secondary

End point timeframe

Screening visit, Month 3, Month 6, Month 9, and Termination visit

Notes
[19] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Baseline period arms are not mutually exclusive. Details see under description of period arms.

End point values	On-demand arm	Prophylaxis arm
Number of subjects analysed	1	1
Units: seconds
median (inter-quartile range (Q1-Q3))
Screening visit (n= 1, 1)	9.4 (9.4 to 9.4)	9.6 (9.6 to 9.6)
Month 3 (n= 1, 0)	9.5 (9.5 to 9.5)	99999 (99999 to 99999)
Month 6 (n= 0, 1)	99999 (99999 to 99999)	12.5 (12.5 to 12.5)
Month 9 (n= 1, 1)	12.7 (12.7 to 12.7)	13.6 (13.6 to 13.6)
Termination visit (n= 0, 1)	99999 (99999 to 99999)	13.4 (13.4 to 13.4)

No statistical analyses for this end point

Secondary: Abnormal Thrombin-Antithrombin III (TAT) Assay Results

Top of page

End point title

Abnormal Thrombin-Antithrombin III (TAT) Assay Results ^[20]

End point description

The normal reference range of values for TAT is 1-4.1 ug/L. Note: 99999 entered where there were no abnormal Abnormal Thrombin-Antithrombin II assay results for this arm/group at this time point

End point type

Secondary

End point timeframe

Screening visit, Month 3, Month 6, Month 9, and Termination visit

Notes
[20] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Baseline period arms are not mutually exclusive. Details see under description of period arms.

End point values	On-demand arm	Prophylaxis arm
Number of subjects analysed	4	7
Units: ug/L
median (inter-quartile range (Q1-Q3))
Screening visit (n= 4, 1)	5.1 (4.4 to 5.9)	5.6 (5.6 to 5.6)
Month 3 (n= 3, 7)	4.7 (4.5 to 5.9)	12.3 (4.4 to 40.8)
Month 6 (n= 3, 6)	7.9 (6.3 to 10.5)	5.6 (4.4 to 6.1)
Month 9 (n= 0, 3)	99999 (99999 to 99999)	6 (5.6 to 52.9)
Termination visit (n= 2, 5)	10.3 (8 to 12.5)	5.6 (5.1 to 7.3)

No statistical analyses for this end point

Secondary: Viral Serology from Screening Visit and Study Termination Visit: Hepatitis A, Hepatitis B, and Hepatitis C

Top of page

End point title

Viral Serology from Screening Visit and Study Termination Visit: Hepatitis A, Hepatitis B, and Hepatitis C ^[21]

End point description

-Hepatitis A Virus Antibody (HAV Ab) -Hepatitis B Virus Core Antibody (HBcAb) -Hepatitis B Virus Surface Antibody (HBsAb) -Hepatitis B Virus Surface Antigen (HBsAg) -Hepatitis C Virus (HCV)

End point type

Secondary

End point timeframe

12 months ± 14 days

Notes
[21] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Baseline period arms are not mutually exclusive. Details see under description of period arms.

End point values	On-demand arm	Prophylaxis arm
Number of subjects analysed	19	17
Units: participants
HAV Ab: Screening Negative; Termination Positive	1	0
HAV Ab: Screening Negative; Termination Negative	8	11
HAV Ab: Screening Positive; Termination Positive	8	4
HAV Ab: Screening Positive; Termination Negative	1	1
HAV Ab: Serology not available	1	1
HBcAb: Screening Negative; Termination Positive	0	1
HBcAb: Screening Negative; Termination Negative	8	11
HBcAb: Screening Positive; Termination Positive	9	4
HBcAb: Screening Positive; Termination Negative	1	0
HBcAb: Serology not available	1	1
HBsAb: Screening Negative; Termination Positive	2	5
HBsAb: Screening Negative; Termination Negative	2	2
HBsAb: Screening Positive; Termination Positive	13	9
HBsAb: Screening Positive; Termination Negative	1	0
HBsAb: Serology not available	1	1
HBsAg: Screening Negative; Termination Positive	0	0
HBsAg: Screening Negative; Termination Negative	18	16
HBsAg: Serology not available	1	1
HCV: Screening Negative; Termination Positive	0	0
HCV: Screening Negative; Termination Negative	6	10
HCV: Screening Positive; Termination Positive	12	6
HCV: Screening Positive; Termination Negative	0	0
HCV: Serology not available	1	1

No statistical analyses for this end point

Secondary: Viral Serology From Screening Visit and Study Termination Visit: HIV-1/2 Antibody (Ab)

Top of page

End point title

Viral Serology From Screening Visit and Study Termination Visit: HIV-1/2 Antibody (Ab) ^[22]

End point description

End point type

Secondary

End point timeframe

12 months ± 14 days

Notes
[22] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Baseline period arms are not mutually exclusive. Details see under description of period arms.

End point values	On-demand	Prophylaxis
Number of subjects analysed	19	17
Units: participants
HIV 1/2 Ab: Screen Negative; Termination Positive	0	0
HIV 1/2 Ab: Screen Negative; Termination Negative	18	16
HIV 1/2 Ab: : Serology not available	1	1

No statistical analyses for this end point

Secondary: Viral Serology From Screening Visit and Study Termination Visit: Parvovirus B19 IgG Antibody [IV]

Top of page

End point title

Viral Serology From Screening Visit and Study Termination Visit: Parvovirus B19 IgG Antibody [IV] ^[23]

End point description

Normal range (0 - 0.89 IV); High (> 0.89 IV) - Parvovirus B19 IgG Antibody [IV] (Parvo IgG Ab)

End point type

Secondary

End point timeframe

12 months ± 14 days

Notes
[23] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Baseline period arms are not mutually exclusive. Details see under description of period arms.

End point values	On-demand	Prophylaxis
Number of subjects analysed	19	17
Units: participants
Parvo IgG Ab: Screening High ; Termination Normal	3	1
Parvo IgG Ab: Screening High ; Termination High	14	13
Parvo IgG Ab: Screening Normal; Termination Normal	0	2
Parvo IgG Ab: Screening Normal ; Termination High	1	0
Parvo IgG Ab: Serology not available	1	1

No statistical analyses for this end point

Secondary: Viral Serology From Screening Visit and Study Termination Visit: Parvovirus B19 IgM Antibody [IV]

Top of page

End point title

Viral Serology From Screening Visit and Study Termination Visit: Parvovirus B19 IgM Antibody [IV] ^[24]

End point description

Normal range (0 - 0.89 IV); High (> 0.89 IV) - Parvovirus B19 IgM Antibody [IV] (Parvo IgM Ab)

End point type

Secondary

End point timeframe

12 months ± 14 days

Notes
[24] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Baseline period arms are not mutually exclusive. Details see under description of period arms.

End point values	On-demand	Prophylaxis
Number of subjects analysed	19	17
Units: participants
Parvo IgM Ab: Screening High ; Termination Normal	0	0
Parvo IgM Ab: Screening High ; Termination High	1	0
Parvo IgM Ab: Screening Normal; Termination Normal	17	16
Parvo IgM Ab: Screening Normal ; Termination High	0	0
Parvo IgM Ab: Serology not available	1	1

No statistical analyses for this end point

Secondary: Rate of Related Adverse Events (AEs) per Year

Top of page

End point title

Rate of Related Adverse Events (AEs) per Year ^[25]

End point description

End point type

Secondary

End point timeframe

12 months ± 14 days

Notes
[25] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Baseline period arms are not mutually exclusive. Details see under description of period arms.

End point values	On-demand arm	Prophylaxis arm
Number of subjects analysed	19	17
Units: Related AEs per year
median (inter-quartile range (Q1-Q3))	0 (0 to 0)	0 (0 to 0.979)

No statistical analyses for this end point

Secondary: Rate of Related Adverse Events (AEs) during or within 1 Hour of Infusion per Year

Top of page

End point title

Rate of Related Adverse Events (AEs) during or within 1 Hour of Infusion per Year ^[26]

End point description

End point type

Secondary

End point timeframe

12 months ± 14 days

Notes
[26] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Baseline period arms are not mutually exclusive. Details see under description of period arms.

