Study to Evaluate the Safety, Efficacy, and Pharmacokinetics of Recombinant Coagulation Factor VIII Fc Fusion Protein (rFVIIIFc) in Previously Treated Pediatric Subjects With Hemophilia A

An inhibitor test result ≥0.6 Bethesda units (BU)/mL, confirmed on 2 separate samples drawn 2 to 4 weeks apart, was considered positive. Both tests were to be performed by the central laboratory using the Nijmegen-modified Bethesda Assay. Incidences were summarized for any positive inhibitor for participants with ≥50 EDs to rFVIIIFc. In addition, the incidence for all participants, regardless of their EDs to rFVIIIFc, was also summarized. An exact 95% CI for the proportion of participants with a confirmed inhibitor was calculated using the Clopper-Pearson exact method for a binomial proportion.

Time frame: Up to Week 26 +/- 7 days, or up to 50 exposure days (EDs) if reached prior to Week 26

Population: Safety Analysis Set: participants who received at least 1 dose of prestudy FVIII, or at least 1 dose of rFVIIIFc; n=number of participants with given number of exposure days who had a valid inhibitor test.

Annualized bleeding rate = (number of bleeding episodes during the efficacy period / total number of days during the efficacy period)\*365.25. The efficacy period begins with the first prophylactic dose of rFVIIIFc and ends with the last dose (for prophylaxis or a bleed). Surgery/rehabilitation periods and PK evaluation periods are not included in the efficacy period. A bleeding episode started from the first sign of a bleed and ended no more than 72 hours after the last treatment for the bleed, within which any symptoms of bleeding at the same location or injections less than or equal to 72 hours apart were considered the same bleeding episode. Any injection to treat the bleeding episode taken more than 72 hours after the preceding one was considered the first injection to treat a new bleeding episode at the same location. Any bleeding at a different location was considered a separate bleeding episode, regardless of time from last injection.

Time frame: Up to Week 26 +/- 7 days (efficacy period as defined in description)

Population: Full Analysis Set: participants who received at least 1 dose of rFVIIIFc; based on the number of participants whose efficacy period was of at least 1 day in duration.

Annualized bleeding rate for spontaneous joint bleed=(number of bleeding episodes meeting those criteria during the efficacy period/total number of days during the efficacy period)\*365.25. The efficacy period begins with the first prophylactic dose of rFVIIIFc and ends with the last dose (for prophylaxis or a bleed). Surgery/rehabilitation periods and PK evaluation periods are not included in the efficacy period. A bleeding episode started from the first sign of a bleed and ended no more than 72 hours after the last treatment for the bleed, within which any symptoms of bleeding at the same location or injections less than or equal to 72 hours apart were considered the same bleeding episode. Any injection to treat the bleeding episode taken more than 72 hours after the preceding one was considered the first injection to treat a new bleeding episode at the same location. Any bleeding at a different location was considered a separate bleeding episode, regardless of time from last inject

Time frame: Up to Week 26 +/- 7 days (efficacy period as defined in description)

Population: Full Analysis Set: participants who received at least 1 dose of rFVIIIFc; based on the number of participants whose efficacy period is of at least 1 day in duration.

Consumption is calculated for the efficacy period. The efficacy period begins with the first prophylactic dose of rFVIIIFc and ends with the last dose (for prophylaxis or a bleed). Surgery/rehabilitation periods and PK evaluation periods are not included in the efficacy period. Annualized consumption = (total IU/kg of study treatment received during the efficacy period / total number of days during the efficacy period)\*365.25. Consumption was calculated overall for all participants and for the last 3 months (91 days) on study, counted backwards from the end of the efficacy period, for participants with at least 24 weeks on study.

Time frame: Up to Week 26 +/- 7 days (efficacy period as defined in description)

Population: Full Analysis Set: participants who received at least 1 dose of rFVIIIFc. 'Overall' n=participants in the Full Analysis Set with evaluable data in the efficacy period; 'Last 3 Months on Study' n=participants in the Full Analysis Set with evaluable data and ≥ 24 weeks on study.

Dose normalized area under the FVIII activity-time curve to infinity for participants in the PK subgroup. The 95% confidence interval on the geometric mean is based on the t-statistic back-transformed from the log scale.

