Trial Outcomes & Findings for Pharmacokinetic, Efficacy, and Safety Study of Recombinant Factor VIII Single Chain (rVIII-SingleChain) in Children With Severe Hemophilia A (NCT NCT02093897)

NCT ID: NCT02093897

Last Updated: 2017-01-27

Results Overview

Rate of treatment success where treatment success of a bleeding episode is defined as a rating of "excellent" or "good" based on the investigator's overall clinical assessment of hemostatic efficacy (using a 4-point scale of excellent, good, moderate or poor/no response) on the on-demand and prophylaxis regimens combined. The rate of success was based on the number of treated bleeding events; there were 347 treated bleeding events in the Efficacy Population.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 84 participants
• Primary outcome timeframe: Up to 1 year
• Results posted on: 2017-01-27

Participant Flow

This multicenter, multinational study enrolled subjects at 37 participating study centers in Australia, Europe, Georgia, Lebanon, Malaysia, Philippines, Switzerland, Thailand, Turkey, Ukraine, and the United States.

Screening took place 4 to 28 days prior to first dose of study product (rVIII-SingleChain). A total of 88 subjects were screened, 4 of these did not fulfill all eligibility criteria and were therefore screening failures.

Participant milestones

Measure	rVIII-SingleChain Subjects were assigned to either an on-demand or prophylaxis regimen and received rVIII-SingleChain as an intravenous (IV) infusion. Subjects assigned to a prophylaxis regimen were treated with 15 to 50 IU/kg of rVIII-SingleChain every second day or 2 to 3 times per week, or at the investigator's discretion, based on available PK data, the FVIII treatment regimen used before enrollment and/or the subject's bleeding phenotype. The dose for on-demand treatment of a bleeding episode was based on the recommendations of the World Federation of Hemophilia (WFH), with a minimum dose of 15 IU/kg. All subjects were to be treated for a minimum of 50 EDs. For the PK evaluation, the subjects received a single IV dose of 50 IU/kg of rVIII-SingleChain on Day 1 at the start of the PK evaluation period.
Overall Study STARTED	84
Overall Study COMPLETED	65
Overall Study NOT COMPLETED	19

Reasons for withdrawal

Measure	rVIII-SingleChain Subjects were assigned to either an on-demand or prophylaxis regimen and received rVIII-SingleChain as an intravenous (IV) infusion. Subjects assigned to a prophylaxis regimen were treated with 15 to 50 IU/kg of rVIII-SingleChain every second day or 2 to 3 times per week, or at the investigator's discretion, based on available PK data, the FVIII treatment regimen used before enrollment and/or the subject's bleeding phenotype. The dose for on-demand treatment of a bleeding episode was based on the recommendations of the World Federation of Hemophilia (WFH), with a minimum dose of 15 IU/kg. All subjects were to be treated for a minimum of 50 EDs. For the PK evaluation, the subjects received a single IV dose of 50 IU/kg of rVIII-SingleChain on Day 1 at the start of the PK evaluation period.
Overall Study Physician Decision	1
Overall Study Planned age group closure - no's reached	17
Overall Study Adverse event, non-fatal	1

Baseline Characteristics

Pharmacokinetic, Efficacy, and Safety Study of Recombinant Factor VIII Single Chain (rVIII-SingleChain) in Children With Severe Hemophilia A

