Von Willebrand Disease
Conditions
Brief summary
The purpose of this phase 3 study is to investigate the efficacy and safety, including immunogenicity, thrombogenicity and hypersensitivity reactions, as well as pharmacokinetics (PK), health related quality of life (HRQoL) and pharmacoeconomics of prophylactic treatment with recombinant von Willebrand factor (rVWF) (vonicog alfa) in adult participants with severe von Willebrand disease (VWD).
Interventions
BIOLOGICALvon Willebrand factor (Recombinant)
OD participants will receive intravenous (IV) rVWF:RCo at an initial prophylactic dose of 50 +/- 10 International Unit per Kilogram (IU/kg) twice (two infusions) a week for at least 12 months up to 15 months and may be increased up to 80 IU/kg. pdVWF switch cohort participants will receive rVWF:RCo equivalent (± 10%) to the weekly VWF dose received during prophylactic treatment with pdVWF.
BIOLOGICALAntihemophilic Factor (Recombinant)
During prophylaxis period any bleeding episodes requiring substitution therapy with VWF concentrate to control bleeding will be treated with rVWF with or without ADVATE. Participants will receive rFVIII IV if necessary for OD treatment of breakthrough bleeds or for peri-operative. The dose will be according to the bleeding type and severity and it will be adjusted to the clinical response.
Sponsors
Baxalta Innovations GmbH, now part of Shire
Takeda
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Participant has a documented diagnosis of severe von Willebrand disease (VWD) (baseline Von Willebrand factor: Ristocetin cofactor activity (VWF:RCo) less than (\<) 20 International Units/Deciliter \[IU/dL\]) with a history of requiring substitution therapy with von Willebrand factor concentrate to control bleeding 1. Type 1 (VWF:RCo \<20 IU/dL) or, 2. Type 2A (as verified by multimer pattern), Type 2B (as diagnosed by genotype), Type 2M or, 3. Type 3 (Von Willebrand factor antigen (VWF:Ag) less than or equal to \[\< or =\] 3 IU/dL). 2. Diagnosis is confirmed by genetic testing and multimer analysis, documented in patient history or at screening. 3. For on-demand patient group, participant currently receiving on-demand treatment for whom prophylactic treatment is recommended by the investigator. 4. For Plasma derived von Willebrand factor (pdVWF) product switch patient group, participant has been receiving prophylactic treatment of pdVWF products for no less than 12 months prior to screening. 5. For on-demand patient group, participant has greater than or equal to (\>or=) 3 documented spontaneous bleeds (not including menorrhagia) requiring von Willebrand factor (VWF) treatment during the past 12 months. 6. Availability of records to reliably evaluate type, frequency and treatment of bleeding episodes during at least 12 months preceding enrollment. Up to 24 months retrospective data should be collected if available. Availability of dosing and factor consumption during 12 months (up to 24 months) of treatment prior to enrollment is required for pdVWF switch participants and is desired (but not a requirement) for on-demand participants. 7. Participant is \> or = 18 years old at the time of screening and has a body mass index \> or = 15 but \<40 kilogram per meter square (kg/m\^2). 8. If female of childbearing potential, participant presents with a negative blood/urine pregnancy test at screening and agrees to employ adequate birth control measures for the duration of the study. 9. Participant is willing and able to comply with the requirements of the protocol.
Exclusion criteria
1. The participant has been diagnosed with Type 2N Von Willebrand disease (VWD), pseudo VWD, or another hereditary or acquired coagulation disorder other than VWD (eg qualitative and quantitative platelet disorders or prothrombin time \[PT\]/international normalized ratio \[INR\] greater than \[\>\]1.4). 2. The participant is currently receiving prophylactic treatment with more than 5 infusions per week. 3. The participant is currently receiving prophylactic treatment with a weekly dose exceeding 240 IU/kg. 4. The participant has a history or presence of a VWF inhibitor at screening. 5. The participant has a history or presence of a Factor VIII (FVIII) inhibitor with a titer ≥0.4 Bethesda units (BU) (by Nijmegen modified Bethesda assay) or \> or = 0.6 Bethesda Unit (BU) (by Bethesda assay). 6. The participant has a known hypersensitivity to any of the components of the study drugs, such as to mouse or hamster proteins. 7. The participant has a medical history of immunological disorders, excluding seasonal allergic rhinitis/conjunctivitis, mild asthma, food allergies or animal allergies. 8. The participant has a medical history of a thromboembolic event. 9. The participant is human immunodeficiency virus (HIV) positive with an absolute Helper T cell (CD4) count \<200/ cubic millimeter (mm\^3). 10. The participant has been diagnosed with significant liver disease per investigator's medical assessment of the participant's current condition or medical history or as evidenced by any of the following: serum alanine aminotransferase (ALT) greater than 5 times the upper limit of normal; hypoalbuminemia; portal vein hypertension (e.g., presence of otherwise unexplained splenomegaly, history of esophageal varices). 11. The participant has been diagnosed with renal disease, with a serum creatinine (CR) level \> or = 2.5 milligram per deciliter (mg/dL). 12. The participant has a platelet count \<100,000/ milliliter (mL) at screening. 13. The participant has been treated with an immunomodulatory drug, excluding topical treatment (e.g., ointments, nasal sprays), within 30 days prior to signing the informed consent. 14. The participant is pregnant or lactating at the time of enrollment. 15. Patient has cervical or uterine conditions causing menorrhagia or metrorrhagia (including infection, dysplasia). 16. The participant has participated in another clinical study involving another Investigational product (IP) or investigational device within 30 days prior to enrollment or is scheduled to participate in another clinical study involving an IP or investigational device during the course of this study. 17. The participant has a progressive fatal disease and/or life expectancy of less than 15 months. 18. The participant is scheduled for a surgical intervention. 19. The participant is identified by the investigator as being unable or unwilling to cooperate with study procedures. 20. The participant has a mental condition rendering him/her unable to understand the nature, scope and possible consequences of the study and/or evidence of an uncooperative attitude. 