An Open-label Safety, Efficacy and Pharmacokinetic Study... | NCT01486927

NCT01486927

ID	Type	Description	Link
2011-002393-23	EudraCT Number

Status Module

Description Module

Design Module

Interventional Study Design

Biospecimen

No data available

No data is available for this block.

Arms/Interventions Module

Label	Type	Description	Intervention Names
Recombinant Factor VIII (rFVIII)	Experimental		Biological: rVIII-SingleChain Biological: Octocog alfa

Interventions

Name	Type	Description	Arm Group Labels	Other Names
rVIII-SingleChain	Biological	In Part 1 of the study, subjects received a single intravenous infusion of 50 IU/kg recombinant, single-chain coagulation factor VIII (rVIII-SingleChain) preceded by a 4-day washout period. In Parts 2 and 3 of the study, subjects received repeat injections of rVIII-SingleChain either as an on-demand or prophylaxis regimen at a dose and frequency determined by their study doctor. Subjects participating in the Part 3 PK analyses received a single infusion of 50 IU/kg rVIII-SingleChain and a repeat dose of the same strength of rVIII-SingleChain after 3 to 6 months. Subjects from Parts 2 and 3 participating in the surgical substudy received an individualized dose regimen of rVIII-SingleChain, based on the type of surgery and the clinical status of the subject.

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Treatment Success	The investigator rated the efficacy of the treatment based on a 4-point rating scale "excellent, good, moderate or poor/no response". Efficacy ratings of "excellent" or "good" were considered treatment success for this end point; the percentage of bleeding events with a rating of excellent or good and the 95% confidence interval are presented. The denominator includes all treated bleeding events. The 95% confidence interval is based on a model to account for within-subject correlation.	Up to 24 months
Inhibitor Formation to FVIII	Number of subjects who develop inhibitors to FVIII	Up to 24 months
Annualized Spontaneous Bleeding Rate	The annualized spontaneous bleeding rate (AsBR) was derived for each subject as follows: 365.25*(number of spontaneous bleeding episodes requiring treatment) / (observed treatment period of interest).	Up to 24 months
Treatment Success During the Peri-operative Surgical Sub-study	Subjects received rVIII-SingleChain before and during surgery based on the type of surgery and the clinical status of the subject. The investigator rated the efficacy of the treatment based on a 4-point surgical treatment rating scale of "excellent, good, moderate or poor/no response". Efficacy ratings of "excellent" or "good" were considered treatment success for this end point. The rate of success, defined as the percentage of surgeries with a rating of excellent or good for hemostatic efficacy on the surgical treatment scale is presented for the Surgical Population, based on the total number of surgeries (N=16) as denominator.	From the start of surgery through the post-operative recovery (generally up to 14 days after surgery)

Secondary Outcomes

Measure	Description	Time Frame
AUC0-∞ (Part 1)	AUC0-∞ (AUC from 0 extrapolated to infinity) of a single infusion of octocog alfa and rVIII-SingleChain without correction for subject's predose plasma FVIII activity. FVIII activity values for octocog alfa are dose-adjusted for chromogenic potency.	Before infusion and at up to 10 time points within 72 hours of infusion

Other Outcomes

Measure	Description	Time Frame
Incremental Recovery (Part 3)	Incremental recovery of an initial and repeat infusion of rVIII-SingleChain with correction for subject's predose plasma FVIII activity.	At 30 minutes after infusion
Volume of Distribution at Steady-state (Vss) (Part 3)

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Diagnosis of severe hemophilia A defined as <1% FVIII:C documented in medical records.
Males between 18 and 65 years of age (Parts 1 and 2).
Males between 12 and 65 years of age (Part 3).
Subjects who have received or are currently receiving FVIII products (plasma-derived and/or recombinant FVIII) and have had >150 exposure days (EDs) with a FVIII product
Written informed consent for study participation obtained before undergoing any study specific procedures.