Time frame: Baseline (28 ±7 days prior to Day 1) Prestudy FVIII Dosing: predose; 30 ±5 min, 3 hours ±30 min, 24 ±3 hours, 48 ±4 hours post-dose. Day 1 (rFVIIIFc Dosing): predose; 30 ±5 min, 3 hours ±30 min, 24 ±3 hours, 48 ±4 hours, 72 ±7 hours post-dose

Population: PK Analysis Set: All participants in the PK subgroup with adequate PK data, defined as complete and evaluable PK samples through 72 hours after rFVIIIFc dosing. Complete means the availability of the 72-hour sample and at least enough other samples to allow for all the PK parameters to be estimated.

Dose normalized area under the FVIII activity-time curve to infinity for participants in the PK subgroup. The 95% confidence interval on the geometric mean is based on the t-statistic back-transformed from the log scale.

Time frame: Baseline (28 ±7 days prior to Day 1) Prestudy FVIII Dosing: predose; 30 ±5 min, 3 hours ±30 min, 24 ±3 hours, 48 ±4 hours post-dose. Day 1 (rFVIIIFc Dosing): predose; 30 ±5 min, 3 hours ±30 min, 24 ±3 hours, 48 ±4 hours, 72 ±7 hours post-dose

Population: PK Analysis Set: All participants in the PK subgroup with adequate PK data, defined as complete and evaluable PK samples through 72 hours after rFVIIIFc dosing. Complete means the availability of the 72-hour sample and at least enough other samples to allow for all the PK parameters to be estimated.

Dose-normalized area under the FVIII activity-time curve to the last measurable timepoint for participants in the PK subgroup. The 95% confidence interval on the geometric mean is based on the t-statistic back-transformed from the log scale.

Time frame: Baseline (28 ±7 days prior to Day 1) Prestudy FVIII Dosing: predose; 30 ±5 min, 3 hours ±30 min, 24 ±3 hours, 48 ±4 hours post-dose. Day 1 (rFVIIIFc Dosing): predose; 30 ±5 min, 3 hours ±30 min, 24 ±3 hours, 48 ±4 hours, 72 ±7 hours post-dose

Population: PK Analysis Set: All participants in the PK subgroup with adequate PK data, defined as complete and evaluable PK samples through 72 hours after rFVIIIFc dosing. Complete means the availability of the 72-hour sample and at least enough other samples to allow for all the PK parameters to be estimated.

Dose-normalized area under the FVIII activity-time curve to the last measurable timepoint for participants in the PK subgroup. The 95% confidence interval on the geometric mean is based on the t-statistic back-transformed from the log scale.

Time frame: Baseline (28 ±7 days prior to Day 1) Prestudy FVIII Dosing: predose; 30 ±5 min, 3 hours ±30 min, 24 ±3 hours, 48 ±4 hours post-dose. Day 1 (rFVIIIFc Dosing): predose; 30 ±5 min, 3 hours ±30 min, 24 ±3 hours, 48 ±4 hours, 72 ±7 hours post-dose

Population: PK Analysis Set: All participants in the PK subgroup with adequate PK data, defined as complete and evaluable PK samples through 72 hours after rFVIIIFc dosing. Complete means the availability of the 72-hour sample and at least enough other samples to allow for all the PK parameters to be estimated.

Rate at which the body removes the drug, measured as the volume of the plasma cleared of drug per unit time per unit weight for participants in the PK subgroup. The 95% confidence interval on the geometric mean is based on the t-statistic back-transformed from the log scale.

Time frame: Baseline (28 ±7 days prior to Day 1) Prestudy FVIII Dosing: predose; 30 ±5 min, 3 hours ±30 min, 24 ±3 hours, 48 ±4 hours post-dose. Day 1 (rFVIIIFc Dosing): predose; 30 ±5 min, 3 hours ±30 min, 24 ±3 hours, 48 ±4 hours, 72 ±7 hours post-dose

Population: PK Analysis Set: All participants in the PK subgroup with adequate PK data, defined as complete and evaluable PK samples through 72 hours after rFVIIIFc dosing. Complete means the availability of the 72-hour sample and at least enough other samples to allow for all the PK parameters to be estimated.

Rate at which the body removes the drug, measured as the volume of the plasma cleared of drug per unit time per unit weight for participants in the PK subgroup. The 95% confidence interval on the geometric mean is based on the t-statistic back-transformed from the log scale.