End point values	On-demand arm	Prophylaxis arm
Number of subjects analysed	19	17
Units: Related AEs within/during 1hr per year
median (inter-quartile range (Q1-Q3))	0 (0 to 0)	0 (0 to 0)

No statistical analyses for this end point

Secondary: Number of Related Thromboembolic Adverse Events (AEs)

Top of page

End point title

Number of Related Thromboembolic Adverse Events (AEs) ^[27]

End point description

End point type

Secondary

End point timeframe

12 months ± 14 days

Notes
[27] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Baseline period arms are not mutually exclusive. Details see under description of period arms.

End point values	On-demand arm	Prophylaxis arm
Number of subjects analysed	19	17
Units: Related thromboembolic AEs	0	0

No statistical analyses for this end point

Secondary: Absolute Changes in Inhibitor Titer of Hemophilia A Participants with Shifts in Factor VIII (FVIII) Inhibitor Titer Levels

Top of page

End point title

Absolute Changes in Inhibitor Titer of Hemophilia A Participants with Shifts in Factor VIII (FVIII) Inhibitor Titer Levels ^[28]

End point description

Absolute Changes in Inhibitor Titer (or no change in low or high titer status): -Inhibitor Titer went from Low (≤5 BU) to Low (≤5 BU) -Inhibitor Titer went from Low (≤5 BU) to High (>5 BU) -Inhibitor Titer went from High (>5 BU) to Low (≤5 BU) -Inhibitor Titer went from High (>5 BU) to High (>5 BU) Note: 99999 entered where there were no inhibitor titer shifts for this arm/group at this time point

End point type

Secondary

End point timeframe

12 months ± 14 days

Notes
[28] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Baseline period arms are not mutually exclusive. Details see under description of period arms.

End point values	On-demand arm	Prophylaxis arm
Number of subjects analysed	17	16
Units: Bethesda Units (BU)
median (inter-quartile range (Q1-Q3))
Screening to 3 Month- Low to High (N=2, 3)	12.1 (12.1 to 12.1)	4 (0.7 to 16.8)
Screening to 3 Month- High to Low (N=1, 0)	2 (2 to 2)	99999 (99999 to 99999)
Screening to 6 Month- Low to High (N=2, 1)	12.9 (4.9 to 20.8)	5.3 (5.3 to 5.3)
Screening to 6 Month- High to Low (N=1, 0)	3.4 (3.4 to 3.4)	99999 (99999 to 99999)
Screening to 9 Month- Low to High (N=2, 1)	5 (4.3 to 5.6)	3.7 (3.7 to 3.7)
Screening to 9 Month- High to Low (N=0, 2)	99999 (99999 to 99999)	2.1 (0.9 to 3.2)
Screening to Termination- Low to High (N=2, 1)	39.2 (3.8 to 74.7)	5.8 (5.8 to 5.8)
Screening to Termination- High to Low (N=1, 2)	14.6 (14.6 to 14.6)	3.3 (3.3 to 3.3)

No statistical analyses for this end point

Secondary: Absolute Changes in Inhibitor Titer of Hemophilia B Participants with Shifts in Factor IX (FIX) Inhibitor Titer Levels

Top of page

End point title

Absolute Changes in Inhibitor Titer of Hemophilia B Participants with Shifts in Factor IX (FIX) Inhibitor Titer Levels ^[29]

End point description

End point type

Secondary

End point timeframe

12 months ± 14 days

Notes
[29] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Baseline period arms are not mutually exclusive. Details see under description of period arms.

End point values	On-demand arm	Prophylaxis arm
Number of subjects analysed	1	1
Units: Bethesda Units (BU)
median (inter-quartile range (Q1-Q3))
Screening to 3 Month- Low to Low (N=1, 0)	3.2 (3.2 to 3.2)	99999 (99999 to 99999)
Screening to 3 Month- Low to High (N=0, 0)	99999 (99999 to 99999)	99999 (99999 to 99999)
Screening to 3 Month- High to Low (N=0, 0)	99999 (99999 to 99999)	99999 (99999 to 99999)
Screening to 3 Month- High to High (N=1, 1)	0.3 (0.3 to 0.3)	10.7 (10.7 to 10.7)
Screening to 6 Month- Low to Low (N=1, 0)	1.5 (1.5 to 1.5)	99999 (99999 to 99999)
Screening to 6 Month- Low to High (N=0, 0)	99999 (99999 to 99999)	99999 (99999 to 99999)
Screening to 6 Month- High to Low (N=0, 0)	99999 (99999 to 99999)	99999 (99999 to 99999)
Screening to 6 Month- High to High (N=1, 1)	1.7 (1.7 to 1.7)	23.2 (23.2 to 23.2)
Screening to 9 Month- Low to Low (N=1, 0)	3.2 (3.2 to 3.2)	99999 (99999 to 99999)
Screening to 9 Month- Low to High (N=0, 0)	99999 (99999 to 99999)	99999 (99999 to 99999)
Screening to 9 Month- High to Low (N=0, 0)	99999 (99999 to 99999)	99999 (99999 to 99999)
Screening to 9 Month- High to High (N=0, 1)	99999 (99999 to 99999)	37 (37 to 37)
Screening to Termination - Low to Low (N=0, 0)	99999 (99999 to 99999)	99999 (99999 to 99999)
Screening to Termination- Low to High (N=0, 0)	99999 (99999 to 99999)	99999 (99999 to 99999)
Screening to Termination- High to Low (N=0, 0)	99999 (99999 to 99999)	99999 (99999 to 99999)
Screening to Termination - High to High (N=1, 1)	11.3 (11.3 to 11.3)	21.4 (21.4 to 21.4)

No statistical analyses for this end point

Secondary: Pharmacoeconomics: Annual days lost due to bleeding (work or school)

Top of page

End point title

Pharmacoeconomics: Annual days lost due to bleeding (work or school) ^[30]

End point description

End point type

Secondary

End point timeframe

12 months ± 14 days

Notes
[30] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Baseline period arms are not mutually exclusive. Details see under description of period arms.

End point values	On-demand arm	Prophylaxis arm
Number of subjects analysed	17	16
Units: days
arithmetic mean (standard deviation)	16.4 ± 25.76	8.8 ± 14.42

No statistical analyses for this end point

Secondary: Pharmacoeconomics: Annual number of hospitalizations for bleeding

Top of page

End point title

Pharmacoeconomics: Annual number of hospitalizations for bleeding ^[31]

End point description

End point type

Secondary

End point timeframe

12 months ± 14 days

Notes
[31] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Baseline period arms are not mutually exclusive. Details see under description of period arms.

End point values	On-demand arm	Prophylaxis arm
Number of subjects analysed	18	16
Units: hospitalizations
arithmetic mean (standard deviation)	0.6 ± 1.15	0.6 ± 2.03

No statistical analyses for this end point

Secondary: Pharmacoeconomics: Annual number of hospitalizations for indwelling line

Top of page

End point title

Pharmacoeconomics: Annual number of hospitalizations for indwelling line ^[32]

End point description

End point type

Secondary

End point timeframe

12 months ± 14 days

Notes
[32] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Baseline period arms are not mutually exclusive. Details see under description of period arms.

End point values	On-demand arm	Prophylaxis arm
Number of subjects analysed	18	16
Units: hospitalizations
arithmetic mean (standard deviation)	0.1 ± 0.32	0.1 ± 0.25

No statistical analyses for this end point

Secondary: Pharmacoeconomics: Annual number of emergency room visits

Top of page

End point title

Pharmacoeconomics: Annual number of emergency room visits ^[33]

End point description

End point type

Secondary

End point timeframe

12 months ± 14 days

Notes
[33] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Baseline period arms are not mutually exclusive. Details see under description of period arms.