21. The participant is in prison or compulsory detention by regulatory and/or juridical order. 22. The participant is member of the study team or in a dependent relationship with one of the study team members which includes close relatives (i.e., children, partner/spouse, siblings and parents) as well as employees.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Ratio of Annualized Bleeding Rate (ABR) for Spontaneous Bleeding Episodes (BEs) (On-study ABR / Historical ABR) Assessed by Investigator During Prophylactic Treatment With rVWF Through Month 12 | Up to 12 months | ABR for treated spontaneous BEs while on prophylactic treatment with rVWF through month 12 of treatment period/observation period (in years), where an observation period = (date of completion/termination - date of first dose + 1)/365.2425. Bleeds occurred at the same anatomical location with the same etiology within 24 hours after onset of the first bleed were considered a single bleed. Bleeding occurred at multiple locations related to the same injury were considered as a single bleeding episode. Historical observation period for historical BEs was 365 days prior to first dose of study drug. On-study observation period started on the day of first administration of study drug and continuing through the date of completion/discontinuation from study. The comparison of the two ABRs (on-study and historical) for spontaneous bleeding episodes (not related to trauma) during prophylactic treatment with rVWF was reported as a ratio of mean ABRs (on-study ABR:historical ABR). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Prior On-demand Participants Achieved Spontaneous ABR Percent Reduction Success Through Month 12 | Up to 12 months | For prior on-demand participants, spontaneous ABR percent reduction success was defined as at least 25% reduction of the ABR for treated spontaneous (not related to trauma) BEs during the first 12 months of rVWF (vonicog alfa) prophylaxis relative to the participant's own historical treated spontaneous ABR. Percentage of participants with ABR percent reduction success for on-demand cohort was reported. |
| Percentage of Switch Participants With Spontaneous ABR Preservation Success Through Month 12 | Up to 12 months | For switch participants, spontaneous ABR preservation success was defined as achieving an ABR for treated spontaneous BEs during first 12 months of rVWF (vonicog alfa) prophylaxis that was no greater than the participant's own historical ABR for treated spontaneous BEs during prophylactic treatment with pdVWF. Percentage of participants with ABR preservation success in switch cohort was reported. |
| Number of Participants Based on Categorized Spontaneous ABR (sABR) Through Month 12 | Baseline through Month 12 | The sABR was the number of spontaneous bleeds divided by the observation period in years, where an observation period = (date of completion/termination-date of first dose+1)/365.2425.sABR was categorized based on number of BEs as 0, greater than (\>) 0 through 2,\>2 through 5,\>5 during the prophylactic treatment with rVWF (vonicog alfa) through 12 months. Bleeding at multiple locations related to the same injury was counted as single bleeding episode. BEs of unknown cause were counted as spontaneous bleeds. Observation period for historical BEs was 365 days prior to first dose of study drug. The baseline sABR for treated BEs was based on historical BE data and on-study sABR was based on treated spontaneous BEs during prophylaxis with rVWF through Month 12. On-study observation period started on the day of first administration of study drug continuing through the date of completion/discontinuation from study. Number of participants based on categorized sABR was calculated and reported. |
| Total Number of Infusions Administered Per Participant During Prophylactic Treatment With rVWF Through Month 12 | Up to 12 months | For each participant, the total number of infusions was counted as the total number of unique infusions of rVWF which were administered between the dates of informed consent and termination from the study, inclusive, regardless of the date and time of administration. The total number of infusions administered during the study was entered in electronic case record form (eCRF), and recorded in ERT system. Total number of infusions administered per participant during prophylactic treatment With rVWF through 12 months was calculated. |
| Average Number of Infusions Per Week Per Participant During Prophylactic Treatment With rVWF Through Month 12 | Up to 12 months | Average number of infusions per week per participant during prophylactic treatment With rVWF through 12 months was calculated. |
| Total Weight Adjusted Consumption of rVWF Per Participant During Prophylactic Treatment Through Month 12 | Up to 12 months | For each participant, the body weight-adjusted dose (IU/kg) was derived as the number of units of rVWF infused (IU) divided by the last available body weight (kilogram \[kg\]) prior to the infusion. Total weight adjusted consumption of rVWF (vonicog alfa) per participant during prophylactic treatment was reported. |
| Number of Treated Spontaneous BEs by Location of Bleeding While on Prophylactic Treatment With rVWF Through Month 12 | Up to 12 months | Number of treated spontaneous BEs by location of bleeding (for example: oral and other mucosa, menorrhagia, hemarthrosis, etc.) while on prophylactic treatment with rVWF was reported. |
| Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs | From first dose of study drug up to end of study (approximately 32 months) | An adverse event (AE) is defined as any untoward medical occurrence in a participant administered IP that does not necessarily have a causal relationship with the treatment. TEAEs were events which occurred on or after the date and time of administration of the first dose of study medication. TEAEs included both serious AEs and non-serious AEs. Number of participants with TEAEs and serious TEAEs were reported. |
| Number of Participants Based on Severity of TEAEs | From first dose of study drug up to end of study (approximately 32 months) | An AE is defined as any untoward medical occurrence in a participant administered IP that does not necessarily have a causal relationship with the treatment. TEAEs were events which occurred on or after the date and time of administration of the first dose of study medication. TEAEs included both serious AEs and non-serious AEs. Severity of TEAEs was determined by following definitions: Mild: No limitation of usual activities; Moderate: Some limitation of usual activities and may required therapeutic intervention; Severe: Inability to carry out usual activities with sequelae, which required therapeutic intervention. Participants were counted by considering the maximum severity of TEAEs. |