Baseline characteristics by cohort

Measure	rVIII-SingleChain n=84 Participants Subjects were assigned to either an on-demand or prophylaxis regimen and received rVIII-SingleChain as an IV infusion. Subjects assigned to a prophylaxis regimen were treated with 15 to 50 IU/kg of rVIII-SingleChain every second day or 2 to 3 times per week, or at the investigator's discretion, based on available PK data, the FVIII treatment regimen used before enrollment and/or the subject's bleeding phenotype. The dose for on-demand treatment of a bleeding episode was based on the recommendations of the WFH, with a minimum dose of 15 IU/kg. All subjects were to be treated for a minimum of 50 EDs. For the PK evaluation, the subjects received a single IV dose of 50 IU/kg of rVIII-SingleChain on Day 1 at the start of the PK evaluation period.
Age, Categorical <=18 years	84 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	0 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants
Age, Continuous	6.6 years STANDARD_DEVIATION 3.11 • n=5 Participants
Gender Female	0 Participants n=5 Participants
Gender Male	84 Participants n=5 Participants
Type of FVIII product used before enrollment Plasma product	33 participants n=5 Participants
Type of FVIII product used before enrollment Recombinant Product	49 participants n=5 Participants
Type of FVIII product used before enrollment Unknown	2 participants n=5 Participants
Treatment modality of FVIII therapy before enrollment Prophylaxis	60 participants n=5 Participants
Treatment modality of FVIII therapy before enrollment On-Demand	24 participants n=5 Participants

PRIMARY outcome

Timeframe: Up to 1 year

Population: Efficacy Population

Rate of treatment success where treatment success of a bleeding episode is defined as a rating of "excellent" or "good" based on the investigator's overall clinical assessment of hemostatic efficacy (using a 4-point scale of excellent, good, moderate or poor/no response) on the on-demand and prophylaxis regimens combined. The rate of success was based on the number of treated bleeding events; there were 347 treated bleeding events in the Efficacy Population.

Outcome measures

Measure	Efficacy Population n=347 Treated bleeding events The Efficacy Population consisted of all subjects who received at least 1 dose of rVIII-SingleChain as part of either a routine prophylaxis or on-demand regimen during the study. One subject was excluded from the efficacy population because of a pre-existing inhibitor to FVIII (confirmed by reexamination of a screening sample initially reported as negative due to laboratory error).	Prophylaxis Subjects receiving routine prophylaxis treatment were initially treated with 15-50 IU/kg of rVIII-SingleChain every second day or 2 to 3 times per week, or at the investigator's discretion, based upon available PK data, the FVIII treatment regimen used before enrollment and/or the subject's bleeding phenotype. The dose or dosing frequency may have been adjusted if necessary.
Treatment Success	96.3 Percentage of treated bleeding events Interval 91.3 to 98.4	—

SECONDARY outcome

Timeframe: Up to 1 year

Population: The Efficacy Population comprised all subjects who received at least 1 rVIII-SingleChain dose for prophylaxis or on-demand treatment. One subject was excluded from the efficacy population because of a pre-existing inhibitor to FVIII (confirmed by reexamination of a screening sample initially reported as negative due to laboratory error).

The annualized bleeding rate was defined as the number of bleeding episodes requiring treatment divided by the efficacy evaluation period in days, x 365.25, and is presented separately for the on-demand regimen and the prophylaxis regimens.

Outcome measures

Measure	Efficacy Population n=3 Participants The Efficacy Population consisted of all subjects who received at least 1 dose of rVIII-SingleChain as part of either a routine prophylaxis or on-demand regimen during the study. One subject was excluded from the efficacy population because of a pre-existing inhibitor to FVIII (confirmed by reexamination of a screening sample initially reported as negative due to laboratory error).	Prophylaxis n=80 Participants Subjects receiving routine prophylaxis treatment were initially treated with 15-50 IU/kg of rVIII-SingleChain every second day or 2 to 3 times per week, or at the investigator's discretion, based upon available PK data, the FVIII treatment regimen used before enrollment and/or the subject's bleeding phenotype. The dose or dosing frequency may have been adjusted if necessary.
Annualized Bleeding Rate	78.56 Treated bleeding episodes per year Interval 35.12 to 86.62	3.69 Treated bleeding episodes per year Interval 0.0 to 7.2