End point values	On-demand arm	Prophylaxis arm
Number of subjects analysed	18	16
Units: Emergency room visits
arithmetic mean (standard deviation)	0.4 ± 0.98	0.4 ± 1.09

No statistical analyses for this end point

Secondary: Pharmacoeconomics: Annual number of physician’s office visits

Top of page

End point title

Pharmacoeconomics: Annual number of physician’s office visits ^[34]

End point description

End point type

Secondary

End point timeframe

12 months ± 14 days

Notes
[34] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Baseline period arms are not mutually exclusive. Details see under description of period arms.

End point values	On-demand arm	Prophylaxis arm
Number of subjects analysed	18	16
Units: Physician's office visits
arithmetic mean (standard deviation)	2.2 ± 4.15	2.6 ± 4.6

No statistical analyses for this end point

Secondary: Pharmacoeconomics: Annual total length of hospitalization for bleeding

Top of page

End point title

Pharmacoeconomics: Annual total length of hospitalization for bleeding ^[35]

End point description

End point type

Secondary

End point timeframe

12 months ± 14 days

Notes
[35] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Baseline period arms are not mutually exclusive. Details see under description of period arms.

End point values	On-demand arm	Prophylaxis arm
Number of subjects analysed	18	16
Units: Days
arithmetic mean (standard deviation)	5 ± 9.48	5.3 ± 17

No statistical analyses for this end point

Secondary: Pharmacoeconomics: Annual total length of hospitalization for indwelling line

Top of page

End point title

Pharmacoeconomics: Annual total length of hospitalization for indwelling line ^[36]

End point description

End point type

Secondary

End point timeframe

12 months ± 14 days

Notes
[36] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Baseline period arms are not mutually exclusive. Details see under description of period arms.

End point values	On-demand arm	Prophylaxis arm
Number of subjects analysed	18	16
Units: Days
arithmetic mean (standard deviation)	0.7 ± 2.61	0.7 ± 2.75

No statistical analyses for this end point

Secondary: Pharmacoeconomics: Annual total number of days lost (work or school)

Top of page

End point title

Pharmacoeconomics: Annual total number of days lost (work or school) ^[37]

End point description

End point type

Secondary

End point timeframe

12 months ± 14 days

Notes
[37] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Baseline period arms are not mutually exclusive. Details see under description of period arms.

End point values	On-demand arm	Prophylaxis arm
Number of subjects analysed	17	16
Units: Days
arithmetic mean (standard deviation)	17.4 ± 25.42	15.4 ± 24.28

No statistical analyses for this end point

Secondary: Health-Related Quality of Life (HRQoL): EuroQoL (Quality of Life)-5 Dimensions (EQ-5D) Index Scores

Top of page

End point title

Health-Related Quality of Life (HRQoL): EuroQoL (Quality of Life)-5 Dimensions (EQ-5D) Index Scores ^[38]

End point description

EQ-5D is a participant answered questionnaire scoring 5 dimensions - mobility, self-care, usual activities, pain/discomfort and anxiety/depression. The EQ-5D total score ranges from 0 (worst health state) to 1 (perfect health state) and 1 reflects the best outcome. EQ-5D Index scores based on EQ-5D questionnaire were calculated for participants ≥14 years of age, at screening, 6 months, and at termination visit. Changes in scores at 6 months and termination were also calculated. A relatively higher score represents better quality of life.

End point type

Secondary

End point timeframe

12 months ± 14 days

Notes
[38] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Baseline period arms are not mutually exclusive. Details see under description of period arms.

End point values	On-demand arm	Prophylaxis arm
Number of subjects analysed	16	12
Units: Scores on a scale
arithmetic mean (standard deviation)
Screening (N= 16, 12)	0.627 ± 0.2067	0.62 ± 0.1841
6 Months (N= 15, 11)	0.621 ± 0.188	0.729 ± 0.1392
Termination (N= 15, 10)	0.605 ± 0.2146	0.7 ± 0.1233
Change (Screening - Month 6) (N= 15, 11)	-0.006 ± 0.2088	-0.096 ± 0.2403
Change (Screening - Termination) (N= 15, 10)	0.01 ± 0.247	-0.075 ± 0.2594
Change (Month 6 - Termination) (N= 15, 10)	0.016 ± 0.1765	0.001 ± 0.1493

No statistical analyses for this end point

Secondary: Hemophilia-specific Quality of Life questionnaire for adults (Haem-A-QoL) ≥ 16 Years Old

Top of page

End point title

Hemophilia-specific Quality of Life questionnaire for adults (Haem-A-QoL) ≥ 16 Years Old ^[39]

End point description

The Haem-A-QoL instrument has been developed and used in Hemophilia A patients. As a hemophilia-specific instrument, this measure assesses very specific aspects of dealing with hemophilia. The areas covered by this instrument are: Physical Health (PH), Sports & Leisure (S&L), School & Work (W&S), Dealing with Hemophilia (Dealing), Family Planning (FP), Feeling, Relationships (R'ships), Treatment, View, and Outlook for the Future (Future). A Haem-A-QoL Total Score (Total) was also calculated. For the Haem-A-QoL, higher scores indicate a worse quality of life. Scores on a scale range between 0 and 100. Haem-A-QoL scores at screening, 6 months, and at termination visit were collected. Changes in scores at 6 months and termination were also calculated.

End point type

Secondary

End point timeframe

12 months ± 14 days

Notes
[39] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Baseline period arms are not mutually exclusive. Details see under description of period arms.