| Number of Participants With TEAEs Based Causality | From first dose of study drug up to end of study (approximately 32 months) | An AE was defined as any untoward medical occurrence in a participant administered IP that does not necessarily have a causal relationship with the treatment. TEAEs were events which occurred on or after the date and time of administration of the first dose of study medication. TEAEs included both serious AEs and non-serious AEs. For each AE, the investigator assessed the causal relationship between the IP and the AE based on clinical expertise and judgment according to the following circumstances of the AE: Not related, Unlikely related, Possibly related, or Probably related. A related TEAE was defined as any TEAE indicated as 'possibly related' or 'probably related'. Number of participants with TEAEs based causality was reported. |
| Number of Participants With Thromboembolic Events | From first dose of study drug up to end of study (approximately 32 months) | Thromboembolism defined as formation in a blood vessel of a clot (thrombus) that breaks loose and carried by the blood stream and could plug another vessel. Number of participants with thromboembolic events as TEAEs of special interest was reported. A broad standard search query approach was used (broad SMQ) to identify all potential thromboembolic events of interest which were then medically assessed. Number of participants with thromboembolic events as TEAEs of special interest was reported. |
| Number of Participants With Hypersensitivity Reactions | From first dose of study drug up to end of study (approximately 32 months) | Hypersensitivity (also called hypersensitivity reaction or intolerance) defined as undesirable reactions produced by the normal immune system, including allergies and autoimmunity. Potential hypersensitivity events were identified by broad search criteria and then medically assessed. Number of participants with hypersensitivity reactions as TEAEs of special interest was calculated. |
| Number of Participants Who Developed Neutralizing Antibodies to Von Willebrand Factor (rVWF) and Factor VIII (FVIII) | Baseline through Month 12 | Three functional VWF assays for von Willebrand factor collagen binding (VWF:CB), von Willebrand factor: Ristocetin Cofactor (VWF:RCo) and von Willebrand factor VIII B (VWF:FVIIIB) were used to test the presence of neutralizing anti-VWF antibodies. Neutralizing antibodies to VWF:RCo, VWF:CB and VWF:FVIIIB activities was measured by assays based on the Bethesda assay established for quantitative analysis of FVIII inhibitors (Nijmegen modification of the Bethesda assay). Only confirmed neutralizing anti -VWF antibodies were considered inhibitors. Number of participants who developed neutralizing antibodies to rVWF and FVIII were assessed. |
| Number of Participants Who Developed of Total Binding Antibodies to Von Willebrand Factor (rVWF) and Factor VIII (FVIII) | Baseline through Month 12 | The presence of total binding anti-VWF antibodies was determined by an enzyme-linked immunosorbent assay (ELISA) employing polyclonal anti-human Immunoglobulin (Ig) antibodies (IgG, IgM and IgA). Binding antibodies against FVIII was analyzed using a proprietary enzyme immunoassay. Number of participants who developed of total binding antibodies to rVWF and FVIII was assessed. |
| Number of Participants Who Developed Binding Antibodies to Chinese Hamster Ovary (CHO) Proteins, Mouse Immunoglobulin G (IgG) and/or rFurin | Baseline through Month 12 | Total Ig antibodies (IgG, IgA, IgM) against CHO protein and human furin was analyzed using ELISA. For detection and quantification of IgG antibodies originating from human plasma that were directed against mouse-IgG (HAMA: human anti- mouse antibodies) was assessed using ELISA (Medac, Hamburg, Germany). Number of participants who developed binding antibodies to CHO proteins, Mouse IgG and/or rFurin was assessed. |
| Number of Participants With Clinically Significant Change From Baseline in Vital Signs | Baseline up to end of study (approximately 32 months) | Vital signs included blood pressure (systolic and diastolic), pulse rate, respiratory rate and body temperature. Number of participants with clinically significant change from baseline in vital signs was assessed. |
| Number of Participants With Clinically Significant Change From Baseline in Clinical Laboratory Parameters | Baseline up to end of study (approximately 32 months) | Clinical laboratory parameters included hematology and clinical chemistry assessments. Number of participants with clinically significant change from baseline in clinical laboratory parameters was assessed. |
| Pharmacokinetic (PK) Assessment: Incremental Recovery (IR) Based on Von Willebrand Factor: Ristocetin Cofactor (VWF:Rco) Activity | At baseline: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours | IR at the maximum plasma concentration of VWF:RCo activity at initial PK assessment was reported. Unit of measure: International Units per deciliter/International Units per kilogram (\[IU/dL\]/\[IU/kg\]). |
| Pharmacokinetic Assessment: Incremental Recovery (IR) Based on Von Willebrand Factor Antigen (VWF:Ag) Activity | At baseline: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours | IR based on VWF:Ag activity at initial PK assessment was reported. |
| Pharmacokinetic Assessment: Incremental Recovery (IR) Based on Von Willebrand Factor Collagen Binding (VWF:CB) Activity | At baseline: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours | IR at the maximum plasma concentration of VWF:CB activity at initial PK assessment was reported. |
| Pharmacokinetic Assessment: Terminal Half-life (T1/2) Based on Von Willebrand Factor: Ristocetin Cofactor (VWF:Rco) Activity | At baseline: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours | T1/2 defined as the time in hours required for the concentration of the drug to reach half of its original value. T1/2 based on VWF:Rco activity at initial PK assessment was reported. |
| Pharmacokinetic Assessment: Terminal Half-life (T1/2) Based on Von Willebrand Factor Antigen (VWF:Ag) Activity | At baseline: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours | T1/2 defined as the time in hours required for the concentration of the drug to reach half of its original value. T1/2 based on VWF:Ag activity at initial PK assessment was reported. |
