Hemophilia A
Conditions
Brief summary
The main aim of the study is to determine how well Adynovate works to decrease bleeding in previously treated Chinese men and boys with severe hemophilia A when given prophylactically. Participants will be treated with Adynovate twice a week for 26 weeks or until participants have received 50 days of treatment with Adynovate (whichever takes longer). Participants will need to visit their study clinic several times during their participation.
Interventions
BIOLOGICALAdynovate
Adynovate was injected intravenously using an appropriately sized syringe as a bolus infusion over a period of less than or equal to (\<=) 5 minutes (maximum infusion rate, 10 milliliters per minute \[mL/min\]).
Sponsors
Takeda
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
12 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
1. Participant and/or legally authorized representative must voluntarily sign a written informed consent form (ICF) after all relevant aspects of the study have been explained and discussed with the Participant. For the participants less than (\<) 18 years old, participants will give assent AND their parents/legally authorized representative should sign the ICF accordingly. 2. Participant and/or legally authorized representative understands and is willing and able to comply with all requirements of the study protocol. 3. Participant should be ethnic Chinese. 4. Participant is 12 to 65 years of age at screening and male. 5. Participant has severe hemophilia A (FVIII clotting activity \<1 percent \[%\]) as confirmed by the central laboratory at screening after a washout period of at least 72 to 96 hours. 6. The last on-demand or prophylactic treatment received is within 3 months before screening. 7. Participant has documented previous treatment with plasma-derived FVIII concentrates or recombinant FVIII for greater than (\>) 150 EDs. 8. Participant is human immunodeficiency virus (HIV)-negative, or HIV-positive with stable disease and CD4+ count greater than or equal to (\>=) 200 cells per cubic millimeter (/mm\^3). 9. Participant is hepatitis C virus (HCV) negative by antibody testing (if positive, additional polymerase chain reaction testing will be performed to confirm), as confirmed at screening; or HCV-positive with chronic stable hepatitis, as assessed by the investigator.
Exclusion criteria
1. Participant has detectable FVIII inhibitory antibodies (\>=0.6 Bethesda units \[BU\] per milliliter \[/mL\] using the Nijmegen modification of the Bethesda assay) as confirmed by the central laboratory at screening. 2. Participant has a confirmed history of FVIII inhibitory antibodies (\>=0.6 BU using the Nijmegen modification of the Bethesda assay or \>=0.6 BU using the Bethesda assay) at any time prior to screening. 3. Participant has a known hypersensitivity to Adynovate or ADVATE or any of the components of the study drugs, such as mouse or hamster proteins, or other FVIII products. 4. Participant has been diagnosed with an inherited or acquired hemostatic defect other than hemophilia A (example, qualitative platelet defect or von Willebrand's disease). 5. Participant has severe hepatic dysfunction (example, \>=5 times the upper limit of normal \[ULN\] for alanine aminotransferase \[ALT\] or aspartate aminotransferase \[AST\], a recent or persistent international normalized ratio \[INR\] \>1.5, as confirmed by the local laboratory at screening). 6. Participant has severe renal impairment (serum creatinine \>1.5 times the ULN) as confirmed by the local laboratory at screening. 7. Participant is planned or likely to undergo major surgery during the study period. 8. Participant has current or recent (\<30 days) use of other PEGylated drugs before study participation or scheduled use of such drugs during study participation. 9. Participant has received emicizumab therapy within 6 months of screening. 10. Participant is currently receiving, or scheduled to receive during the study, an immunomodulating drug (example, systemic corticosteroid agent at a dose equivalent to hydrocortisone \>10 milligram per day \[mg/day\], or alpha-interferon) other than antiretroviral chemotherapy. 11. Participant has participated in another clinical study involving the use of an investigational product (IP) other than Adynovate or an investigational device within 30 days before the screening visit or is scheduled to participate in another clinical study involving an IP or investigational device during this study. 12. Participant has a medical, psychiatric, or cognitive illness or recreational drug/alcohol use that, in the opinion of the investigator, would affect participant safety or compliance. 13. Participant, in the opinion of the investigator, is unable or unwilling to comply with the study protocol.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Total Annualized Bleeding Rates (ABR) | Baseline through study completion or ≥50 EDs whichever occurred last (approximately 28 weeks) | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| ABR Based on Bleeding Cause | Baseline through study completion or ≥50 EDs whichever occurred last (approximately 28 weeks) | 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. |
| Number of Adynovate Infusions Per Week During the Prophylactic Treatment Period | Baseline through study completion or ≥50 EDs whichever occurred last (approximately 28 weeks) | — |
| Number of Adynovate Infusions Per Month During the Prophylactic Treatment Period | Baseline through study completion or ≥50 EDs whichever occurred last (approximately 28 weeks) | — |
