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| ID | Type | Description | Link |
|---|---|---|---|
| 2023-000502-26 | EudraCT Number |
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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Adynovate 45±5 IU/kg | Experimental | Participants received prophylactic treatment with Adynovate (45 [±5] IU/kg), infusion, IV, twice weekly, for at least 50 EDs, or approximately 28 weeks. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Adynovate | Biological | 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]). |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | Baseline through study completion or ≥50 EDs whichever occurred last (approximately 28 weeks) |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | Baseline through study completion or ≥50 EDs whichever occurred last (approximately 28 weeks) |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Medical Director | Takeda | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Beijing Children's Hospital, Capital Medical University | Beijing | China | ||||
| Peking Union Medical College Hospital, Chinese Academy of Medical Sciences |
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| Label | URL |
|---|---|
| To obtain more information on the study, click here/on this link | View source |
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Takeda provides access to the de-identified individual participant data (IPD) for eligible studies to aid qualified researchers in addressing legitimate scientific objectives (Takeda's data sharing commitment is available on https://clinicaltrials.takeda.com/takedas-commitment?commitment=5). These IPDs will be provided in a secure research environment following approval of a data sharing request, and under the terms of a data sharing agreement.
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IPD from eligible studies will be shared with qualified researchers according to the criteria and process described on https://vivli.org/ourmember/takeda/. For approved requests, the researchers will be provided access to anonymized data (to respect patient privacy in line with applicable laws and regulations) and with information necessary to address the research objectives under the terms of a data sharing agreement.
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 took part in the study at various investigative sites in China from 27 March 2023 to 05 September 2024.
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| ID | Title | Description |
|---|---|---|
| FG000 | 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. |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
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The Full Analysis Set (FAS) included all participants who were assigned to receive a treatment regimen of Adynovate.
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| ID | Title | Description |
|---|---|---|
| BG000 | Adynovate | Participants received prophylactic treatment with Adynovate (45 [±5] IU/kg), infusion, IV, twice weekly, for at least 50 EDs, or approximately 28 weeks. |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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. | The FAS included all participants who were assigned to receive a treatment regimen of Adynovate. | Posted | Mean | Standard Deviation | bleeds per year | Baseline through study completion or ≥50 EDs whichever occurred last (approximately 28 weeks) |
|
Up to approximately 28 weeks
The SAS included all participants treated with at least 1 Adynovate dose.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Adynovate | Participants received prophylactic treatment with Adynovate (45 [±5] IU/kg), infusion, IV, twice weekly, for at least 50 EDs or approximately 28 weeks. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Liver injury | Hepatobiliary disorders | MedDRA 27.0 | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Alanine aminotransferase increased | Investigations | MedDRA 27.0 | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Study Director | Takeda | +1-877-825-3327 | TrialDisclosures@takeda.com |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Apr 16, 2023 | Mar 4, 2025 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Aug 30, 2024 | Mar 4, 2025 | SAP_001.pdf |
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| ID | Term |
|---|---|
| D006467 | Hemophilia A |
| ID | Term |
|---|---|
| D025861 | Blood Coagulation Disorders, Inherited |
| D001778 | Blood Coagulation Disorders |
| D006402 | Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
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| ID | Term |
|---|---|
| C000609799 | BAX 855 |
| D005169 | Factor VIII |
| ID | Term |
|---|---|
| D001779 | Blood Coagulation Factors |
| D001798 | Blood Proteins |
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
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|
| 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. | Baseline through study completion or ≥50 EDs whichever occurred last (approximately 28 weeks) |
| 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 | 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. | Baseline through study completion or ≥50 EDs whichever occurred last (approximately 28 weeks) |
| 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. | Baseline through study completion or ≥50 EDs whichever occurred last (approximately 28 weeks) |
| Percentage of Participants With Zero Bleeding Episodes During the Study | Percentages were rounded off to the nearest single decimal place. | Baseline through study completion or ≥50 EDs whichever occurred last (approximately 28 weeks) |