End point values	On-demand arm	Prophylaxis arm
Number of subjects analysed	15	12
Units: Scores on a scale
arithmetic mean (standard deviation)
Dealing- Screening (N=15, 12)	35 ± 19.72	26 ± 15.84
Dealing- Month 6 (N=14, 11)	25 ± 16.67	18.9 ± 21.11
Dealing- Termination (N=14, 11)	25.6 ± 25.21	23.7 ± 22.15
Dealing- Change (Screening - Month 6) (N=14, 11)	10.7 ± 18.61	3.4 ± 22.62
Dealing- Change(Screening - Termination)(N=14, 11)	10.1 ± 27.19	-1.4 ± 21.37
Dealing- Change (Month 6 - Termination)(N=14, 11)	-0.6 ± 16.81	-4.8 ± 21.26
FP- Screening (N=9, 8)	16.7 ± 20.49	34.9 ± 31.31
FP- Month 6 (N=12, 7)	20.5 ± 26.71	14.3 ± 11.25
FP- Termination (N=13, 8)	19.1 ± 16.25	21.1 ± 22.14
FP- Change (Screening - Month 6) (N=9, 7)	-3.7 ± 26.94	14.9 ± 28.73
FP- Change(Screening - Termination)(N=9, 7)	-2.5 ± 25.57	13.1 ± 20.26
FP- Change (Month 6 - Termination)(N=11, 6)	-0.8 ± 32.68	-8.3 ± 28.41
Feeling- Screening (N=15, 12)	39.6 ± 28.22	48.2 ± 29.02
Feeling- Month 6 (N=14, 11)	33.9 ± 28.77	29 ± 17.29
Feeling- Termination (N=14, 11)	30.8 ± 28.53	26.1 ± 20.69
Feeling- Change (Screening - Month 6) (N=14, 11)	4.9 ± 27.75	17.3 ± 34.72
Feeling- Change(Screening - Termination)(N=14, 11)	8 ± 31.91	20.2 ± 24.58
Feeling- Change (Month 6 - Termination)(N=14, 11)	3.1 ± 16.4	2.8 ± 23.94
Future- Screening (N=14, 12)	46.8 ± 28.46	48.6 ± 23.32
Future- Month 6 (N=14, 11)	40.2 ± 26.14	46 ± 18.03
Future- Termination (N=14, 11)	47.9 ± 25.47	46.8 ± 18.74
Future- Change (Screening - Month 6) (N=13, 11)	4 ± 26.84	1.1 ± 24.34
Future- Change(Screening - Termination)(N=13, 11)	-3.8 ± 20.53	0.3 ± 16.58
Future- Change (Month 6 - Termination)(N=14, 11)	-7.7 ± 20.25	-0.8 ± 16.3
PH- Screening (N=15, 12)	64 ± 22.46	66.4 ± 24.21
PH- Month 6 (N=14, 11)	50.8 ± 27.55	43.1 ± 25.24
PH- Termination (N=14, 11)	56.1 ± 24.98	42.3 ± 18.86
PH- Change (Screening - Month 6) (N=14, 11)	14.6 ± 21.7	21.1 ± 28.77
PH- Change(Screening - Termination)(N=14, 11)	9.3 ± 23.93	21.9 ± 24.79
PH- Change (Month 6 - Termination)(N=14, 11)	-5.3 ± 10.65	0.8 ± 20.2
R'ships- Screening (N=15, 11)	28.3 ± 36.57	26.9 ± 28.83
R'ships- Month 6 (N=14, 11)	19 ± 28.2	15.2 ± 13.85
R'ships- Termination (N=14, 10)	17.9 ± 22.13	15 ± 17.48
R'ships- Change (Screening - Month 6) (N=14, 10)	7.7 ± 34.04	10.4 ± 27.45
R'ships- Change(Screening - Termination)(N=14, 10)	8.9 ± 30.57	12.1 ± 25.49
R'ships- Change (Month 6 - Termination)(N=14, 10)	1.2 ± 21.4	1.7 ± 16.57
S&L- Screening (N=12, 8)	69.3 ± 17.11	83.1 ± 14.13
S&L- Month 6 (N=12, 8)	63.1 ± 23.09	69.7 ± 19.75
S&L- Termination (N=12, 8)	72.3 ± 17.3	78.1 ± 12.52
S&L- Change (Screening - Month 6) (N=9, 5)	9.9 ± 19.75	20.5 ± 27.97
S&L- Change(Screening - Termination)(N=9, 5)	1.2 ± 15.91	7 ± 21.68
S&L- Change (Month 6 - Termination)(N=11, 7)	-10.2 ± 13.44	-2.5 ± 15.61
Treatment- Screening (N=15, 12)	36.9 ± 13.32	39.6 ± 20.7
Treatment- Month 6 (N=14, 11)	30.4 ± 19.82	40.9 ± 16.96
Treatment- Termination (N=14, 11)	34.8 ± 14.87	42.6 ± 17.8
Treatment- Change (Screening - Month 6) (N=14, 11)	6.5 ± 23.72	0 ± 16.74
Treatment-Change(Screening -Termination)(N=14, 11)	2.1 ± 17.81	-1.7 ± 23.86
Treatment- Change (Month 6- Termination)(N=14, 11)	-4.4 ± 15.07	-1.7 ± 18.7
View- Screening (N=15, 12)	52.3 ± 24.49	55.6 ± 11.97
View- Month 6 (N=14, 11)	44.3 ± 27.66	40 ± 13.23
View- Termination (N=14, 11)	47.9 ± 22.59	37.7 ± 21.26
View- Change (Screening - Month 6) (N=14, 11)	7.5 ± 23.68	14.3 ± 17.25
View- Change (Screening -Termination)(N=14, 11)	3.9 ± 23.79	16.6 ± 15.01
View- Change (Month 6- Termination)(N=14, 11)	-3.6 ± 17.03	2.3 ± 20.78
W&S-Screening (N=13, 10)	43.8 ± 25.9	57.7 ± 17.87
W&S- Month 6 (N=13, 9)	31.7 ± 26.82	37.5 ± 20.73
W&S- Termination (N=12, 9)	28.6 ± 22.53	36.8 ± 19.63
W&S- Change (Screening - Month 6) (N=12, 8)	10.9 ± 30.98	25.3 ± 25.6
W&S- Change (Screening -Termination)(N=12, 8)	16.1 ± 33.86	25.3 ± 19.01
W&S- Change (Month 6- Termination)(N=12, 9)	5.2 ± 15.95	0.7 ± 21.75
Total- Screening (N=14, 12)	44 ± 15.5	49.2 ± 15.43
Total- Month 6 (N=14, 11)	37.4 ± 19.37	38.1 ± 11.34
Total- Termination (N=14, 11)	40.2 ± 17.55	38.7 ± 14.21
Total- Change (Screening - Month 6) (N=13, 11)	9.2 ± 18.44	10.2 ± 17.84
Total- Change (Screening -Termination)(N=13, 11)	6.1 ± 15.41	9.5 ± 12.77
Total- Change (Month 6- Termination)(N=14, 11)	-2.7 ± 9.21	-0.7 ± 14.4

No statistical analyses for this end point

Secondary: Hemophilia-specific Quality of Life questionnaire for Children and Adolescents < 16 Years Old (Haemo-QoL) - Parent's Evaluation

Top of page

End point title

Hemophilia-specific Quality of Life questionnaire for Children and Adolescents < 16 Years Old (Haemo-QoL) - Parent's Evaluation ^[40]

End point description

The Haemo-QoL is a quality of life (QoL) assessment instrument for children and adolescents with haemophilia. As a hemophilia-specific instrument, this measure assesses very specific aspects of dealing with hemophilia. The areas covered by this instrument are: Physical Health (PH), Sports & School (S&S), Dealing with Hemophilia (Dealing), Family, Feeling, Relationships (R'ships), Treatment, View, Outlook for the Future (Future), Friends, Others, and Support. A Haemo-QoL Total Score (Total) was also calculated. For the Haemo-QoL, higher scores indicate a worse quality of life. Scores on a scale range between 0 and 100. Haemo-QoL scores at screening, 6 months, and at termination visit were collected. Changes in scores at 6 months and termination were also calculated.

End point type

Secondary

End point timeframe

12 months ± 14 days

Notes
[40] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Baseline period arms are not mutually exclusive. Details see under description of period arms.