| Weight-adjusted Consumption of Adynovate Per Week During the Prophylactic Treatment Period | Baseline through study completion or ≥50 EDs whichever occurred last (approximately 28 weeks) | 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 of Adynovate Per Month During the Prophylactic Treatment Period | Baseline through study completion or ≥50 EDs whichever occurred last (approximately 28 weeks) | 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. |
| Percentage of Participants With Zero Bleeding Episodes During the Study | Baseline through study completion or ≥50 EDs whichever occurred last (approximately 28 weeks) | Percentages were rounded off to the nearest single decimal place. |
| Average Time Interval Between Bleeding Episodes (BEs) | Baseline through study completion or ≥50 EDs whichever occurred last (approximately 28 weeks) | 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. |
| Number of Bleeding Events in Each Category of Hemostatic Efficacy Rating at Resolution of Breakthrough Bleeding Episode | Baseline through study completion or ≥50 EDs whichever occurred last (approximately 28 weeks) | 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. |
| Number of Adynovate Infusions Per Bleeding Episode | Baseline through study completion or ≥50 EDs whichever occurred last (approximately 28 weeks) | — |
| Weight-adjusted Consumption of Adynovate Per Bleeding Episode | Baseline through study completion or ≥50 EDs whichever occurred last (approximately 28 weeks) | 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. |
| Number of Minor Surgeries With Hemostatic Efficacy Based on Global Hemostatic Efficacy Assessment (GHEA) Score as Assessed by the Operating Surgeon/Investigator | Baseline through study completion or ≥50 EDs whichever occurred last (approximately 28 weeks) | 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. |
| Volume of Actual and Predicted Intra-operative and Post-operative Blood Loss After the Surgery as Assessed by the Operating Surgeon/Investigator | Post-operative: Day 1 and at discharge Week 26 | — |
| Number of Participants Who Required Perioperative Transfusion of Blood, Red Blood Cells, Platelets, and Other Blood Products | Baseline through study completion or ≥50 EDs whichever occurred last (approximately 28 weeks) | — |
| ABR Based on Bleeding Site | Baseline through study completion or ≥50 EDs whichever occurred last (approximately 28 weeks) | 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. |
| Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Treatment-emergent Adverse Events (Serious TEAEs) | Up to approximately 28 weeks | 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. |
| Number of Participants With Confirmed Inhibitory Antibodies to Factor VIII (FVIII), Binding Immunoglobulin G (IgG) and Immunoglobulin M (IgM) Antibodies to Adynovate and Chinese Hamster Ovary (CHO) Protein | Up to approximately 28 weeks | — |
| FVIII Activity Level in Plasma Assessed by a 1-stage Clotting Assay | Day -1 and Week 20: pre-infusion, post-infusion at multiple time-points up to 96 hours | 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 Over Time During Adynovate Prophylactic Treatment | Baseline, Week 6, and Study Completion (approximately Week 28) | 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). |
| Pre-dose Level of FVIII Activity in Plasma | Baseline, Weeks 2, 6, 12, and Study Completion (approximately Week 28): Within 30 minutes pre-infusion | — |
| Pre-dose Level of FVIII Antigen in Plasma | Baseline, Weeks 2, 6, 12, 20, and Study Completion (approximately Week 28): Within 30 minutes pre-infusion | IU/mL stands for international units per milliliter. |
| Pre-dose Level of Von Willebrand Factor (VWF) Antigen in Plasma | Baseline, Weeks 2, 6, 12, 20, and Study Completion (approximately Week 28): Within 30 minutes pre-infusion | — |
| Clearance (CL) for FVIII Activity Following an Initial Single Dose and Steady-state Dose of Adynovate | Day -1 and Week 20: pre-infusion, post-infusion at multiple timepoints up to 96 hours | 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 for FVIII Activity Following an Initial Single Dose and Steady-state Dose of Adynovate | Day -1 and Week 20: pre-infusion, post-infusion at multiple timepoints up to 96 hours | 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. |
| Area Under the Concentration Versus Time Curve From 0 to 96 Hours (AUC0-96) for FVIII Activity Following an Initial Single Dose and Steady-state Dose of Adynovate | Day -1 and Week 20: pre-infusion, post-infusion at multiple timepoints up to 96 hours | 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. |
| Maximum Concentration (Cmax) for FVIII Activity Following an Initial Single Dose and Steady-state Dose of Adynovate | Day -1 and Week 20: pre-infusion, post-infusion at multiple timepoints up to 96 hours | 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. |
| Pre-dose Concentration (Cpredose) for FVIII Activity Following an Initial Single Dose and Steady-state Dose of Adynovate | Day -1 and Week 20: pre-infusion, post-infusion at multiple timepoints up to 96 hours | 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. |
| Terminal Phase Elimination Half-life (T1/2) for FVIII Activity Following an Initial Single Dose and Steady-state Dose of Adynovate | Day -1 and Week 20: pre-infusion, post-infusion at multiple timepoints up to 96 hours | 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. |
| Daily Intra-Operative and Post-Operative Weight-Adjusted Consumption Dose of Adynovate | Baseline through study completion or ≥50 EDs whichever occurred last (approximately 28 weeks) | — |
Countries
China
Participant flow
Recruitment details
Participants took part in the study at various investigative sites in China from 27 March 2023 to 05 September 2024.
