Trial Outcomes & Findings for A Study of Adynovate in Previously Treated Chinese Teenagers and Adults With Severe Hemophilia A (NCT NCT05707351)

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

37 participants

Primary outcome timeframe

Baseline through study completion or ≥50 EDs whichever occurred last (approximately 28 weeks)

Results posted on

2025-05-01

Participant Flow

Participants took part in the study at various investigative sites in China from 27 March 2023 to 05 September 2024.

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).

Participant milestones

Participant milestones
Measure	Adynovate Participants received prophylactic treatment with Adynovate (45 \[±5\] IU/kg), infusion, IV, twice weekly, for at least 50 exposure days (EDs), or approximately 28 weeks.
Overall Study STARTED	37
Overall Study COMPLETED	34
Overall Study NOT COMPLETED	3

Reasons for withdrawal

Reasons for withdrawal
Measure	Adynovate Participants received prophylactic treatment with Adynovate (45 \[±5\] IU/kg), infusion, IV, twice weekly, for at least 50 exposure days (EDs), or approximately 28 weeks.
Overall Study Withdrawal by Subject	2
Overall Study Reason Not Specified	1

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Adynovate n=37 Participants Participants received prophylactic treatment with Adynovate (45 \[±5\] IU/kg), infusion, IV, twice weekly, for at least 50 EDs, or approximately 28 weeks.
Age, Continuous	24.1 years STANDARD_DEVIATION 8.15 • n=5 Participants
Sex: Female, Male Female	0 Participants n=5 Participants
Sex: Female, Male Male	37 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	37 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	37 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants
Race (NIH/OMB) White	0 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants

PRIMARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Adynovate n=37 Participants Participants received prophylactic treatment with Adynovate (45 \[±5\] IU/kg), infusion, IV, twice weekly, for at least 50 EDs, or approximately 28 weeks.
Total Annualized Bleeding Rates (ABR)	4.1 bleeds per year Standard Deviation 13.61

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Adynovate n=37 Participants Participants received prophylactic treatment with Adynovate (45 \[±5\] IU/kg), infusion, IV, twice weekly, for at least 50 EDs, or approximately 28 weeks.
ABR Based on Bleeding Site Bleeding Site: Joint	2.7 bleeds per year Standard Deviation 8.35
ABR Based on Bleeding Site Bleeding Site: Non-Joint	1.4 bleeds per year Standard Deviation 5.48

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Adynovate n=37 Participants Participants received prophylactic treatment with Adynovate (45 \[±5\] IU/kg), infusion, IV, twice weekly, for at least 50 EDs, or approximately 28 weeks.
ABR Based on Bleeding Cause Bleeding Cause: Injury	0.3 bleeds per year Standard Deviation 0.99
ABR Based on Bleeding Cause Bleeding Cause: Spontaneous/Unknown	3.8 bleeds per year Standard Deviation 13.65

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Adynovate n=37 Participants Participants received prophylactic treatment with Adynovate (45 \[±5\] IU/kg), infusion, IV, twice weekly, for at least 50 EDs, or approximately 28 weeks.
Number of Adynovate Infusions Per Week During the Prophylactic Treatment Period	2.003 infusions per week Standard Deviation 0.0563

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Adynovate n=37 Participants Participants received prophylactic treatment with Adynovate (45 \[±5\] IU/kg), infusion, IV, twice weekly, for at least 50 EDs, or approximately 28 weeks.
Number of Adynovate Infusions Per Month During the Prophylactic Treatment Period	8.711 infusions per month Standard Deviation 0.2447

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Adynovate n=37 Participants Participants received prophylactic treatment with Adynovate (45 \[±5\] IU/kg), infusion, IV, twice weekly, for at least 50 EDs, or approximately 28 weeks.
Weight-adjusted Consumption of Adynovate Per Week During the Prophylactic Treatment Period	89.637 IU/kg per week Standard Deviation 3.6807

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Adynovate n=37 Participants Participants received prophylactic treatment with Adynovate (45 \[±5\] IU/kg), infusion, IV, twice weekly, for at least 50 EDs, or approximately 28 weeks.
Weight-adjusted Consumption of Adynovate Per Month During the Prophylactic Treatment Period	389.760 IU/kg per month Standard Deviation 16.0045

SECONDARY outcome

Timeframe: 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.