Exclusion Criteria:

Any history of or current FVIII inhibitors
Any first order family history of FVIII inhibitors
Use of an Investigational Medicinal Product within 30 days prior to the first rVIII-SingleChain administration.
Administration of any cryoprecipitate, whole blood or plasma within 30 days prior to administration of rVIII-SingleChain or reference product.
Known hypersensitivity (allergic reaction or anaphylaxis) to any FVIII product or hamster protein.
Any known congenital or acquired coagulation disorder other than congenital FVIII deficiency.
Platelet count < 100,000/µL at screening.
Human immunodeficiency virus (HIV) positive subjects with a CD4 count < 200/mm3, in their medical history or at screening if available results are older than one year. (HIV positive subjects may participate in the study and antiviral therapy are permitted, at the discretion of the Investigator).
Subject currently receiving IV immunomodulating agents such as immunoglobulin or chronic systemic corticosteroid treatment.
Subject with serum aspartate aminotransferase (AST) or serum alanine aminotransferase (ALT) values > 5 times (x) the upper limit of normal (ULN) at Screening.
Subjects with serum creatinine values > 2 x ULN at Screening.
Evidence of thrombosis, including deep vein thrombosis, stroke, pulmonary embolism, myocardial infarction and arterial embolus within 3 months prior to Day 1.
Experienced life-threatening bleeding episode or had major surgery or an orthopedic surgical procedure during the 3 months prior to Day 1.

Name	Affiliation	Role
Program Director	CSL Behring	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Study Site		Sacramento	California	95817	United States
Study Site

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
27330001	Derived	Mahlangu J, Kuliczkowski K, Karim FA, Stasyshyn O, Kosinova MV, Lepatan LM, Skotnicki A, Boggio LN, Klamroth R, Oldenburg J, Hellmann A, Santagostino E, Baker RI, Fischer K, Gill JC, P'Ng S, Chowdary P, Escobar MA, Khayat CD, Rusen L, Bensen-Kennedy D, Blackman N, Limsakun T, Veldman A, St Ledger K, Pabinger I; AFFINITY Investigators. Efficacy and safety of rVIII-SingleChain: results of a phase 1/3 multicenter clinical trial in severe hemophilia A. Blood. 2016 Aug 4;128(5):630-7. doi: 10.1182/blood-2016-01-687434. Epub 2016 Jun 21.

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Recombinant Factor VIII (rFVIII)	In Part 1 of the study (a single-sequence crossover pharmacokinetic [PK] analysis), 27 subjects received a single injection of octocog alfa followed by a single injection of rVIII-SingleChain. Twenty-six of the 27 subjects from Part 1 then entered Part 2 of the study where they were assigned either to an on-demand or prophylaxis regimen with repeat injections of rVIII-SingleChain until they reached 50 exposure days (EDs). In Part 3 of the study, 148 additional subjects were enrolled and were assigned either to an on-demand or prophylaxis regimen with repeat injections of rVIII-SingleChain until they reached 50 EDs; 64 of these subjects participated in additional PK analyses. Overall, 174 subjects received rVIII-SingleChain as either on-demand or prophylaxis regimens, and 13 subjects participated in the surgical substudy.

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Arm/Group Information

ID	Title	Description
BG000	Recombinant Factor VIII (rFVIII)	In Part 1 of the study (a single-sequence crossover PK analysis), 27 subjects received a single injection of octocog alfa followed by a single injection of rVIII-SingleChain. Twenty-six of the 27 subjects from Part 1 then entered Part 2 of the study where they were assigned either to an on-demand or prophylaxis regimen with repeat injections of rVIII-SingleChain until they reached 50 EDs. In Part 3 of the study, 148 additional subjects were enrolled and were assigned either to an on-demand or prophylaxis regimen with repeat injections of rVIII-SingleChain until they reached 50 EDs; 64 of these subjects participated in additional PK analyses. Overall, 174 subjects received rVIII-SingleChain as either on-demand or prophylaxis regimens, and 13 subjects participated in the surgical substudy.