SECONDARY outcome

Timeframe: Up to 1 year

Population: Efficacy Population

Outcome measures

Measure	Efficacy Population n=347 Number of Treated Bleeds The Efficacy Population consisted of all subjects who received at least 1 dose of rVIII-SingleChain as part of either a routine prophylaxis or on-demand regimen during the study. One subject was excluded from the efficacy population because of a pre-existing inhibitor to FVIII (confirmed by reexamination of a screening sample initially reported as negative due to laboratory error).	Prophylaxis Subjects receiving routine prophylaxis treatment were initially treated with 15-50 IU/kg of rVIII-SingleChain every second day or 2 to 3 times per week, or at the investigator's discretion, based upon available PK data, the FVIII treatment regimen used before enrollment and/or the subject's bleeding phenotype. The dose or dosing frequency may have been adjusted if necessary.
Percentage of Bleeding Episodes Requiring 1, 2, 3, or More Than 3 Infusions of rVIII-SingleChain to Achieve Hemostasis. Requiring 1 infusion	85.9 Percentage (%) of bleeding episodes	—
Percentage of Bleeding Episodes Requiring 1, 2, 3, or More Than 3 Infusions of rVIII-SingleChain to Achieve Hemostasis. Requiring 2 infusions	9.8 Percentage (%) of bleeding episodes	—
Percentage of Bleeding Episodes Requiring 1, 2, 3, or More Than 3 Infusions of rVIII-SingleChain to Achieve Hemostasis. Requiring 3 infusions	2.3 Percentage (%) of bleeding episodes	—
Percentage of Bleeding Episodes Requiring 1, 2, 3, or More Than 3 Infusions of rVIII-SingleChain to Achieve Hemostasis. Requiring > 3 infusions	2.0 Percentage (%) of bleeding episodes	—

SECONDARY outcome

Timeframe: Up to 1 year

Population: The Efficacy Population comprised all subjects who received at least 1 rVIII-SingleChain dose for prophylaxis or on-demand treatment. One subject was excluded from the efficacy population because of a pre-existing inhibitor to FVIII (confirmed by reexamination of a screening sample initially reported as negative due to laboratory error).

Outcome measures

Measure	Efficacy Population n=3 Participants The Efficacy Population consisted of all subjects who received at least 1 dose of rVIII-SingleChain as part of either a routine prophylaxis or on-demand regimen during the study. One subject was excluded from the efficacy population because of a pre-existing inhibitor to FVIII (confirmed by reexamination of a screening sample initially reported as negative due to laboratory error).	Prophylaxis n=80 Participants Subjects receiving routine prophylaxis treatment were initially treated with 15-50 IU/kg of rVIII-SingleChain every second day or 2 to 3 times per week, or at the investigator's discretion, based upon available PK data, the FVIII treatment regimen used before enrollment and/or the subject's bleeding phenotype. The dose or dosing frequency may have been adjusted if necessary.
Consumption of rVIII-SingleChain - IU/kg Per Subject Per Month	202 IU/kg per subject per month Interval 126.0 to 231.0	378 IU/kg per subject per month Interval 153.0 to 1394.0

SECONDARY outcome

Timeframe: Up to 1 year

Population: The Efficacy Population comprised all subjects who received at least 1 rVIII-SingleChain dose for prophylaxis or on-demand treatment. One subject was excluded from the efficacy population because of a pre-existing inhibitor to FVIII (confirmed by reexamination of a screening sample initially reported as negative due to laboratory error).

Outcome measures

Measure	Efficacy Population n=3 Participants The Efficacy Population consisted of all subjects who received at least 1 dose of rVIII-SingleChain as part of either a routine prophylaxis or on-demand regimen during the study. One subject was excluded from the efficacy population because of a pre-existing inhibitor to FVIII (confirmed by reexamination of a screening sample initially reported as negative due to laboratory error).	Prophylaxis n=80 Participants Subjects receiving routine prophylaxis treatment were initially treated with 15-50 IU/kg of rVIII-SingleChain every second day or 2 to 3 times per week, or at the investigator's discretion, based upon available PK data, the FVIII treatment regimen used before enrollment and/or the subject's bleeding phenotype. The dose or dosing frequency may have been adjusted if necessary.
Consumption of rVIII-SingleChain - IU/kg Per Subject Per Year	2429 IU/kg per subject per year Interval 1508.0 to 2771.0	4541 IU/kg per subject per year Interval 1839.0 to 16727.0