| Pharmacokinetic Assessment: Terminal Half-life (T1/2) Based on Von Willebrand Factor Collagen Binding (VWF:CB) Activity | At baseline: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours | T1/2 defined as the time in hours required for the concentration of the drug to reach half of its original value. T1/2 based on VWF:CB activity at initial PK assessment was reported. |
| Pharmacokinetic Assessment: Mean Residence Time (MRT) Based on Von Willebrand Factor: Ristocetin Cofactor (VWF:Rco) Activity | At baseline: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours | MRT was calculated as (AUMC0-∞/AUC0-∞) - T1/2 where T1 represented the time duration of infusion, where AUMC represented the area under the first moment curve. MRT based on VWF:Rco activity at initial PK assessment was reported. |
| Pharmacokinetic Assessment: Mean Residence Time (MRT) Based on Von Willebrand Factor Antigen (VWF:Ag) Activity | At baseline: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours | MRT was calculated as (AUMC0-∞/AUC0-∞) - T1/2 where T1 represented the time duration of infusion, where AUMC represented the area under the first moment curve. MRT based on VWF:Ag activity at initial PK assessment was reported. |
| Pharmacokinetic Assessment: Mean Residence Time (MRT) Based on Von Willebrand Factor Collagen Binding (VWF:CB) Activity | At baseline: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours | MRT was calculated as (AUMC0-∞/AUC0-∞) - T1/2 where T1 represented the time duration of infusion, where AUMC represented the area under the first moment curve. MRT based on VWF:CB activity at initial PK assessment was reported. |
| Pharmacokinetic Assessment: Area Under the Plasma Concentration Versus Time Curve From Time 0 Extrapolated to Infinity (AUC0-∞) Based on Von Willebrand Factor: Ristocetin Cofactor (VWF:Rco) Activity | At baseline: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours | AUC0-∞ based on VWF:Rco activity at initial PK assessment was reported. Unit of measure: International Units\*hour per deciliter (IU\*h/dL). |
| Pharmacokinetic Assessment: Area Under the Plasma Concentration Versus Time Curve From Time 0 Extrapolated to Infinity (AUC0-∞) Based on Von Willebrand Factor Antigen (VWF:Ag) Activity | At baseline: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours | AUC0-∞ based on VWF:Ag activity at initial PK assessment was reported. |
| Pharmacokinetic Assessment: Area Under the Plasma Concentration Versus Time Curve From Time 0 Extrapolated to Infinity (AUC0-∞) Based on Von Willebrand Factor Collagen Binding (VWF:CB) Activity | At baseline: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours | AUC0-∞ based on VWF:CB activity at initial PK assessment was reported. |
| Pharmacokinetic Assessment: Area Under the Plasma Concentration Versus Time Curve From Time 0 to the Last Measurable Concentration (AUC0-tlast) Based on Von Willebrand Factor: Ristocetin Cofactor (VWF:Rco) Activity | At baseline: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours | AUC0-tlast based on VWF:Rco activity at initial PK assessment was reported. |
| Pharmacokinetic Assessment: Area Under the Plasma Concentration Versus Time Curve From Time 0 to the Last Measurable Concentration (AUC0-tlast) Based on Von Willebrand Factor Antigen (VWF:Ag) Activity | At baseline: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours | AUC0-tlast based on VWF:Ag activity at initial PK assessment was reported. |
| Pharmacokinetic Assessment: Area Under the Plasma Concentration Versus Time Curve From Time 0 to the Last Measurable Concentration (AUC0-tlast) Based on Von Willebrand Factor Collagen Binding (VWF:CB) Activity | At baseline: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours | AUC0-tlast based on VWF:CB activity at initial PK assessment was reported. |
| Pharmacokinetic Assessment: Maximum Plasma Concentration (Cmax) Based on Von Willebrand Factor: Ristocetin Cofactor (VWF:Rco) Activity | At baseline: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours | Cmax based on VWF:Rco at initial PK assessment was reported. Unit of measure: International Units per deciliter (IU/dL). |
| Pharmacokinetic Assessment: Maximum Plasma Concentration (Cmax) Based on Von Willebrand Factor Antigen (VWF:Ag) Activity | At baseline: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours | Cmax based on VWF:Ag activity at initial PK assessment was reported. |
| Pharmacokinetic Assessment: Maximum Plasma Concentration (Cmax) Based on Von Willebrand Factor Collagen Binding (VWF:CB) Activity | At baseline: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours | Cmax based on VWF:CB activity at initial PK assessment was reported. |
| Pharmacokinetic Assessment: Minimum Time to Reach the Maximum Plasma Concentration (Tmax) Based on Von Willebrand Factor: Ristocetin Cofactor (VWF:Rco) Activity | At baseline: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours | Tmax based on VWF:Rco activity at initial PK assessment was reported. |
| Pharmacokinetic Assessment: Minimum Time to Reach the Maximum Plasma Concentration (Tmax) Based on Von Willebrand Factor Antigen (VWF:Ag) Activity | At baseline: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours | Tmax based on VWF:Ag activity at initial PK assessment was reported. |
| Pharmacokinetic Assessment: Minimum Time to Reach the Maximum Plasma Concentration (Tmax) Based on Von Willebrand Factor Collagen Binding (VWF:CB) Activity | At baseline: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours | Tmax based on VWF:CB activity at initial PK assessment was reported. |
| Pharmacokinetic Assessment: Volume of Distribution at Steady State (Vss) Based on Von Willebrand Factor: Ristocetin Cofactor (VWF:Rco) Activity | At baseline: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours | Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. Vss based on VWF:Rco activity at initial assessment was reported. |
| Pharmacokinetic Assessment: Volume of Distribution at Steady State (Vss) Based on Von Willebrand Factor Antigen (VWF:Ag) Activity | At baseline: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours | Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. Vss based on VWF:Ag activity at initial assessment was reported. |
| Pharmacokinetic Assessment: Volume of Distribution at Steady State (Vss) Based on Von Willebrand Factor Collagen Binding (VWF:CB) Activity | At baseline: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours | Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. Vss based on VWF:CB activity at initial assessment was reported. |