Pre-assignment details
Participants with a diagnosis of severe hemophilia A were enrolled in this study to receive Adynovate (45 \[±5\] international units per kilogram \[IU/kg\]), infusion, intravenously (IV).
Participants by arm
| Arm | Count |
|---|---|
| Adynovate Participants received prophylactic treatment with Adynovate (45 \[±5\] IU/kg), infusion, IV, twice weekly, for at least 50 EDs, or approximately 28 weeks. | 37 |
| Total | 37 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Reason Not Specified | 1 |
| Overall Study | Withdrawal by Subject | 2 |
Baseline characteristics
| Characteristic | Adynovate |
|---|---|
| Age, Continuous | 24.1 years STANDARD_DEVIATION 8.15 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 37 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 37 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 0 Participants |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 37 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 37 |
| other Total, other adverse events | 8 / 37 |
| serious Total, serious adverse events | 1 / 37 |
Outcome results
Primary
Total Annualized Bleeding Rates (ABR)
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.
Time frame: Baseline through study completion or ≥50 EDs whichever occurred last (approximately 28 weeks)
Population: The FAS included all participants who were assigned to receive a treatment regimen of Adynovate.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Adynovate | Total Annualized Bleeding Rates (ABR) | 4.1 bleeds per year | Standard Deviation 13.61 |
Secondary
ABR Based on Bleeding Cause
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.
Time frame: Baseline through study completion or ≥50 EDs whichever occurred last (approximately 28 weeks)
Population: The FAS included all participants who were assigned to receive a treatment regimen of Adynovate.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Adynovate | ABR Based on Bleeding Cause | Bleeding Cause: Spontaneous/Unknown | 3.8 bleeds per year | Standard Deviation 13.65 |
| Adynovate | ABR Based on Bleeding Cause | Bleeding Cause: Injury | 0.3 bleeds per year | Standard Deviation 0.99 |
Secondary
ABR Based on Bleeding Site
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.
Time frame: Baseline through study completion or ≥50 EDs whichever occurred last (approximately 28 weeks)
Population: The FAS included all participants who were assigned to receive a treatment regimen of Adynovate.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Adynovate | ABR Based on Bleeding Site | Bleeding Site: Joint | 2.7 bleeds per year | Standard Deviation 8.35 |
| Adynovate | ABR Based on Bleeding Site | Bleeding Site: Non-Joint | 1.4 bleeds per year | Standard Deviation 5.48 |
Secondary
Area Under the Concentration Versus Time Curve From 0 to 96 Hours (AUC0-96) for FVIII Activity Following an Initial Single Dose and Steady-state Dose of Adynovate
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.
Time frame: Day -1 and Week 20: pre-infusion, post-infusion at multiple timepoints up to 96 hours
Population: The PK AS, a subset of the PK FAS, included all PK participants who received at least 1 Adynovate PK dose with a sufficient number of evaluable PK concentrations post dose for the estimation of PK parameters using an NCA. Number analyzed is the number of participants with data available for analysis for the specified time-point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Adynovate | Area Under the Concentration Versus Time Curve From 0 to 96 Hours (AUC0-96) for FVIII Activity Following an Initial Single Dose and Steady-state Dose of Adynovate | Initial PK Assessment | 2348 h*IU/dL | Standard Deviation 737 |
| Adynovate | Area Under the Concentration Versus Time Curve From 0 to 96 Hours (AUC0-96) for FVIII Activity Following an Initial Single Dose and Steady-state Dose of Adynovate | Second PK Assessment | 2582 h*IU/dL | Standard Deviation 736 |
Secondary
Average Time Interval Between Bleeding Episodes (BEs)
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.
Time frame: Baseline through study completion or ≥50 EDs whichever occurred last (approximately 28 weeks)
Population: The FAS included all participants who were assigned to receive a treatment regimen of Adynovate. Overall number of participants analyzed is the number of participants with more than 1 unique BEs.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Adynovate | Average Time Interval Between Bleeding Episodes (BEs) | 61.869 days | Standard Deviation 30.9437 |
Secondary
Clearance (CL) for FVIII Activity Following an Initial Single Dose and Steady-state Dose of Adynovate
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.
