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Clinical Trial Results:
BAX326 (recombinant Factor IX): A Phase 1/3 Prospective, Controlled, Multicenter Study Evaluating Pharmacokinetics, Efficacy, Safety, and Immunogenicity in Previously Treated Patients With Severe (FIX level <1%) or Moderately Severe (FIX level ≤ 2%) Hemophilia B

Due to the EudraCT – Results system being out of service between 31 July 2015 and 12 January 2016, these results have been published in compliance with revised timelines.

Summary
EudraCT number	2009-016720-31
Trial protocol	GB DE CZ ES BG SE
Global end of trial date	03 May 2012

Results information
Results version number	v1(current)
This version publication date	13 Feb 2016
First version publication date	13 Feb 2016
Other versions

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

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Trial information

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Sponsor protocol code

250901

ISRCTN number

US NCT number

NCT01174446

WHO universal trial number (UTN)

Sponsor organisation name

Baxalta US Inc.

Sponsor organisation address

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

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)

Yes

EMA paediatric investigation plan number(s)

EMEA-001139-PIP01-11

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

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

Yes

Analysis stage

Final

Date of interim/final analysis

11 Sep 2012

Is this the analysis of the primary completion data?

Yes

Primary completion date

03 May 2012

Global end of trial reached?

Yes

Global end of trial date

03 May 2012

Was the trial ended prematurely?

Main objective of the trial

The objective of Part 1 of the study was to compare the PK parameters of BAX326 with those of BeneFIX and to determine pharmacokinetic (PK) equivalence. Part 2 of the study was to assess the hemostatic efficacy, safety, and immunogenicity of BAX326 and health-related quality of life in those subjects receiving BAX326 for prevention and treatment of bleeding episodes. The objective of Part 3 was to re-evaluate the PK parameters for BAX326 after a period of 6 months of treatment, in 27 subjects who had accumulated at least 30 exposure days to BAX326, and to compare them with those determined in the same subjects who participated in Part 1.

Protection of trial subjects

This study was conducted in accordance with the clinical protocol, the International Conference on Harmonization Guideline for Good Clinical Practice E6 (ICH GCP, April 1996), Title 21 of the US Code of Federal Regulations (US CFR), the European Clinical Trial Directive (2001/20/EC and 2005/28/EC), and applicable national and local regulatory requirements.

Background therapy

Evidence for comparator

BeneFIX was the comparator product used in Part 1 of this study.The objective was to compare the pharmacokinetic (PK) parameters of BAX326 with BeneFIX and to determine PK equivalence. BeneFIX, manufactured by Wyeth (recently acquired by Pfizer), was the only recombinant FIX product available on the hemophilia B market at the time of the study.

Actual start date of recruitment

29 Jul 2011

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Yes

Number of subjects enrolled per country

Country: Number of subjects enrolled

Poland: 12

Country: Number of subjects enrolled

Russian Federation: 12

Country: Number of subjects enrolled

Bulgaria: 10

Country: Number of subjects enrolled

Ukraine: 8

Country: Number of subjects enrolled

Romania: 8

Country: Number of subjects enrolled

Colombia: 5

Country: Number of subjects enrolled

Japan: 5

Country: Number of subjects enrolled

Chile: 4

Country: Number of subjects enrolled

United Kingdom: 2

Country: Number of subjects enrolled

Czech Republic: 2

Country: Number of subjects enrolled

Argentina: 2

Country: Number of subjects enrolled

Spain: 1

Country: Number of subjects enrolled

Sweden: 1

Country: Number of subjects enrolled

Brazil: 1

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

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Recruitment details

Enrollment was conducted at 32 clinical sites in Europe, the United States, South America, and Japan.

Screening details

86 subjects were enrolled. 13 subjects discontinued before treatment: 7 withdrew consent, 1 was withdrawn due to an adverse event (suicide attempt), 2 were screen failures, and 3 withdrew due to site closure.

Number of subjects started

Number of subjects completed

73 ^[1]

Notes
[1] - The number of subjects reported to be in the pre-assignment period is not consistent with the number starting period 1. It is expected that the number completing the pre-assignment period are also present in the arms in period 1.
Justification: 86 subjects were enrolled. 13 subjects discontinued before treatment.

Period 1 title

Part 1 -Pharmacokinetic Crossover

Is this the baseline period?

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator

Blinding implementation details

Subjects and investigators in study Part 1 were blinded. To maintain the blind, the investigational products were reconstituted by the hospital pharmacist in the hospital pharmacy who was unblinded.

Pharmacokinetic Crossover with BAX326 and BeneFIX

Arm description

In Part 1, randomized subjects received 2 infusions each, 1 infusion with BAX326 and 1 infusion with BeneFIX, at a dose of 75 ± 5 IU/kg, each in a randomized order.

Arm type

Experimental

Investigational medicinal product name

BAX326

Investigational medicinal product code

Recombinant factor IX (rFIX)

Other name

Rixubis

Pharmaceutical forms

Powder and solvent for solution for injection

Routes of administration

Intravenous use

Dosage and administration details

Study Part 1: PK Crossover with BAX326 and BeneFIX, at a dose of 75 ± 5 IU/kg - Study Part 2: Open-label evaluation of prophylaxis and on-demand - Study Part 3: Open-label repeat of PK evaluation (repeat Study Part 1) with BAX326 only in the same study subjects as in Study Part 1

Investigational medicinal product name

BeneFIX

Investigational medicinal product code

Recombinant factor IX (rFIX)

Other name

Pharmaceutical forms

Powder and solvent for solution for injection

Routes of administration

Intravenous use

Dosage and administration details

Study Part 1: PK Crossover with BAX326 and BeneFIX, at a dose of 75 ± 5 IU/kg

Number of subjects in period 1	Pharmacokinetic Crossover with BAX326 and BeneFIX
Started	28
Completed	28

Period 2 title

Part 2 -BAX326 Prophylaxis and On-demand

Is this the baseline period?

Yes ^[2]

Allocation method

Not applicable

Blinding used

Not blinded

Are arms mutually exclusive

Yes

Part 2 Only: BAX326 Prophylaxis

Arm description

Participants were only in Study Part 2 (i.e., did not participate in Study Parts 1 and 3)

Arm type

Experimental

Investigational medicinal product name

BAX326

Investigational medicinal product code

Recombinant factor IX (rFIX)

Other name

Rixubis

Pharmaceutical forms

Powder and solvent for solution for injection

Routes of administration

Intravenous use

Dosage and administration details

Part 2 Only: BAX326 On-Demand

Arm description

Participants were only in Study Part 2 (i.e., did not participate in Study Parts 1 and 3)

Arm type

Experimental

Investigational medicinal product name

BAX326

Investigational medicinal product code

Recombinant factor IX (rFIX)

Other name

Rixubis

Pharmaceutical forms

Powder and solvent for solution for injection

Routes of administration

Intravenous use

Dosage and administration details

Part 1: PK crossover - Part 2: Prophylaxis - Part 3: PK BAX326

Arm description

-Study Part 1: Pharmacokinetic (PK) Crossover with BeneFIX (75 ± 5 IU/kg) and BAX326 (75 ± 5 IU/kg). -Study Part 2: Open-label evaluation of prophylaxis -Study Part 3: Open-label repeat of PK evaluation (repeat Study Part 1) with BAX326 (75 ± 5 IU/kg) only and same study participants as Study Part 1

Arm type

Experimental

Investigational medicinal product name

BAX326

Investigational medicinal product code

Recombinant factor IX (rFIX)

Other name

Rixubis

Pharmaceutical forms

Powder and solvent for solution for injection

Routes of administration

Intravenous use

Dosage and administration details

Notes
[2] - Period 1 is not the baseline period. It is expected that period 1 will be the baseline period.
Justification: Period 1 corresponds to Part 1 - Pharmacokinetic Crossover. Randomized subjects received 2 infusions each, 1 infusion with BAX326 and 1 infusion with BeneFIX, at a dose of 75 ± 5 IU/kg, each in a randomized order. All subjects from Part 1 transitioned to Part 2, which is the main part of the study and is defined as the baseline period.

Number of subjects in period 2	Part 2 Only: BAX326 Prophylaxis	Part 2 Only: BAX326 On-Demand	Part 1: PK crossover - Part 2: Prophylaxis - Part 3: PK BAX326
Started	31	14	28
Completed	29	14	28
Not completed	2	0	0
Consent withdrawn by subject	1	-	-
Physician decision	1	-	-

Period 3 title

Part 3 -Pharmacokinetic BAX326 Only

Is this the baseline period?

Allocation method

Randomised - controlled

Blinding used

Not blinded

PK BAX326 Only

Arm description

Open-label repeat of PK evaluation (repeat Study Part 1) with BAX326 (75 ± 5 IU/kg) only and same study participants as Study Part 1

Arm type

Experimental

Investigational medicinal product name

BAX326

Investigational medicinal product code

Recombinant factor IX (rFIX)

Other name

Rixubis

Pharmaceutical forms

Powder and solvent for solution for injection

Routes of administration

Intravenous use

Dosage and administration details

Number of subjects in period 3	PK BAX326 Only
Started	28
Completed	25
Not completed	3
Emergency surgery	1
Protocol deviation	2

Baseline characteristics

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Reporting group title

Part 2 -BAX326 Prophylaxis and On-demand

Reporting group description

Part 2 -BAX326 Prophylaxis and On-demand

Reporting group values	Part 2 -BAX326 Prophylaxis and On-demand	Total
Number of subjects	73
Age categorical
Units: Subjects
Age continuous
Age continuous description
Units: years
arithmetic mean (standard deviation)	34.5 ± 12.2	-
Gender categorical
Gender categorical description
Units: Subjects
Female	0	0
Male	73	73
Region of Enrollment
Units: Subjects
Spain	1	1
Ukraine	8	8
Chile	4	4
Russian Federation	12	12
Colombia	5	5
United Kingdom	2	2
Czech Republic	2	2
Argentina	2	2
Brazil	1	1
Poland	12	12
Romania	8	8
Bulgaria	10	10
Japan	5	5
Sweden	1	1

Subject analysis set title

Study Part 1: PK with BAX326

Subject analysis set type

Sub-group analysis

Subject analysis set description

In Part 1, randomized subjects received 2 infusions each, 1 infusion with BAX326 and 1 infusion with BeneFIX, at a dose of 75 ± 5 IU/kg, each in a randomized order.