| Pharmacokinetic Assessment: Clearance (CL) Based on Von Willebrand Factor: Ristocetin Cofactor (VWF:Rco) Activity | At baseline: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours | Clearance is defined as a quantitative measure of the rate at which a drug substance is removed from the body. CL based on VWF:Rco activity at initial PK assessment was reported. Unit of measure: deciliter per kilogram per hour (dL/kg/h). |
| Pharmacokinetic Assessment: Clearance (CL) Based on Von Willebrand Factor Antigen (VWF:Ag) Activity | At baseline: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours | Clearance is defined as a quantitative measure of the rate at which a drug substance is removed from the body. CL based on VWF:Ag activity at initial PK assessment was reported. |
| Pharmacokinetic Assessment: Clearance (CL) Based on Von Willebrand Factor Collagen Binding (VWF:CB) Activity | At baseline: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours | Clearance is defined as a quantitative measure of the rate at which a drug substance is removed from the body. CL based on VWF:CB activity at initial PK assessment was reported. |
| Pharmacodynamic (PD) Assessment: Maximum Plasma Concentration (Cmax) Based on Factor VIII Clotting (FVIII:C) Activity | At baseline: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours | Cmax based on FVIII:C activity at initial PD assessment by the 1-stage clotting assay was reported. |
| Pharmacodynamic Assessment: Minimum Time to Reach the Maximum Plasma Concentration (Tmax) Based on Factor VIII Clotting (FVIII:C) Activity | At baseline: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours | Tmax based on FVIII:C activity at initial PD assessment by the 1-stage clotting assay was reported. |
| Pharmacodynamic Assessment: Area Under the Plasma Concentration Versus Time Curve From Time 0 to the Last Measurable Concentration (AUC0-tlast) Based on Factor VIII Clotting (FVIII:C) Activity | At baseline: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours | AUC0-tlast based on FVIII:C activity at initial PD assessment by the 1-stage clotting assay was reported. |
| Pharmacokinetic Assessment at Steady State: Area Under the Plasma Concentration Versus Time Curve From Time 0 to End of the Partial Dosing Interval (AUC0- Tau;ss) Based on Von Willebrand Factor: Ristocetin Cofactor (VWF:Rco) Activity | At Month 12: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours | AUC0-tau;ss based on VWF:Rco activity at steady state during end of study (Month 12) was reported. |
| Pharmacokinetic Assessment at Steady State: Area Under the Plasma Concentration Versus Time Curve From Time 0 to End of the Partial Dosing Interval (AUC0- Tau;ss) Based on Von Willebrand Factor Antigen (VWF:Ag) Activity | At Month 12: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours | AUC0-tau;ss based on VWF:Ag activity at steady state during end of study (Month 12) was reported. |
| Pharmacokinetic Assessment at Steady State: Area Under the Plasma Concentration Versus Time Curve From Time 0 to End of the Partial Dosing Interval (AUC0- Tau;ss) Based on Von Willebrand Factor Collagen Binding (VWF:CB) Activity | At Month 12: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours | AUC0-tau;ss based on VWF:CB activity at steady state during end of study (Month 12) was reported. |
| Pharmacokinetics Assessment at Steady State: Maximum Plasma Concentration During the Partial Dosing Interval at Steady State (Cmax;ss) Based on Von Willebrand Factor: Ristocetin Cofactor (VWF:Rco) Activity | At Month 12: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours | Cmax;ss based on VWF:Rco activity at steady state during end of study (Month 12) was reported. |
| Pharmacokinetics Assessment at Steady State: Maximum Plasma Concentration During the Partial Dosing Interval at Steady State (Cmax;ss) Based on Von Willebrand Factor Antigen (VWF:Ag) Activity | At Month 12: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours | Cmax;ss based on VWF:Ag activity at steady state during end of study (Month 12) was reported. |
| Pharmacokinetics Assessment at Steady State: Maximum Plasma Concentration During the Partial Dosing Interval at Steady State (Cmax;ss) Based on Von Willebrand Factor Collagen Binding (VWF:CB) Activity | At Month 12: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours | Cmax;ss based on VWF:CB activity at steady state during end of study (Month 12) was reported. |
| Pharmacokinetics Assessment at Steady State: Minimum Time to Reach the Maximum Plasma Concentration at Steady State (Tmax;ss) Based on Von Willebrand Factor: Ristocetin Cofactor (VWF:Rco) Activity | At Month 12: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours | Tmax;ss based on VWF:Rco activity at steady state during end of study (Month 12) was reported. |
| Pharmacokinetics Assessment at Steady State: Minimum Time to Reach the Maximum Plasma Concentration at Steady State (Tmax;ss) Based on Von Willebrand Factor Antigen (VWF:Ag) Activity | At Month 12: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours | Tmax;ss based on VWF:Ag activity at steady state during end of study (Month 12) was reported. |
| Pharmacokinetics Assessment at Steady State: Minimum Time to Reach the Maximum Plasma Concentration at Steady State (Tmax;ss) Based on Von Willebrand Factor Collagen Binding (VWF:CB) Activity | At Month 12: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours | Tmax;ss based on VWF:CB activity at steady state during end of study (Month 12) was reported. |
| Pharmacokinetics Assessment at Steady State: Minimum Plasma Concentration During the Partial Dosing Interval at Steady State (Cmin;ss) Based on Von Willebrand Factor: Ristocetin Cofactor (VWF:Rco) Activity | At Month 12: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours | Cmin;ss based on VWF:Rco activity at steady state during end of study (Month 12) was reported. |
| Pharmacokinetics Assessment at Steady State: Minimum Plasma Concentration During the Partial Dosing Interval at Steady State (Cmin;ss) Based on Von Willebrand Factor Antigen (VWF:Ag) Activity | At Month 12: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours | Cmin;ss based on VWF:Rco activity at steady state during end of study (Month 12) was reported. |