End point values	On-demand arm	Prophylaxis arm
Number of subjects analysed	4	5
Units: Scores on a scale
arithmetic mean (standard deviation)
Dealing- Screening (N=4, 4)	25.9 ± 11.8	39.3 ± 17
Dealing- Month 6 (N=4, 4)	25.6 ± 19.31	36.6 ± 16.07
Dealing- Termination (N=4, 5)	21.4 ± 16.24	28.6 ± 13.36
Dealing- Change (Screening - Month 6) (N=4, 4)	0.3 ± 8.61	2.7 ± 7.92
Dealing- Change(Screening - Termination)(N=4, 4)	4.5 ± 7.92	13.4 ± 5.36
Dealing- Change (Month 6 - Termination)(N=4, 4)	4.2 ± 11.85	10.7 ± 7.72
Family- Screening (N=4, 5)	55.3 ± 19.05	50.9 ± 8.72
Family- Month 6 (N=4, 5)	50.3 ± 27.65	49.1 ± 10.27
Family- Termination (N=4, 5)	45.8 ± 31.03	39.8 ± 13.77
Family- Change (Screening - Month 6) (N=4, 5)	5 ± 9.26	1.7 ± 15.65
Family- Change(Screening - Termination)(N=4, 5)	9.5 ± 15.52	11.1 ± 19.22
Family- Change (Month 6 - Termination)(N=4, 5)	4.5 ± 12.16	9.3 ± 5.24
Feeling- Screening (N=4, 5)	44.1 ± 14.25	38.2 ± 2.77
Feeling- Month 6 (N=4, 5)	50.3 ± 27.02	37.5 ± 22.21
Feeling- Termination (N=4, 5)	33.6 ± 36.07	27.8 ± 16.97
Feeling- Change (Screening - Month 6) (N=4, 5)	-6.3 ± 24.27	0.7 ± 24.02
Feeling- Change(Screening - Termination)(N=4, 5)	10.5 ± 27.92	10.5 ± 19.45
Feeling- Change (Month 6 - Termination)(N=4, 5)	16.7 ± 13.85	9.7 ± 20.64
Friends- Screening (N=4, 5)	35.9 ± 20.65	52.1 ± 17.18
Friends- Month 6 (N=4, 5)	26.6 ± 17.95	36.3 ± 29.78
Friends- Termination (N=4, 5)	34.4 ± 14.88	66.3 ± 20.06
Friends- Change (Screening - Month 6) (N=4, 5)	9.4 ± 27.72	15.8 ± 21.88
Friends- Change(Screening - Termination)(N=4, 5)	1.6 ± 17.95	-14.2 ± 28.31
Friends- Change (Month 6 - Termination)(N=4, 5)	-7.8 ± 22.46	-30 ± 31.68
Future- Screening (N=2, 2)	53.1 ± 13.26	43.8 ± 17.68
Future- Month 6 (N=2, 2)	40.6 ± 13.26	37.5 ± 8.84
Future- Termination (N=2, 2)	31.3 ± 0	43.8 ± 8.84
Future- Change (Screening - Month 6) (N=2, 2)	12.5 ± 0	6.3 ± 8.84
Future- Change(Screening - Termination)(N=2, 2)	21.9 ± 13.26	0 ± 8.84
Future- Change (Month 6 - Termination)(N=2, 2)	9.4 ± 13.26	-6.3 ± 0
Others- Screening (N=4, 5)	27.1 ± 34.44	29.2 ± 16.67
Others- Month 6 (N=4, 5)	42.7 ± 39.14	24.2 ± 15.7
Others- Termination (N=4, 5)	28.1 ± 32.87	25.8 ± 13.63
Others- Change (Screening - Month 6) (N=4, 5)	-15.6 ± 16.8	5 ± 20.28
Others- Change(Screening - Termination)(N=4, 5)	-1 ± 15.36	3.3 ± 15.98
Others- Change (Month 6 - Termination)(N=4, 5)	14.6 ± 19.98	-1.7 ± 10.87
PH- Screening (N=4, 5)	58 ± 11.06	52.1 ± 23.23
PH- Month 6 (N=4, 5)	53.6 ± 13.98	48 ± 17.23
PH- Termination (N=4, 5)	41.1 ± 11.85	40.4 ± 17.02
PH- Change (Screening - Month 6) (N=4, 5)	4.5 ± 12.16	4.1 ± 32.71
PH- Change(Screening - Termination)(N=4, 5)	17 ± 17.1	11.8 ± 29.6
PH- Change (Month 6 - Termination)(N=4, 5)	12.5 ± 22.87	7.7 ± 22.25
R'ships- Screening (N=2, 2)	12.5 ± 17.68	43.8 ± 8.84
R'ships- Month 6 (N=2, 2)	25 ± 35.36	43.8 ± 8.84
R'ships- Termination (N=2, 2)	0 ± 0	37.5 ± 17.68
R'ships- Change (Screening - Month 6) (N=2, 2)	-12.5 ± 17.68	0 ± 0
R'ships-Change(Screening -Termination)(N=2, 2)	12.5 ± 17.68	6.3 ± 8.84
R'ships- Change (Month 6- Termination)(N=2, 2)	25 ± 35.36	6.3 ± 8.84
S&S- Screening (N=4, 5)	67.1 ± 10.68	59.1 ± 23.73
S&S- Month 6 (N=4, 5)	62.5 ± 7.74	56.5 ± 9.07
S&S- Termination (N=4, 5)	55.6 ± 17.16	57.2 ± 17.29
S&S- Change (Screening - Month 6) (N=4, 5)	4.6 ± 6.89	2.6 ± 16.32
S&S- Change (Screening -Termination)(N=4, 5)	11.5 ± 12.02	1.9 ± 10.22
S&S- Change (Month 6- Termination)(N=4, 5)	6.9 ± 18.07	-0.8 ± 8.94
Support-Screening (N=4, 4)	28.1 ± 25.77	51.6 ± 9.38
Support-Month 6 (N=4, 4)	18.8 ± 29.32	42.2 ± 17.95
Support- Termination (N=4, 5)	32.8 ± 32.02	48.8 ± 20.44
Support- Change (Screening - Month 6) (N=4, 4)	9.4 ± 24.21	9.4 ± 10.83
Support- Change (Screening -Termination)(N=4, 4	-4.7 ± 13.86	3.1 ± 15.73
Support- Change (Month 6- Termination)(N=4, 4)	-14.1 ± 21.27	-6.3 ± 8.84
Treatment- Screening (N=4, 5)	29 ± 13.23	64.2 ± 22.6
Treatment- Month 6 (N=4, 5)	21.9 ± 6.9	54.8 ± 14.53
Treatment- Termination (N=4, 5)	17.1 ± 22.12	41 ± 13.34
Treatment- Change (Screening - Month 6) (N=4, 5)	7.1 ± 10.1	9.4 ± 13.06
Treatment- Change(Screening -Termination)(N=4, 5)	11.9 ± 17.16	23.2 ± 16.94
Treatment- Change (Month 6- Termination)(N=4, 5)	4.8 ± 22.47	13.8 ± 11.14
View-Screening (N=4, 5)	47.4 ± 18.25	36.7 ± 16.94
View-Month 6 (N=4, 5)	46.3 ± 24.45	36.4 ± 22.04
View- Termination (N=4, 5)	32.8 ± 35.68	30.8 ± 12.85
View- Change (Screening - Month 6) (N=4, 5)	1.1 ± 6.38	0.3 ± 7.63
View- Change (Screening -Termination)(N=4, 5)	14.7 ± 18.62	5.9 ± 10.08
View- Change (Month 6- Termination)(N=4, 5)	13.5 ± 13.02	5.6 ± 16.7
Total-Screening (N=4, 5)	43.7 ± 13.67	48.1 ± 8.84
Total-Month 6 (N=4, 5)	42 ± 13.84	42.3 ± 11.08
Total- Termination (N=4, 5)	34.5 ± 21.83	39.5 ± 8.52
Total- Change (Screening - Month 6) (N=4, 5)	1.7 ± 1.19	5.7 ± 14.97
Total- Change (Screening -Termination)(N=4, 5)	9.1 ± 8.57	8.6 ± 8.72
Total- Change (Month 6- Termination)(N=4, 5)	7.4 ± 8.91	2.8 ± 7.06

No statistical analyses for this end point

Secondary: Hemophilia-specific Quality of Life questionnaire for Children and Adolescents < 16 Years Old (Haemo-QoL) - Child's Evaluation

Top of page

End point title

Hemophilia-specific Quality of Life questionnaire for Children and Adolescents < 16 Years Old (Haemo-QoL) - Child's Evaluation ^[41]

End point description

End point type

Secondary

End point timeframe

12 months ± 14 days

Notes
[41] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Baseline period arms are not mutually exclusive. Details see under description of period arms.