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Continuous

Mean

Standard Deviation

years

Title

Denominators

Categories

Title	Measurements
	BG00031.3± 11.77

Age, Customized

Number

participants

Title

Denominators

Categories

Adolescents (12-17 years)

Title	Measurements
	BG00014

Adults (18-65 years)

Title	Measurements
	BG000

Sex: Female, Male

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG0000
Male	BG000174

Type of FVIII product used before enrollment

Type of FVIII product used by the subjects before enrollment into the study. This could have been a plasma-derived FVIII product or a recombinant FVIII product.

Number

participants

Title

Denominators

Categories

Plasma-derived Product

Title	Measurements
	BG00083

Recombinant Product

Title	Measurements
	BG000

Treatment modality of FVIII therapy before enrollment

Treatment modality of FVIII therapy before enrollment, ie, routine prophylaxis or on-demand treatment. If a subject used both modalities, only the most recent one was counted.

Number

participants

Title

Denominators

Categories

Prophylaxis

Title	Measurements
	BG00082

On-demand

Title	Measurements
	BG000

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Treatment Success

The investigator rated the efficacy of the treatment based on a 4-point rating scale "excellent, good, moderate or poor/no response". Efficacy ratings of "excellent" or "good" were considered treatment success for this end point; the percentage of bleeding events with a rating of excellent or good and the 95% confidence interval are presented. The denominator includes all treated bleeding events. The 95% confidence interval is based on a model to account for within-subject correlation.

Posted

Number

95% Confidence Interval

% bleeding events successfully treated

Up to 24 months

Number of treated bleeding events

Participants

ID	Title	Description
OG000	rVIII-SingleChain On-demand	The rVIII-SingleChain On-demand group consisted of all subjects in the efficacy population who received at least 1 dose rVIII-SingleChain as part of on-demand treatment during Parts 2 or 3 of the study. There were 27 subjects in the rVIII-SingleChain On-demand group.
OG001	rVIII-SingleChain Prophylaxis	The rVIII-SingleChain Prophylaxis group consisted of all subjects in the efficacy population who received at least 1 dose rVIII-SingleChain as part of routine prophylaxis treatment during Parts 2 or 3 of the study. There were 146 subjects in the rVIII-SingleChain Prophylaxis group.
OG002	rVIII-SingleChain	The Efficacy population consisted of all subjects who received at least 1 dose of rVIII-SingleChain as part of either routine prophylaxis treatment or on-demand treatment during Parts 2 or 3 of the study. There were 173 subjects in the Efficacy population.

Units	Counts
Participants	OG00027 OG001146 OG002173
Number of treated bleeding events	OG000

Title

Denominators

Categories

Title	Measurements
	OG00092.4(87.8 to 95.3) OG00192.2(86.3 to 95.8) OG00292.3(88.9 to 94.8)

Primary

Inhibitor Formation to FVIII

Number of subjects who develop inhibitors to FVIII

Posted

Number

participants

Up to 24 months

ID	Title	Description
OG000	Recombinant Factor VIII (rFVIII)	In Part 1 of the study (a single-sequence crossover PK analysis), 27 subjects received a single injection of octocog alfa followed by a single injection of rVIII-SingleChain. Twenty-six of the 27 subjects from Part 1 then entered Part 2 of the study where they were assigned either to an on-demand or prophylaxis regimen with repeat injections of rVIII-SingleChain until they reached 50 EDs. In Part 3 of the study, 148 additional subjects were enrolled and were assigned either to an on-demand or prophylaxis regimen with repeat injections of rVIII-SingleChain until they reached 50 EDs; 64 of these subjects participated in additional PK analyses. Overall, 174 subjects received rVIII-SingleChain as either on-demand or prophylaxis regimens, and 13 subjects participated in the surgical substudy.