Time frame: Baseline (28 ±7 days prior to Day 1) Prestudy FVIII Dosing: predose; 30 ±5 min, 3 hours ±30 min, 24 ±3 hours, 48 ±4 hours post-dose. Day 1 (rFVIIIFc Dosing): predose; 30 ±5 min, 3 hours ±30 min, 24 ±3 hours, 48 ±4 hours, 72 ±7 hours post-dose

Population: PK Analysis Set: All participants in the PK subgroup with adequate PK data, defined as complete and evaluable PK samples through 72 hours after rFVIIIFc dosing. Complete means the availability of the 72-hour sample and at least enough other samples to allow for all the PK parameters to be estimated.

Dose normalized area under the FVIII activity-time curve for participants in the PK subgroup. The 95% confidence interval on the geometric mean is based on the t-statistic back-transformed from the log scale.

Time frame: Baseline (28 ±7 days prior to Day 1) Prestudy FVIII Dosing: predose; 30 ±5 min, 3 hours ±30 min, 24 ±3 hours, 48 ±4 hours post-dose. Day 1 (rFVIIIFc Dosing): predose; 30 ±5 min, 3 hours ±30 min, 24 ±3 hours, 48 ±4 hours, 72 ±7 hours post-dose

Population: PK Analysis Set: All participants in the PK subgroup with adequate PK data, defined as complete and evaluable PK samples through 72 hours after rFVIIIFc dosing. Complete means the availability of the 72-hour sample and at least enough other samples to allow for all the PK parameters to be estimated.

Dose normalized area under the FVIII activity-time curve for participants in the PK subgroup. The 95% confidence interval on the geometric mean is based on the t-statistic back-transformed from the log scale.

Time frame: Baseline (28 ±7 days prior to Day 1) Prestudy FVIII Dosing: predose; 30 ±5 min, 3 hours ±30 min, 24 ±3 hours, 48 ±4 hours post-dose. Day 1 (rFVIIIFc Dosing): predose; 30 ±5 min, 3 hours ±30 min, 24 ±3 hours, 48 ±4 hours, 72 ±7 hours post-dose

Population: PK Analysis Set: All participants in the PK subgroup with adequate PK data, defined as complete and evaluable PK samples through 72 hours after rFVIIIFc dosing. Complete means the availability of the 72-hour sample and at least enough other samples to allow for all the PK parameters to be estimated.

Time required for the activity of the drug to reach half of its original value for participants in the PK subgroup. The 95% confidence interval on the geometric mean is based on the t-statistic back-transformed from the log scale.

Time frame: Baseline (28 ±7 days prior to Day 1) Prestudy FVIII Dosing: predose; 30 ±5 min, 3 hours ±30 min, 24 ±3 hours, 48 ±4 hours post-dose. Day 1 (rFVIIIFc Dosing): predose; 30 ±5 min, 3 hours ±30 min, 24 ±3 hours, 48 ±4 hours, 72 ±7 hours post-dose

Population: PK Analysis Set: All participants in the PK subgroup with adequate PK data, defined as complete and evaluable PK samples through 72 hours after rFVIIIFc dosing. Complete means the availability of the 72-hour sample and at least enough other samples to allow for all the PK parameters to be estimated.

Time required for the activity of the drug to reach half of its original value for participants in the PK subgroup. The 95% confidence interval on the geometric mean is based on the t-statistic back-transformed from the log scale.

Time frame: Baseline (28 ±7 days prior to Day 1) Prestudy FVIII Dosing: predose; 30 ±5 min, 3 hours ±30 min, 24 ±3 hours, 48 ±4 hours post-dose. Day 1 (rFVIIIFc Dosing): predose; 30 ±5 min, 3 hours ±30 min, 24 ±3 hours, 48 ±4 hours, 72 ±7 hours post-dose

Population: PK Analysis Set: All participants in the PK subgroup with adequate PK data, defined as complete and evaluable PK samples through 72 hours after rFVIIIFc dosing. Complete means the availability of the 72-hour sample and at least enough other samples to allow for all the PK parameters to be estimated.

The rise in FVIII activity in IU/dL per unit dose administered in IU/kg for participants in the PK subgroup. The 95% confidence interval on the geometric mean is based on the t-statistic back-transformed from the log scale.

