Study Evaluating Prophylaxis Treatment & Characterizing Efficacy, Safety, & PK Of B-Domain Deleted Recombinant FVIII

ABR for each participant was calculated as the number of bleeds requiring administration of moroctocog alfa (AF-CC) divided by the total therapy duration (in days), then multiplied by 365.25 (days in a year).

Time frame: Day 1 up to Month 6 (OD Cohort, OD Therapy, Period 1); Month 7 up to Month 18 (OD Cohort, RP 25 IU/kg, Period 2)

Population: Intent-to-treat (ITT) analysis population included all participants for whom a legal acceptable representative had signed the informed consent/assent form. Here, Overall Number of Participants Analyzed signifies participants who were evaluable for this outcome measure.

Area under FVIII activity-time profile from time zero extrapolated to infinite time. AUCinf is reported in units: international units\*hour per milliliter (IU\*hour/mL).

Time frame: 0.5, 8, 24, 28 and 32 hours post dose on Day 1

Population: Analysis population included all participants for whom a legal acceptable representative had signed the informed consent/assent form, were in a non bleeding state, participated in a single PK assessment at the start of the study and for whom an adequate PK profile had been obtained.

Area under the FVIII activity -versus-time curve from time zero to the time of the last quantifiable concentration.

Time frame: 0.5, 8, 24, 28 and 32 hours post dose on Day 1

Population: Analysis population included all participants for whom a legal acceptable representative had signed the informed consent/assent form, were in a non bleeding state, participated in a single PK assessment at the start of the study and for whom an adequate PK profile had been obtained.

Clearance is a measure of the volume of plasma from which FVIII activity is removed per unit time. It was reported in units milliliter per hour per kilogram (mL/hr/kg).

Time frame: 0.5, 8, 24, 28 and 32 hours post dose on Day 1

Population: Analysis population included all participants for whom a legal acceptable representative had signed the informed consent/assent form, were in a non bleeding state, participated in a single PK assessment at the start of the study and for whom an adequate PK profile had been obtained.

Incremental recovery was the increase in circulating FVIII activity for every international unit (IU) of moroctocog alfa (AF-CC) administered per kilogram of body weight of participant. It was measured in international units per deciliter per international units per kilogram (\[IU/dL\]/\[IU/kg\]).

Time frame: Day 1, Month 6

Population: Analysis population included all participants for whom legal acceptable representative had signed informed consent/assent form, were in non-bleeding state, participated in single PK assessment at start of study and for whom an adequate PK profile had been obtained. Number analyzed signifies participants evaluable at specified time points.

Maximum concentration of FVIII activity was measured in international units per milliliter (IU/mL).

Time frame: 0.5, 8, 24, 28 and 32 hours post dose on Day 1

Population: Analysis population included all participants for whom a legal acceptable representative had signed the informed consent/assent form, were in a non bleeding state, participated in a single PK assessment at the start of the study and for whom an adequate PK profile had been obtained.

ABR for each participant was calculated as the number of bleeds requiring administration of moroctocog alfa (AF-CC) divided by the total therapy duration (in days), then multiplied by 365.25 (days in a year).

Time frame: Day 1 up to Month 24 (RP Cohort, Period 1 and Period 2)

Population: ITT analysis population included all participants for whom a legal acceptable representative had signed the informed consent/assent form. Here, Overall Number of Participants Analyzed signifies participants who were evaluable for this outcome measure.

In this outcome measure, the mean of total number of moroctocog alfa (AF-CC) on-demand infusions administered to treat each bleeding episode was reported, regardless of participant cohort or period during which it occurred.

Time frame: Day 1 up to Month 24

Population: ITT analysis population included all participants for whom a legal acceptable representative had signed the informed consent/assent form. Here, Overall Number of Participants Analyzed signifies participants who were evaluable for this outcome measure.

In this outcome measure mean of total number of infusions of moroctocog alfa (AF-CC) received by participant is reported. For reporting arm: Moroctocog alfa (AF-CC),OD and RP Cohort: RP Therapy 25 IU/kg, cumulative data for routine prophylaxis cohort (Day 1 up to Month 24, Period 1 and Period 2) and on demand cohort (Month 7 up to Month 18, Period 2) is reported.