Units	Counts
Participants	OG000

Primary

Annualized Spontaneous Bleeding Rate

The annualized spontaneous bleeding rate (AsBR) was derived for each subject as follows: 365.25*(number of spontaneous bleeding episodes requiring treatment) / (observed treatment period of interest).

Posted

Median

Inter-Quartile Range

Number of spontaneous bleeds per year

Up to 24 months

ID	Title	Description
OG000	rVIII-SingleChain On-demand	The rVIII-SingleChain On-demand group consisted of all subjects in the efficacy population who received at least 1 dose rVIII-SingleChain as part of on-demand treatment during Parts 2 or 3 of the study. There were 27 subjects in the rVIII-SingleChain On-demand group.
OG001	rVIII-SingleChain Prophylaxis	The rVIII-SingleChain Prophylaxis group consisted of all subjects in the efficacy population who received at least 1 dose rVIII-SingleChain as part of routine prophylaxis treatment during Parts 2 or 3 of the study. There were 146 subjects in the rVIII-SingleChain Prophylaxis group.

Units	Counts
Participants

Primary

Treatment Success During the Peri-operative Surgical Sub-study

Subjects received rVIII-SingleChain before and during surgery based on the type of surgery and the clinical status of the subject. The investigator rated the efficacy of the treatment based on a 4-point surgical treatment rating scale of "excellent, good, moderate or poor/no response". Efficacy ratings of "excellent" or "good" were considered treatment success for this end point. The rate of success, defined as the percentage of surgeries with a rating of excellent or good for hemostatic efficacy on the surgical treatment scale is presented for the Surgical Population, based on the total number of surgeries (N=16) as denominator.

Posted

Number

% of surgeries with successful treatment

From the start of surgery through the post-operative recovery (generally up to 14 days after surgery)

ID	Title	Description
OG000	rVIII-SingleChain Surgical	The rVIII-SingleChain Surgical group included all subjects enrolled in the surgical sub-study who received at least 1 dose of rVIII-SingleChain during the surgical sub-study. There were 13 subjects in the rVIII-SingleChain Surgical group.

Units	Counts
Participants	OG000

Secondary

AUC0-∞ (Part 1)

AUC0-∞ (AUC from 0 extrapolated to infinity) of a single infusion of octocog alfa and rVIII-SingleChain without correction for subject's predose plasma FVIII activity. FVIII activity values for octocog alfa are dose-adjusted for chromogenic potency.

Posted

Mean

Standard Deviation

IU*h/dL

Before infusion and at up to 10 time points within 72 hours of infusion

ID	Title	Description
OG000	PK Population (Part 1)	The PK population (Part 1) consisted of subjects who had received 1 dose of 50 IU/kg of rVIII-SingleChain and for whom a sufficient number of analyzable PK samples were obtained to permit the evaluation of the PK profile. In the Part 1 PK analysis, these subjects also received 1 dose of 50 IU/kg octocog alfa. There were 27 subjects in the PK population (Part 1).

Units	Counts
Participants	OG000

Secondary

Cmax (Part 1)

Cmax of a single infusion of octocog alfa and rVIII-SingleChain with correction for subject's predose plasma FVIII activity. FVIII activity values for octocog alfa are dose-adjusted for chromogenic potency.

Posted

Mean

Standard Deviation

IU/dL

Before infusion and at up to 10 time points within 72 hours of infusion

ID	Title	Description
OG000	PK Population (Part 1)	The PK population (Part 1) consisted of subjects who had received 1 dose of 50 IU/kg of rVIII-SingleChain and for whom a sufficient number of analyzable PK samples were obtained to permit the evaluation of the PK profile. In the Part 1 PK analysis, these subjects also received 1 dose of 50 IU/kg octocog alfa. There were 27 subjects in the PK population (Part 1).

Units	Counts
Participants	OG000

Secondary

Tmax (Part 1)

Tmax = time of Cmax (with correction for subject's predose plasma FVIII activity) after a single infusion of octocog alfa and rVIII-SingleChain.