Percentages were rounded off to the nearest single decimal place.

Outcome measures

Outcome measures
Measure	Adynovate n=37 Participants Participants received prophylactic treatment with Adynovate (45 \[±5\] IU/kg), infusion, IV, twice weekly, for at least 50 EDs, or approximately 28 weeks.
Percentage of Participants With Zero Bleeding Episodes During the Study	54.1 percentage of participants

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Adynovate n=9 Participants Participants received prophylactic treatment with Adynovate (45 \[±5\] IU/kg), infusion, IV, twice weekly, for at least 50 EDs, or approximately 28 weeks.
Average Time Interval Between Bleeding Episodes (BEs)	61.869 days Standard Deviation 30.9437

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Adynovate n=31 bleeding episodes Participants received prophylactic treatment with Adynovate (45 \[±5\] IU/kg), infusion, IV, twice weekly, for at least 50 EDs, or approximately 28 weeks.
Number of Bleeding Events in Each Category of Hemostatic Efficacy Rating at Resolution of Breakthrough Bleeding Episode Excellent	7 bleeding events
Number of Bleeding Events in Each Category of Hemostatic Efficacy Rating at Resolution of Breakthrough Bleeding Episode Good	14 bleeding events
Number of Bleeding Events in Each Category of Hemostatic Efficacy Rating at Resolution of Breakthrough Bleeding Episode Fair	4 bleeding events
Number of Bleeding Events in Each Category of Hemostatic Efficacy Rating at Resolution of Breakthrough Bleeding Episode None	0 bleeding events
Number of Bleeding Events in Each Category of Hemostatic Efficacy Rating at Resolution of Breakthrough Bleeding Episode Missing	6 bleeding events

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Adynovate n=31 treated bleeding episodes Participants received prophylactic treatment with Adynovate (45 \[±5\] IU/kg), infusion, IV, twice weekly, for at least 50 EDs, or approximately 28 weeks.
Number of Adynovate Infusions Per Bleeding Episode	2.839 infusions/bleeding episode Standard Deviation 2.9337

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Adynovate n=31 treated bleeding episodes Participants received prophylactic treatment with Adynovate (45 \[±5\] IU/kg), infusion, IV, twice weekly, for at least 50 EDs, or approximately 28 weeks.
Weight-adjusted Consumption of Adynovate Per Bleeding Episode	77.766 IU/kg per bleeding episode Standard Deviation 81.7538

SECONDARY outcome

Timeframe: 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.

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".

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Adynovate n=37 Participants Participants received prophylactic treatment with Adynovate (45 \[±5\] IU/kg), infusion, IV, twice weekly, for at least 50 EDs, or approximately 28 weeks.
Number of Participants Who Required Perioperative Transfusion of Blood, Red Blood Cells, Platelets, and Other Blood Products	0 Participants

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Up to approximately 28 weeks

Population: The SAS included all participants treated with at least 1 Adynovate dose.

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.