Subject analysis set title

Study Part 1: PK with BeneFIX

Subject analysis set type

Sub-group analysis

Subject analysis set description

In Part 1, randomized subjects received 2 infusions each, 1 infusion with BAX326 and 1 infusion with BeneFIX, at a dose of 75 ± 5 IU/kg, each in a randomized order.

Subject analysis set title

Study Part 2: Prophylactic cohort

Subject analysis set type

Full analysis

Subject analysis set description

Subjects in the prophylactic cohort were to be treated with a prophylactic regimen of 50 IU/kg BAX326 twice weekly for a period of 6 months or for at least 50 EDs, whichever occurred last. 56 subjects received a minimum of 3 months of prophylactic treatment with BAX326. A further 3 subjects received less than 3 months of prophylactic treatment with BAX326.

Subject analysis set title

Study Part 2: On-demand cohort

Subject analysis set type

Full analysis

Subject analysis set description

Subjects in the on-demand cohort were to receive BAX326 for on-demand treatment.

Subject analysis set title

Study Part 3: Repeat PK with BAX326 only

Subject analysis set type

Sub-group analysis

Subject analysis set description

In Part 3, subjects who had participated in Part 1 and had a minimum of 30 exposure days to BAX326 in Part 2 underwent a repeat PK with BAX326 only, at a dose of 75 ± 5 IU/kg.

Subject analysis set title

Full Analysis Set

Subject analysis set type

Full analysis

Subject analysis set description

Comprises 73 subjects who were exposed to investigational product.

Subject analysis sets values	Study Part 1: PK with BAX326	Study Part 1: PK with BeneFIX	Study Part 2: Prophylactic cohort	Study Part 2: On-demand cohort	Study Part 3: Repeat PK with BAX326 only	Full Analysis Set
Number of subjects	28	28	59	14	25	73
Age categorical
Units: Subjects
Age continuous
Age continuous description
Units: years
arithmetic mean (standard deviation)	33.9 ± 11.2	33.9 ± 11.2	34.7 ± 12	33.1 ± 12.4	33.9 ± 11.3	34.5 ± 12.2
Gender categorical
Gender categorical description
Units: Subjects
Female	0	0	0	0	0	0
Male	28	28	59	14	25	73
Region of Enrollment
Units: Subjects
Spain	0	0	1	0	0	1
Ukraine	1	1	5	3	1	8
Chile	0	0	4	0	0	4
Russian Federation	4	4	7	5	4	12
Colombia	4	4	5	0	3	5
United Kingdom	2	2	2	0	1	2
Czech Republic	0	0	1	1	0	2
Argentina	1	1	2	0	1	2
Brazil	0	0	1	0	0	1
Poland	7	7	12	0	6	12
Romania	1	1	7	1	1	8
Bulgaria	6	6	6	4	6	10
Japan	2	2	5	0	2	5
Sweden	0	0	1	0	0	1

End points

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Reporting group title

Pharmacokinetic Crossover with BAX326 and BeneFIX

Reporting group description

In Part 1, randomized subjects received 2 infusions each, 1 infusion with BAX326 and 1 infusion with BeneFIX, at a dose of 75 ± 5 IU/kg, each in a randomized order.

Reporting group title

Part 2 Only: BAX326 Prophylaxis

Reporting group description

Participants were only in Study Part 2 (i.e., did not participate in Study Parts 1 and 3)

Reporting group title

Part 2 Only: BAX326 On-Demand

Reporting group description

Participants were only in Study Part 2 (i.e., did not participate in Study Parts 1 and 3)

Reporting group title

Part 1: PK crossover - Part 2: Prophylaxis - Part 3: PK BAX326

Reporting group description

Reporting group title

PK BAX326 Only

Reporting group description

Open-label repeat of PK evaluation (repeat Study Part 1) with BAX326 (75 ± 5 IU/kg) only and same study participants as Study Part 1

Subject analysis set title

Study Part 1: PK with BAX326

Subject analysis set type

Sub-group analysis

Subject analysis set description

In Part 1, randomized subjects received 2 infusions each, 1 infusion with BAX326 and 1 infusion with BeneFIX, at a dose of 75 ± 5 IU/kg, each in a randomized order.

Subject analysis set title

Study Part 1: PK with BeneFIX

Subject analysis set type

Sub-group analysis

Subject analysis set description

In Part 1, randomized subjects received 2 infusions each, 1 infusion with BAX326 and 1 infusion with BeneFIX, at a dose of 75 ± 5 IU/kg, each in a randomized order.

Subject analysis set title

Study Part 2: Prophylactic cohort

Subject analysis set type

Full analysis

Subject analysis set description

Subject analysis set title

Study Part 2: On-demand cohort

Subject analysis set type

Full analysis

Subject analysis set description

Subjects in the on-demand cohort were to receive BAX326 for on-demand treatment.

Subject analysis set title

Study Part 3: Repeat PK with BAX326 only

Subject analysis set type

Sub-group analysis

Subject analysis set description

In Part 3, subjects who had participated in Part 1 and had a minimum of 30 exposure days to BAX326 in Part 2 underwent a repeat PK with BAX326 only, at a dose of 75 ± 5 IU/kg.

Subject analysis set title

Full Analysis Set

Subject analysis set type

Full analysis

Subject analysis set description

Comprises 73 subjects who were exposed to investigational product.

Primary: Study Part 1- Area under the plasma concentration versus time curve from 0 to 72 hours per dose

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End point title

Study Part 1- Area under the plasma concentration versus time curve from 0 to 72 hours per dose

End point description

Computed using the linear trapezoidal method. The concentration at 72 hours was interpolated from the two nearest sampling time points or extrapolated using the last quantifiable concentration and the terminal rate constant λz. λz was estimated from the slope of natural log-linear fitting to latter quantifiable concentrations, with largest adjusted R^2. The pharmacokinetic per-protocol analysis set comprises 25 subjects who participated in Parts 1 and 3 and completed Part 1 without any major protocol deviation.

End point type

Primary

End point timeframe

72 hours

End point values	Study Part 1: PK with BAX326	Study Part 1: PK with BeneFIX
Number of subjects analysed	25	25
Units: (IU·hr/dL) / (IU/kg)
median (inter-quartile range (Q1-Q3))	14.3 (11.2 to 15.95)	13.42 (11.08 to 15.1)

PK equivalence of BAX326 with BeneFIX

Statistical analysis description

To assess PK equivalence of BAX326 and BeneFIX, the 90% confidence interval for the difference of the mean natural logarithms of the area under the plasma concentration versus time curve from 0 to 72 hours per dose (AUC0-72h/dose) between the 2 groups was calculated. To establish the equivalence in AUC0-72h /dose with a type I error of 5%, the calculated two-sided 90% confidence interval for the ratio had to be contained completely within the margins of equivalence defined as 80% to 125%.

Comparison groups

Study Part 1: PK with BAX326 v Study Part 1: PK with BeneFIX

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

equivalence

Method

Parameter type

Ratio of Geometric Means

Point estimate

1.063

Confidence interval

level

90%

sides

2-sided

lower limit

1.03

upper limit

1.09

Secondary: Study Parts 1 and 3: Area under the plasma concentration/time curve from time 0 to infinity per dose (AUC0-∞/ dose)

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End point title

Study Parts 1 and 3: Area under the plasma concentration/time curve from time 0 to infinity per dose (AUC0-∞/ dose)

End point description

Defined as (AUC0-t + Ct)/ λz/ dose, where t is the time of last quantifiable concentration, Ct is the last quantifiable concentration. λz will be estimated from the slope of natural log-linear fitting to latter quantifiable concentrations, with largest adjusted R^2. The objective of Study Part 3 was to re-evaluate the Pharmacokinetic (PK) parameters for BAX 326 after a period of 6 months of treatment, in participants who accumulated at least 30 EDs to BAX 326, and to compare them with those determined in the same participants participating in Study Part 1. The PK per-protocol analysis set comprises 25 subjects for Part 1 and 23 subjects for Part 3.

End point type

Secondary

End point timeframe

0-30 minutes before infusion up to 72 hours post-infusion

End point values	Study Part 1: PK with BAX326	Study Part 1: PK with BeneFIX	Study Part 3: Repeat PK with BAX326 only
Number of subjects analysed	25	25	23
Units: (IU·hr)/ dL/ (IU/kg)
median (inter-quartile range (Q1-Q3))	16.07 (13.43 to 17.48)	15.26 (13.71 to 17.05)	17.38 (14.17 to 20.7)

No statistical analyses for this end point

Secondary: Study Parts 1 and 3: Mean residence time (MRT)

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End point title

Study Parts 1 and 3: Mean residence time (MRT)

End point description

Computed as Area under the moment curve 0-∞ (AUMC0-∞) / AUC0-∞- TI/2, where AUMC0-∞ will be determined in a similar manner as AUC0-∞ and TI represents infusion duration [hr] The objective of Study Part 3 was to re-evaluate the Pharmacokinetic (PK) parameters for BAX 326 after a period of 6 months of treatment, in participants who accumulated at least 30 EDs to BAX 326, and to compare them with those determined in the same participants participating in Study Part 1. The PK per-protocol analysis set comprises 25 subjects for Part 1 and 23 subjects for Part 3.