Posted

Median

Full Range

hours

Before infusion and at up to 10 time points within 72 hours of infusion

ID	Title	Description
OG000	PK Population (Part 1)	The PK population (Part 1) consisted of subjects who had received 1 dose of 50 IU/kg of rVIII-SingleChain and for whom a sufficient number of analyzable PK samples were obtained to permit the evaluation of the PK profile. In the Part 1 PK analysis, these subjects also received 1 dose of 50 IU/kg octocog alfa. There were 27 subjects in the PK population (Part 1).

Units	Counts
Participants	OG000

Secondary

Half-life (t1/2) (Part 1)

Half-life (t1/2) of a single infusion of octocog alfa and rVIII-SingleChain without correction for subject's predose plasma FVIII activity.

Posted

Mean

Standard Deviation

hours

Before infusion and at up to 10 time points within 72 hours of infusion.

ID	Title	Description
OG000	PK Population (Part 1)	The PK population (Part 1) consisted of subjects who had received 1 dose of 50 IU/kg of rVIII-SingleChain and for whom a sufficient number of analyzable PK samples were obtained to permit the evaluation of the PK profile. In the Part 1 PK analysis, these subjects also received 1 dose of 50 IU/kg octocog alfa. There were 27 subjects in the PK population (Part 1).

Units	Counts
Participants	OG000

Secondary

Mean Residence Time (MRT) (Part 1)

Mean residence time (MRT) of a single infusion of octocog alfa and rVIII-SingleChain without correction for subject's predose plasma FVIII activity.

Posted

Mean

Standard Deviation

hours

Before infusion and at up to 10 time points within 72 hours of infusion

ID	Title	Description
OG000	PK Population (Part 1)	The PK population (Part 1) consisted of subjects who had received 1 dose of 50 IU/kg of rVIII-SingleChain and for whom a sufficient number of analyzable PK samples were obtained to permit the evaluation of the PK profile. In the Part 1 PK analysis, these subjects also received 1 dose of 50 IU/kg octocog alfa. There were 27 subjects in the PK population (Part 1).

Units	Counts
Participants	OG000

Secondary

Clearance (Cl) (Part 1)

Clearance (Cl) of a single infusion of octocog alfa and rVIII-SingleChain without correction for subject's predose plasma FVIII activity. FVIII activity values for octocog alfa are dose-adjusted for chromogenic potency.

Posted

Mean

Standard Deviation

mL/h/kg

Before infusion and at up to 10 time points within 72 hours of infusion

ID	Title	Description
OG000	PK Population (Part 1)	The PK population (Part 1) consisted of subjects who had received 1 dose of 50 IU/kg of rVIII-SingleChain and for whom a sufficient number of analyzable PK samples were obtained to permit the evaluation of the PK profile. In the Part 1 PK analysis, these subjects also received 1 dose of 50 IU/kg octocog alfa. There were 27 subjects in the PK population (Part 1).

Units	Counts
Participants	OG000

Secondary

Volume of Distribution at Steady-state (Vss) (Part 1)

Volume of distribution at steady-state (Vss) of a single infusion of octocog alfa and rVIII-SingleChain without correction for subject's predose plasma FVIII activity. FVIII activity values for octocog alfa are dose-adjusted for chromogenic potency.

Posted

Mean

Standard Deviation

mL/kg

Before infusion and at up to 10 time points within 72 hours of infusion

ID	Title	Description
OG000	PK Population (Part 1)	The PK population (Part 1) consisted of subjects who had received 1 dose of 50 IU/kg of rVIII-SingleChain and for whom a sufficient number of analyzable PK samples were obtained to permit the evaluation of the PK profile. In the Part 1 PK analysis, these subjects also received 1 dose of 50 IU/kg octocog alfa. There were 27 subjects in the PK population (Part 1).