End point values	On-demand arm	Prophylaxis arm
Number of subjects analysed	4	5
Units: Scores on a scale
arithmetic mean (standard deviation)
Dealing- Screening (N=4, 4)	33 ± 17.1	44.6 ± 20.72
Dealing- Month 6 (N=4, 4)	21.4 ± 2.92	37.5 ± 13.2
Dealing- Termination (N=4, 5)	25 ± 9.22	32.9 ± 12.73
Dealing- Change (Screening - Month 6) (N=4, 4)	11.6 ± 15.26	7.1 ± 8.75
Dealing- Change(Screening - Termination)(N=4, 4)	8 ± 15.26	14.3 ± 12.37
Dealing- Change (Month 6 - Termination)(N=4, 4)	-3.6 ± 6.52	7.1 ± 6.52
Family- Screening (N=4, 5)	50.5 ± 23.94	35.6 ± 22.05
Family- Month 6 (N=4, 5)	43.4 ± 28.78	36.4 ± 23.06
Family- Termination (N=4, 5)	38.3 ± 21.25	32.5 ± 21.09
Family- Change (Screening - Month 6) (N=4, 5)	7 ± 20.31	-0.7 ± 16.38
Family- Change(Screening - Termination)(N=4, 5)	12.2 ± 25.72	3.1 ± 15.51
Family- Change (Month 6 - Termination)(N=4, 5)	5.2 ± 13.66	3.9 ± 12.2
Feeling- Screening (N=4, 5)	54.8 ± 31.91	34.9 ± 12.89
Feeling- Month 6 (N=4, 5)	41.4 ± 43.03	22 ± 18.68
Feeling- Termination (N=4, 5)	34.4 ± 39.48	19.2 ± 15.39
Feeling- Change (Screening - Month 6) (N=4, 5)	13.4 ± 16.91	12.9 ± 27.77
Feeling- Change(Screening - Termination)(N=4, 5)	20.4 ± 11.77	15.7 ± 23.2
Feeling- Change (Month 6 - Termination)(N=4, 5)	7 ± 7.79	2.8 ± 15.26
Friends- Screening (N=4, 5)	34.4 ± 25.26	58.8 ± 20.54
Friends- Month 6 (N=4, 5)	28.1 ± 15.73	42.5 ± 29.78
Friends- Termination (N=4, 5)	32.8 ± 12.88	56.3 ± 27.24
Friends- Change (Screening - Month 6) (N=4, 5)	6.3 ± 25.52	16.3 ± 24.84
Friends- Change(Screening - Termination)(N=4, 5)	1.6 ± 28.58	2.5 ± 22.79
Friends- Change (Month 6 - Termination)(N=4, 5)	-4.7 ± 17.95	-13.8 ± 20.44
Future- Screening (N=2, 2)	40.6 ± 13.26	43.8 ± 17.68
Future- Month 6 (N=2, 2)	43.8 ± 17.68	43.8 ± 17.68
Future- Termination (N=2, 2)	46.9 ± 22.1	28.1 ± 22.1
Future- Change (Screening - Month 6) (N=2, 2)	-3.1 ± 4.42	0 ± 0
Future- Change(Screening - Termination)(N=2, 2)	-6.3 ± 8.84	15.6 ± 4.42
Future- Change (Month 6 - Termination)(N=2, 2)	-3.1 ± 4.42	15.6 ± 4.42
Others- Screening (N=4, 5)	42.7 ± 33.74	26.7 ± 20.11
Others- Month 6 (N=4, 5)	33.3 ± 40.11	16.7 ± 15.02
Others- Termination (N=4, 5)	18.8 ± 21.11	13.3 ± 12.64
Others- Change (Screening - Month 6) (N=4, 5)	9.4 ± 8.59	10 ± 25.79
Others- Change(Screening - Termination)(N=4, 5)	24 ± 14.18	13.3 ± 23.09
Others- Change (Month 6 - Termination)(N=4, 5)	14.6 ± 19.39	3.3 ± 16.24
PH- Screening (N=4, 5)	67 ± 24.98	42.1 ± 32.28
PH- Month 6 (N=4, 5)	49.1 ± 14.69	33.9 ± 16.66
PH- Termination (N=4, 5)	41.1 ± 23.05	25.7 ± 10.83
PH- Change (Screening - Month 6) (N=4, 5)	17.9 ± 19.56	8.2 ± 34.43
PH- Change(Screening - Termination)(N=4, 5)	25.9 ± 14.4	16.4 ± 29.73
PH- Change (Month 6 - Termination)(N=4, 5)	8 ± 12.16	8.2 ± 20.66
R'ships- Screening (N=2, 2)	6.3 ± 8.84	43.8 ± 8.84
R'ships- Month 6 (N=2, 2)	18.8 ± 26.52	43.8 ± 8.84
R'ships- Termination (N=2, 2)	6.3 ± 8.84	18.8 ± 26.52
R'ships- Change (Screening - Month 6) (N=2, 2)	-12.5 ± 17.68	0 ± 0
R'ships-Change(Screening -Termination)(N=2, 2)	0 ± 0	25 ± 17.68
R'ships- Change (Month 6- Termination)(N=2, 2)	12.5 ± 17.68	25 ± 17.68
S&S- Screening (N=4, 5)	53.3 ± 14.74	51.3 ± 19.82
S&S- Month 6 (N=4, 5)	46.8 ± 13.42	54.2 ± 5.53
S&S- Termination (N=4, 5)	33.2 ± 5.64	49.8 ± 18.49
S&S- Change (Screening - Month 6) (N=4, 5)	6.5 ± 11.42	-2.8 ± 18.53
S&S- Change (Screening -Termination)(N=4, 5)	20.1 ± 14.74	1.5 ± 18.74
S&S- Change (Month 6- Termination)(N=4, 5)	13.5 ± 9.1	4.4 ± 15.19
Support-Screening (N=4, 4)	32.8 ± 3.13	62.5 ± 31.04
Support-Month 6 (N=4, 4)	28.1 ± 10.83	56.3 ± 31.87
Support- Termination (N=4, 5)	17.2 ± 17.21	65 ± 15.69
Support- Change (Screening - Month 6) (N=4, 4)	4.7 ± 12.88	6.3 ± 31.46
Support- Change (Screening -Termination)(N=4, 4	15.6 ± 18.75	-3.1 ± 18.75
Support- Change (Month 6- Termination)(N=4, 4)	10.9 ± 10.67	-9.4 ± 25.77
Treatment- Screening (N=4, 5)	27.3 ± 15.38	69.6 ± 25.63
Treatment- Month 6 (N=4, 5)	30.6 ± 16.5	56.8 ± 15.89
Treatment- Termination (N=4, 5)	35.9 ± 26.1	44.2 ± 27.1
Treatment- Change (Screening - Month 6) (N=4, 5)	-3.2 ± 4.43	12.9 ± 21.22
Treatment- Change(Screening -Termination)(N=4, 5)	-8.6 ± 13.86	25.4 ± 28
Treatment- Change (Month 6- Termination)(N=4, 5)	-5.3 ± 11.25	12.6 ± 15.53
View-Screening (N=4, 5)	46 ± 19.33	31.9 ± 14.36
View-Month 6 (N=4, 5)	39.3 ± 33.02	32.4 ± 19.41
View- Termination (N=4, 5)	32.5 ± 32.75	32.2 ± 8.6
View- Change (Screening - Month 6) (N=4, 5)	6.7 ± 14.96	-0.5 ± 18.94
View- Change (Screening -Termination)(N=4, 5)	13.5 ± 16.56	-0.3 ± 10.77
View- Change (Month 6- Termination)(N=4, 5)	6.8 ± 8.67	0.2 ± 13.48
Total-Screening (N=4, 5)	44.9 ± 12.28	45.1 ± 9.16
Total-Month 6 (N=4, 5)	37.4 ± 17.91	37.7 ± 9.87
Total- Termination (N=4, 5)	32.2 ± 17.96	35.3 ± 9.06
Total- Change (Screening - Month 6) (N=4, 5)	7.5 ± 7.21	7.4 ± 16.57
Total- Change (Screening -Termination)(N=4, 5)	12.7 ± 8.69	9.8 ± 12.35
Total- Change (Month 6- Termination)(N=4, 5)	5.2 ± 3.55	2.5 ± 9.46

No statistical analyses for this end point

Secondary: Health-Related Quality of Life (HRQoL) - General Pain Assessment Using a Visual Analogue Scale (VAS) in Adults and Adolescents ≥12 Years Old

Top of page

End point title

Health-Related Quality of Life (HRQoL) - General Pain Assessment Using a Visual Analogue Scale (VAS) in Adults and Adolescents ≥12 Years Old ^[42]

End point description

General pain was assessed using a VAS pain scale at screening, 6 months, and at termination. Unlike the VAS pain assessment for pain of bleeding episodes (Outcome above), this general pain assessment did not take use of analgesics into account. For the pain scale, a higher number indicates worse pain. The visual analog scale ranges from 0 to 100 where the endpoints are labeled 'Worst imaginable health state' (=0) and 'Best imaginable health state' (=100). A positive change from baseline indicates improvement. Change in VAS scores at 6 months and study termination were also compared relative to Baseline/Screening scores (ie, (Baseline/Screening VAS score) - (VAS score at 6 months and study termination).