End point type

Secondary

End point timeframe

0-30 minutes before infusion up to 72 hours post-infusion

End point values	Study Part 1: PK with BAX326	Study Part 1: PK with BeneFIX	Study Part 3: Repeat PK with BAX326 only
Number of subjects analysed	25	25	23
Units: Hour
median (inter-quartile range (Q1-Q3))	28.93 (26.45 to 31.5)	30.59 (28.13 to 34.84)	29.04 (28 to 32.31)

No statistical analyses for this end point

Secondary: Study Parts 1 and 3: Clearance (CL)

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End point title

Study Parts 1 and 3: Clearance (CL)

End point description

Computed as Dose/ AUC0-∞. The objective of Study Part 3 was to re-evaluate the Pharmacokinetic (PK) parameters for BAX 326 after a period of 6 months of treatment, in participants who accumulated at least 30 EDs to BAX 326, and to compare them with those determined in the same participants participating in Study Part 1. The pharmacokinetic per-protocol analysis set comprises 25 subjects for Part 1 and 23 subjects for Part 3.

End point type

Secondary

End point timeframe

0-30 minutes before infusion up to 72 hours post-infusion

End point values	Study Part 1: PK with BAX326	Study Part 1: PK with BeneFIX	Study Part 3: Repeat PK with BAX326 only
Number of subjects analysed	25	25	23
Units: dL/(kg·hr)
median (inter-quartile range (Q1-Q3))	0.0622 (0.0572 to 0.0745)	0.0655 (0.0587 to 0.073)	0.0576 (0.0483 to 0.0706)

No statistical analyses for this end point

Secondary: Study Parts 1 and 3: Incremental Recovery at Cmax (IR at Cmax)

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End point title

Study Parts 1 and 3: Incremental Recovery at Cmax (IR at Cmax)

End point description

Defined as (Cmax - Cpre-infusion)/Dose, where maximum concentration (Cmax) will be determined as the highest concentration achieved within one hour after infusion. The objective of Study Part 3 was to re-evaluate the Pharmacokinetic (PK) parameters for BAX 326 after a period of 6 months of treatment, in participants who accumulated at least 30 EDs to BAX 326, and to compare them with those determined in the same participants participating in Study Part 1. The pharmacokinetic per-protocol analysis set comprises 25 subjects for Part 1 and 23 subjects for Part 3.

End point type

Secondary

End point timeframe

0-30 minutes before infusion up to 1 hour post-infusion

End point values	Study Part 1: PK with BAX326	Study Part 1: PK with BeneFIX	Study Part 3: Repeat PK with BAX326 only
Number of subjects analysed	25	25	23
Units: (IU/dL) / (IU/kg)
median (inter-quartile range (Q1-Q3))	0.88 (0.79 to 0.98)	0.73 (0.66 to 0.87)	0.93 (0.76 to 1.18)

No statistical analyses for this end point

Secondary: Incremental Recovery (IR) at 30 Minutes Over Time

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End point title

Incremental Recovery (IR) at 30 Minutes Over Time

End point description

IR at 30 Minutes was measured at the following time points during the study: - Part 1 or Part 2, Exposure Day (ED) 1. (If participant was present for Study Part 1, then ED 1 from Part 1 was used. If Participant entered study in Study Part 2, then ED 1 from Part 2 was used.) - Part 2: Week 5 - Part 2: Week 13 - Part 2 or Part 3: Week 26 (Week 26 of study participation) - Study Completion or Termination Visit

End point type

Secondary

End point timeframe

0-30 minutes before infusion and 30 minutes post-infusion

End point values	Full Analysis Set
Number of subjects analysed	73
Units: (IU/dL) / (IU/kg)
median (inter-quartile range (Q1-Q3))
Part 1 or Part 2, Exposure Day 1 (n=73)	0.78 (0.7 to 0.91)
Part 2: Week 5 (n=71)	0.79 (0.68 to 0.96)
Part 2: Week 13 (n=68)	0.83 (0.655 to 1.015)
Part 2 or 3: Week 26 (n=55)	0.88 (0.75 to 1.04)
Study Completion or Termination Visit (n=23)	0.89 (0.73 to 0.96)

No statistical analyses for this end point

Secondary: Change in Incremental Recovery (IR) at 30 Minutes Over Time

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End point title

Change in Incremental Recovery (IR) at 30 Minutes Over Time

End point description

The median changes in IR at 30 Minutes, calculated as the change in IR value from exposure day 1 (ED1).

End point type

Secondary

End point timeframe

0-30 minutes before infusion and 30 minutes post-infusion

End point values	Full Analysis Set
Number of subjects analysed	71
Units: (IU/dL) / (IU/kg)
median (inter-quartile range (Q1-Q3))
Part 2: Week 5 (n=71)	0.03 (-0.09 to 0.11)
Part 2: Week 13 (n=68)	0.075 (-0.07 to 0.17)
Part 2 or Part 3: Week 26 (n=55)	0.06 (0.02 to 0.17)
Study Completion or Termination Visit (n=23)	0.12 (0 to 0.21)

No statistical analyses for this end point

Secondary: Study Parts 1 and 3: Half Life (T 1/2)

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End point title

Study Parts 1 and 3: Half Life (T 1/2)

End point description

Elimination phase half-life will be determined as ln2/ λz. The objective of Study Part 3 was to re-evaluate the Pharmacokinetic (PK) parameters for BAX 326 after a period of 6 months of treatment, in participants who accumulated at least 30 EDs to BAX 326, and to compare them with those determined in the same participants participating in Study Part 1. The pharmacokinetic per-protocol analysis set comprises 25 subjects for Part 1 and 23 subjects for Part 3.

End point type

Secondary

End point timeframe

0-30 minutes before infusion up to 72 hours post-infusion

End point values	Study Part 1: PK with BAX326	Study Part 1: PK with BeneFIX	Study Part 3: Repeat PK with BAX326 only
Number of subjects analysed	25	25	23
Units: Hour
median (inter-quartile range (Q1-Q3))	24.58 (20.98 to 29.68)	26.28 (22.51 to 29.46)	24.59 (19.68 to 29.14)

No statistical analyses for this end point

Secondary: Study Parts 1 and 3: Volume of distribution at steady state (Vss)

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End point title

Study Parts 1 and 3: Volume of distribution at steady state (Vss)

End point description

Vss computed as CL·MRT. The objective of Study Part 3 was to re-evaluate the Pharmacokinetic (PK) parameters for BAX 326 after a period of 6 months of treatment, in participants who accumulated at least 30 EDs to BAX 326, and to compare them with those determined in the same participants participating in Study Part 1. The pharmacokinetic per-protocol analysis set comprises 25 subjects for Part 1 and 23 subjects for Part 3.

End point type

Secondary

End point timeframe

0-30 minutes before infusion up to 72 hours post-infusion

End point values	Study Part 1: PK with BAX326	Study Part 1: PK with BeneFIX	Study Part 3: Repeat PK with BAX326 only
Number of subjects analysed	25	25	23
Units: dL/kg
median (inter-quartile range (Q1-Q3))	1.72 (1.56 to 2.3)	1.98 (1.76 to 2.51)	1.74 (1.49 to 2.05)

No statistical analyses for this end point

Secondary: Study Part 2: Annualized Bleed Rate (ABR) during prophylactic treatment with BAX326

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End point title

Study Part 2: Annualized Bleed Rate (ABR) during prophylactic treatment with BAX326

End point description

ABR during prophylaxis (twice-weekly) in Part 2 was calculated as (Number of bleeding episodes/observed treatment period in days) * 365.25. The treatment period on prophylaxis was defined as time between the first and the last prophylactic infusions and ABR on prophylaxis was calculated for participants who received a minimum of 3 months of prophylactic treatment with BAX326.

End point type

Secondary

End point timeframe

Study Part 2 = 26 weeks ± 1 week (Note: Study Part 1 = 2-4 weeks)

End point values	Study Part 2: Prophylactic cohort
Number of subjects analysed	56
Units: Bleeds per year
median (inter-quartile range (Q1-Q3))
Joint bleeding episode	0 (0 to 4.5)
Non-Joint bleeding episode	0 (0 to 2)
Spontaneous bleeding episode	0 (0 to 2)
Bleeding episode caused by injury	0 (0 to 2.1)
Unknown cause of bleeding episode	0 (0 to 0)
All bleeding episodes	1.99 (0 to 6.5)

No statistical analyses for this end point

Secondary: Bleeding Episodes Treated With 1, 2 or ≥3 Infusions of BAX326

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End point title

Bleeding Episodes Treated With 1, 2 or ≥3 Infusions of BAX326

End point description

The number of bleeding episodes treated with 1, 2, or ≥3 infusions of BAX326 to achieve adequate hemostasis. Only infusions required until resolution of bleed were considered. There were a total of 249 bleeding episodes in 47 subjects in the Full Analysis Set (ie, in all 14 on-demand subjects and in 33 of 59 subjects who received prophylaxis).

End point type

Secondary

End point timeframe

Study Part 2 = 26 weeks ± 1 week (Study Part 2 began at week 3-5)

End point values	Full Analysis Set
Number of subjects analysed	47
Units: Bleeding episodes
1 infusion	153
2 infusions	58
3 or more infusions	38

No statistical analyses for this end point

Secondary: Hemostatic Efficacy at Resolution of All Bleeding Episodes (BEs) Treated with BAX326

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End point title

Hemostatic Efficacy at Resolution of All Bleeding Episodes (BEs) Treated with BAX326

End point description

There were a total of 249 bleeding episodes in 47 subjects in the Full Analysis Set (ie, in all 14 on-demand subjects and in 33 of 59 subjects who received prophylaxis). Rating Scale for Treatment of BEs (4-point ordinal scale): -Excellent: Full relief of pain and cessation of objective signs of bleeding (eg, swelling, tenderness, and decreased range of motion in the case of musculoskeletal hemorrhage) after a single infusion. No additional infusion required for the control of bleeding. Administration of further infusions to maintain hemostasis did not affect this scoring. -Good: Definite pain relief and/or improvement in signs of bleeding after a single infusion. Possibly requires more than 1 infusion for complete resolution. -Fair: Probable and/or slight relief of pain and slight improvement in signs of bleeding after single infusion. Required more than 1 infusion for complete resolution. -None: No improvement or condition worsens.