Time frame: Day -1 and Week 20: pre-infusion, post-infusion at multiple timepoints up to 96 hours
Population: The Pharmacokinetic Analysis Set (PK AS), a subset of the PK FAS, included all PK participants who received at least 1 Adynovate PK dose with a sufficient number of evaluable PK concentrations post dose for the estimation of PK parameters using a noncompartmental analysis (NCA). Number analyzed is the number of participants with data available for analysis at the specified time-point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Adynovate | Clearance (CL) for FVIII Activity Following an Initial Single Dose and Steady-state Dose of Adynovate | Initial PK Assessment | 0.0206 (dL/h)/kg | Standard Deviation 0.00629 |
| Adynovate | Clearance (CL) for FVIII Activity Following an Initial Single Dose and Steady-state Dose of Adynovate | Second PK Assessment | 0.0192 (dL/h)/kg | Standard Deviation 0.00594 |
Secondary
Daily Intra-Operative and Post-Operative Weight-Adjusted Consumption Dose of Adynovate
Time frame: Baseline through study completion or ≥50 EDs whichever occurred last (approximately 28 weeks)
Population: The FAS included all participants treated with at least 1 Adynovate dose. Only participants who were administered Adynovate for minor surgeries were to be assessed for this outcome measure. Overall number of participants analyzed is zero as no participants were administered Adynovate for minor surgeries.
Secondary
FVIII Activity Level in Plasma Assessed by a 1-stage Clotting Assay
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.
Time frame: Day -1 and Week 20: pre-infusion, post-infusion at multiple time-points up to 96 hours
Population: The Pharmacokinetic Full Analysis Set (PK FAS) included all participants who consented to PK evaluation, were treated with at least 1 Adynovate dose, and had at least 1 evaluable PK concentration post dose. Number analyzed is the number of participants with data available for analysis at the specified time-point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Adynovate | FVIII Activity Level in Plasma Assessed by a 1-stage Clotting Assay | Initial PK Assessment: Pre-Infusion | 0.00 International units per deciliter(IU/dL) | Standard Deviation 0 |
| Adynovate | FVIII Activity Level in Plasma Assessed by a 1-stage Clotting Assay | Initial PK Assessment: Post-Infusion, 30 Minutes | 112.02 International units per deciliter(IU/dL) | Standard Deviation 26.739 |
| Adynovate | FVIII Activity Level in Plasma Assessed by a 1-stage Clotting Assay | Initial PK Assessment: Post-Infusion: 1 Hour | 106.67 International units per deciliter(IU/dL) | Standard Deviation 22.066 |
| Adynovate | FVIII Activity Level in Plasma Assessed by a 1-stage Clotting Assay | Initial PK Assessment: Post-Infusion: 2 Hours | 94.64 International units per deciliter(IU/dL) | Standard Deviation 32.185 |
| Adynovate | FVIII Activity Level in Plasma Assessed by a 1-stage Clotting Assay | Initial PK Assessment: Post-Infusion: 4 Hours | 87.67 International units per deciliter(IU/dL) | Standard Deviation 21.186 |
| Adynovate | FVIII Activity Level in Plasma Assessed by a 1-stage Clotting Assay | Initial PK Assessment: Post-Infusion: 8 Hours | 71.87 International units per deciliter(IU/dL) | Standard Deviation 16.929 |
| Adynovate | FVIII Activity Level in Plasma Assessed by a 1-stage Clotting Assay | Initial PK Assessment: Post-Infusion: 12 Hours | 58.96 International units per deciliter(IU/dL) | Standard Deviation 14.378 |
| Adynovate | FVIII Activity Level in Plasma Assessed by a 1-stage Clotting Assay | Initial PK Assessment: Post-Infusion: 24 Hours | 37.24 International units per deciliter(IU/dL) | Standard Deviation 11.573 |
| Adynovate | FVIII Activity Level in Plasma Assessed by a 1-stage Clotting Assay | Initial PK Assessment: Post-Infusion: 48 Hours | 14.60 International units per deciliter(IU/dL) | Standard Deviation 7.616 |
| Adynovate | FVIII Activity Level in Plasma Assessed by a 1-stage Clotting Assay | Initial PK Assessment: Post-Infusion: 72 Hours | 5.17 International units per deciliter(IU/dL) | Standard Deviation 3.876 |
| Adynovate | FVIII Activity Level in Plasma Assessed by a 1-stage Clotting Assay | Initial PK Assessment: Post-Infusion: 96 Hours | 2.06 International units per deciliter(IU/dL) | Standard Deviation 2.04 |
| Adynovate | FVIII Activity Level in Plasma Assessed by a 1-stage Clotting Assay | Second PK Assessment: Pre-Infusion | 0.00 International units per deciliter(IU/dL) | Standard Deviation 0 |
| Adynovate | FVIII Activity Level in Plasma Assessed by a 1-stage Clotting Assay | Second PK Assessment: Post-Infusion, 30 Minutes | 109.75 International units per deciliter(IU/dL) | Standard Deviation 18.192 |
| Adynovate | FVIII Activity Level in Plasma Assessed by a 1-stage Clotting Assay | Second PK Assessment: Post-Infusion: 1 Hour | 109.51 International units per deciliter(IU/dL) | Standard Deviation 20.705 |
| Adynovate | FVIII Activity Level in Plasma Assessed by a 1-stage Clotting Assay | Second PK Assessment: Post-Infusion: 2 Hours | 98.82 International units per deciliter(IU/dL) | Standard Deviation 20.196 |