Time frame: Day 1 up to Month 24 (RP Cohort, RP 25 IU/kg and 45 IU/kg, Period 1 and 2); Month 7 up to Month 18 (OD Cohort, RP 25 IU/kg, Period 2)

Population: ITT analysis population included all participants for whom a legal acceptable representative had signed the informed consent/assent form. Here, Overall Number of Participants Analyzed signifies participants who were evaluable for this outcome measure.

For reporting arm: Moroctocog alfa (AF-CC),OD and RP Cohort: RP Therapy 25 IU/kg, cumulative data for routine prophylaxis cohort (Day 1 up to Month 24, Period 1 and Period 2) and on demand cohort (Month 7 up to Month 18, Period 2) is reported.

Time frame: Day 1 up to Month 24 (RP Cohort, RP 25 IU/kg and 45 IU/kg, Period 1 and 2); Month 7 up to Month 18 (OD Cohort, RP 25 IU/kg, Period 2)

Population: ITT analysis population included all participants for whom a legal acceptable representative had signed the informed consent/assent form. Here, Overall Number of Participants Analyzed signifies participants who were evaluable for this outcome measure.

Participants' compliance to their assigned prophylaxis regimen was measured by following: a) number of infusions received per week and b) dose received. In this outcome measure mean of total number of infusions of moroctocog alfa (AF-CC) received by participants per week is reported. For reporting arm: Moroctocog alfa (AF-CC),OD and RP Cohort: RP Therapy 25 IU/kg cumulative data for routine prophylaxis cohort (Day 1 up to Month 24, Period 1 and Period 2) and on demand cohort (Month 7 up to Month 18, Period 2) is reported.

Time frame: Day 1 up to Month 24 (RP Cohort, RP 25 IU/kg and 45 IU/kg, Period 1 and 2); Month 7 up to Month 18 (OD Cohort, RP 25 IU/kg, Period 2)

Population: ITT analysis population included all participants for whom a legal acceptable representative had signed the informed consent/assent form. Here, Overall Number of Participants Analyzed signifies participants who were evaluable for this outcome measure.

MRT was calculated as AUMCinf /AUCinf-TI/2, where AUMCinf is the area under the moment curve from time zero to infinity and TI is the duration of infusion.

Time frame: 0.5, 8, 24, 28 and 32 hours post dose on Day 1

Population: Analysis population included all participants for whom a legal acceptable representative had signed the informed consent/assent form, were in a non bleeding state, participated in a single PK assessment at the start of the study and for whom an adequate PK profile had been obtained.

Mean RP dose (by weight) for each participant was calculated as his total moroctocog alfa (AF-CC) consumption (in IU) divided by weight (in kg). For reporting arm: Moroctocog alfa (AF-CC),OD and RP Cohort: RP Therapy 25 IU/kg, cumulative data for routine prophylaxis cohort (Day 1 up to Month 24, Period 1 and Period 2) and on demand cohort (Month 7 up to Month 18, Period 2) is reported.

Time frame: Day 1 up to Month 24 (RP Cohort, RP 25 IU/kg and 45 IU/kg, Period 1 and 2); Month 7 up to Month 18 (OD Cohort, RP 25 IU/kg, Period 2)

Population: ITT analysis population included all participants for whom a legal acceptable representative had signed the informed consent/assent form. Here, Overall Number of Participants Analyzed signifies participants who were evaluable for this outcome measure.

During prophylaxis, criteria for prophylaxis regimen escalation are the occurrence, over a 4-week duration (and in the absence of a confirmed FVIII inhibitor), of (a) 2 or more spontaneous bleeds into a major joint and/or target joint, or (b) 3 or more spontaneous bleeds (consisting of joint bleeds and/or significant soft tissue/muscle or other site bleeds). If either criterion was met, the participant was escalated to a more intense prophylaxis regimen of 45 IU/kg, administered every other day. Participant who meet dose escalation criteria while on prophylaxis regimen of 45 IU/kg, were escalated to a higher intensity regimen designated by the investigator. Significant spontaneous bleeds were those that led to a transient or persistent loss of function. For reporting arm: Moroctocog alfa (AF-CC),OD and RP Cohort: RP Therapy 25 IU/kg, cumulative data for RP cohort (Day 1 up to Month 24, Period 1 and Period 2) and OD cohort (Month 7 up to Month 18, Period 2) is reported.

