A Study of Adynovate in Previously Treated Chinese Teenagers and Adults With Severe Hemophilia A

Total ABR was defined as the number of treated and non-treated bleeding episodes (BEs) that occurred during the treatment period, calculated as, ABR= number of unique bleeds during treatment period/(length of treatment period [days]/365.25). Total ABR for all BEs, spontaneous or traumatic, recorded in the participant's electronic diary and/or recorded in the physician/nurse/study site notes were reported.

ABR= number of unique bleeds during treatment period/(length of treatment period [days]/365.25). ABR for BEs based on bleeding site: joint or non-joint, recorded in the participant's electronic diary and/or recorded in the physician/nurse/study site notes were reported.

ABR= number of unique bleeds during treatment period/(length of treatment period [days]/365.25). ABR for BEs based on bleeding cause: spontaneous/unknown or injury, recorded in the participant's electronic diary and/or recorded in the physician/nurse/study site notes were reported.

Weight-adjusted consumption (IU/kg) was derived as the total units infused (IU) divided by the last available body weight (kg) prior to the infusion.

Weight-adjusted consumption (IU/kg) was derived as the total units infused (IU) divided by the last available body weight (kg) prior to the infusion.

Percentages were rounded off to the nearest single decimal place.

Average time interval between bleeding episodes (days)= Length of treatment period (days)/ Number of unique bleeds during treatment period. Average time interval was computed for participants with more than 1 unique BEs.

Hemostatic efficacy for treatment of BEs was rated on 4-point Likert scale as: excellent=full relief of pain and cessation of objective signs of bleeding after a single infusion, no additional infusion is required for the control of bleeding and administration of further infusion to maintain hemostasis would not affect the scoring; good=definite pain relief and/or improvement in signs of bleeding after a single infusion, possibly requires more than 2 infusions for complete resolution and administration of further infusion to maintain hemostasis would not affect the scoring; fair=probable and/or slight relief of pain and slight improvement in signs of bleeding after a single infusion, required multiple infusions for complete resolution; none=no improvement of signs or symptoms or conditions worsen. Missing indicates the number of unique bleeding episodes without any overall hemostatic efficacy rating at resolution of breakthrough bleeding episode.

Weight-adjusted consumption (IU/kg) was derived as the total units infused (IU) divided by the last available body weight (kg) prior to the infusion.

GHEA score consisted of 3 individual rating scales: (1) Intra-operative Efficacy Assessment Scale, (2) Post-operative Efficacy Assessment Scale, and (3) Peri-operative Efficacy Assessment Scale. Each rating scale is based on 4 points scale ranging from: 3 (Excellent), 2 (Good), 1 (Fair), and 0 (None). The scores of 3 individual ratings scales were added together to form a GHEA score. Total score ranged from 0 to 9, where scores evaluate as: excellent (7 to 9), good (5 to 7), fair (3 to 4), and none (0 to 2). For a GHEA score of 7 to be rated "excellent" no individual assessment scores could be less than (<) 2 and at least 1 assessment score had to be equal to (=) 3; otherwise a score of 7 was rated "good".

An adverse event (AE): any untoward medical occurrence in a participant administered a pharmaceutical product; the untoward medical occurrence does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product whether or not it is related to medicinal product. TEAE: any AE either reported for the first time or worsening of a pre-existing event after first dose of study drug and within 30 days of the last administration of study drug. Serious TEAEs: any untoward medical occurrence that: 1) results in death, 2) is life-threatening, 3) requires inpatient hospitalization or prolongation of existing hospitalization, 4) results in persistent or significant disability/incapacity, 5) leads to a congenital anomaly/birth defect in the offspring of the participant or 6) is a medically important.

As per planned analysis, data for this outcome measure was collected and reported for initial pharmacokinetic (PK) assessment and second PK assessment. The initial PK assessment was performed prior to the baseline visit at Day -1. The second PK assessment was performed during the Week 20 visit. FVIII activity level reported was corrected for pre-infusion measurement.

Incremental recovery (IR) was calculated as IR (international units per deciliter)/(international units per kilogram [(IU/dL)/(IU/kg)] = [PostFVIII (IU/dL)-PreFVIII (IU/dL)]/Weight Adjusted Dose (IU/kg).

IU/mL stands for international units per milliliter.

Clearance reported was calculated based on pre-infusion corrected concentration data. As per planned analysis, data for this outcome measure was collected and reported for initial PK assessment and second PK assessment. The initial PK assessment was performed prior to the baseline visit at Day -1. The second PK assessment was performed during the Week 20 visit. [(dL/h)/kg] stands for deciliters per hour per kilogram.

Volume of distribution was calculated based on pre-infusion corrected concentration data. As per planned analysis, data for this outcome measure was collected and reported for initial PK assessment and second PK assessment. The initial PK assessment was performed prior to the baseline visit at Day -1. The second PK assessment was performed during the Week 20 visit.

AUC0-96 was calculated based on pre-infusion corrected concentration data. As per planned analysis, data for this outcome measure was collected and reported for initial PK assessment and second PK assessment. The initial PK assessment was performed prior to the baseline visit at Day -1. The second PK assessment was performed during the Week 20 visit. h*IU/dL stands for hour*international units per deciliter.

Cmax was calculated based on pre-infusion corrected concentration data. As per planned analysis, data for this outcome measure was collected and reported for initial PK assessment and second PK assessment. The initial PK assessment was performed prior to the baseline visit at Day -1. The second PK assessment was performed during the Week 20 visit.

Cpredose was calculated based on pre-infusion corrected concentration data. As per planned analysis, data for this outcome measure was collected and reported for initial PK assessment and second PK assessment. The initial PK assessment was performed prior to the baseline visit at Day -1. The second PK assessment was performed during the Week 20 visit.

T1/2 was calculated based on pre-infusion corrected concentration data. As per planned analysis, data for this outcome measure was collected and reported for initial PK assessment and second PK assessment. The initial PK assessment was performed prior to the baseline visit at Day -1. The second PK assessment was performed during the Week 20 visit.