End point type

Secondary

End point timeframe

At bleed resolution throughout the study period of 22 months (Study Parts 1, 2, and 3)

End point values	Full Analysis Set
Number of subjects analysed	47
Units: Bleeding episodes
Excellent	102
Good	137
Fair	5
None	0
Not Reported	5

No statistical analyses for this end point

Secondary: Total Weight-adjusted Dose per Bleeding Episode (BEs) of All BEs Treated with BAX326 by Bleeding Site and Cause

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End point title

Total Weight-adjusted Dose per Bleeding Episode (BEs) of All BEs Treated with BAX326 by Bleeding Site and Cause

End point description

There were a total of 249 bleeding episodes in 47 subjects in the Full Analysis Set (ie, in all 14 on-demand subjects and in 33 of 59 subjects who received prophylaxis).

End point type

Secondary

End point timeframe

Study Part 2 = 26 weeks ± 1 week (Note: Study Part 1 = 2-4 weeks)

End point values	Full Analysis Set
Number of subjects analysed	47
Units: IU/kg
median (inter-quartile range (Q1-Q3))
Bleeding Site: Target Joint (107 BEs)	56.5 (48 to 97)
Bleeding Site: Non-Target Joint (90 BEs)	59 (46 to 97)
Bleeding Site: All Joint (197 BEs)	56.5 (47 to 97)
Bleeding Site: Non-Joint (52 BEs)	68.7 (50 to 130)
Bleeding Cause: Spontaneous (130 BEs)	52.3 (45 to 92)
Bleeding Cause: Inury (90 BEs)	70 (48 to 116)
Bleeding Cause: Unknown (29 BEs)	56.5 (51 to 108)

No statistical analyses for this end point

Secondary: Consumption of BAX326 per Event per Subject

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End point title

Consumption of BAX326 per Event per Subject

End point description

Weight-adjusted consumption of BAX326 by event per participant, i.e., for prophylactic treatment and for treatment of bleeds until resolution of bleed. Includes all participants who received any infusions for bleeding treatment in the Full Analysis Set (ie, includes all on-demand arm (n=14) and 33 subjects from the prophylaxis arm who experienced a bleeding episode).

End point type

Secondary

End point timeframe

Study Part 2 = 26 weeks ± 1 week (Note: Study Part 1 = 2-4 weeks)

End point values	Full Analysis Set
Number of subjects analysed	73 ^[1]
Units: IU/kg
median (inter-quartile range (Q1-Q3))
Prophylactic Treatment (n=59)	50.5 (46 to 52)
Bleeding Treatment (n=47)	87.1 (56 to 125)

Notes
[1] - Of 73 subjects in the FAS, 59 had prophylactic treatment and 47 had bleed treatment.

No statistical analyses for this end point

Secondary: Consumption of BAX326 per Subject: Median Number of Infusions per Month

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End point title

Consumption of BAX326 per Subject: Median Number of Infusions per Month

End point description

End point type

Secondary

End point timeframe

Study Part 1 = 2-4 weeks, Study Part 2 = 26 weeks ± 1 week (Prophylaxis and On-Demand period), Study Part 3 = 1 week (Total = 29-31 weeks)

End point values	Study Part 2: Prophylactic cohort	Study Part 2: On-demand cohort
Number of subjects analysed	59	14
Units: Infusions
median (inter-quartile range (Q1-Q3))	6.7 (6 to 7)	2.7 (2 to 4)

No statistical analyses for this end point

Secondary: Consumption of BAX326 per Subject: Median Weight-adjusted Consumption per Month

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End point title

Consumption of BAX326 per Subject: Median Weight-adjusted Consumption per Month

End point description

End point type

Secondary

End point timeframe

Study Part 1 = 2-4 weeks, Study Part 2 = 26 weeks ± 1 week (Prophylaxis and On-Demand period), Study Part 3 = 1 week (Total = 29-31 weeks)

End point values	Study Part 2: Prophylactic cohort	Study Part 2: On-demand cohort
Number of subjects analysed	59	14
Units: IU/kg
median (inter-quartile range (Q1-Q3))	347.8 (320 to 396)	167.3 (102 to 234)

No statistical analyses for this end point

Secondary: Number of Participants Who Developed Inhibitory Antibodies to Factor IX (FIX)

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End point title

Number of Participants Who Developed Inhibitory Antibodies to Factor IX (FIX)

End point description

End point type

Secondary

End point timeframe

Study Part 1 = 2-4 weeks, Study Part 2 = 26 weeks ± 1 week, Study Part 3 = 1 week (Total = 29-31 weeks)

End point values	Full Analysis Set
Number of subjects analysed	73
Units: participants	0

No statistical analyses for this end point

Secondary: Occurrence of total binding antibodies of indeterminate specificity (within assay variability)

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End point title

Occurrence of total binding antibodies of indeterminate specificity (within assay variability)

End point description

Occurrence of total binding antibodies of indeterminate specificity (within assay variability) to FIX, antibodies to CHO proteins and rFurin is defined by a dilution of 2 or less increase as compared to levels at screening visit (e.g. negative to 1:20 or 1:40).

End point type

Secondary

End point timeframe

Study Part 1 = 2-4 weeks, Study Part 2 = 26 weeks ± 1 week, Study Part 3 = 1 week (Total = 29-31 weeks)

End point values	Full Analysis Set
Number of subjects analysed	73
Units: participants
Binding Antibody to Factor IX (FIX)	6
Antibody to Chinese hamster ovary (CHO) Protein	0
Antibody to recombinant Furin (rFurin)	9

No statistical analyses for this end point

Secondary: Occurrence of treatment related total binding antibodies

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End point title

Occurrence of treatment related total binding antibodies

End point description

Occurrence of treatment related total binding antibodies to Factor IX (FIX), antibodies to Chinese hamster ovary (CHO) proteins, and recombinant furin (rFurin) is defined by more than 2-dilution increase as compared to levels at screening visit and confirmed specificity (e.g. negative to 1:80)

End point type

Secondary

End point timeframe

Study Part 1 = 2-4 weeks, Study Part 2 = 26 weeks ± 1 week, Study Part 3 = 1 week (Total = 29-31 weeks)

End point values	Full Analysis Set
Number of subjects analysed	73
Units: participants
Treatment Related Binding Antibody to Factor IX	0
Treatment Related Antibody to CHO Protein	0
Treatment Related Antibody to rFurin	0

No statistical analyses for this end point

Secondary: Number of Subjects Who Experienced Severe Allergic Reactions (e.g. Anaphylaxis)

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End point title

Number of Subjects Who Experienced Severe Allergic Reactions (e.g. Anaphylaxis)

End point description

End point type

Secondary

End point timeframe

Study Part 1 = 2-4 weeks, Study Part 2 = 26 weeks ± 1 week, Study Part 3 = 1 week (Total = 29-31 weeks)

End point values	Full Analysis Set
Number of subjects analysed	73
Units: subjects	0

No statistical analyses for this end point

Secondary: Number of Subjects Who Experienced Thrombotic Events

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End point title

Number of Subjects Who Experienced Thrombotic Events

End point description

End point type

Secondary

End point timeframe

Study Part 1 = 2-4 weeks, Study Part 2 = 26 weeks ± 1 week, Study Part 3 = 1 week (Total = 29-31 weeks)

End point values	Full Analysis Set
Number of subjects analysed	73
Units: subjects	0

No statistical analyses for this end point

Secondary: Number of subjects with clinically significant changes in laboratory parameters: clinical chemistry

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End point title

Number of subjects with clinically significant changes in laboratory parameters: clinical chemistry

End point description

Clinically significant changes in chemistry assessments for Alanine Aminotransferase, Albumin, Alkaline Phosphatase, Aspartate Aminotransferase, Bicarbonate, Bilirubin, Blood Urea Nitrogen, Chloride, Glucose, Potassium, Protein (Serum), Sodium. Clinically Significant (CS) defined as: -1. The abnormal value constitutes an adverse event (AE) and, -2. The abnormal value is a symptom of or related to a disease that is already recorded as an AE in Case Report Form (CRF).

End point type

Secondary

End point timeframe

Study Part 1 = 2-4 weeks, Study Part 2 = 26 weeks ± 1 week, Study Part 3 = 1 week (Total = 29-31 weeks)

End point values	Full Analysis Set
Number of subjects analysed	73
Units: subjects	0

No statistical analyses for this end point

Secondary: Number of subjects with clinically significant changes in laboratory parameters: hematology

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End point title

Number of subjects with clinically significant changes in laboratory parameters: hematology

End point description

Clinically significant changes in hematology assessments for Basophils, Basophils/Leukocytes, Eosinophils, Eosinophils/Leukocytes, Erythrocyte Mean Corpuscular Hemoglobin Concentration, Erythrocyte Mean Corpuscular Volume, Erythrocytes, Hematocrit, Hemoglobin, Leukocytes, Lymphocytes, Lymphocytes/Leukocytes, Monocytes, Monocytes/Leukocytes, Neutrophils, Neutrophils/Leukocytes, Platelets,

End point type

Secondary

End point timeframe

Study Part 1 = 2-4 weeks, Study Part 2 = 26 weeks ± 1 week, Study Part 3 = 1 week (Total = 29-31 weeks)

End point values	Full Analysis Set
Number of subjects analysed	73
Units: subjects	0

No statistical analyses for this end point

Secondary: Number of Subjects With Clinically significant changes in laboratory parameters: vital signs

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End point title

Number of Subjects With Clinically significant changes in laboratory parameters: vital signs

End point description

Clinically significant changes in vital signs assessments for pulse rate, systolic/diastolic blood pressure, respiratory rate, body temperature

End point type

Secondary

End point timeframe

Study Part 1 = 2-4 weeks, Study Part 2 = 26 weeks ± 1 week, Study Part 3 = 1 week (Total = 29-31 weeks)

End point values	Full Analysis Set
Number of subjects analysed	73
Units: subjects	0

No statistical analyses for this end point

Secondary: Number of Subjects With Clinically significant changes in laboratory parameters: thrombogenic markers

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End point title

Number of Subjects With Clinically significant changes in laboratory parameters: thrombogenic markers

End point description

Clinically significant changes in thrombogenic markers assessments for thrombin-antithrombin (TAT), prothrombin fragment 1.2, and D-dimer as evaluated by an independent Data Monitoring Committee (DMC)

End point type

Secondary

End point timeframe

Study Part 1 = 2-4 weeks, Study Part 2 = 26 weeks ± 1 week, Study Part 3 = 1 week (Total = 29-31 weeks)

End point values	Full Analysis Set
Number of subjects analysed	73
Units: subjects	0

No statistical analyses for this end point

Secondary: Number of Adverse Events (AEs) Considered Related to BAX326 Treatment

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End point title

Number of Adverse Events (AEs) Considered Related to BAX326 Treatment

End point description

Probable, possible, or unknown causality assessment of an AE was to be counted as "related".