| Adynovate | FVIII Activity Level in Plasma Assessed by a 1-stage Clotting Assay | Second PK Assessment: Post-Infusion: 4 Hours | 86.41 International units per deciliter(IU/dL) | Standard Deviation 9.587 |
| Adynovate | FVIII Activity Level in Plasma Assessed by a 1-stage Clotting Assay | Second PK Assessment: Post-Infusion: 8 Hours | 73.57 International units per deciliter(IU/dL) | Standard Deviation 15.75 |
| Adynovate | FVIII Activity Level in Plasma Assessed by a 1-stage Clotting Assay | Second PK Assessment: Post-Infusion: 12 Hours | 62.31 International units per deciliter(IU/dL) | Standard Deviation 14.766 |
| Adynovate | FVIII Activity Level in Plasma Assessed by a 1-stage Clotting Assay | Second PK Assessment: Post-Infusion: 24 Hours | 40.53 International units per deciliter(IU/dL) | Standard Deviation 11.918 |
| Adynovate | FVIII Activity Level in Plasma Assessed by a 1-stage Clotting Assay | Second PK Assessment: Post-Infusion: 48 Hours | 16.13 International units per deciliter(IU/dL) | Standard Deviation 8.275 |
| Adynovate | FVIII Activity Level in Plasma Assessed by a 1-stage Clotting Assay | Second PK Assessment: Post-Infusion: 72 Hours | 7.20 International units per deciliter(IU/dL) | Standard Deviation 4.754 |
| Adynovate | FVIII Activity Level in Plasma Assessed by a 1-stage Clotting Assay | Second PK Assessment: Post-Infusion: 96 Hours | 3.25 International units per deciliter(IU/dL) | Standard Deviation 2.811 |
Secondary
Incremental Recovery Over Time During Adynovate Prophylactic Treatment
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).
Time frame: Baseline, Week 6, and Study Completion (approximately Week 28)
Population: The SAS included all participants treated with at least 1 Adynovate dose. Overall number of participants analyzed is the number of participants with data available for analyses. Number analyzed is the number of participants with data available for analysis at the specified time-point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Adynovate | Incremental Recovery Over Time During Adynovate Prophylactic Treatment | Baseline | 2.4777 (IU/dL)/(IU/kg) | Standard Deviation 0.67876 |
| Adynovate | Incremental Recovery Over Time During Adynovate Prophylactic Treatment | Week 6 | 2.5147 (IU/dL)/(IU/kg) | Standard Deviation 0.64379 |
| Adynovate | Incremental Recovery Over Time During Adynovate Prophylactic Treatment | Study Completion | 2.4083 (IU/dL)/(IU/kg) | Standard Deviation 0.50714 |
Secondary
Maximum Concentration (Cmax) for FVIII Activity Following an Initial Single Dose and Steady-state Dose of Adynovate
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.
Time frame: Day -1 and Week 20: pre-infusion, post-infusion at multiple timepoints up to 96 hours
Population: The PK AS, a subset of the PK FAS, included all PK participants who received at least 1 Adynovate PK dose with a sufficient number of evaluable PK concentrations post dose for the estimation of PK parameters using an NCA. Number analyzed is the number of participants with data available for analysis for the specified time-point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Adynovate | Maximum Concentration (Cmax) for FVIII Activity Following an Initial Single Dose and Steady-state Dose of Adynovate | Initial PK Assessment | 113 IU/dL | Standard Deviation 26.1 |
| Adynovate | Maximum Concentration (Cmax) for FVIII Activity Following an Initial Single Dose and Steady-state Dose of Adynovate | Second PK Assessment | 115 IU/dL | Standard Deviation 20 |
Secondary
Number of Adynovate Infusions Per Bleeding Episode
Time frame: Baseline through study completion or ≥50 EDs whichever occurred last (approximately 28 weeks)
Population: The Safety Analysis Set (SAS) included all participants treated with at least 1 Adynovate dose. Overall number of participants analyzed is the number of participants with treated bleeding episodes.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Adynovate | Number of Adynovate Infusions Per Bleeding Episode | 2.839 infusions/bleeding episode | Standard Deviation 2.9337 |
Secondary
Number of Adynovate Infusions Per Month During the Prophylactic Treatment Period
Time frame: Baseline through study completion or ≥50 EDs whichever occurred last (approximately 28 weeks)
Population: The FAS included all participants who were assigned to receive a treatment regimen of Adynovate.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Adynovate | Number of Adynovate Infusions Per Month During the Prophylactic Treatment Period | 8.711 infusions per month | Standard Deviation 0.2447 |
Secondary
Number of Adynovate Infusions Per Week During the Prophylactic Treatment Period
Time frame: Baseline through study completion or ≥50 EDs whichever occurred last (approximately 28 weeks)
Population: The FAS included all participants who were assigned to receive a treatment regimen of Adynovate.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Adynovate | Number of Adynovate Infusions Per Week During the Prophylactic Treatment Period | 2.003 infusions per week | Standard Deviation 0.0563 |
Secondary
Number of Bleeding Events in Each Category of Hemostatic Efficacy Rating at Resolution of Breakthrough Bleeding Episode
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.