Time frame: Baseline (28 ±7 days prior to Day 1) Prestudy FVIII Dosing: predose; 30 ±5 min, 3 hours ±30 min, 24 ±3 hours, 48 ±4 hours post-dose. Day 1 (rFVIIIFc Dosing): predose; 30 ±5 min, 3 hours ±30 min, 24 ±3 hours, 48 ±4 hours, 72 ±7 hours post-dose

Population: PK Analysis Set: All participants in the PK subgroup with adequate PK data, defined as complete and evaluable PK samples through 72 hours after rFVIIIFc dosing. Complete means the availability of the 72-hour sample and at least enough other samples to allow for all the PK parameters to be estimated.

The rise in FVIII activity in IU/dL per unit dose administered in IU/kg for participants in the PK subgroup. The 95% confidence interval on the geometric mean is based on the t-statistic back-transformed from the log scale.

Time frame: Baseline (28 ±7 days prior to Day 1) Prestudy FVIII Dosing: predose; 30 ±5 min, 3 hours ±30 min, 24 ±3 hours, 48 ±4 hours post-dose. Day 1 (rFVIIIFc Dosing): predose; 30 ±5 min, 3 hours ±30 min, 24 ±3 hours, 48 ±4 hours, 72 ±7 hours post-dose

Population: PK Analysis Set: All participants in the PK subgroup with adequate PK data, defined as complete and evaluable PK samples through 72 hours after rFVIIIFc dosing. Complete means the availability of the 72-hour sample and at least enough other samples to allow for all the PK parameters to be estimated.

First order rate constant associated with the terminal portion of the curve (lambda z) for participants in the PK subgroup. The 95% confidence interval on the geometric mean is based on the t-statistic back-transformed from the log scale.

Time frame: Baseline (28 ±7 days prior to Day 1) Prestudy FVIII Dosing: predose; 30 ±5 min, 3 hours ±30 min, 24 ±3 hours, 48 ±4 hours post-dose. Day 1 (rFVIIIFc Dosing): predose; 30 ±5 min, 3 hours ±30 min, 24 ±3 hours, 48 ±4 hours, 72 ±7 hours post-dose

Population: PK Analysis Set: All participants in the PK subgroup with adequate PK data, defined as complete and evaluable PK samples through 72 hours after rFVIIIFc dosing. Complete means the availability of the 72-hour sample and at least enough other samples to allow for all the PK parameters to be estimated.

First order rate constant associated with the terminal portion of the curve (lambda z) for participants in the PK subgroup. The 95% confidence interval on the geometric mean is based on the t-statistic back-transformed from the log scale.

Time frame: Baseline (28 ±7 days prior to Day 1) Prestudy FVIII Dosing: predose; 30 ±5 min, 3 hours ±30 min, 24 ±3 hours, 48 ±4 hours post-dose. Day 1 (rFVIIIFc Dosing): predose; 30 ±5 min, 3 hours ±30 min, 24 ±3 hours, 48 ±4 hours, 72 ±7 hours post-dose

Population: PK Analysis Set: All participants in the PK subgroup with adequate PK data, defined as complete and evaluable PK samples through 72 hours after rFVIIIFc dosing. Complete means the availability of the 72-hour sample and at least enough other samples to allow for all the PK parameters to be estimated.

Maximum plasma activity during a dosing interval for participants in the PK subgroup. The values for Cmax were adjusted to the nominal dose of 50 IU/kg. The 95% confidence interval on the geometric mean is based on the t-statistic back-transformed from the log scale.

Time frame: Baseline (28 ±7 days prior to Day 1) Prestudy FVIII Dosing: predose; 30 ±5 min, 3 hours ±30 min, 24 ±3 hours, 48 ±4 hours post-dose. Day 1 (rFVIIIFc Dosing): predose; 30 ±5 min, 3 hours ±30 min, 24 ±3 hours, 48 ±4 hours, 72 ±7 hours post-dose

Population: PK Analysis Set: All participants in the PK subgroup with adequate PK data, defined as complete and evaluable PK samples through 72 hours after rFVIIIFc dosing. Complete means the availability of the 72-hour sample and at least enough other samples to allow for all the PK parameters to be estimated.

Maximum plasma activity during a dosing interval for participants in the PK subgroup. The values for Cmax were adjusted to the nominal dose of 50 IU/kg. The 95% confidence interval on the geometric mean is based on the t-statistic back-transformed from the log scale.