SECONDARY outcome

Timeframe: Up to 1 year

Population: The Efficacy Population comprised all subjects who received at least 1 rVIII-SingleChain dose for prophylaxis or on-demand treatment. One subject was excluded from the efficacy population because of a pre-existing inhibitor to FVIII (confirmed by reexamination of a screening sample initially reported as negative due to laboratory error).

Outcome measures

Measure	Efficacy Population n=3 Participants The Efficacy Population consisted of all subjects who received at least 1 dose of rVIII-SingleChain as part of either a routine prophylaxis or on-demand regimen during the study. One subject was excluded from the efficacy population because of a pre-existing inhibitor to FVIII (confirmed by reexamination of a screening sample initially reported as negative due to laboratory error).	Prophylaxis n=80 Participants Subjects receiving routine prophylaxis treatment were initially treated with 15-50 IU/kg of rVIII-SingleChain every second day or 2 to 3 times per week, or at the investigator's discretion, based upon available PK data, the FVIII treatment regimen used before enrollment and/or the subject's bleeding phenotype. The dose or dosing frequency may have been adjusted if necessary.
Consumption of rVIII-SingleChain - IU/kg Per Bleeding Event	25.9 IU/kg per event Interval 21.0 to 78.0	37.0 IU/kg per event Interval 16.0 to 282.0

SECONDARY outcome

Timeframe: Up to 1 year

Population: Subjects assigned to the on-demand treatment regimen.

Outcome measures

Measure	Efficacy Population n=3 Participants The Efficacy Population consisted of all subjects who received at least 1 dose of rVIII-SingleChain as part of either a routine prophylaxis or on-demand regimen during the study. One subject was excluded from the efficacy population because of a pre-existing inhibitor to FVIII (confirmed by reexamination of a screening sample initially reported as negative due to laboratory error).	Prophylaxis Subjects receiving routine prophylaxis treatment were initially treated with 15-50 IU/kg of rVIII-SingleChain every second day or 2 to 3 times per week, or at the investigator's discretion, based upon available PK data, the FVIII treatment regimen used before enrollment and/or the subject's bleeding phenotype. The dose or dosing frequency may have been adjusted if necessary.
Consumption of rVIII-SingleChain (On-demand Regimen) - Number of Infusions Per Subject Per Month	7.58 number of infusion per subject per month Interval 5.1 to 7.7	—

SECONDARY outcome

Timeframe: Up to 1 year

Population: Subjects assigned to the on-demand treatment regimen.

Outcome measures

Measure	Efficacy Population n=3 Participants The Efficacy Population consisted of all subjects who received at least 1 dose of rVIII-SingleChain as part of either a routine prophylaxis or on-demand regimen during the study. One subject was excluded from the efficacy population because of a pre-existing inhibitor to FVIII (confirmed by reexamination of a screening sample initially reported as negative due to laboratory error).	Prophylaxis Subjects receiving routine prophylaxis treatment were initially treated with 15-50 IU/kg of rVIII-SingleChain every second day or 2 to 3 times per week, or at the investigator's discretion, based upon available PK data, the FVIII treatment regimen used before enrollment and/or the subject's bleeding phenotype. The dose or dosing frequency may have been adjusted if necessary.
Consumption of rVIII-SingleChain (On-demand Regimen) - Number of Infusions Per Subject Per Year	90.95 number of infusions per subject per year Interval 60.9 to 92.3	—

SECONDARY outcome

Timeframe: At 1 hour after the start of infusion

Population: PK Population

Incremental recovery expressed as (IU/dL)/(IU/kg) corrected for subject's predose plasma FVIII activity measured using the chromogenic substrate assay.