Outcome measures

Outcome measures
Measure	Adynovate n=37 Participants Participants received prophylactic treatment with Adynovate (45 \[±5\] IU/kg), infusion, IV, twice weekly, for at least 50 EDs, or approximately 28 weeks.
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Treatment-emergent Adverse Events (Serious TEAEs) TEAEs	16 Participants
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Treatment-emergent Adverse Events (Serious TEAEs) Serious TEAEs	1 Participants

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Adynovate n=37 Participants Participants received prophylactic treatment with Adynovate (45 \[±5\] IU/kg), infusion, IV, twice weekly, for at least 50 EDs, or approximately 28 weeks.
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
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
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
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 outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Adynovate n=15 Participants Participants received prophylactic treatment with Adynovate (45 \[±5\] IU/kg), infusion, IV, twice weekly, for at least 50 EDs, or approximately 28 weeks.
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 0.000
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
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
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
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
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
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
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
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
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
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 2.040
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 0.000
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
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
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
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
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 15.750
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
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
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
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
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 outcome

Timeframe: 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.

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).

Outcome measures

Outcome measures
Measure	Adynovate n=34 Participants Participants received prophylactic treatment with Adynovate (45 \[±5\] IU/kg), infusion, IV, twice weekly, for at least 50 EDs, or approximately 28 weeks.
Incremental Recovery Over Time During Adynovate Prophylactic Treatment Baseline	2.4777 (IU/dL)/(IU/kg) Standard Deviation 0.67876
Incremental Recovery Over Time During Adynovate Prophylactic Treatment Week 6	2.5147 (IU/dL)/(IU/kg) Standard Deviation 0.64379
Incremental Recovery Over Time During Adynovate Prophylactic Treatment Study Completion	2.4083 (IU/dL)/(IU/kg) Standard Deviation 0.50714

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Adynovate n=36 Participants Participants received prophylactic treatment with Adynovate (45 \[±5\] IU/kg), infusion, IV, twice weekly, for at least 50 EDs, or approximately 28 weeks.
Pre-dose Level of FVIII Activity in Plasma Baseline	0.06 IU/dL Standard Deviation 0.232
Pre-dose Level of FVIII Activity in Plasma Week 2	3.28 IU/dL Standard Deviation 4.999
Pre-dose Level of FVIII Activity in Plasma Week 6	2.91 IU/dL Standard Deviation 2.802
Pre-dose Level of FVIII Activity in Plasma Week 12	3.61 IU/dL Standard Deviation 3.994
Pre-dose Level of FVIII Activity in Plasma Study Completion	7.06 IU/dL Standard Deviation 16.365

SECONDARY outcome

Timeframe: 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.

IU/mL stands for international units per milliliter.

Outcome measures

Outcome measures
Measure	Adynovate n=37 Participants Participants received prophylactic treatment with Adynovate (45 \[±5\] IU/kg), infusion, IV, twice weekly, for at least 50 EDs, or approximately 28 weeks.
Pre-dose Level of FVIII Antigen in Plasma Week 2	0.0782 IU/mL Standard Deviation 0.07888
Pre-dose Level of FVIII Antigen in Plasma Week 6	0.0689 IU/mL Standard Deviation 0.04518
Pre-dose Level of FVIII Antigen in Plasma Week 12	0.0649 IU/mL Standard Deviation 0.04286
Pre-dose Level of FVIII Antigen in Plasma Week 20	0.0856 IU/mL Standard Deviation 0.05404
Pre-dose Level of FVIII Antigen in Plasma Study Completion	0.1011 IU/mL Standard Deviation 0.11326
Pre-dose Level of FVIII Antigen in Plasma Baseline	0.0276 IU/mL Standard Deviation 0.06577

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Adynovate n=37 Participants Participants received prophylactic treatment with Adynovate (45 \[±5\] IU/kg), infusion, IV, twice weekly, for at least 50 EDs, or approximately 28 weeks.
Pre-dose Level of Von Willebrand Factor (VWF) Antigen in Plasma Baseline	83.69 percent (%) Standard Deviation 35.967
Pre-dose Level of Von Willebrand Factor (VWF) Antigen in Plasma Week 2	84.46 percent (%) Standard Deviation 30.811
Pre-dose Level of Von Willebrand Factor (VWF) Antigen in Plasma Week 6	84.99 percent (%) Standard Deviation 34.216
Pre-dose Level of Von Willebrand Factor (VWF) Antigen in Plasma Week 12	86.57 percent (%) Standard Deviation 30.024
Pre-dose Level of Von Willebrand Factor (VWF) Antigen in Plasma Week 20	91.26 percent (%) Standard Deviation 34.240
Pre-dose Level of Von Willebrand Factor (VWF) Antigen in Plasma Study Completion	90.26 percent (%) Standard Deviation 31.714