Time frame: Baseline (28 ±7 days prior to Day 1) Prestudy FVIII Dosing: predose; 30 ±5 min, 3 hours ±30 min, 24 ±3 hours, 48 ±4 hours post-dose. Day 1 (rFVIIIFc Dosing): predose; 30 ±5 min, 3 hours ±30 min, 24 ±3 hours, 48 ±4 hours, 72 ±7 hours post-dose

Population: PK Analysis Set: All participants in the PK subgroup with adequate PK data, defined as complete and evaluable PK samples through 72 hours after rFVIIIFc dosing. Complete means the availability of the 72-hour sample and at least enough other samples to allow for all the PK parameters to be estimated.

The average time that a drug molecule is present in the systemic circulation for participants in the PK subgroup. The 95% confidence interval on the geometric mean is based on the t-statistic back-transformed from the log scale.

Time frame: Baseline (28 ±7 days prior to Day 1) Prestudy FVIII Dosing: predose; 30 ±5 min, 3 hours ±30 min, 24 ±3 hours, 48 ±4 hours post-dose. Day 1 (rFVIIIFc Dosing): predose; 30 ±5 min, 3 hours ±30 min, 24 ±3 hours, 48 ±4 hours, 72 ±7 hours post-dose

Population: PK Analysis Set: All participants in the PK subgroup with adequate PK data, defined as complete and evaluable PK samples through 72 hours after rFVIIIFc dosing. Complete means the availability of the 72-hour sample and at least enough other samples to allow for all the PK parameters to be estimated.

The average time that a drug molecule is present in the systemic circulation for participants in the PK subgroup. The 95% confidence interval on the geometric mean is based on the t-statistic back-transformed from the log scale.

Time frame: Baseline (28 ±7 days prior to Day 1) Prestudy FVIII Dosing: predose; 30 ±5 min, 3 hours ±30 min, 24 ±3 hours, 48 ±4 hours post-dose. Day 1 (rFVIIIFc Dosing): predose; 30 ±5 min, 3 hours ±30 min, 24 ±3 hours, 48 ±4 hours, 72 ±7 hours post-dose

Population: PK Analysis Set: All participants in the PK subgroup with adequate PK data, defined as complete and evaluable PK samples through 72 hours after rFVIIIFc dosing. Complete means the availability of the 72-hour sample and at least enough other samples to allow for all the PK parameters to be estimated.

The number of days from the last prophylaxis injection to the onset of a new spontaneous bleeding episode, analyzed across all evaluable bleeding episodes per participant and per episode, based on the efficacy period. Evaluable bleeding episodes are those for which both a date and time are available for both the onset of the bleeding episode and the previous prophylactic injection. The efficacy period begins with the first prophylactic dose of rFVIIIFc and ends with the last dose (for prophylaxis or a bleed). Surgery/rehabilitation periods and PK evaluation periods are not included in the efficacy period. For 'Per participant' values, the number of days from the last prophylactic injection to a spontaneous bleeding episode is averaged across all evaluable spontaneous bleeding episodes per participant.

Time frame: Up to Week 26 +/- 7 days (efficacy period as defined in description)

Population: Full Analysis Set: participants who received at least 1 dose of rFVIIIFc; number of participants and number of episodes were determined for participants with at least 1 evaluable spontaneous bleeding episode.

The number of injections required to resolve a bleeding episode per participant and per episode, based on the efficacy period. The efficacy period begins with the first prophylactic dose of rFVIIIFc and ends with the last dose (for prophylaxis or a bleed). Surgery/rehabilitation periods and PK evaluation periods are not included in the efficacy period. All injections given from the initial sign of a bleed, until the last date/time within the bleed window are counted. The resolution of a bleed is defined as no sign of bleeding following injection for the bleed. For 'Per participant' values, the number of injections required to resolve each bleed is averaged across all bleeding episodes per participant.

Time frame: Up to Week 26 +/- 7 days (efficacy period as defined in description)

Population: Full Analysis Set: participants who received at least 1 dose of rFVIIIFc; number of participants and number of episodes were determined for participants with at least 1 evaluable bleeding episode.

Participant's assessment (provided by the caregiver) of the response to the first rFVIIIFc injection for each bleeding episode. Percentages were based on the number of first injections for which a response was provided, using the following 4-point scale: excellent=abrupt pain relief and/or improvement in signs of bleeding within approximately 8 hours after the initial injection; good=definite pain relief and/or improvement in signs of bleeding within approximately 8 hours after a single injection, but possibly requiring more than one injection after 24 to 48 hours for complete resolution; moderate=probable or slight beneficial effect within approximately 8 hours after the initial injection and requiring more than one injection; no response=no improvement, or condition worsened, within approximately 8 hours after the initial injection.