End point type

Secondary

End point timeframe

Baseline, 6 months and 12 months ± 14 days

Notes
[42] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Baseline period arms are not mutually exclusive. Details see under description of period arms.

End point values	On-demand arm	Prophylaxis arm
Number of subjects analysed	17	15
Units: Scores on a scale
arithmetic mean (standard deviation)
Screening (N= 17, 15)	35.2 ± 30.15	55.5 ± 23.68
Month 6 (N= 16, 14)	36.6 ± 25.81	32.7 ± 26.24
Termination (N= 16, 14)	32.4 ± 21.97	29.8 ± 30.48
Change (Screening - Month 6) (N= 16, 14)	0.8 ± 31.77	20.3 ± 38.91
Change (Screening - Termination) (N= 16, 14)	5 ± 28.7	23.2 ± 46.61
Change (Month 6 - Termination) (N= 16, 14)	4.2 ± 21.82	2.9 ± 19.62

No statistical analyses for this end point

Secondary: Health-Related Quality of Life (HRQoL) - General Pain Assessment Using a Visual Analogue Scale (VAS) in Pediatrics <12 Years Old

Top of page

End point title

Health-Related Quality of Life (HRQoL) - General Pain Assessment Using a Visual Analogue Scale (VAS) in Pediatrics <12 Years Old ^[43]

End point description

General pain was assessed using the children’s VAS pain scale (a facial expression scale with one end marked as no pain and the opposite end marked as the worst possible pain). Assessments were done at the screening, 6 months, and termination visits. Scores on the children's VAS scale are presented as: -No Pain -Mild Pain -Moderate pain -Severe pain -Very severe pain Unlike the VAS pain assessment for pain of bleeding episodes (Outcome above), this general pain assessment did not take use of analgesics into account. Change in VAS scores at 6 months and study termination were also compared relative to Baseline/Screening scores (ie, (Baseline/Screening VAS score) - (VAS score at 6 months and study termination).

End point type

Secondary

End point timeframe

Baseline, 6 months and 12 months ± 14 days

Notes
[43] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Baseline period arms are not mutually exclusive. Details see under description of period arms.

End point values	On-demand arm	Prophylaxis arm
Number of subjects analysed	2	2
Units: participants
Screening - No Pain	1	0
Screening - Mild Pain	0	1
Screening - Moderate Pain	1	0
Screening - Severe Pain	0	1
Screening - Very Severe Pain	0	0
Month 6 - No Pain	0	0
Month 6 - Mild Pain	1	2
Month 6 - Moderate Pain	1	0
Month 6 - Severe Pain	0	0
Month 6 - Very Severe Pain	0	0
Termination visit - No Pain	0	1
Termination visit - Mild Pain	0	0
Termination visit - Moderate Pain	1	1
Termination visit - Severe Pain	0	0
Termination visit - Very Severe Pain	1	0

No statistical analyses for this end point

Adverse events

Top of page

Timeframe for reporting adverse events

Throughout the study period of 3 years and 7 months

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

15.0

Reporting group title

On-demand arm

Reporting group description

Factor VIII Inhibitor Bypassing Activity (nanofiltered, vapor heat-treated) : Standard FEIBA NF dose and dosing interval as prescribed by the treating physician

Reporting group title

Prophylaxis arm

Reporting group description

Factor VIII Inhibitor Bypassing Activity (nanofiltered, vapor heat-treated) : 85 ± 15 U/kg of FEIBA NF every other day during the 12-month ± 14 days prophylactic period

Serious adverse events	On-demand arm	Prophylaxis arm
Total subjects affected by serious adverse events
subjects affected / exposed	7 / 19 (36.84%)	6 / 17 (35.29%)
number of deaths (all causes)	1	0
number of deaths resulting from adverse events
Investigations
Hepatitis B Surface Antibody Positive
subjects affected / exposed	1 / 19 (5.26%)	2 / 17 (11.76%)
occurrences causally related to treatment / all	1 / 1	2 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Injury, poisoning and procedural complications
Femoral Neck Fracture
subjects affected / exposed	1 / 19 (5.26%)	0 / 17 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Vascular disorders
Arteriosclerosis
subjects affected / exposed	1 / 19 (5.26%)	0 / 17 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0
Haematoma
subjects affected / exposed	0 / 19 (0.00%)	1 / 17 (5.88%)
occurrences causally related to treatment / all	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Haemorrhage
subjects affected / exposed	1 / 19 (5.26%)	0 / 17 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Hypertensive Crisis
subjects affected / exposed	1 / 19 (5.26%)	0 / 17 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Surgical and medical procedures
Catheter Removal
subjects affected / exposed	1 / 19 (5.26%)	0 / 17 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Gastrointestinal disorders
Abdominal Wall Haematoma
subjects affected / exposed	0 / 19 (0.00%)	1 / 17 (5.88%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Hepatobiliary disorders
Cholecystitis Acute
subjects affected / exposed	1 / 19 (5.26%)	0 / 17 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Respiratory, thoracic and mediastinal disorders
Epistaxis
subjects affected / exposed	1 / 19 (5.26%)	0 / 17 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Renal and urinary disorders
Haematuria
subjects affected / exposed	1 / 19 (5.26%)	0 / 17 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Musculoskeletal and connective tissue disorders
Arthropathy
subjects affected / exposed	1 / 19 (5.26%)	0 / 17 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Haemarthrosis
subjects affected / exposed	1 / 19 (5.26%)	2 / 17 (11.76%)
occurrences causally related to treatment / all	0 / 3	0 / 8
deaths causally related to treatment / all	0 / 0	0 / 0
Muscle Haemorrhage
subjects affected / exposed	0 / 19 (0.00%)	1 / 17 (5.88%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Infections and infestations
Haematoma Infection
subjects affected / exposed	1 / 19 (5.26%)	0 / 17 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0

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

Non-serious adverse events	On-demand arm	Prophylaxis arm
Total subjects affected by non serious adverse events
subjects affected / exposed	4 / 19 (21.05%)	3 / 17 (17.65%)
Blood and lymphatic system disorders
Anaemia
subjects affected / exposed	2 / 19 (10.53%)	0 / 17 (0.00%)
occurrences all number	2	0
General disorders and administration site conditions
Pyrexia
subjects affected / exposed	2 / 19 (10.53%)	0 / 17 (0.00%)
occurrences all number	4	0
Gastrointestinal disorders
Diarrhoea
subjects affected / exposed	1 / 19 (5.26%)	1 / 17 (5.88%)
occurrences all number	2	1
Nausea
subjects affected / exposed	2 / 19 (10.53%)	0 / 17 (0.00%)
occurrences all number	2	0
Vomiting
subjects affected / exposed	2 / 19 (10.53%)	0 / 17 (0.00%)
occurrences all number	2	0
Respiratory, thoracic and mediastinal disorders
Cough
subjects affected / exposed	1 / 19 (5.26%)	1 / 17 (5.88%)
occurrences all number	1	1
Oropharyngeal Pain
subjects affected / exposed	1 / 19 (5.26%)	1 / 17 (5.88%)
occurrences all number	1	1
Skin and subcutaneous tissue disorders
Acne
subjects affected / exposed	1 / 19 (5.26%)	1 / 17 (5.88%)
occurrences all number	1	1
Musculoskeletal and connective tissue disorders
Arthralgia
subjects affected / exposed	2 / 19 (10.53%)	1 / 17 (5.88%)
occurrences all number	3	1
Arthropathy
subjects affected / exposed	1 / 19 (5.26%)	0 / 17 (0.00%)
occurrences all number	1	0