| 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. | Baseline through study completion or ≥50 EDs whichever occurred last (approximately 28 weeks) |
| 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. | Baseline through study completion or ≥50 EDs whichever occurred last (approximately 28 weeks) |
| 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 | 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. | Baseline through study completion or ≥50 EDs whichever occurred last (approximately 28 weeks) |
| 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". | Baseline through study completion or ≥50 EDs whichever occurred last (approximately 28 weeks) |
| 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) |
| 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) |
| 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. | Up to 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 | Up to approximately 28 weeks |
| 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. | Day -1 and Week 20: pre-infusion, post-infusion at multiple time-points up to 96 hours |
| 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). | Baseline, Week 6, and Study Completion (approximately Week 28) |
| 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 | IU/mL stands for international units per milliliter. | Baseline, Weeks 2, 6, 12, 20, and Study Completion (approximately Week 28): Within 30 minutes pre-infusion |
| 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 | 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. | Day -1 and Week 20: pre-infusion, post-infusion at multiple timepoints up to 96 hours |
| 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. | Day -1 and Week 20: pre-infusion, post-infusion at multiple timepoints up to 96 hours |
| 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. | Day -1 and Week 20: pre-infusion, post-infusion at multiple timepoints up to 96 hours |
| 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. | Day -1 and Week 20: pre-infusion, post-infusion at multiple timepoints up to 96 hours |
| 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. | Day -1 and Week 20: pre-infusion, post-infusion at multiple timepoints up to 96 hours |
| 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. | Day -1 and Week 20: pre-infusion, post-infusion at multiple timepoints up to 96 hours |
| Beijing |
| China |
| Xiangya Hospital of Central South University | Changsha | China |
| Fujian Medical University Union Hospital | Fuzhou | China |
| Nanfang Hospital Southern Medical University | Guangzhou | China |
| Anhui Province Hospital | Hefei | China |
| Jinan Central Hospital | Jinan | China |
| Shenzhen Second People's Hospital | Shenzhen | China |
| The First Affiliated Hospital of Soochow University | Suzhou | China |
| Institute of Hematology and Blood Diseases Hospital Chinese Academy of Medical Sciences | Tianjin | China |
| Tongji Hospital Tongji Medical College Huazhong University of Science and Technology | Wuhan | China |
| Union Hospital Tongji Medical College Huazhong University of Science and Technology | Wuhan | China |
| years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Ethnicity (NIH/OMB) | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
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| 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. | The FAS included all participants who were assigned to receive a treatment regimen of Adynovate. | Posted | Mean | Standard Deviation | bleeds per year | Baseline through study completion or ≥50 EDs whichever occurred last (approximately 28 weeks) |
|
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| 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. | The FAS included all participants who were assigned to receive a treatment regimen of Adynovate. | Posted | Mean | Standard Deviation | bleeds per year | Baseline through study completion or ≥50 EDs whichever occurred last (approximately 28 weeks) |
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| Secondary | Number of Adynovate Infusions Per Week During the Prophylactic Treatment Period | The FAS included all participants who were assigned to receive a treatment regimen of Adynovate. | Posted | Mean | Standard Deviation | infusions per week | Baseline through study completion or ≥50 EDs whichever occurred last (approximately 28 weeks) |
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| Secondary | Number of Adynovate Infusions Per Month During the Prophylactic Treatment Period | The FAS included all participants who were assigned to receive a treatment regimen of Adynovate. | Posted | Mean | Standard Deviation | infusions per month | Baseline through study completion or ≥50 EDs whichever occurred last (approximately 28 weeks) |
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| 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. | The FAS included all participants who were assigned to receive a treatment regimen of Adynovate. | Posted | Mean | Standard Deviation | IU/kg per week | Baseline through study completion or ≥50 EDs whichever occurred last (approximately 28 weeks) |
|
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| 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. | The FAS included all participants who were assigned to receive a treatment regimen of Adynovate. | Posted | Mean | Standard Deviation | IU/kg per month | Baseline through study completion or ≥50 EDs whichever occurred last (approximately 28 weeks) |
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| Secondary | Percentage of Participants With Zero Bleeding Episodes During the Study | Percentages were rounded off to the nearest single decimal place. | The FAS included all participants who were assigned to receive a treatment regimen of Adynovate. | Posted | Number | percentage of participants | Baseline through study completion or ≥50 EDs whichever occurred last (approximately 28 weeks) |