Time frame: Up to Week 26 +/- 7 days

Population: Full Analysis Set: participants who received at least 1 dose of rFVIIIFc and had a bleeding episode; participants with a non-evaluable bleed are counted in the number of participants analyzed, but not the percentages.

Percentage of AUCinf extrapolated from the last data point to infinity for participants in the PK subgroup. The 95% confidence interval on the geometric mean is based on the t-statistic back-transformed from the log scale.

Time frame: Baseline (28 ±7 days prior to Day 1) Prestudy FVIII Dosing: predose; 30 ±5 min, 3 hours ±30 min, 24 ±3 hours, 48 ±4 hours post-dose. Day 1 (rFVIIIFc Dosing): predose; 30 ±5 min, 3 hours ±30 min, 24 ±3 hours, 48 ±4 hours, 72 ±7 hours post-dose

Population: PK Analysis Set: All participants in the PK subgroup with adequate PK data, defined as complete and evaluable PK samples through 72 hours after rFVIIIFc dosing. Complete means the availability of the 72-hour sample and at least enough other samples to allow for all the PK parameters to be estimated.

Percentage of AUCinf extrapolated from the last data point to infinity for participants in the PK subgroup. The 95% confidence interval on the geometric mean is based on the t-statistic back-transformed from the log scale.

Time frame: Baseline (28 ±7 days prior to Day 1) Prestudy FVIII Dosing: predose; 30 ±5 min, 3 hours ±30 min, 24 ±3 hours, 48 ±4 hours post-dose. Day 1 (rFVIIIFc Dosing): predose; 30 ±5 min, 3 hours ±30 min, 24 ±3 hours, 48 ±4 hours, 72 ±7 hours post-dose

Population: PK Analysis Set: All participants in the PK subgroup with adequate PK data, defined as complete and evaluable PK samples through 72 hours after rFVIIIFc dosing. Complete means the availability of the 72-hour sample and at least enough other samples to allow for all the PK parameters to be estimated.

Investigators assessed each participant's response to his rFVIIIFc regimen using a 4-point scale: excellent=bleeding episodes responded to ≤ the usual number of injections or ≤ the usual dose of rFVIIIFc or the rate of breakthrough bleeding during prophylaxis was ≤ that usually observed; effective=most bleeding episodes responded to the same number of injections and dose, but some required more injections or higher doses, or there was a minor increase in the rate of breakthrough bleeding; partially effective=bleeding episodes most often required more injections and/or higher doses than expected, or adequate breakthrough bleeding prevention during prophylaxis required more frequent injections and/or higher doses; ineffective=routine failure to control hemostasis, or hemostatic control required additional agents. Percentages are based on the total number of responses; multiple responses per participant are counted.

Time frame: Up to Week 26 +/- 7 days

Population: Full Analysis Set: participants who received at least 1 dose of rFVIIIFc; based on the number of responses.

Time at which maximum activity (Cmax) is observed for participants in the PK subgroup. The 95% confidence interval on the geometric mean is based on the t-statistic back-transformed from the log scale.

Time frame: Baseline (28 ±7 days prior to Day 1) Prestudy FVIII Dosing: predose; 30 ±5 min, 3 hours ±30 min, 24 ±3 hours, 48 ±4 hours post-dose. Day 1 (rFVIIIFc Dosing): predose; 30 ±5 min, 3 hours ±30 min, 24 ±3 hours, 48 ±4 hours, 72 ±7 hours post-dose

Population: PK Analysis Set: All participants in the PK subgroup with adequate PK data, defined as complete and evaluable PK samples through 72 hours after rFVIIIFc dosing. Complete means the availability of the 72-hour sample and at least enough other samples to allow for all the PK parameters to be estimated.

Time at which maximum activity (Cmax) is observed for participants in the PK subgroup. The 95% confidence interval on the geometric mean is based on the t-statistic back-transformed from the log scale.

Time frame: Baseline (28 ±7 days prior to Day 1) Prestudy FVIII Dosing: predose; 30 ±5 min, 3 hours ±30 min, 24 ±3 hours, 48 ±4 hours post-dose. Day 1 (rFVIIIFc Dosing): predose; 30 ±5 min, 3 hours ±30 min, 24 ±3 hours, 48 ±4 hours, 72 ±7 hours post-dose

Population: PK Analysis Set: All participants in the PK subgroup with adequate PK data, defined as complete and evaluable PK samples through 72 hours after rFVIIIFc dosing. Complete means the availability of the 72-hour sample and at least enough other samples to allow for all the PK parameters to be estimated.