| Pharmacokinetics Assessment at Steady State: Minimum Plasma Concentration During the Partial Dosing Interval at Steady State (Cmin;ss) Based on Von Willebrand Factor Collagen Binding (VWF:CB) Activity | At Month 12: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours | Cmin;ss based on VWF:CB activity at steady state during end of study (Month 12) was reported. |
| Pharmacodynamic Assessment at Steady State: Area Under the Plasma Concentration Versus Time Curve From Time 0 to End of the Partial Dosing Interval (AUC0- Tau;ss) Based on Factor VIII Clotting (FVIII:C) Activity | At Month 12: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours | AUC0-tau;ss based on FVIII:C activity at steady state during end of study (Month 12) was reported. |
| Pharmacodynamic Assessment at Steady State: Maximum Plasma Concentration During the Partial Dosing Interval at Steady State (Cmax;ss) Based on Factor VIII Clotting (FVIII:C) Activity | At Month 12: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours | Cmax;ss based on FVIII:C activity was assessed at steady state during end of study (Month 12) was reported. |
| Pharmacodynamic Assessment at Steady State: Minimum Time to Reach the Maximum Plasma Concentration at Steady State (Tmax;ss) Based on Factor VIII Clotting (FVIII:C) Activity | At Month 12: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours | Tmax;ss based on FVIII:C activity at steady state during end of study (Month 12) was reported. |
| Pharmacodynamic Assessment at Steady State: Minimum Plasma Concentration During the Partial Dosing Interval at Steady State (Cmin;ss) Based on Factor VIII Clotting (FVIII:C) Activity | At Month 12: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours | Cmin;ss based on FVIII:C activity at steady state during end of study (Month 12) was reported. |
| Factor VIII (FVIII) Clotting Activity | At Month 12: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours | FVIII clotting activity (FVIII:C) levels was assessed and reported as per pre-specified PK time points at Month 12. |
Countries
Canada, France, Germany, Italy, Netherlands, Russia, Spain, Turkey (Türkiye), United States
Participant flow
Recruitment details
This study was conducted at 32 sites in the United States, Canada, France, Germany, Italy, Netherlands, Russia, Spain, and Turkey between 16 November 2017 (first participant first visit) and 06 July 2020 (last participant last visit).
Pre-assignment details
A total of 29 participants were screened, out of which 6 participants were screen failures and 23 participants were grouped into 2 cohorts: Prior On-demand and Switch (based on the previous von Willebrand disease \[VWD\] treatment they received prior to the study) and received prophylactic treatment with recombinant von Willebrand factor (rVWF).
Participants by arm
| Arm | Count |
|---|---|
| Prior On-demand Participants Participants who had taken only on-demand VWF prior to the current study received rVWF (vonicog alpha) initial prophylactic treatment at a dose range of 50 +/- 10 IU/kg, intravenous infusion, twice per week for a planned period of 12 months. Dose escalation to higher dose (up to 80 IU/kg per infusion) or frequency (up to 3 times a week) was based on medical indication and investigator judgment. During this prophylactic treatment period, any breakthrough bleeding episodes requiring replacement therapy with VWF concentrate was treated with rVWF with or without ADVATE (rFVIII); the dose was determined according to the bleeding type and severity, and was adjusted based on the participant's clinical response. | 13 |
| Switch Participants Participants who had taken prophylactic treatment with pdVWF prior to current study and switched to prophylaxis with rVWF (vonicog alpha) during the study for a planned period of 12 months; received rVWF twice weekly at an initial prophylactic dose of +/- 10 percent (%) of VWF in the pdVWF weekly dose received prior to this study. Dosing with rVWF up to 80 IU/kg per infusion or at a frequency up to 3 times a week or once a week were allowed depending on the total weekly dose and the dosing regimen used in their previous pdVWF prophylaxis regimen and based on medical indication and investigator judgment. During this prophylactic treatment period, any breakthrough bleeding episodes requiring replacement therapy with VWF concentrate was treated with rVWF with or without ADVATE (rFVIII); the dose was determined according to the bleeding type and severity, and was adjusted based on the participant's clinical response. | 10 |
| Total | 23 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 |
| Overall Study | other | 1 | 1 |
| Overall Study | Withdrawal by Subject | 2 | 1 |
Baseline characteristics
| Characteristic | Switch Participants | Total | Prior On-demand Participants |
|---|---|---|---|
| Age, Continuous | 43.9 years STANDARD_DEVIATION 21.8 | 40.6 years STANDARD_DEVIATION 19.3 | 38.0 years STANDARD_DEVIATION 17.6 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants | 2 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 7 Participants | 20 Participants | 13 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) White | 9 Participants | 22 Participants | 13 Participants |
| Sex: Female, Male Female | 3 Participants | 11 Participants | 8 Participants |
| Sex: Female, Male Male | 7 Participants | 12 Participants | 5 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 13 | 0 / 10 |
| other Total, other adverse events | 10 / 13 | 6 / 10 |
| serious Total, serious adverse events | 1 / 13 | 2 / 10 |
Outcome results
Primary
Ratio of Annualized Bleeding Rate (ABR) for Spontaneous Bleeding Episodes (BEs) (On-study ABR / Historical ABR) Assessed by Investigator During Prophylactic Treatment With rVWF Through Month 12
ABR for treated spontaneous BEs while on prophylactic treatment with rVWF through month 12 of treatment period/observation period (in years), where an observation period = (date of completion/termination - date of first dose + 1)/365.2425. Bleeds occurred at the same anatomical location with the same etiology within 24 hours after onset of the first bleed were considered a single bleed. Bleeding occurred at multiple locations related to the same injury were considered as a single bleeding episode. Historical observation period for historical BEs was 365 days prior to first dose of study drug. On-study observation period started on the day of first administration of study drug and continuing through the date of completion/discontinuation from study. The comparison of the two ABRs (on-study and historical) for spontaneous bleeding episodes (not related to trauma) during prophylactic treatment with rVWF was reported as a ratio of mean ABRs (on-study ABR:historical ABR).