Time frame: Baseline through study completion or ≥50 EDs whichever occurred last (approximately 28 weeks)
Population: The FAS included all participants who were assigned to receive a treatment regimen of Adynovate. Overall number of participants analyzed is the number of participants with treated bleeding episodes.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Adynovate | Number of Bleeding Events in Each Category of Hemostatic Efficacy Rating at Resolution of Breakthrough Bleeding Episode | Excellent | 7 bleeding events |
| Adynovate | Number of Bleeding Events in Each Category of Hemostatic Efficacy Rating at Resolution of Breakthrough Bleeding Episode | Good | 14 bleeding events |
| Adynovate | Number of Bleeding Events in Each Category of Hemostatic Efficacy Rating at Resolution of Breakthrough Bleeding Episode | Fair | 4 bleeding events |
| Adynovate | Number of Bleeding Events in Each Category of Hemostatic Efficacy Rating at Resolution of Breakthrough Bleeding Episode | None | 0 bleeding events |
| Adynovate | Number of Bleeding Events in Each Category of Hemostatic Efficacy Rating at Resolution of Breakthrough Bleeding Episode | Missing | 6 bleeding events |
Secondary
Number of Minor Surgeries With Hemostatic Efficacy Based on Global Hemostatic Efficacy Assessment (GHEA) Score as Assessed by the Operating Surgeon/Investigator
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.
Time frame: Baseline through study completion or ≥50 EDs whichever occurred last (approximately 28 weeks)
Population: The FAS included all participants treated with at least 1 Adynovate dose. Only participants with hemostatic efficacy were to be assessed for this outcome measure. Overall number analyzed is zero as there were no participants who met the hemostatic assessment criteria for this outcome measure.
Secondary
Number of Participants Who Required Perioperative Transfusion of Blood, Red Blood Cells, Platelets, and Other Blood Products
Time frame: Baseline through study completion or ≥50 EDs whichever occurred last (approximately 28 weeks)
Population: The FAS included all participants treated with at least 1 Adynovate dose.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Adynovate | Number of Participants Who Required Perioperative Transfusion of Blood, Red Blood Cells, Platelets, and Other Blood Products | 0 Participants |
Secondary
Number of Participants With Confirmed Inhibitory Antibodies to Factor VIII (FVIII), Binding Immunoglobulin G (IgG) and Immunoglobulin M (IgM) Antibodies to Adynovate and Chinese Hamster Ovary (CHO) Protein
Time frame: Up to approximately 28 weeks
Population: The SAS included all participants treated with at least 1 Adynovate dose. Number analyzed is the number of participants with data available for analysis for the specified category.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Adynovate | Number of Participants With Confirmed Inhibitory Antibodies to Factor VIII (FVIII), Binding Immunoglobulin G (IgG) and Immunoglobulin M (IgM) Antibodies to Adynovate and Chinese Hamster Ovary (CHO) Protein | Binding IgM Antibodies to Adynovate | 0 Participants |
| Adynovate | Number of Participants With Confirmed Inhibitory Antibodies to Factor VIII (FVIII), Binding Immunoglobulin G (IgG) and Immunoglobulin M (IgM) Antibodies to Adynovate and Chinese Hamster Ovary (CHO) Protein | Inhibitory Antibodies to FVIII | 0 Participants |
| Adynovate | Number of Participants With Confirmed Inhibitory Antibodies to Factor VIII (FVIII), Binding Immunoglobulin G (IgG) and Immunoglobulin M (IgM) Antibodies to Adynovate and Chinese Hamster Ovary (CHO) Protein | Binding IgG Antibodies to Adynovate | 0 Participants |
| Adynovate | Number of Participants With Confirmed Inhibitory Antibodies to Factor VIII (FVIII), Binding Immunoglobulin G (IgG) and Immunoglobulin M (IgM) Antibodies to Adynovate and Chinese Hamster Ovary (CHO) Protein | Binding Antibodies to CHO Proteins | 0 Participants |
Secondary
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Treatment-emergent Adverse Events (Serious TEAEs)
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.