The total dose required to resolve a bleeding episode per participant and per episode, based on the efficacy period. The efficacy period begins with the first prophylactic dose of rFVIIIFc and ends with the last dose (for prophylaxis or a bleed). Surgery/rehabilitation periods and PK evaluation periods are not included in the efficacy period. For 'Per bleeding episode' values, for each bleeding episode, the total dose is the sum of the doses (IU/kg) administered across all injections given to treat that bleeding episode. For 'Per participant' values, the total dose (IU/kg) used to resolve each bleed is averaged across all bleeding episodes per participant.

Time frame: Up to Week 26 +/- 7 days (efficacy period as defined in description)

Population: Full Analysis Set: participants who received at least 1 dose of rFVIIIFc; number of participants and number of episodes were determined for participants who had complete information on the dose administered to treat a bleeding episode.

Volume of distribution at steady state for participants in the PK subgroup. The 95% confidence interval on the geometric mean is based on the t-statistic back-transformed from the log scale.

Time frame: Baseline (28 ±7 days prior to Day 1) Prestudy FVIII Dosing: predose; 30 ±5 min, 3 hours ±30 min, 24 ±3 hours, 48 ±4 hours post-dose. Day 1 (rFVIIIFc Dosing): predose; 30 ±5 min, 3 hours ±30 min, 24 ±3 hours, 48 ±4 hours, 72 ±7 hours post-dose

Population: PK Analysis Set: All participants in the PK subgroup with adequate PK data, defined as complete and evaluable PK samples through 72 hours after rFVIIIFc dosing. Complete means the availability of the 72-hour sample and at least enough other samples to allow for all the PK parameters to be estimated.

Volume of distribution at steady state for participants in the PK subgroup. The 95% confidence interval on the geometric mean is based on the t-statistic back-transformed from the log scale.

Time frame: Baseline (28 ±7 days prior to Day 1) Prestudy FVIII Dosing: predose; 30 ±5 min, 3 hours ±30 min, 24 ±3 hours, 48 ±4 hours post-dose. Day 1 (rFVIIIFc Dosing): predose; 30 ±5 min, 3 hours ±30 min, 24 ±3 hours, 48 ±4 hours, 72 ±7 hours post-dose

Population: PK Analysis Set: All participants in the PK subgroup with adequate PK data, defined as complete and evaluable PK samples through 72 hours after rFVIIIFc dosing. Complete means the availability of the 72-hour sample and at least enough other samples to allow for all the PK parameters to be estimated.

Volume of distribution estimated from the terminal phase for participants in the PK subgroup. The 95% confidence interval on the geometric mean is based on the t-statistic back-transformed from the log scale.

Time frame: Baseline (28 ±7 days prior to Day 1) Prestudy FVIII Dosing: predose; 30 ±5 min, 3 hours ±30 min, 24 ±3 hours, 48 ±4 hours post-dose. Day 1 (rFVIIIFc Dosing): predose; 30 ±5 min, 3 hours ±30 min, 24 ±3 hours, 48 ±4 hours, 72 ±7 hours post-dose

Population: PK Analysis Set: All participants in the PK subgroup with adequate PK data, defined as complete and evaluable PK samples through 72 hours after rFVIIIFc dosing. Complete means the availability of the 72-hour sample and at least enough other samples to allow for all the PK parameters to be estimated.

Volume of distribution estimated from the terminal phase for participants in the PK subgroup. The 95% confidence interval on the geometric mean is based on the t-statistic back-transformed from the log scale.

Time frame: Baseline (28 ±7 days prior to Day 1) Prestudy FVIII Dosing: predose; 30 ±5 min, 3 hours ±30 min, 24 ±3 hours, 48 ±4 hours post-dose. Day 1 (rFVIIIFc Dosing): predose; 30 ±5 min, 3 hours ±30 min, 24 ±3 hours, 48 ±4 hours, 72 ±7 hours post-dose

Population: PK Analysis Set: All participants in the PK subgroup with adequate PK data, defined as complete and evaluable PK samples through 72 hours after rFVIIIFc dosing. Complete means the availability of the 72-hour sample and at least enough other samples to allow for all the PK parameters to be estimated.