Outcome measures

Measure	Efficacy Population n=39 Participants The Efficacy Population consisted of all subjects who received at least 1 dose of rVIII-SingleChain as part of either a routine prophylaxis or on-demand regimen during the study. One subject was excluded from the efficacy population because of a pre-existing inhibitor to FVIII (confirmed by reexamination of a screening sample initially reported as negative due to laboratory error).	Prophylaxis Subjects receiving routine prophylaxis treatment were initially treated with 15-50 IU/kg of rVIII-SingleChain every second day or 2 to 3 times per week, or at the investigator's discretion, based upon available PK data, the FVIII treatment regimen used before enrollment and/or the subject's bleeding phenotype. The dose or dosing frequency may have been adjusted if necessary.
Incremental Recovery	1.63 (IU/dL)/(IU/kg) Standard Deviation 0.329	—

SECONDARY outcome

Timeframe: Immediately before dosing, and at approximately 1, 5, 10, 24, and 48 hours after dosing.

Population: PK Population

Half-life (t1/2) of rVIII-SingleChain, baseline uncorrected; plasma FVIII activity measured using the chromogenic substrate assay.

Outcome measures

Measure	Efficacy Population n=39 Participants The Efficacy Population consisted of all subjects who received at least 1 dose of rVIII-SingleChain as part of either a routine prophylaxis or on-demand regimen during the study. One subject was excluded from the efficacy population because of a pre-existing inhibitor to FVIII (confirmed by reexamination of a screening sample initially reported as negative due to laboratory error).	Prophylaxis Subjects receiving routine prophylaxis treatment were initially treated with 15-50 IU/kg of rVIII-SingleChain every second day or 2 to 3 times per week, or at the investigator's discretion, based upon available PK data, the FVIII treatment regimen used before enrollment and/or the subject's bleeding phenotype. The dose or dosing frequency may have been adjusted if necessary.
Half-life (t1/2) of rVIII-SingleChain	10.3 hour Standard Deviation 2.51	—

SECONDARY outcome

Timeframe: Immediately before dosing, and at approximately 1, 5, 10, 24, and 48 hours after dosing.

Population: PK Population

AUC to the last sample with quantifiable drug concentration (AUC0-t), baseline uncorrected; plasma FVIII activity measured using the chromogenic substrate assay.

Outcome measures

Measure	Efficacy Population n=39 Participants The Efficacy Population consisted of all subjects who received at least 1 dose of rVIII-SingleChain as part of either a routine prophylaxis or on-demand regimen during the study. One subject was excluded from the efficacy population because of a pre-existing inhibitor to FVIII (confirmed by reexamination of a screening sample initially reported as negative due to laboratory error).	Prophylaxis Subjects receiving routine prophylaxis treatment were initially treated with 15-50 IU/kg of rVIII-SingleChain every second day or 2 to 3 times per week, or at the investigator's discretion, based upon available PK data, the FVIII treatment regimen used before enrollment and/or the subject's bleeding phenotype. The dose or dosing frequency may have been adjusted if necessary.
Area Under the Concentration Curve (AUC)	1050 IU*h/dL Standard Deviation 286	—

SECONDARY outcome

Timeframe: Immediately before dosing, and at approximately 1, 5, 10, 24, and 48 hours after dosing.

Population: PK Population

Clearance (Cl) of rVIII-SingleChain, baseline uncorrected; plasma FVIII activity measured using the chromogenic substrate assay.

Outcome measures

Measure	Efficacy Population n=39 Participants The Efficacy Population consisted of all subjects who received at least 1 dose of rVIII-SingleChain as part of either a routine prophylaxis or on-demand regimen during the study. One subject was excluded from the efficacy population because of a pre-existing inhibitor to FVIII (confirmed by reexamination of a screening sample initially reported as negative due to laboratory error).	Prophylaxis Subjects receiving routine prophylaxis treatment were initially treated with 15-50 IU/kg of rVIII-SingleChain every second day or 2 to 3 times per week, or at the investigator's discretion, based upon available PK data, the FVIII treatment regimen used before enrollment and/or the subject's bleeding phenotype. The dose or dosing frequency may have been adjusted if necessary.
Clearance (Cl) of rVIII-SingleChain	4.86 mL/h/kg Standard Deviation 1.43	—

SECONDARY outcome

Timeframe: At screening, then after dosing at approximately monthly intervals for 6 months, then every 3 months until reaching 50 EDs, and at the end of study visit (up to approximately 12 months).