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Adynovate n=15 Participants Participants received prophylactic treatment with Adynovate (45 \[±5\] IU/kg), infusion, IV, twice weekly, for at least 50 EDs, or approximately 28 weeks.
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
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 outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Adynovate n=15 Participants Participants received prophylactic treatment with Adynovate (45 \[±5\] IU/kg), infusion, IV, twice weekly, for at least 50 EDs, or approximately 28 weeks.
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
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 outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Adynovate n=15 Participants Participants received prophylactic treatment with Adynovate (45 \[±5\] IU/kg), infusion, IV, twice weekly, for at least 50 EDs, or approximately 28 weeks.
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
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 outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Adynovate n=15 Participants Participants received prophylactic treatment with Adynovate (45 \[±5\] IU/kg), infusion, IV, twice weekly, for at least 50 EDs, or approximately 28 weeks.
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
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 20.0

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Adynovate n=15 Participants Participants received prophylactic treatment with Adynovate (45 \[±5\] IU/kg), infusion, IV, twice weekly, for at least 50 EDs, or approximately 28 weeks.
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
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 outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Adynovate n=15 Participants Participants received prophylactic treatment with Adynovate (45 \[±5\] IU/kg), infusion, IV, twice weekly, for at least 50 EDs, or approximately 28 weeks.
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
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

Adverse Events

Adynovate

Serious events: 1 serious events

Other events: 8 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Adynovate n=37 participants at risk Participants received prophylactic treatment with Adynovate (45 \[±5\] IU/kg), infusion, IV, twice weekly, for at least 50 EDs or approximately 28 weeks.
Hepatobiliary disorders Liver injury	2.7% 1/37 • Up to approximately 28 weeks The SAS included all participants treated with at least 1 Adynovate dose.

Other adverse events

Other adverse events
Measure	Adynovate n=37 participants at risk Participants received prophylactic treatment with Adynovate (45 \[±5\] IU/kg), infusion, IV, twice weekly, for at least 50 EDs or approximately 28 weeks.
Investigations Alanine aminotransferase increased	5.4% 2/37 • Up to approximately 28 weeks The SAS included all participants treated with at least 1 Adynovate dose.
Musculoskeletal and connective tissue disorders Arthralgia	8.1% 3/37 • Up to approximately 28 weeks The SAS included all participants treated with at least 1 Adynovate dose.
Investigations Aspartate aminotransferase increased	5.4% 2/37 • Up to approximately 28 weeks The SAS included all participants treated with at least 1 Adynovate dose.
Gastrointestinal disorders Diarrhoea	8.1% 3/37 • Up to approximately 28 weeks The SAS included all participants treated with at least 1 Adynovate dose.
Metabolism and nutrition disorders Hyperlipidaemia	5.4% 2/37 • Up to approximately 28 weeks The SAS included all participants treated with at least 1 Adynovate dose.
Metabolism and nutrition disorders Hypertriglyceridaemia	5.4% 2/37 • Up to approximately 28 weeks The SAS included all participants treated with at least 1 Adynovate dose.
Musculoskeletal and connective tissue disorders Myalgia	5.4% 2/37 • Up to approximately 28 weeks The SAS included all participants treated with at least 1 Adynovate dose.
Infections and infestations Upper respiratory tract infection	5.4% 2/37 • Up to approximately 28 weeks The SAS included all participants treated with at least 1 Adynovate dose.

Additional Information

Study Director

Takeda

Phone: +1-877-825-3327

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place