End point type

Secondary

End point timeframe

Study Part 1 = 2-4 weeks, Study Part 2 = 26 weeks ± 1 week, and Study Part 3 = 1 week (Total = 29-31 weeks)

End point values	Full Analysis Set
Number of subjects analysed	73
Units: related adverse events
Serious- Mild	0
Serious- Moderate	0
Serious- Severe	0
Serious- Unknown	0
Non-Serious- Mild	2
Non-Serious- Moderate	0
Non-Serious- Severe	0
Non-Serious- Unknown	1

No statistical analyses for this end point

Secondary: Number of Subjects with Adverse Events (AEs) Considered Related to BAX326 Treatment

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End point title

Number of Subjects with Adverse Events (AEs) Considered Related to BAX326 Treatment

End point description

End point type

Secondary

End point timeframe

Study Part 1 = 2-4 weeks, Study Part 2 = 26 weeks ± 1 week, and Study Part 3 = 1 week (Total = 29-31 weeks)

End point values	Full Analysis Set
Number of subjects analysed	73
Units: subjects
Serious- Mild	0
Serious- Moderate	0
Serious- Severe	0
Serious- Unknown	0
Non-Serious- Mild	1
Non-Serious- Moderate	0
Non-Serious- Severe	0
Non-Serious- Unknown	1

No statistical analyses for this end point

Secondary: EuroQoL (Quality of Life)-5 Dimensions (EQ-5D) Total Index Scores

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End point title

EuroQoL (Quality of Life)-5 Dimensions (EQ-5D) Total Index Scores

End point description

EQ-5D is a subject 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.

End point type

Secondary

End point timeframe

Baseline at either Study Part 1, or Study Part 2, and End of Study (study weeks 29-31)

End point values	Study Part 2: Prophylactic cohort	Study Part 2: On-demand cohort
Number of subjects analysed	55 ^[2]	14
Units: Score on a scale
arithmetic mean (standard deviation)
Part 1 or Part 2, Exposure Day 1 (Baseline)	0.75 ± 0.16	0.72 ± 0.14
End of Study	0.75 ± 0.16	0.73 ± 0.09
Change from Baseline	0.01 ± 0.18	0 ± 0.13

Notes
[2] - N=56 at baseline, N=55 at end of study

No statistical analyses for this end point

Secondary: EuroQoL (Quality of Life)-5 Dimensions Visual Analogue Scale (EQ-5D VAS) Scores

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End point title

EuroQoL (Quality of Life)-5 Dimensions Visual Analogue Scale (EQ-5D VAS) Scores

End point description

Subject rated questionnaire to assess health-related quality of life in terms of a single index value. The VAS component rates current health state on a scale from 0 (worst imaginable health state) to 100 (best imaginable health state); higher scores indicate a better quality of life.

End point type

Secondary

End point timeframe

Baseline at either Study Part 1, or Study Part 2, and End of Study (study weeks 29-31)

End point values	Study Part 2: Prophylactic cohort	Study Part 2: On-demand cohort
Number of subjects analysed	54 ^[3]	14
Units: Score on a scale
arithmetic mean (standard deviation)
Part 1 or Part 2, Exposure Day 1 (Baseline)	58.75 ± 24.89	56.64 ± 25.97
End of Study	68.22 ± 22.78	62.07 ± 19
Change from Baseline	9.98 ± 25.41	5.43 ± 24.02

Notes
[3] - N=56 at baseline, N=54 at end of study

No statistical analyses for this end point

Secondary: General pain assessment through a visual analog scale (VAS)

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End point title

General pain assessment through a visual analog scale (VAS)

End point description

Participant rated assessment of health-related quality of life. The VAS Pain Scale rates current health state on a scale from 0 (no pain) to 100 (worst imaginable pain). For the pain scale, a higher score indicates worse pain.

End point type

Secondary

End point timeframe

Baseline at either Study Part 1, or Study Part 2, and End of Study (study weeks 29-31)

End point values	Study Part 2: Prophylactic cohort	Study Part 2: On-demand cohort
Number of subjects analysed	54 ^[4]	14
Units: Score on a scale
arithmetic mean (standard deviation)
Part 1 or Part 2, Exposure Day 1 (Baseline)	32.67 ± 26.62	47.57 ± 30.82
End of Study	33.09 ± 25.9	39.93 ± 22.57
Change from Baseline	0.35 ± 21.77	-7.64 ± 33.58

Notes
[4] - N=55 at baseline, N=54 at end of study

No statistical analyses for this end point

Secondary: Short Form (36) Health Survey (SF-36): HRQoL 'Physical Component Score' (PCS)

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End point title

Short Form (36) Health Survey (SF-36): HRQoL 'Physical Component Score' (PCS)

End point description

The PCS is a summary scale of the dimensions physical functioning, role physical, bodily pain, and general health. The component score is normalized to a standard population. Scores range from 0 to 100 with higher scores representing better health. There is no total overall score; scoring is done for both subscores and summary scores.

End point type

Secondary

End point timeframe

Baseline at either Study Part 1, or Study Part 2, and End of Study (study weeks 29-31)

End point values	Study Part 2: Prophylactic cohort	Study Part 2: On-demand cohort
Number of subjects analysed	52 ^[5]	13
Units: Score on a scale
arithmetic mean (standard deviation)
Part 1 or Part 2, Exposure Day 1 (Baseline)	39.08 ± 9.39	37.38 ± 7.2
End of Study	41.35 ± 8.73	38.92 ± 8.53
Change from Baseline	2.6 ± 7.72	1.54 ± 5.11

Notes
[5] - N=54 at baseline, N=52 at end of study

No statistical analyses for this end point

Secondary: SF-36: HRQoL 'Mental Health' (MH)

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End point title

SF-36: HRQoL 'Mental Health' (MH)

End point description

Quality of life survey response as measured using the SF-36 questionnaire. Scores range from 0 to 100 with higher scores representing better health. There is no total overall score; scoring is done for both subscores and summary scores. The raw data from the SF-36 items were transformed to norm based scores for each of the 8 HRQoL/SF-36 health domain scores.

End point type

Secondary

End point timeframe

Baseline at either Study Part 1, or Study Part 2, and End of Study (study weeks 29-31)

End point values	Study Part 2: Prophylactic cohort	Study Part 2: On-demand cohort
Number of subjects analysed	52 ^[6]	13
Units: Score on a scale
arithmetic mean (standard deviation)
Part 1 or Part 2, Exposure Day 1 (Baseline)	47.53 ± 9.46	47.24 ± 8.8
End of Study	49.67 ± 9.3	45.03 ± 9.96
Change from Baseline	2.01 ± 11.17	-2.21 ± 8.28

Notes
[6] - N=54 at baseline, N=52 at end of study

No statistical analyses for this end point

Secondary: SF-36: HRQoL Physical Functioning' (PF)

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End point title

SF-36: HRQoL Physical Functioning' (PF)

End point description

End point type

Secondary

End point timeframe

Baseline at either Study Part 1, or Study Part 2, and End of Study (study weeks 29-31)

End point values	Study Part 2: Prophylactic cohort	Study Part 2: On-demand cohort
Number of subjects analysed	53 ^[7]	13
Units: Score on a scale
arithmetic mean (standard deviation)
Part 1 or Part 2, Exposure Day 1 (Baseline) vs. En	40.2 ± 10.57	40.04 ± 10.57
End of Study	40.75 ± 10.14	39.87 ± 10.55
Change from Baseline	0.68 ± 7.48	-0.16 ± 5.86

Notes
[7] - N=54 at baseline, N=53 at end of study

No statistical analyses for this end point

Secondary: SF-36: HRQoL Role-Physical (RP)

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End point title

SF-36: HRQoL Role-Physical (RP)

End point description

End point type

Secondary

End point timeframe

Baseline at either Study Part 1, or Study Part 2, and End of Study (study weeks 29-31)

End point values	Study Part 2: Prophylactic cohort	Study Part 2: On-demand cohort
Number of subjects analysed	53 ^[8]	13
Units: Score on a scale
arithmetic mean (standard deviation)
Part 1 or Part 2, Exposure Day 1 (Baseline)	40.39 ± 10.7	39.15 ± 8.13
End of Study	43.82 ± 8.67	37.45 ± 10.12
Change from Baseline	3.47 ± 10.15	-1.7 ± 5.86

Notes
[8] - N=54 at baseline, N=53 at end of study

No statistical analyses for this end point

Secondary: SF-36: HRQoL Role-Emotional

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End point title

SF-36: HRQoL Role-Emotional

End point description

End point type

Secondary

End point timeframe

Baseline at either Study Part 1, or Study Part 2, and End of Study (study weeks 29-31)