More information

Top of page

Were there any global substantial amendments to the protocol? No

Were there any global interruptions to the trial? No

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

None reported

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

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

Clinical trials

Clinical Trial Results: FEIBA NF: a prospective, open-label, randomized, parallel study to evaluate efficacy and safety of prophylactic versus on-demand treatment in subjects with hemophilia A or B and a high titer inhibitor

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Reduction in annualized bleeding episode rate (ABR) among participants receiving prophylactic treatment as compared to those treated on-demand

Primary: Reduction in annualized bleeding episode rate (ABR) among participants receiving prophylactic treatment as compared to those treated on-demand

Secondary: Annualized Bleeding Rate by Treatment Regimen, Bleeding Etiology, and Bleed Type

Secondary: Annualized Bleeding Rate by Treatment Regimen, Bleeding Etiology, and Bleed Type

Secondary: Differences in Mean Transformed Annualized Bleeding Rate Between On-Demand and Prophylaxis Treatment Regimens by Bleeding Etiology, and Bleeding Type

Secondary: Differences in Mean Transformed Annualized Bleeding Rate Between On-Demand and Prophylaxis Treatment Regimens by Bleeding Etiology, and Bleeding Type

Secondary: Annualized Bleeding Rate for New Target Joints

Secondary: Annualized Bleeding Rate for New Target Joints

Secondary: Differences in Mean Transformed Annualized Bleeding Rate Between On-Demand and Prophylaxis Treatment Regimens: New Target Joints

Secondary: Differences in Mean Transformed Annualized Bleeding Rate Between On-Demand and Prophylaxis Treatment Regimens: New Target Joints

Secondary: Number of New Target Joints

Secondary: Number of New Target Joints

Secondary: Assessment of Objective Clinical Symptoms- Visual Analog Scale (VAS): Pain in Adolescents and Adults (≥12 years old)

Secondary: Assessment of Objective Clinical Symptoms- Visual Analog Scale (VAS): Pain in Adolescents and Adults (≥12 years old)

Secondary: Assessment of Clinical Symptoms - Visual Analog Scale (VAS): Pain in Pediatrics (<12 years old)

Secondary: Assessment of Clinical Symptoms - Visual Analog Scale (VAS): Pain in Pediatrics (<12 years old)

Secondary: Assessment of Clinical Symptoms - Range of Motion (ROM)

Secondary: Assessment of Clinical Symptoms - Range of Motion (ROM)

Secondary: Assessment of Hemostasis for Treatment of Bleeding Episodes- Overall Efficacy Rating at 6 hours

Secondary: Assessment of Hemostasis for Treatment of Bleeding Episodes- Overall Efficacy Rating at 6 hours

Secondary: Assessment of Hemostasis for Treatment of Bleeding Episodes- Overall Efficacy Rating at 24 hours

Secondary: Assessment of Hemostasis for Treatment of Bleeding Episodes- Overall Efficacy Rating at 24 hours

Secondary: Total Weight Adjusted Dose to Control a Bleeding Episode

Secondary: Total Weight Adjusted Dose to Control a Bleeding Episode

Secondary: The Number of Bleeding Episode (BE) Which Required 1, 2, 3, or ≥4 Infusions to Control Bleeding

Secondary: The Number of Bleeding Episode (BE) Which Required 1, 2, 3, or ≥4 Infusions to Control Bleeding

Secondary: Abnormal Activated Partial Thromboplastin Time (aPTT) Assay Results

Secondary: Abnormal Activated Partial Thromboplastin Time (aPTT) Assay Results

Secondary: Abnormal D-Dimer Assay Results

Secondary: Abnormal D-Dimer Assay Results

Secondary: Abnormal Fibrinogen Assay Results

Secondary: Abnormal Fibrinogen Assay Results

Secondary: Abnormal Fibrin Degradation Products (FDP) Assay Results

Secondary: Abnormal Fibrin Degradation Products (FDP) Assay Results

Secondary: Abnormal Prothrombin Fragment F 1.2 Assay Results

Secondary: Abnormal Prothrombin Fragment F 1.2 Assay Results

Secondary: Abnormal Prothrombin Time Assay Results

Secondary: Abnormal Prothrombin Time Assay Results

Secondary: Abnormal Thrombin-Antithrombin III (TAT) Assay Results

Secondary: Abnormal Thrombin-Antithrombin III (TAT) Assay Results

Secondary: Viral Serology from Screening Visit and Study Termination Visit: Hepatitis A, Hepatitis B, and Hepatitis C

Secondary: Viral Serology from Screening Visit and Study Termination Visit: Hepatitis A, Hepatitis B, and Hepatitis C

Secondary: Viral Serology From Screening Visit and Study Termination Visit: HIV-1/2 Antibody (Ab)

Secondary: Viral Serology From Screening Visit and Study Termination Visit: HIV-1/2 Antibody (Ab)

Secondary: Viral Serology From Screening Visit and Study Termination Visit: Parvovirus B19 IgG Antibody [IV]

Secondary: Viral Serology From Screening Visit and Study Termination Visit: Parvovirus B19 IgG Antibody [IV]

Secondary: Viral Serology From Screening Visit and Study Termination Visit: Parvovirus B19 IgM Antibody [IV]

Secondary: Viral Serology From Screening Visit and Study Termination Visit: Parvovirus B19 IgM Antibody [IV]

Secondary: Rate of Related Adverse Events (AEs) per Year

Secondary: Rate of Related Adverse Events (AEs) per Year

Secondary: Rate of Related Adverse Events (AEs) during or within 1 Hour of Infusion per Year

Secondary: Rate of Related Adverse Events (AEs) during or within 1 Hour of Infusion per Year

Secondary: Number of Related Thromboembolic Adverse Events (AEs)

Secondary: Number of Related Thromboembolic Adverse Events (AEs)

Secondary: Absolute Changes in Inhibitor Titer of Hemophilia A Participants with Shifts in Factor VIII (FVIII) Inhibitor Titer Levels

Secondary: Absolute Changes in Inhibitor Titer of Hemophilia A Participants with Shifts in Factor VIII (FVIII) Inhibitor Titer Levels

Secondary: Absolute Changes in Inhibitor Titer of Hemophilia B Participants with Shifts in Factor IX (FIX) Inhibitor Titer Levels

Secondary: Absolute Changes in Inhibitor Titer of Hemophilia B Participants with Shifts in Factor IX (FIX) Inhibitor Titer Levels

Secondary: Pharmacoeconomics: Annual days lost due to bleeding (work or school)

Secondary: Pharmacoeconomics: Annual days lost due to bleeding (work or school)

Secondary: Pharmacoeconomics: Annual number of hospitalizations for bleeding

Secondary: Pharmacoeconomics: Annual number of hospitalizations for bleeding

Secondary: Pharmacoeconomics: Annual number of hospitalizations for indwelling line

Secondary: Pharmacoeconomics: Annual number of hospitalizations for indwelling line

Secondary: Pharmacoeconomics: Annual number of emergency room visits

Secondary: Pharmacoeconomics: Annual number of emergency room visits

Secondary: Pharmacoeconomics: Annual number of physician’s office visits

Secondary: Pharmacoeconomics: Annual number of physician’s office visits

Secondary: Pharmacoeconomics: Annual total length of hospitalization for bleeding

Secondary: Pharmacoeconomics: Annual total length of hospitalization for bleeding

Clinical Trial Results:
FEIBA NF: a prospective, open-label, randomized, parallel study to evaluate efficacy and safety of prophylactic versus on-demand treatment in subjects with hemophilia A or B and a high titer inhibitor