Units	Counts
Participants	OG000

Secondary

Incremental Recovery (Part 1)

Incremental recovery of a single infusion of octocog alfa and rVIII-SingleChain with correction for subject's predose plasma FVIII activity. FVIII activity values for octocog alfa are dose-adjusted for chromogenic potency.

Posted

Mean

Standard Deviation

[IU/dL]/[IU/kg]

At 30 minutes after infusion

ID	Title	Description
OG000	PK Population (Part 1)	The PK population (Part 1) consisted of subjects who had received 1 dose of 50 IU/kg of rVIII-SingleChain and for whom a sufficient number of analyzable PK samples were obtained to permit the evaluation of the PK profile. In the Part 1 PK analysis, these subjects also received 1 dose of 50 IU/kg octocog alfa. There were 27 subjects in the PK population (Part 1).

Units	Counts
Participants	OG000

Secondary

Annualized Bleeding Rate for Total Bleeds and Traumatic Bleeds

The annualized bleeding rate was derived for each subject as follows: 365.25*(number of bleeding episodes requiring treatment) / (observed treatment period of interest).

Posted

Median

Inter-Quartile Range

Number of bleeds per year

Up to 24 months

ID	Title	Description
OG000	rVIII-SingleChain On-demand	The rVIII-SingleChain On-demand group consisted of all subjects in the efficacy population who received at least 1 dose rVIII-SingleChain as part of on-demand treatment during Parts 2 or 3 of the study. There were 27 subjects in the rVIII-SingleChain On-demand group.
OG001	rVIII-SingleChain Prophylaxis	The rVIII-SingleChain Prophylaxis group consisted of all subjects in the efficacy population who received at least 1 dose rVIII-SingleChain as part of routine prophylaxis treatment during Parts 2 or 3 of the study. There were 146 subjects in the rVIII-SingleChain Prophylaxis group.

Units	Counts
Participants

Secondary

Proportion of Bleeding Episodes Requiring 1, 2, 3 or > 3 Infusions of rVIII-SingleChain to Achieve Hemostasis

Percentage of bleeding episodes requiring 1, 2, 3 or > 3 infusions of rVIII-SingleChain to achieve hemostasis. The denominator includes all treated bleeding episodes.

Posted

Number

Percentage of bleeding episodes

During the study (up to 24 months; assessed at Months 1, 2, 3, 4, 5, 6, 9, 12, 15, 18, 21 and 24)

Treated bleeding episodes

Participants

ID	Title	Description
OG000	rVIII-SingleChain On-demand	The rVIII-SingleChain On-demand group consisted of all subjects in the efficacy population who received at least 1 dose rVIII-SingleChain as part of on-demand treatment during Parts 2 or 3 of the study. There were 27 subjects in the rVIII-SingleChain On-demand group.
OG001	rVIII-SingleChain Prophylaxis	The rVIII-SingleChain Prophylaxis group consisted of all subjects in the efficacy population who received at least 1 dose rVIII-SingleChain as part of routine prophylaxis treatment during Parts 2 or 3 of the study. There were 146 subjects in the rVIII-SingleChain Prophylaxis group.
OG002	rVIII-SingleChain	The Efficacy population consisted of all subjects who received at least one dose of rVIII-SingleChain as part of either routine prophylaxis treatment or on-demand treatment during Parts 2 or 3 of the study. There were 173 subjects in the Efficacy population.

Other Pre-specified

Incremental Recovery (Part 3)

Incremental recovery of an initial and repeat infusion of rVIII-SingleChain with correction for subject's predose plasma FVIII activity.

Posted

Mean

Standard Deviation

[IU/dL]/[IU/kg]

At 30 minutes after infusion

ID	Title	Description
OG000	rVIII-SingleChain PK Population (Part 3)	The rVIII-SingleChain PK population (Part 3) consisted of subjects who received rVIII-SingleChain during Part 3 of the study (initial and repeat dose) and for whom a sufficient number of analyzable PK samples were obtained to permit the evaluation of the PK profile. In Part 3, 64 subjects participated in the initial PK, of whom 30 also participated in the repeat PK.