Time frame: Up to 12 months
Population: Full analysis set (FAS) composed of all participants who received prophylactic IP treatment.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Prior On-demand Participants | Ratio of Annualized Bleeding Rate (ABR) for Spontaneous Bleeding Episodes (BEs) (On-study ABR / Historical ABR) Assessed by Investigator During Prophylactic Treatment With rVWF Through Month 12 | 0.085 ratio |
| Switch Participants | Ratio of Annualized Bleeding Rate (ABR) for Spontaneous Bleeding Episodes (BEs) (On-study ABR / Historical ABR) Assessed by Investigator During Prophylactic Treatment With rVWF Through Month 12 | 0.550 ratio |
Secondary
Average Number of Infusions Per Week Per Participant During Prophylactic Treatment With rVWF Through Month 12
Average number of infusions per week per participant during prophylactic treatment With rVWF through 12 months was calculated.
Time frame: Up to 12 months
Population: FAS composed of all participants who received prophylactic IP treatment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Prior On-demand Participants | Average Number of Infusions Per Week Per Participant During Prophylactic Treatment With rVWF Through Month 12 | 1.88 infusions per week | Standard Deviation 0.7 |
| Switch Participants | Average Number of Infusions Per Week Per Participant During Prophylactic Treatment With rVWF Through Month 12 | 1.85 infusions per week | Standard Deviation 0.4 |
Secondary
Factor VIII (FVIII) Clotting Activity
FVIII clotting activity (FVIII:C) levels was assessed and reported as per pre-specified PK time points at Month 12.
Time frame: At Month 12: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours
Population: FAS will be composed of all participants who receive prophylactic IP treatment. Here overall number of participants analyzed were participants who were evaluable for this outcome measure and number analyzed were participants who were evaluable for the outcome measure at given time points.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Prior On-demand Participants | Factor VIII (FVIII) Clotting Activity | 72 hours post-dose | 40.8 IU/dL | Standard Deviation 37.8 |
| Prior On-demand Participants | Factor VIII (FVIII) Clotting Activity | 30 hours post-dose | 95.4 IU/dL | Standard Deviation 32.6 |
| Prior On-demand Participants | Factor VIII (FVIII) Clotting Activity | 48 hours post-dose | 71.8 IU/dL | Standard Deviation 29.1 |
| Prior On-demand Participants | Factor VIII (FVIII) Clotting Activity | At pre-dose | 22.1 IU/dL | Standard Deviation 23.5 |
| Prior On-demand Participants | Factor VIII (FVIII) Clotting Activity | 15 minutes post-dose | 28.7 IU/dL | Standard Deviation 22.5 |
| Prior On-demand Participants | Factor VIII (FVIII) Clotting Activity | 30 minutes post-dose | 32.1 IU/dL | Standard Deviation 21.5 |
| Prior On-demand Participants | Factor VIII (FVIII) Clotting Activity | 1 hour post-dose | 36.0 IU/dL | Standard Deviation 24.3 |
| Prior On-demand Participants | Factor VIII (FVIII) Clotting Activity | 3 hours post-dose | 51.2 IU/dL | Standard Deviation 23.4 |
| Prior On-demand Participants | Factor VIII (FVIII) Clotting Activity | 6 hours post-dose | 66.4 IU/dL | Standard Deviation 25.1 |
| Prior On-demand Participants | Factor VIII (FVIII) Clotting Activity | 12 hours post-dose | 86.3 IU/dL | Standard Deviation 25 |
| Prior On-demand Participants | Factor VIII (FVIII) Clotting Activity | 96 hours post-dose | 20.0 IU/dL | Standard Deviation 23.5 |
| Prior On-demand Participants | Factor VIII (FVIII) Clotting Activity | 24 hours post-dose | 100.0 IU/dL | Standard Deviation 36.5 |
| Switch Participants | Factor VIII (FVIII) Clotting Activity | 1 hour post-dose | 34.0 IU/dL | Standard Deviation 18.4 |
| Switch Participants | Factor VIII (FVIII) Clotting Activity | 24 hours post-dose | 93.8 IU/dL | Standard Deviation 17.7 |
| Switch Participants | Factor VIII (FVIII) Clotting Activity | 30 hours post-dose | 90.6 IU/dL | Standard Deviation 15.8 |
| Switch Participants | Factor VIII (FVIII) Clotting Activity | 3 hours post-dose | 48.4 IU/dL | Standard Deviation 20.6 |
| Switch Participants | Factor VIII (FVIII) Clotting Activity | 48 hours post-dose | 79.2 IU/dL | Standard Deviation 17.9 |
| Switch Participants | Factor VIII (FVIII) Clotting Activity | 72 hours post-dose | 44.6 IU/dL | Standard Deviation 18 |
| Switch Participants | Factor VIII (FVIII) Clotting Activity | At pre-dose | 28.0 IU/dL | Standard Deviation 21.2 |
| Switch Participants | Factor VIII (FVIII) Clotting Activity | 6 hours post-dose | 69.3 IU/dL | Standard Deviation 18.4 |
| Switch Participants | Factor VIII (FVIII) Clotting Activity | 15 minutes post-dose | 30.9 IU/dL | Standard Deviation 18.7 |