The number of subjects who develop inhibitors to rVIII-SingleChain, defined as a rVIII-SingleChain antibody titer of at least 0.6 Bethesda Units (BU) per mL after receiving study drug.

Outcome measures

Measure	Efficacy Population n=84 Participants The Efficacy Population consisted of all subjects who received at least 1 dose of rVIII-SingleChain as part of either a routine prophylaxis or on-demand regimen during the study. One subject was excluded from the efficacy population because of a pre-existing inhibitor to FVIII (confirmed by reexamination of a screening sample initially reported as negative due to laboratory error).	Prophylaxis Subjects receiving routine prophylaxis treatment were initially treated with 15-50 IU/kg of rVIII-SingleChain every second day or 2 to 3 times per week, or at the investigator's discretion, based upon available PK data, the FVIII treatment regimen used before enrollment and/or the subject's bleeding phenotype. The dose or dosing frequency may have been adjusted if necessary.
Number of Subjects With Inhibitor Formation to rVIII-SingleChain	0 participants	—

Adverse Events

rVIII-SingleChain

Serious events: 9 serious events

Other events: 31 other events

Deaths: 0 deaths

Serious adverse events

Measure	rVIII-SingleChain n=84 participants at risk Subjects were assigned to either an on-demand or prophylaxis regimen and received rVIII-SingleChain as an IV infusion. Subjects assigned to a prophylaxis regimen were treated with 15 to 50 IU/kg of rVIII-SingleChain every second day or 2 to 3 times per week, or at the investigator's discretion, based on available PK data, the FVIII treatment regimen used before enrollment and/or the subject's bleeding phenotype. The dose for on-demand treatment of a bleeding episode was based on the recommendations of the WFH, with a minimum dose of 15 IU/kg. All subjects were to be treated for a minimum of 50 EDs. For the PK evaluation, the subjects received a single IV dose of 50 IU/kg of rVIII-SingleChain on Day 1 at the start of the PK evaluation period.
Injury, poisoning and procedural complications Hand fracture	1.2% 1/84 • Number of events 1 • For the duration of the study, approximately 1 year, 5 months. The Safety Population comprised all subjects treated with rVIII-SingleChain. A total of 5313 CSL627 infusions were administered to 84 subjects during the study.
Injury, poisoning and procedural complications Laceration	1.2% 1/84 • Number of events 1 • For the duration of the study, approximately 1 year, 5 months. The Safety Population comprised all subjects treated with rVIII-SingleChain. A total of 5313 CSL627 infusions were administered to 84 subjects during the study.
Injury, poisoning and procedural complications Splenic rupture	1.2% 1/84 • Number of events 1 • For the duration of the study, approximately 1 year, 5 months. The Safety Population comprised all subjects treated with rVIII-SingleChain. A total of 5313 CSL627 infusions were administered to 84 subjects during the study.
Investigations Inhibiting antibodies positive	1.2% 1/84 • Number of events 1 • For the duration of the study, approximately 1 year, 5 months. The Safety Population comprised all subjects treated with rVIII-SingleChain. A total of 5313 CSL627 infusions were administered to 84 subjects during the study.
Blood and lymphatic system disorders Anaemia	1.2% 1/84 • Number of events 3 • For the duration of the study, approximately 1 year, 5 months. The Safety Population comprised all subjects treated with rVIII-SingleChain. A total of 5313 CSL627 infusions were administered to 84 subjects during the study.
General disorders Device occlusion	1.2% 1/84 • Number of events 1 • For the duration of the study, approximately 1 year, 5 months. The Safety Population comprised all subjects treated with rVIII-SingleChain. A total of 5313 CSL627 infusions were administered to 84 subjects during the study.
General disorders Systemic inflammatory response syndrome	1.2% 1/84 • Number of events 1 • For the duration of the study, approximately 1 year, 5 months. The Safety Population comprised all subjects treated with rVIII-SingleChain. A total of 5313 CSL627 infusions were administered to 84 subjects during the study.
Gastrointestinal disorders Dyspepsia	1.2% 1/84 • Number of events 1 • For the duration of the study, approximately 1 year, 5 months. The Safety Population comprised all subjects treated with rVIII-SingleChain. A total of 5313 CSL627 infusions were administered to 84 subjects during the study.
Infections and infestations Bacteraemia	1.2% 1/84 • Number of events 1 • For the duration of the study, approximately 1 year, 5 months. The Safety Population comprised all subjects treated with rVIII-SingleChain. A total of 5313 CSL627 infusions were administered to 84 subjects during the study.
Infections and infestations Pneumonia	1.2% 1/84 • Number of events 1 • For the duration of the study, approximately 1 year, 5 months. The Safety Population comprised all subjects treated with rVIII-SingleChain. A total of 5313 CSL627 infusions were administered to 84 subjects during the study.