Units	Counts
Participants	OG000

Other Pre-specified

Volume of Distribution at Steady-state (Vss) (Part 3)

Volume of distribution at steady-state (Vss) of an initial and repeat infusion of rVIII-SingleChain without correction for subject's predose plasma FVIII activity.

Posted

Mean

Standard Deviation

mL/kg

Before infusion and at up to 12 time points within 96 hours of infusion.

ID	Title	Description
OG000	rVIII-SingleChain PK Population (Part 3)	The rVIII-SingleChain PK population (Part 3) consisted of subjects who received rVIII-SingleChain during Part 3 of the study (initial and repeat dose) and for whom a sufficient number of analyzable PK samples were obtained to permit the evaluation of the PK profile. In Part 3, 64 subjects participated in the initial PK, of whom 30 also participated in the repeat PK.

Units	Counts
Participants	OG000

Other Pre-specified

Clearance (Cl) (Part 3)

Clearance (Cl) of an initial and repeat infusion of rVIII-SingleChain without correction for subject's predose plasma FVIII activity.

Posted

Mean

Standard Deviation

mL/h/kg

Before infusion and at up to 12 time points within 96 hours of infusion.

ID	Title	Description
OG000	rVIII-SingleChain PK Population (Part 3)	The rVIII-SingleChain PK population (Part 3) consisted of subjects who received rVIII-SingleChain during Part 3 of the study (initial and repeat dose) and for whom a sufficient number of analyzable PK samples were obtained to permit the evaluation of the PK profile. In Part 3, 64 subjects participated in the initial PK, of whom 30 also participated in the repeat PK.

Units	Counts
Participants	OG000

Other Pre-specified

Mean Residence Time (MRT) (Part 3)

Mean residence time (MRT) of an initial and repeat infusion of rVIII-SingleChain without correction for subject's predose plasma FVIII activity.

Posted

Mean

Standard Deviation

hours

Before infusion and at up to 12 time points within 96 hours of infusion.

ID	Title	Description
OG000	rVIII-SingleChain PK Population (Part 3)	The rVIII-SingleChain PK population (Part 3) consisted of subjects who received rVIII-SingleChain during Part 3 of the study (initial and repeat dose) and for whom a sufficient number of analyzable PK samples were obtained to permit the evaluation of the PK profile. In Part 3, 64 subjects participated in the initial PK, of whom 30 also participated in the repeat PK.

Units	Counts
Participants	OG000

Other Pre-specified

Half-life (t1/2) (Part 3)

Half-life (t1/2) of an initial and repeat infusion of rVIII-SingleChain without correction for subject's predose plasma FVIII activity.

Posted

Mean

Standard Deviation

hours

Before infusion and at up to 12 time points within 96 hours of infusion.

ID	Title	Description
OG000	rVIII-SingleChain PK Population (Part 3)	The rVIII-SingleChain PK population (Part 3) consisted of subjects who received rVIII-SingleChain during Part 3 of the study (initial and repeat dose) and for whom a sufficient number of analyzable PK samples were obtained to permit the evaluation of the PK profile. In Part 3, 64 subjects participated in the initial PK, of whom 30 also participated in the repeat PK.

Units	Counts
Participants	OG000

Other Pre-specified

Tmax (Part 3)

Tmax = time of Cmax (with correction for subject's predose plasma FVIII activity) after an initial and repeat infusion of rVIII-SingleChain.

Posted

Median

Full Range

hours

Before infusion and at up to 12 time points within 96 hours of infusion.

ID	Title	Description
OG000	rVIII-SingleChain PK Population (Part 3)	The rVIII-SingleChain PK population (Part 3) consisted of subjects who received rVIII-SingleChain during Part 3 of the study (initial and repeat dose) and for whom a sufficient number of analyzable PK samples were obtained to permit the evaluation of the PK profile. In Part 3, 64 subjects participated in the initial PK, of whom 30 also participated in the repeat PK.