End point values	Study Part 2: Prophylactic cohort	Study Part 2: On-demand cohort
Number of subjects analysed	53 ^[9]	13
Units: Score on a scale
arithmetic mean (standard deviation)
Part 1 or Part 2, Exposure Day 1 (Baseline)	44.22 ± 11.45	40.93 ± 9.1
End of Study	44.8 ± 10.15	39.43 ± 11.57
Change from Baseline	0.37 ± 11.74	-1.5 ± 8.91

Notes
[9] - N=54 at baseline, N=53 at end of study

No statistical analyses for this end point

Secondary: SF-36: HRQoL Bodily Pain

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End point title

SF-36: HRQoL Bodily Pain

End point description

End point type

Secondary

End point timeframe

Baseline at either Study Part 1, or Study Part 2, and End of Study (study weeks 29-31)

End point values	Study Part 2: Prophylactic cohort	Study Part 2: On-demand cohort
Number of subjects analysed	53 ^[10]	13
Units: Score on a scale
arithmetic mean (standard deviation)
Part 1 or Part 2, Exposure Day 1 (Baseline)	42.09 ± 10.21	36.89 ± 7.84
End of Study	45.72 ± 8.68	39.33 ± 8.91
Change from Baseline	3.45 ± 9.95	2.44 ± 10.18

Notes
[10] - N=54 at baseline, N=53 at end of study

No statistical analyses for this end point

Secondary: SF-36: HRQoL Mental Health

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End point title

SF-36: HRQoL Mental Health

End point description

End point type

Secondary

End point timeframe

Baseline at either Study Part 1, or Study Part 2, and End of Study (study weeks 29-31)

End point values	Study Part 2: Prophylactic cohort	Study Part 2: On-demand cohort
Number of subjects analysed	52 ^[11]	13
Units: Score on a scale
arithmetic mean (standard deviation)
Part 1 or Part 2, Exposure Day 1 (Baseline)	45.52 ± 8.78	45.46 ± 10.57
End of Study	47.95 ± 8.84	42.64 ± 10.63
Change from Baseline	2.44 ± 11.29	-2.82 ± 8.53

Notes
[11] - N=54 at baseline, N=52 at end of study

No statistical analyses for this end point

Secondary: SF-36: HRQoL Vitality

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End point title

SF-36: HRQoL Vitality

End point description

End point type

Secondary

End point timeframe

Baseline at either Study Part 1, or Study Part 2, and End of Study (study weeks 29-31)

End point values	Study Part 2: Prophylactic cohort	Study Part 2: On-demand cohort
Number of subjects analysed	52 ^[12]	13
Units: Score on a scale
arithmetic mean (standard deviation)
Part 1 or Part 2, Exposure Day 1 (Baseline)	50.07 ± 8.47	50.17 ± 5.63
End of Study	52.75 ± 8.88	50.89 ± 6.81
Change from Baseline	2.46 ± 10.75	0.72 ± 5.43

Notes
[12] - N=54 at baseline, N=52 at end of study

No statistical analyses for this end point

Secondary: SF-36: HRQoL Social Functioning

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End point title

SF-36: HRQoL Social Functioning

End point description

End point type

Secondary

End point timeframe

Baseline at either Study Part 1, or Study Part 2, and End of Study (study weeks 29-31)

End point values	Study Part 2: Prophylactic cohort	Study Part 2: On-demand cohort
Number of subjects analysed	53 ^[13]	13
Units: Score on a scale
arithmetic mean (standard deviation)
Part 1 or Part 2, Exposure Day 1 (Baseline)	41.8 ± 10.54	43.42 ± 9.61
End of Study	44.6 ± 8.94	42.17 ± 9.8
Change from Baseline	2.78 ± 10.78	-1.26 ± 6.36

Notes
[13] - N=54 at baseline, N=53 at end of study

No statistical analyses for this end point

Secondary: SF-36: HRQoL General Health

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End point title

SF-36: HRQoL General Health

End point description

End point type

Secondary

End point timeframe

Baseline at either Study Part 1, or Study Part 2, and End of Study (study weeks 29-31)

End point values	Study Part 2: Prophylactic cohort	Study Part 2: On-demand cohort
Number of subjects analysed	53 ^[14]	13
Units: Score on a scale
arithmetic mean (standard deviation)
Part 1 or Part 2, Exposure Day 1 (Baseline)	37.84 ± 8.38	37.09 ± 10.47
End of Study	39.98 ± 9.03	39.07 ± 8.88
Change from Baseline	2.2 ± 8.22	1.98 ± 7.94

Notes
[14] - N=54 at baseline, N=53 at end of study

No statistical analyses for this end point

Secondary: Pediatric Quality of Life Questionnaire (PedsQL) Physical Health Summary Score (Ages 12-16)

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End point title

Pediatric Quality of Life Questionnaire (PedsQL) Physical Health Summary Score (Ages 12-16)

End point description

The Peds-QL is a generic Health-Related Quality of Life (HR QoL) instrument designed specifically for a pediatric population. It captures the following domains: general health/activities, feelings/emotional, social functioning, school functioning. For this study, the Peds-QL for 12 to 16-year-old subjects was used. Higher scores indicate better quality of life (QOL) for all domains of the Peds-QL. This modular instrument uses a 5-point scale: from 0 (never) to 4 (almost always). Items are reversed scored and linearly transformed to a 0-100 scale as follows: 0=100, 1=75, 2=50, 3=25, 4=0. 4 dimensions (physical, emotional, social, & school functioning) are scored.

End point type

Secondary

End point timeframe

Baseline at either Study Part 1, or Study Part 2, and End of Study (study weeks 29-31)

End point values	Study Part 2: Prophylactic cohort	Study Part 2: On-demand cohort
Number of subjects analysed	2	1
Units: Score on a scale
arithmetic mean (standard deviation)
Part 1 or Part 2, Exposure Day 1 (Baseline)	65.63 ± 13.26	65.63 ± 0
End of Study	54.69 ± 6.63	65.63 ± 0
Change from Baseline	-10.94 ± 19.89	0 ± 0

No statistical analyses for this end point

Secondary: Pediatric Quality of Life Questionnaire (PedsQL) Psychosocial Health Summary Score (Ages 12-16)

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End point title

Pediatric Quality of Life Questionnaire (PedsQL) Psychosocial Health Summary Score (Ages 12-16)

End point description

End point type

Secondary

End point timeframe

Baseline at either Study Part 1, or Study Part 2, and End of Study (study weeks 29-31)

End point values	Study Part 2: Prophylactic cohort	Study Part 2: On-demand cohort
Number of subjects analysed	2	1
Units: Score on a scale
arithmetic mean (standard deviation)
Part 1 or Part 2, Exposure Day 1 (Baseline)	63.33 ± 11.79	88.33 ± 0
End of Study	55.83 ± 3.54	86.67 ± 0
Change from Baseline	-7.5 ± 8.25	-1.67 ± 0

No statistical analyses for this end point

Secondary: Pediatric Quality of Life Questionnaire (PedsQL) Total Score (Ages 12-16)

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End point title

Pediatric Quality of Life Questionnaire (PedsQL) Total Score (Ages 12-16)

End point description

End point type

Secondary

End point timeframe

Baseline at either Study Part 1, or Study Part 2, and End of Study (study weeks 29-31)

End point values	Study Part 2: Prophylactic cohort	Study Part 2: On-demand cohort
Number of subjects analysed	2	1
Units: Score on a scale
arithmetic mean (standard deviation)
Part 1 or Part 2, Exposure Day 1 (Baseline)	64.13 ± 12.3	80.43 ± 0
End of Study	55.43 ± 0	79.35 ± 0
Change from Baseline	-8.7 ± 12.3	-1.09 ± 0

No statistical analyses for this end point

Secondary: Health-Related Quality of Life (HRQoL) Disease-specific: Haem-A-QoL

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End point title

Health-Related Quality of Life (HRQoL) Disease-specific: Haem-A-QoL

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, sports/leisure, school/work, dealing with hemophilia, and outlook for the future. For the Haem-A-QOL, higher scores indicate a worse quality of life. Scores on a scale range between 0 and 100.

End point type

Secondary

End point timeframe

Baseline at either Study Part 1, or Study Part 2, and End of Study (study weeks 29-31)

End point values	Study Part 2: Prophylactic cohort	Study Part 2: On-demand cohort
Number of subjects analysed	48 ^[15]	13
Units: Score on a scale
arithmetic mean (standard deviation)
Part 1 or Part 2, Exposure Day 1 (Baseline)	40.68 ± 15.33	41.65 ± 15.19
End of Study	37.85 ± 16.57	41.37 ± 16.64
Change from Baseline	-3.52 ± 12.81	-0.28 ± 12.18

Notes
[15] - N=51 at baseline, N=50 at end of study, N=48 for change from baseline

No statistical analyses for this end point

Secondary: Health-Related Quality of Life (HRQoL) Disease-specific: Haemo-QoL - Participants On-Demand (Ages 12-16)

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End point title

Health-Related Quality of Life (HRQoL) Disease-specific: Haemo-QoL - Participants On-Demand (Ages 12-16)

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. For the Haemo-QoL, higher scores indicate a worse quality of life. Scores on a scale range between 0 and 100.