Other adverse events

Measure	rVIII-SingleChain n=84 participants at risk Subjects were assigned to either an on-demand or prophylaxis regimen and received rVIII-SingleChain as an IV infusion. Subjects assigned to a prophylaxis regimen were treated with 15 to 50 IU/kg of rVIII-SingleChain every second day or 2 to 3 times per week, or at the investigator's discretion, based on available PK data, the FVIII treatment regimen used before enrollment and/or the subject's bleeding phenotype. The dose for on-demand treatment of a bleeding episode was based on the recommendations of the WFH, with a minimum dose of 15 IU/kg. All subjects were to be treated for a minimum of 50 EDs. For the PK evaluation, the subjects received a single IV dose of 50 IU/kg of rVIII-SingleChain on Day 1 at the start of the PK evaluation period.
Injury, poisoning and procedural complications Head injury	6.0% 5/84 • Number of events 6 • For the duration of the study, approximately 1 year, 5 months. The Safety Population comprised all subjects treated with rVIII-SingleChain. A total of 5313 CSL627 infusions were administered to 84 subjects during the study.
Respiratory, thoracic and mediastinal disorders Cough	8.3% 7/84 • Number of events 10 • For the duration of the study, approximately 1 year, 5 months. The Safety Population comprised all subjects treated with rVIII-SingleChain. A total of 5313 CSL627 infusions were administered to 84 subjects during the study.
Nervous system disorders Headache	8.3% 7/84 • Number of events 9 • For the duration of the study, approximately 1 year, 5 months. The Safety Population comprised all subjects treated with rVIII-SingleChain. A total of 5313 CSL627 infusions were administered to 84 subjects during the study.
General disorders Pyrexia	6.0% 5/84 • Number of events 5 • For the duration of the study, approximately 1 year, 5 months. The Safety Population comprised all subjects treated with rVIII-SingleChain. A total of 5313 CSL627 infusions were administered to 84 subjects during the study.
Musculoskeletal and connective tissue disorders Arthralgia	9.5% 8/84 • Number of events 8 • For the duration of the study, approximately 1 year, 5 months. The Safety Population comprised all subjects treated with rVIII-SingleChain. A total of 5313 CSL627 infusions were administered to 84 subjects during the study.
Infections and infestations Nasopharyngitis	16.7% 14/84 • Number of events 15 • For the duration of the study, approximately 1 year, 5 months. The Safety Population comprised all subjects treated with rVIII-SingleChain. A total of 5313 CSL627 infusions were administered to 84 subjects during the study.

Additional Information

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