Time frame: Up to approximately 28 weeks
Population: The SAS included all participants treated with at least 1 Adynovate dose.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Adynovate | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Treatment-emergent Adverse Events (Serious TEAEs) | TEAEs | 16 Participants |
| Adynovate | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Treatment-emergent Adverse Events (Serious TEAEs) | Serious TEAEs | 1 Participants |
Secondary
Percentage of Participants With Zero Bleeding Episodes During the Study
Percentages were rounded off to the nearest single decimal place.
Time frame: Baseline through study completion or ≥50 EDs whichever occurred last (approximately 28 weeks)
Population: The FAS included all participants who were assigned to receive a treatment regimen of Adynovate.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Adynovate | Percentage of Participants With Zero Bleeding Episodes During the Study | 54.1 percentage of participants |
Secondary
Pre-dose Concentration (Cpredose) for FVIII Activity Following an Initial Single Dose and Steady-state Dose of Adynovate
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.
Time frame: Day -1 and Week 20: pre-infusion, post-infusion at multiple timepoints up to 96 hours
Population: The PK AS, a subset of the PK FAS, included all PK participants who received at least 1 Adynovate PK dose with a sufficient number of evaluable PK concentrations post dose for the estimation of PK parameters using an NCA. Number analyzed is the number of participants with data available for analysis for the specified time-point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Adynovate | Pre-dose Concentration (Cpredose) for FVIII Activity Following an Initial Single Dose and Steady-state Dose of Adynovate | Initial PK Assessment | 0 IU/dL | Standard Deviation 0 |
| Adynovate | Pre-dose Concentration (Cpredose) for FVIII Activity Following an Initial Single Dose and Steady-state Dose of Adynovate | Second PK Assessment | 0 IU/dL | Standard Deviation 0 |
Secondary
Pre-dose Level of FVIII Activity in Plasma
Time frame: Baseline, Weeks 2, 6, 12, and Study Completion (approximately Week 28): Within 30 minutes pre-infusion
Population: The SAS included all participants treated with at least 1 Adynovate dose. Overall number of participants analyzed is the number of participants with data available for analyses. Number analyzed is the number of participants with data available for analysis at the specified time-point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Adynovate | Pre-dose Level of FVIII Activity in Plasma | Baseline | 0.06 IU/dL | Standard Deviation 0.232 |
| Adynovate | Pre-dose Level of FVIII Activity in Plasma | Week 2 | 3.28 IU/dL | Standard Deviation 4.999 |
| Adynovate | Pre-dose Level of FVIII Activity in Plasma | Week 6 | 2.91 IU/dL | Standard Deviation 2.802 |
| Adynovate | Pre-dose Level of FVIII Activity in Plasma | Week 12 | 3.61 IU/dL | Standard Deviation 3.994 |
| Adynovate | Pre-dose Level of FVIII Activity in Plasma | Study Completion | 7.06 IU/dL | Standard Deviation 16.365 |
Secondary
Pre-dose Level of FVIII Antigen in Plasma
IU/mL stands for international units per milliliter.
Time frame: Baseline, Weeks 2, 6, 12, 20, and Study Completion (approximately Week 28): Within 30 minutes pre-infusion
Population: The SAS included all participants treated with at least 1 Adynovate dose. Number analyzed is the number of participants with data available for analysis at the specified time-point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Adynovate | Pre-dose Level of FVIII Antigen in Plasma | Baseline | 0.0276 IU/mL | Standard Deviation 0.06577 |
| Adynovate | Pre-dose Level of FVIII Antigen in Plasma | Week 2 | 0.0782 IU/mL | Standard Deviation 0.07888 |
| Adynovate | Pre-dose Level of FVIII Antigen in Plasma | Week 6 | 0.0689 IU/mL | Standard Deviation 0.04518 |
| Adynovate | Pre-dose Level of FVIII Antigen in Plasma | Week 12 | 0.0649 IU/mL | Standard Deviation 0.04286 |
| Adynovate | Pre-dose Level of FVIII Antigen in Plasma | Week 20 | 0.0856 IU/mL | Standard Deviation 0.05404 |
| Adynovate | Pre-dose Level of FVIII Antigen in Plasma | Study Completion | 0.1011 IU/mL | Standard Deviation 0.11326 |
Secondary
Pre-dose Level of Von Willebrand Factor (VWF) Antigen in Plasma
Time frame: Baseline, Weeks 2, 6, 12, 20, and Study Completion (approximately Week 28): Within 30 minutes pre-infusion
Population: The SAS included all participants treated with at least 1 Adynovate dose. Number analyzed is the number of participants with data available for analysis at the specified time-point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Adynovate | Pre-dose Level of Von Willebrand Factor (VWF) Antigen in Plasma | Baseline | 83.69 percent (%) | Standard Deviation 35.967 |
| Adynovate | Pre-dose Level of Von Willebrand Factor (VWF) Antigen in Plasma | Week 2 | 84.46 percent (%) | Standard Deviation 30.811 |
| Adynovate | Pre-dose Level of Von Willebrand Factor (VWF) Antigen in Plasma | Week 6 | 84.99 percent (%) | Standard Deviation 34.216 |
| Adynovate | Pre-dose Level of Von Willebrand Factor (VWF) Antigen in Plasma | Week 12 | 86.57 percent (%) | Standard Deviation 30.024 |
| Adynovate | Pre-dose Level of Von Willebrand Factor (VWF) Antigen in Plasma | Week 20 | 91.26 percent (%) | Standard Deviation 34.24 |
| Adynovate | Pre-dose Level of Von Willebrand Factor (VWF) Antigen in Plasma | Study Completion | 90.26 percent (%) | Standard Deviation 31.714 |
Secondary
Terminal Phase Elimination Half-life (T1/2) for FVIII Activity Following an Initial Single Dose and Steady-state Dose of Adynovate
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.