End point type

Secondary

End point timeframe

Baseline at either Study Part 1, or Study Part 2, and End of Study (study weeks 29-31)

End point values	Study Part 2: On-demand cohort
Number of subjects analysed	1
Units: Score on a scale
arithmetic mean (standard deviation)
Part 1 or Part 2, Exposure Day 1 (Baseline)	40 ± 0
End of Study	40 ± 0
Change from Baseline	0 ± 0

No statistical analyses for this end point

Secondary: Health Resource Use - Number of Hospitalizations

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End point title

Health Resource Use - Number of Hospitalizations

End point description

End point type

Secondary

End point timeframe

Study Part 1 = 2-4 weeks, Study Part 2 = 26 weeks ± 1 week, Study Part 3 = 1 week (Total = 29-31 weeks)

End point values	Study Part 2: Prophylactic cohort	Study Part 2: On-demand cohort
Number of subjects analysed	57	14 ^[16]
Units: Hospitalizations
median (full range (min-max))
Part 1 - PK (N= 28/prophy; NA/on-demand)	0 (0 to 0)	0 (0 to 0)
Part 2: Exp Day 1 (N= 31/prophy, 14/on-demand)	0 (0 to 0)	0 (0 to 0)
Part 2: Week 5 (N= 57/prophy, 14/on-demand)	0 (0 to 1)	0 (0 to 0)
Part 2: Week 13 (N= 56/prophy, 12/on-demand)	0 (0 to 0)	0 (0 to 0)
Part 2: Week 26 (N= 30/prophy, NA/on-demand)	0 (0 to 0)	0 (0 to 0)
Part 3 (N= 25/prophy, NA/on-demand)	0 (0 to 3)	0 (0 to 0)
Completion/Termination (N= 20 /prophy, 9/on-dem)	0 (0 to 1)	0 (0 to 0)
Unscheduled Study Visit (N= 1/prophy, NA/on-dem)	0 (0 to 0)	0 (0 to 0)

Notes
[16] - No on-demand subjects in Part 1, in Part 2 at Week 26, in Part 3, and with an unscheduled visit.

No statistical analyses for this end point

Secondary: Health Resource Use - Total Days of Hospital Stay

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End point title

Health Resource Use - Total Days of Hospital Stay

End point description

This endpoint is only applicable to 4 subjects in the propyhlactic cohort who were hospitalized.

End point type

Secondary

End point timeframe

Study Part 1 = 2-4 weeks, Study Part 2 = 26 weeks ± 1 week, Study Part 3 = 1 week (Total = 29-31 weeks)

End point values	Study Part 2: Prophylactic cohort
Number of subjects analysed	4
Units: Days
median (full range (min-max))
Part 2: Week 5 (N= 1)	46 (46 to 46)
Part 2: Week 13 (N= 1)	23 (23 to 23)
Part 3 (N= 3)	2 (1 to 16)
Completion/Termination (N= 2)	5.5 (2 to 9)

No statistical analyses for this end point

Secondary: Health Resource Use - Emergency Room Visits

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End point title

Health Resource Use - Emergency Room Visits

End point description

End point type

Secondary

End point timeframe

Study Part 1 = 2-4 weeks, Study Part 2 = 26 weeks ± 1 week, Study Part 3 = 1 week (Total = 29-31 weeks)

End point values	Study Part 2: Prophylactic cohort	Study Part 2: On-demand cohort
Number of subjects analysed	57	14 ^[17]
Units: Visits
median (full range (min-max))
Part 1 - PK (N= 28/prophy, NA/on-demand)	0 (0 to 0)	0 (0 to 0)
Part 2: Exp Day 1 (N= 31/prophy, 14/on-demand)	0 (0 to 10)	0 (0 to 0)
Part 2: Week 5 (N= 57/prophy, 14/on-demand)	0 (0 to 1)	0 (0 to 0)
Part 2: Week 13 (N= 56/prophy, 12/on-demand)	0 (0 to 1)	0 (0 to 0)
Part 2: Week 26 (N= 30/prophy, NA/on-demand)	0 (0 to 0)	0 (0 to 0)
Part 3 (N= 25/prophy, NA/on-demand)	0 (0 to 0)	0 (0 to 0)
Completion/Termination (N= 20/prophy, 9/on-demand)	0 (0 to 1)	0 (0 to 0)
Unscheduled Study Visit (N= 1/prophy, NA/on-dem)	0 (0 to 0)	0 (0 to 0)

Notes
[17] - No on-demand subjects in Part 1, in Part 2 at Week 26, in Part 3, and with an unscheduled visit.

No statistical analyses for this end point

Secondary: Health Resource Use - Unscheduled Doctor's Office Visits

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End point title

Health Resource Use - Unscheduled Doctor's Office Visits

End point description

End point type

Secondary

End point timeframe

Study Part 1 = 2-4 weeks, Study Part 2 = 26 weeks ± 1 week, Study Part 3 = 1 week (Total = 29-31 weeks)

End point values	Study Part 2: Prophylactic cohort	Study Part 2: On-demand cohort
Number of subjects analysed	57	14 ^[18]
Units: Visits
median (full range (min-max))
Part 1 - PK (N= 28/prophy, NA/on-demand)	0 (0 to 1)	0 (0 to 0)
Part 2: Exp Day 1 (N= 31/prophy, 14/on-demand)	0 (0 to 0)	0 (0 to 0)
Part 2: Week 5 (N= 57/prophy, 14/on-demand)	0 (0 to 3)	0 (0 to 0)
Part 2: Week 13 (N= 56/prophy, 12/on-demand)	0 (0 to 2)	0 (0 to 0)
Part 2: Week 26 (N= 30/prophy, NA/on-demand)	0 (0 to 1)	0 (0 to 0)
Part 3 (N= 25/prophy, NA/on-demand)	0 (0 to 1)	0 (0 to 0)
Completion/Termination (N= 20/prophy, 9/on-demand)	0 (0 to 2)	0 (0 to 1)
Unscheduled Study Visit (N= 1/prophy, NA/on-dem)	1 (1 to 1)	0 (0 to 0)

Notes
[18] - No on-demand subjects in Part 1, in Part 2 at Week 26, in Part 3, and with an unscheduled visit.

No statistical analyses for this end point

Secondary: Health Resource Use - Days Lost from Work or School

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End point title

Health Resource Use - Days Lost from Work or School

End point description

End point type

Secondary

End point timeframe

Study Part 1 = 2-4 weeks, Study Part 2 = 26 weeks ± 1 week, Study Part 3 = 1 week (Total = 29-31 weeks)

End point values	Study Part 2: Prophylactic cohort	Study Part 2: On-demand cohort
Number of subjects analysed	57	14 ^[19]
Units: Days
median (full range (min-max))
Part 1 - PK (N= 28/prophy, NA/on-demand)	0 (0 to 10)	0 (0 to 0)
Part 2: Exp Day 1 (N= 31/prophy, 14/on-demand)	0 (0 to 2)	0 (0 to 0)
Part 2: Week 5 (N= 57/prophy, 14/on-demand)	0 (0 to 8)	0 (0 to 4)
Part 2: Week 13 (N= 56/prophy, 12/on-demand)	0 (0 to 7)	0 (0 to 0)
Part 2: Week 26 (N= 30/prophy, NA/on-demand)	0 (0 to 5)	0 (0 to 0)
Part 3 (N= 25/prophy, NA/on-demand)	0 (0 to 1)	0 (0 to 0)
Completion/Termination (N= 20/prophy, 9/on-demand)	0 (0 to 24)	0 (0 to 0)
Unscheduled Study Visit (N= 1/prophy, NA/on-dem)	0 (0 to 0)	0 (0 to 0)

Notes
[19] - No on-demand subjects in Part 1, in Part 2 at Week 26, in Part 3, and with an unscheduled visit.

No statistical analyses for this end point

Adverse events

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Timeframe for reporting adverse events

Study Part 1 = 2-4 weeks, Study Part 2 = 26 weeks ± 1 week, Study Part 3 = 1 week (Total = 29-31 weeks)

Assessment type

Non-systematic

Dictionary name

MedDRA

Dictionary version

N/A

Reporting group title

BAX326

Reporting group description

BAX326: -Study Part 1: Pharmacokinetic (PK) Crossover with BAX326 and BeneFIX •Study Part 2: Open-label evaluation of prophylaxis and on-demand BAX326 only •Study Part 3: Open-label repeat of PK evaluation (repeat Study Part 1) with BAX326 only and same study participants as Study Part 1

Serious adverse events	BAX326
Total subjects affected by serious adverse events
subjects affected / exposed	4 / 73 (5.48%)
number of deaths (all causes)	0
number of deaths resulting from adverse events	0
Investigations
Hepatitis B Core Antibody Positive
Additional description: The subject´s medical history included chronic hepatitis B.
subjects affected / exposed	1 / 73 (1.37%)
occurrences causally related to treatment / all	0 / 1
deaths causally related to treatment / all	0 / 0
Injury, poisoning and procedural complications
Cervical Vertebral Fracture
subjects affected / exposed	1 / 73 (1.37%)
occurrences causally related to treatment / all	0 / 1
deaths causally related to treatment / all	0 / 0
Traumatic Haematoma
subjects affected / exposed	1 / 73 (1.37%)
occurrences causally related to treatment / all	0 / 1
deaths causally related to treatment / all	0 / 0
Nervous system disorders
Convulsion
subjects affected / exposed	1 / 73 (1.37%)
occurrences causally related to treatment / all	0 / 1
deaths causally related to treatment / all	0 / 0
Gastrointestinal disorders
Intestinal Obstruction
subjects affected / exposed	1 / 73 (1.37%)
occurrences causally related to treatment / all	0 / 1
deaths causally related to treatment / all	0 / 0

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

Non-serious adverse events	BAX326
Total subjects affected by non serious adverse events
subjects affected / exposed	15 / 73 (20.55%)
Investigations
Immunology Test Abnormal
subjects affected / exposed	12 / 73 (16.44%)
occurrences all number	12
Infections and infestations
Nasopharyngitis
subjects affected / exposed	6 / 73 (8.22%)
occurrences all number	8

More information

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Were there any global substantial amendments to the protocol? Yes

05 Jul 2010

- In the eligibility criteria, the acceptable upper limit of normal for ALT and AST was increased from ≥2 times to >5 times. - To ensure that subject weight is within a reasonable range, the following exclusion criterion was added: The subject´s weight is < 35 kg or > 120 kg. - It was clarified that hospitalization for elective surgery would not be considered a serious adverse event (SAE). - It was clarified that in Part 1 thrombotic markers would not only be assessed prior to and following the BAX326 infusion but also prior to and following the BeneFIX infusion. - The number of bleeding episodes (BEs) beginning within 24 and 48 hours of an infusion was added as an exploratory endpoint (per request of FDA). - The assessment time point for the main overall hemostatic efficacy rating for the treatment of BEs was set at “resolution of bleed” to be consistent with previous hemophilia studies. Overall hemostatic efficacy ratings performed at 12 ± 1 and 24 ± 1 h time points were added as exploratory endpoints. - It was emphasized that in case of inadequate response to BAX326, the subject should be managed according to the clinical judgment of the Investigator. - A third interim safety review was added which was to be performed after 24 subjects (20 evaluable) had completed Part 2 of whom 16 subjects had also completed Parts 1 and 3, and had been evaluated for hemostatic efficacy, safety, and immunogenicity for a period 50 EDs or 6 months, whichever occurred last.