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| 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. | 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. | Posted | Mean | Standard Deviation | days | Baseline through study completion or ≥50 EDs whichever occurred last (approximately 28 weeks) |
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| 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. | 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. | Posted | Number | bleeding events | Baseline through study completion or ≥50 EDs whichever occurred last (approximately 28 weeks) | bleeding episodes | bleeding episodes |
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| Secondary | Number of Adynovate Infusions Per Bleeding Episode | 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. | Posted | Mean | Standard Deviation | infusions/bleeding episode | Baseline through study completion or ≥50 EDs whichever occurred last (approximately 28 weeks) | treated bleeding episodes | treated bleeding episodes |
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| 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. | 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. | Posted | Mean | Standard Deviation | IU/kg per bleeding episode | Baseline through study completion or ≥50 EDs whichever occurred last (approximately 28 weeks) | treated bleeding episodes | treated bleeding episodes |
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| 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". | 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. | Posted | Baseline through study completion or ≥50 EDs whichever occurred last (approximately 28 weeks) |
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| Secondary | Volume of Actual and Predicted Intra-operative and Post-operative Blood Loss After the Surgery as Assessed by the Operating Surgeon/Investigator | 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. | Posted | Post-operative: Day 1 and at discharge Week 26 |
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| Secondary | Number of Participants Who Required Perioperative Transfusion of Blood, Red Blood Cells, Platelets, and Other Blood Products | The FAS included all participants treated with at least 1 Adynovate dose. | Posted | Count of Participants | Participants | Baseline through study completion or ≥50 EDs whichever occurred last (approximately 28 weeks) |
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| Secondary | Daily Intra-Operative and Post-Operative Weight-Adjusted Consumption Dose of Adynovate | 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. | Posted | Baseline through study completion or ≥50 EDs whichever occurred last (approximately 28 weeks) |
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| 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. | The SAS included all participants treated with at least 1 Adynovate dose. | Posted | Count of Participants | Participants | Up to approximately 28 weeks |
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| 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 | 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. | Posted | Count of Participants | Participants | Up to approximately 28 weeks |
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| 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. | 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. | Posted | Mean | Standard Deviation | International units per deciliter(IU/dL) | Day -1 and Week 20: pre-infusion, post-infusion at multiple time-points up to 96 hours |
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| 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). | 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. | Posted | Mean | Standard Deviation | (IU/dL)/(IU/kg) | Baseline, Week 6, and Study Completion (approximately Week 28) |
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| Secondary | Pre-dose Level of FVIII Activity in Plasma | 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. | Posted | Mean | Standard Deviation | IU/dL | Baseline, Weeks 2, 6, 12, and Study Completion (approximately Week 28): Within 30 minutes pre-infusion |
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| Secondary | Pre-dose Level of FVIII Antigen in Plasma | IU/mL stands for international units per milliliter. | 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. | Posted | Mean | Standard Deviation | IU/mL | Baseline, Weeks 2, 6, 12, 20, and Study Completion (approximately Week 28): Within 30 minutes pre-infusion |
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| Secondary | Pre-dose Level of Von Willebrand Factor (VWF) Antigen in Plasma | 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. | Posted | Mean | Standard Deviation | percent (%) | Baseline, Weeks 2, 6, 12, 20, and Study Completion (approximately Week 28): Within 30 minutes pre-infusion |
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| 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. | 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. | Posted | Mean | Standard Deviation | (dL/h)/kg | Day -1 and Week 20: pre-infusion, post-infusion at multiple timepoints up to 96 hours |
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| 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. | 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. | Posted | Mean | Standard Deviation | deciliters per kilogram (dL/kg) | Day -1 and Week 20: pre-infusion, post-infusion at multiple timepoints up to 96 hours |