Time frame: Day -1 and Week 20: pre-infusion, post-infusion at multiple timepoints up to 96 hours
Population: The PK AS, a subset of the PK FAS, included all PK participants who received at least 1 Adynovate PK dose with a sufficient number of evaluable PK concentrations post dose for the estimation of PK parameters using an NCA. Number analyzed is the number of participants with data available for analysis for the specified time-point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Adynovate | Terminal Phase Elimination Half-life (T1/2) for FVIII Activity Following an Initial Single Dose and Steady-state Dose of Adynovate | Initial PK Assessment | 16.0 hour | Standard Deviation 3.27 |
| Adynovate | Terminal Phase Elimination Half-life (T1/2) for FVIII Activity Following an Initial Single Dose and Steady-state Dose of Adynovate | Second PK Assessment | 18.5 hour | Standard Deviation 4.61 |
Secondary
Volume of Actual and Predicted Intra-operative and Post-operative Blood Loss After the Surgery as Assessed by the Operating Surgeon/Investigator
Time frame: Post-operative: Day 1 and at discharge Week 26
Population: The FAS included all participants treated with at least 1 Adynovate dose. Only participants with blood loss for minor surgeries were to be assessed for this outcome measure. Overall number of participants analyzed is zero as there were no participants with blood loss for minor surgeries.
Secondary
Volume of Distribution for FVIII Activity Following an Initial Single Dose and Steady-state Dose of Adynovate
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.
Time frame: Day -1 and Week 20: pre-infusion, post-infusion at multiple timepoints up to 96 hours
Population: The PK AS, a subset of the PK FAS, included all PK participants who received at least 1 Adynovate PK dose with a sufficient number of evaluable PK concentrations post dose for the estimation of PK parameters using an NCA. Number analyzed is the number of participants with data available for analysis at the specified time-point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Adynovate | Volume of Distribution for FVIII Activity Following an Initial Single Dose and Steady-state Dose of Adynovate | Initial PK Assessment | 0.458 deciliters per kilogram (dL/kg) | Standard Deviation 0.107 |
| Adynovate | Volume of Distribution for FVIII Activity Following an Initial Single Dose and Steady-state Dose of Adynovate | Second PK Assessment | 0.480 deciliters per kilogram (dL/kg) | Standard Deviation 0.0953 |
Secondary
Weight-adjusted Consumption of Adynovate Per 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.
Time frame: Baseline through study completion or ≥50 EDs whichever occurred last (approximately 28 weeks)
Population: The SAS included all participants treated with at least 1 Adynovate dose. Overall number of participants analyzed is the number of participants with treated bleeding episodes.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Adynovate | Weight-adjusted Consumption of Adynovate Per Bleeding Episode | 77.766 IU/kg per bleeding episode | Standard Deviation 81.7538 |
Secondary
Weight-adjusted Consumption of Adynovate Per Month During the Prophylactic Treatment Period
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.
Time frame: Baseline through study completion or ≥50 EDs whichever occurred last (approximately 28 weeks)
Population: The FAS included all participants who were assigned to receive a treatment regimen of Adynovate.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Adynovate | Weight-adjusted Consumption of Adynovate Per Month During the Prophylactic Treatment Period | 389.760 IU/kg per month | Standard Deviation 16.0045 |
Secondary
Weight-adjusted Consumption of Adynovate Per Week During the Prophylactic Treatment Period
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.
Time frame: Baseline through study completion or ≥50 EDs whichever occurred last (approximately 28 weeks)
Population: The FAS included all participants who were assigned to receive a treatment regimen of Adynovate.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Adynovate | Weight-adjusted Consumption of Adynovate Per Week During the Prophylactic Treatment Period | 89.637 IU/kg per week | Standard Deviation 3.6807 |