03 May 2011

- An additional on-demand cohort of 15 to 20 subjects was added to Part 2 of the study. The total sample size was therefore increased from 60 up to 75-80 PTPs. The 2 cohorts are described as ‘prophylactic cohort’ and ‘on-demand cohort’. The reason for adding an on-demand cohort was to ensure sufficient data on the hemostatic efficacy of BAX326 in the treatment of BEs. It was specified that the decision regarding the type of treatment regimen was at the discretion of the Investigator and subject. However, once enrollment in the prophylactic cohort was completed (n = 60), only subjects willing to receive on-demand treatment would be recruited. The on-demand cohort would basically follow the same study schedule as the prophylactic cohort, except that they would only receive BAX326 to treat BEs and to determine IR at the scheduled study visits. - The following subject participation periods for the respective cohorts (prophylactic and on-demand) were added: a) Prophylactic cohort: 8-12 months for subjects taking part in Parts 1, 2 and 3; approximately 7-10 months for subject taking part in Part 2 only (unless prematurely discontinued) b) On-demand cohort: approximately 2-10 months, depending on when the subject is enrolled. - The upper acceptable limit of the International Normalized Ratio (INR) in the eligibility criteria was increased from 1.2 (upper limit of normal as defined by the central laboratory) to 1.4 to account for the fluctuating INR values between 1.1 and 1.4, in particular in subjects with hepatitis. - It was clarified that only vials with a nominal potency of 500 IU could be used for the PK parts and the determination of IR. - Although the required minimum wash-out period prior to the PK infusions in Parts 1 and 3 and prior to all study visits in Part 2 was 5 days, it was added that a wash-out period of 7 days would be preferable to ensure that the baseline FIX activity level was reached.

02 Mar 2012

The sample size for the third interim safety review was increased from 24 to 50 subjects (as suggested by FDA).

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

http://www.ncbi.nlm.nih.gov/pubmed/24832133
http://www.ncbi.nlm.nih.gov/pubmed/23834666
http://www.ncbi.nlm.nih.gov/pubmed/24251442

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Clinical trials

Clinical Trial Results: BAX326 (recombinant Factor IX): A Phase 1/3 Prospective, Controlled, Multicenter Study Evaluating Pharmacokinetics, Efficacy, Safety, and Immunogenicity in Previously Treated Patients With Severe (FIX level <1%) or Moderately Severe (FIX level ≤ 2%) Hemophilia B

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Study Part 1- Area under the plasma concentration versus time curve from 0 to 72 hours per dose

Primary: Study Part 1- Area under the plasma concentration versus time curve from 0 to 72 hours per dose

Secondary: Study Parts 1 and 3: Area under the plasma concentration/time curve from time 0 to infinity per dose (AUC0-∞/ dose)

Secondary: Study Parts 1 and 3: Area under the plasma concentration/time curve from time 0 to infinity per dose (AUC0-∞/ dose)

Secondary: Study Parts 1 and 3: Mean residence time (MRT)

Secondary: Study Parts 1 and 3: Mean residence time (MRT)

Secondary: Study Parts 1 and 3: Clearance (CL)

Secondary: Study Parts 1 and 3: Clearance (CL)

Secondary: Study Parts 1 and 3: Incremental Recovery at Cmax (IR at Cmax)

Secondary: Study Parts 1 and 3: Incremental Recovery at Cmax (IR at Cmax)

Secondary: Incremental Recovery (IR) at 30 Minutes Over Time

Secondary: Incremental Recovery (IR) at 30 Minutes Over Time

Secondary: Change in Incremental Recovery (IR) at 30 Minutes Over Time

Secondary: Change in Incremental Recovery (IR) at 30 Minutes Over Time

Secondary: Study Parts 1 and 3: Half Life (T 1/2)

Secondary: Study Parts 1 and 3: Half Life (T 1/2)

Secondary: Study Parts 1 and 3: Volume of distribution at steady state (Vss)

Secondary: Study Parts 1 and 3: Volume of distribution at steady state (Vss)

Secondary: Study Part 2: Annualized Bleed Rate (ABR) during prophylactic treatment with BAX326

Secondary: Study Part 2: Annualized Bleed Rate (ABR) during prophylactic treatment with BAX326

Secondary: Bleeding Episodes Treated With 1, 2 or ≥3 Infusions of BAX326

Secondary: Bleeding Episodes Treated With 1, 2 or ≥3 Infusions of BAX326

Secondary: Hemostatic Efficacy at Resolution of All Bleeding Episodes (BEs) Treated with BAX326

Secondary: Hemostatic Efficacy at Resolution of All Bleeding Episodes (BEs) Treated with BAX326

Secondary: Total Weight-adjusted Dose per Bleeding Episode (BEs) of All BEs Treated with BAX326 by Bleeding Site and Cause

Secondary: Total Weight-adjusted Dose per Bleeding Episode (BEs) of All BEs Treated with BAX326 by Bleeding Site and Cause

Secondary: Consumption of BAX326 per Event per Subject

Secondary: Consumption of BAX326 per Event per Subject

Secondary: Consumption of BAX326 per Subject: Median Number of Infusions per Month

Secondary: Consumption of BAX326 per Subject: Median Number of Infusions per Month

Secondary: Consumption of BAX326 per Subject: Median Weight-adjusted Consumption per Month

Secondary: Consumption of BAX326 per Subject: Median Weight-adjusted Consumption per Month

Secondary: Number of Participants Who Developed Inhibitory Antibodies to Factor IX (FIX)

Secondary: Number of Participants Who Developed Inhibitory Antibodies to Factor IX (FIX)

Secondary: Occurrence of total binding antibodies of indeterminate specificity (within assay variability)

Secondary: Occurrence of total binding antibodies of indeterminate specificity (within assay variability)

Secondary: Occurrence of treatment related total binding antibodies

Secondary: Occurrence of treatment related total binding antibodies

Secondary: Number of Subjects Who Experienced Severe Allergic Reactions (e.g. Anaphylaxis)

Secondary: Number of Subjects Who Experienced Severe Allergic Reactions (e.g. Anaphylaxis)

Secondary: Number of Subjects Who Experienced Thrombotic Events

Secondary: Number of Subjects Who Experienced Thrombotic Events

Secondary: Number of subjects with clinically significant changes in laboratory parameters: clinical chemistry

Secondary: Number of subjects with clinically significant changes in laboratory parameters: clinical chemistry

Secondary: Number of subjects with clinically significant changes in laboratory parameters: hematology

Secondary: Number of subjects with clinically significant changes in laboratory parameters: hematology

Secondary: Number of Subjects With Clinically significant changes in laboratory parameters: vital signs

Secondary: Number of Subjects With Clinically significant changes in laboratory parameters: vital signs

Secondary: Number of Subjects With Clinically significant changes in laboratory parameters: thrombogenic markers

Secondary: Number of Subjects With Clinically significant changes in laboratory parameters: thrombogenic markers

Secondary: Number of Adverse Events (AEs) Considered Related to BAX326 Treatment

Secondary: Number of Adverse Events (AEs) Considered Related to BAX326 Treatment

Secondary: Number of Subjects with Adverse Events (AEs) Considered Related to BAX326 Treatment

Secondary: Number of Subjects with Adverse Events (AEs) Considered Related to BAX326 Treatment

Secondary: EuroQoL (Quality of Life)-5 Dimensions (EQ-5D) Total Index Scores

Secondary: EuroQoL (Quality of Life)-5 Dimensions (EQ-5D) Total Index Scores

Secondary: EuroQoL (Quality of Life)-5 Dimensions Visual Analogue Scale (EQ-5D VAS) Scores

Secondary: EuroQoL (Quality of Life)-5 Dimensions Visual Analogue Scale (EQ-5D VAS) Scores

Secondary: General pain assessment through a visual analog scale (VAS)

Secondary: General pain assessment through a visual analog scale (VAS)

Secondary: Short Form (36) Health Survey (SF-36): HRQoL 'Physical Component Score' (PCS)

Secondary: Short Form (36) Health Survey (SF-36): HRQoL 'Physical Component Score' (PCS)

Secondary: SF-36: HRQoL 'Mental Health' (MH)

Secondary: SF-36: HRQoL 'Mental Health' (MH)

Secondary: SF-36: HRQoL Physical Functioning' (PF)

Secondary: SF-36: HRQoL Physical Functioning' (PF)

Secondary: SF-36: HRQoL Role-Physical (RP)

Secondary: SF-36: HRQoL Role-Physical (RP)

Secondary: SF-36: HRQoL Role-Emotional

Secondary: SF-36: HRQoL Role-Emotional

Clinical Trial Results:
BAX326 (recombinant Factor IX): A Phase 1/3 Prospective, Controlled, Multicenter Study Evaluating Pharmacokinetics, Efficacy, Safety, and Immunogenicity in Previously Treated Patients With Severe (FIX level <1%) or Moderately Severe (FIX level ≤ 2%) Hemophilia B