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| 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. | 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. | Posted | Mean | Standard Deviation | h*IU/dL | Day -1 and Week 20: pre-infusion, post-infusion at multiple timepoints up to 96 hours |
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| 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. | 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. | Posted | Mean | Standard Deviation | IU/dL | Day -1 and Week 20: pre-infusion, post-infusion at multiple timepoints up to 96 hours |
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| 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. | 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. | Posted | Mean | Standard Deviation | IU/dL | Day -1 and Week 20: pre-infusion, post-infusion at multiple timepoints up to 96 hours |
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| 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. | 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. | Posted | Mean | Standard Deviation | hour | Day -1 and Week 20: pre-infusion, post-infusion at multiple timepoints up to 96 hours |
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| 0 |
| 37 |
| 1 |
| 37 |
| 8 |
| 37 |
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA 27.0 | Systematic Assessment |
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| Aspartate aminotransferase increased | Investigations | MedDRA 27.0 | Systematic Assessment |
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| Diarrhoea | Gastrointestinal disorders | MedDRA 27.0 | Systematic Assessment |
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| Hyperlipidaemia | Metabolism and nutrition disorders | MedDRA 27.0 | Systematic Assessment |
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| Hypertriglyceridaemia | Metabolism and nutrition disorders | MedDRA 27.0 | Systematic Assessment |
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| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA 27.0 | Systematic Assessment |
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| Upper respiratory tract infection | Infections and infestations | MedDRA 27.0 | Systematic Assessment |
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Not provided
Not provided
| D020147 | Coagulation Protein Disorders |
| D006474 | Hemorrhagic Disorders |
| D030342 | Genetic Diseases, Inborn |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D011498 |
| Protein Precursors |
| D001685 | Biological Factors |
| Title | Measurements |
|---|
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| None |
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| Missing |
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| Binding IgM Antibodies to Adynovate |
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| Binding Antibodies to CHO Proteins |
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| Initial PK Assessment: Post-Infusion: 1 Hour |
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| Initial PK Assessment: Post-Infusion: 2 Hours |
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| Initial PK Assessment: Post-Infusion: 4 Hours |
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| Initial PK Assessment: Post-Infusion: 8 Hours |
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| Initial PK Assessment: Post-Infusion: 12 Hours |
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| Initial PK Assessment: Post-Infusion: 24 Hours |
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| Initial PK Assessment: Post-Infusion: 48 Hours |
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| Initial PK Assessment: Post-Infusion: 72 Hours |
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| Initial PK Assessment: Post-Infusion: 96 Hours |
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| Second PK Assessment: Pre-Infusion |
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| Second PK Assessment: Post-Infusion, 30 Minutes |
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| Second PK Assessment: Post-Infusion: 1 Hour |
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| Second PK Assessment: Post-Infusion: 2 Hours |
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| Second PK Assessment: Post-Infusion: 4 Hours |
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| Second PK Assessment: Post-Infusion: 8 Hours |
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| Second PK Assessment: Post-Infusion: 12 Hours |
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| Second PK Assessment: Post-Infusion: 24 Hours |
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| Second PK Assessment: Post-Infusion: 48 Hours |
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| Second PK Assessment: Post-Infusion: 72 Hours |
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| Second PK Assessment: Post-Infusion: 96 Hours |
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| Study Completion |
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| Week 6 |
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| Week 12 |
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| Study Completion |
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| Week 6 |
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| Week 12 |
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| Week 20 |
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| Study Completion |
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|
| Week 6 |
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| Week 12 |
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| Week 20 |
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| Study Completion |
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