Time frame: Day 1 up to Month 24 (RP Cohort, RP 25 IU/kg and 45 IU/kg, Period 1 and 2); Month 7 up to Month 18 (OD Cohort, RP 25 IU/kg, Period 2)

Population: ITT analysis population included all participants for whom a legal acceptable representative had signed the informed consent/assent form. Here, Overall Number of Participants Analyzed signifies participants who were evaluable for this outcome measure.

Confirmed FVIII inhibitors were defined as a neutralizing antibody to FVIII with a titer value of greater than or equal to (\>=) 0.6 Bethesda units (BU) per millimeter in a sample assayed using the Nijmegen assay at the central laboratory.

Time frame: Day 1 up to Month 24

Population: Analysis population included all participants for whom legal acceptable representative had signed informed consent/assent form and who received 1 dose of moroctocog alfa (AF-CC) and were at risk for confirmed FVIII inhibitor development.

LETE occurs in OD setting if participant recorded 2 successive No Response (no improvement at all between infusions, or condition worsens) ratings after 2 successive infusions of study drug. Infusions must have been given within 24 hours (hr) of each other for treatment of same bleeding event in absence of confounding factors (known presence or subsequent identification of a FVIII inhibitor, known inadequate dose for type and/or severity of bleed in opinion of investigator, delay of \>4 hr between onset of bleed to infusion, delay of \>24 hr before administration of a follow-up infusion, known compromised study drug, faulty administration of study drug, participant had an underlying, predisposing condition responsible for bleed in opinion of investigator. For reporting arm: Moroctocog alfa (AF-CC), OD and RP Cohort: RP Therapy 25 IU/kg, cumulative data for RP cohort (Day 1 up to Month 24, Period 1 and Period 2) and OD cohort (Month 7 up to Month 18, Period 2) is reported.

Time frame: Day 1 up to Month 24 (RP Cohort, RP 25 IU/kg and 45 IU/kg, Period 1 and 2); Day 1 up to Month 6 (OD Cohort, OD Therapy, Period 1); Month 7 up to Month 18 (OD Cohort, RP 25 IU/kg, Period 2)

Population: ITT analysis population included all participants for whom a legal acceptable representative had signed the informed consent/assent form. Here, Overall Number of Participants Analyzed signifies participants who were evaluable for this outcome measure.

LETE in prophylaxis setting if there was a spontaneous bleed within 48 hours after a regularly scheduled prophylactic dose of study drug (which was not used to treat a bleed) in the absence of confounding factors (known presence or subsequent identification of a FVIII inhibitor, known inadequate prophylactic dose \[a dose less than that prescribed in participant's regimen\], known lack of adherence to the prescribed prophylaxis regimen, bleed occurs in a target joint identified at the start of the study, known compromised study drug, faulty administration of study drug, participant had an underlying, predisposing condition responsible for the bleed in the opinion of the investigator. Therefore, LETE in the prophylaxis setting was the occurrence of a bleed. For reporting arm: Moroctocog alfa (AF-CC), OD and RP Cohort: RP Therapy 25 IU/kg, cumulative data for RP cohort (Day 1 up to Month 24, Period 1 and Period 2) and OD cohort (Month 7 up to Month 18, Period 2) is reported.

Time frame: Day 1 up to Month 24 (RP Cohort, RP 25 IU/kg and 45 IU/kg, Period 1 and 2); Month 7 up to Month 18 (OD Cohort, RP 25 IU/kg, Period 2)

Population: ITT analysis population included all participants for whom a legal acceptable representative had signed the informed consent/assent form. Here, Overall Number of Participants Analyzed signifies participants who were evaluable for this outcome measure.