Units	Counts
Participants	OG000

Other Pre-specified

Cmax (Part 3)

Cmax of an initial and repeat infusion of rVIII-SingleChain with correction for subject's predose plasma FVIII activity.

Posted

Mean

Standard Deviation

IU/dL

Before infusion and at up to 12 time points within 96 hours of infusion

ID	Title	Description
OG000	rVIII-SingleChain PK Population (Part 3)	The rVIII-SingleChain PK population (Part 3) consisted of subjects who received rVIII-SingleChain during Part 3 of the study (initial and repeat dose) and for whom a sufficient number of analyzable PK samples were obtained to permit the evaluation of the PK profile. In Part 3, 64 subjects participated in the initial PK, of whom 30 also participated in the repeat PK.

Units	Counts
Participants	OG000

Other Pre-specified

AUC0-∞ (Part 3)

AUC0-∞ (AUC from 0 extrapolated to infinity) of an initial and repeat infusion of rVIII-SingleChain without correction for subject's predose plasma FVIII activity.

Posted

Mean

Standard Deviation

IU*h/dL

Before infusion and at up to 12 time points within 96 hours of infusion

ID	Title	Description
OG000	rVIII-SingleChain PK Population (Part 3)	The rVIII-SingleChain PK population (Part 3) consisted of subjects who received rVIII-SingleChain during Part 3 of the study (initial and repeat dose) and for whom a sufficient number of analyzable PK samples were obtained to permit the evaluation of the PK profile. In Part 3, 64 subjects participated in the initial PK, of whom 30 also participated in the repeat PK.

Units	Counts
Participants	OG000

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Ankle fracture	Injury, poisoning and procedural complications	MedDRA (14.1)	Systematic Assessment	EG0001 events1 affected174 at risk
Blood uric acid increased	Investigations	MedDRA (14.1)	Systematic Assessment	EG0001 events1 affected174 at risk
Tonsillar haemorrhage	Respiratory, thoracic and mediastinal disorders	MedDRA (14.1)	Systematic Assessment	EG0001 events1 affected174 at risk
Hypersensitivity	Immune system disorders	MedDRA (14.1)	Systematic Assessment	EG0001 events1 affected174 at risk
Anaemia	Blood and lymphatic system disorders	MedDRA (14.1)	Systematic Assessment	EG0001 events1 affected174 at risk
Thrombocytopenia	Blood and lymphatic system disorders	MedDRA (14.1)	Systematic Assessment	EG0001 events1 affected174 at risk
Suicidal ideation	Psychiatric disorders	MedDRA (14.1)	Systematic Assessment	EG0001 events1 affected174 at risk
Varices oesophageal	Gastrointestinal disorders	MedDRA (14.1)	Systematic Assessment	EG0001 events1 affected174 at risk
Postoperative wound infection	Infections and infestations	MedDRA (14.1)	Systematic Assessment	EG0001 events1 affected174 at risk
Viral infection	Infections and infestations	MedDRA (14.1)	Systematic Assessment	EG0001 events1 affected174 at risk

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

ID	Term
D005169	Factor VIII
C078147	F8 protein, human
D004275	DNA, Ribosomal

ID	Term
D001779	Blood Coagulation Factors
D001798	Blood Proteins
D011506	Proteins
D000602	Amino Acids, Peptides, and Proteins
D011498	Protein Precursors
D001685	Biological Factors
D004247	DNA
D009696	Nucleic Acids
D009706	Nucleic Acids, Nucleotides, and Nucleosides

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Headache	Nervous system disorders	MedDRA (14.1)	Systematic Assessment	EG00014 events13 affected174 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA (14.1)	Systematic Assessment	EG00022 events20 affected174 at risk
Nasopharyngitis	Infections and infestations	MedDRA (14.1)	Systematic Assessment	EG00022 events18 affected174 at risk