AE is untoward medical occurrence in clinical investigation participant administered product or medical device;event need not necessarily had causal relationship with treatment or usage.Treatment-emergent are events between first dose of study drug and up to 28 days after last dose of study drug (up to 25 months)that were absent before treatment or that worsened relative to pretreatment state.AEs were classified into following on basis of severity:1)mild = did not interfere with participant's usual function;2)moderate=interfered to some extent with participant's usual function;3)severe=interfered significantly with participant's usual function;4)life threatening=AE required discontinuation of study drug,participant was at immediate risk of death.All participants in study received AF-CC.AEs were not collected separately for each intervention for participants.All participants were properly combined for analysis,regardless of regimen were following at time,regardless of OD or RP cohort.

Time frame: Day 1 up to Month 25

Population: Analysis population included all participants for whom a legal acceptable representative had signed the informed consent/assent form and were analyzed for safety. Here, Overall Number of Participants Analyzed signifies those participants who were evaluable for this outcome measure.

A treatment related AE is any untoward medical occurrence in a clinical investigation participant administered a product or medical device; the event had a causal relationship with the treatment or usage. All participants in the study received moroctocog alfa-(AF-CC). Adverse events were not collected separately for each intervention for the participants. All participants were properly combined for the analysis and was regardless of the regimen they were following at the time, and regardless of OD or RP cohort.

Time frame: Day 1 up to Month 25

Population: Analysis population included all participants for whom a legal acceptable representative had signed the informed consent/assent form and were analyzed for safety.

Number (no.) of bleeds treated are reported on basis of response to first infusion of study drug, at 4-point scale: excellent, good, moderate, no response. Excellent:definite pain relief and/or improvement in bleeding signs within 8 hours (hr) after infusion, no additional infusion administered; Good:definite pain relief and/or improvement in bleeding signs within 8 hr after infusion, at least 1 additional infusion administered for complete resolution or with no additional infusion administered; Moderate:probable or slight improvement starting after 8 hr following infusion,at least 1 additional infusion administered for complete resolution; No Response: no improvement at all between infusions or during 24 hr interval following infusion or condition worsen. Bleeds for which response not recorded, reported as:Data Not Recorded. Total no. of first infusions may not be equal to total no. of bleeds if bleed was: missing start date/dose information or treated initially with non-study FVIII.

Time frame: Day 1 up to Month 24

Population: ITT analysis population included all participants for whom a legal acceptable representative had signed the informed consent/assent form. Here, Overall Number of Participants Analyzed signifies participants who were evaluable for this outcome measure.

In this outcome measure number of treated spontaneous bleeds are reported according to the time interval between bleed onset and prior moroctocog alfa (AF-CC) routine prophylaxis dose. Following time intervals used to report this outcome measure: lesser than or equal to (\<=) 24 hours, greater than (\>) 24 hours to \<=48 hours, \>48 hours to \<=72 hours, \>72 hours. For reporting arm: Moroctocog alfa (AF-CC),OD and RP Cohort: RP Therapy 25 IU/kg cumulative data for routine prophylaxis cohort (Day 1 up to Month 24, Period 1 and Period 2) and on demand cohort (Month 7 up to Month 18, Period 2) is reported.

Time frame: Day 1 up to Month 24 (RP Cohort, RP 25 IU/kg and 45 IU/kg, Period 1 and 2); Month 7 up to Month 18 (OD Cohort, RP 25 IU/kg, Period 2)

Population: Analysis population included all participants for whom a legal acceptable representative had signed the informed consent/assent form and who reported a spontaneous bleeding episode following a routine prophylaxis dose.

Volume of distribution is defined as the theoretical volume in which the total amount of FVIII would need to be uniformly distributed to produce the observed plasma concentration of FVIII. Steady state volume of distribution (Vss) is the apparent volume of distribution at steady-state.

Time frame: 0.5, 8, 24, 28 and 32 hours post dose on Day 1

Population: Analysis population included all participants for whom a legal acceptable representative had signed the informed consent/assent form, were in a non bleeding state, participated in a single PK assessment at the start of the study and for whom an adequate PK profile had been obtained.

Plasma decay half-life is the time measured for the FVIII activity to decrease by one half.

Time frame: 0.5, 8, 24, 28 and 32 hours post dose on Day 1

Population: Analysis population included all participants for whom a legal acceptable representative had signed the informed consent/assent form, were in a non bleeding state, participated in a single pharmacokinetic (PK) assessment at the start of the study and for whom an adequate PK profile had been obtained.