| Switch Participants | Factor VIII (FVIII) Clotting Activity | 96 hours post-dose | 16.0 IU/dL | Standard Deviation 11.6 |
| Switch Participants | Factor VIII (FVIII) Clotting Activity | 30 minutes post-dose | 33.4 IU/dL | Standard Deviation 19.5 |
| Switch Participants | Factor VIII (FVIII) Clotting Activity | 12 hours post-dose | 78.0 IU/dL | Standard Deviation 18.2 |
Secondary
Number of Participants Based on Categorized Spontaneous ABR (sABR) Through Month 12
The sABR was the number of spontaneous bleeds divided by the observation period in years, where an observation period = (date of completion/termination-date of first dose+1)/365.2425.sABR was categorized based on number of BEs as 0, greater than (\>) 0 through 2,\>2 through 5,\>5 during the prophylactic treatment with rVWF (vonicog alfa) through 12 months. Bleeding at multiple locations related to the same injury was counted as single bleeding episode. BEs of unknown cause were counted as spontaneous bleeds. Observation period for historical BEs was 365 days prior to first dose of study drug. The baseline sABR for treated BEs was based on historical BE data and on-study sABR was based on treated spontaneous BEs during prophylaxis with rVWF through Month 12. On-study observation period started on the day of first administration of study drug continuing through the date of completion/discontinuation from study. Number of participants based on categorized sABR was calculated and reported.
Time frame: Baseline through Month 12
Population: FAS composed of all participants who received prophylactic IP treatment.
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Prior On-demand Participants | Number of Participants Based on Categorized Spontaneous ABR (sABR) Through Month 12 | On-Study Through Month 12 | >0 through 2 BEs | 0 Participants |
| Prior On-demand Participants | Number of Participants Based on Categorized Spontaneous ABR (sABR) Through Month 12 | On-Study Through Month 12 | >2 through 5 BEs | 1 Participants |
| Prior On-demand Participants | Number of Participants Based on Categorized Spontaneous ABR (sABR) Through Month 12 | Historical | >2 through 5 BEs | 10 Participants |
| Prior On-demand Participants | Number of Participants Based on Categorized Spontaneous ABR (sABR) Through Month 12 | On-Study Through Month 12 | >5 BEs | 1 Participants |
| Prior On-demand Participants | Number of Participants Based on Categorized Spontaneous ABR (sABR) Through Month 12 | On-Study Through Month 12 | 0 BEs | 11 Participants |
| Prior On-demand Participants | Number of Participants Based on Categorized Spontaneous ABR (sABR) Through Month 12 | Historical | 0 BEs | 0 Participants |
| Prior On-demand Participants | Number of Participants Based on Categorized Spontaneous ABR (sABR) Through Month 12 | Historical | >0 through 2 BEs | 0 Participants |
| Prior On-demand Participants | Number of Participants Based on Categorized Spontaneous ABR (sABR) Through Month 12 | Historical | >5 BEs | 3 Participants |
| Switch Participants | Number of Participants Based on Categorized Spontaneous ABR (sABR) Through Month 12 | On-Study Through Month 12 | >0 through 2 BEs | 1 Participants |
| Switch Participants | Number of Participants Based on Categorized Spontaneous ABR (sABR) Through Month 12 | Historical | >0 through 2 BEs | 3 Participants |
| Switch Participants | Number of Participants Based on Categorized Spontaneous ABR (sABR) Through Month 12 | Historical | >2 through 5 BEs | 0 Participants |
| Switch Participants | Number of Participants Based on Categorized Spontaneous ABR (sABR) Through Month 12 | Historical | >5 BEs | 1 Participants |
| Switch Participants | Number of Participants Based on Categorized Spontaneous ABR (sABR) Through Month 12 | On-Study Through Month 12 | 0 BEs | 7 Participants |
| Switch Participants | Number of Participants Based on Categorized Spontaneous ABR (sABR) Through Month 12 | On-Study Through Month 12 | >2 through 5 BEs | 1 Participants |
| Switch Participants | Number of Participants Based on Categorized Spontaneous ABR (sABR) Through Month 12 | On-Study Through Month 12 | >5 BEs | 1 Participants |
| Switch Participants | Number of Participants Based on Categorized Spontaneous ABR (sABR) Through Month 12 | Historical | 0 BEs | 6 Participants |
Secondary
Number of Participants Based on Severity of TEAEs
An AE is defined as any untoward medical occurrence in a participant administered IP that does not necessarily have a causal relationship with the treatment. TEAEs were events which occurred on or after the date and time of administration of the first dose of study medication. TEAEs included both serious AEs and non-serious AEs. Severity of TEAEs was determined by following definitions: Mild: No limitation of usual activities; Moderate: Some limitation of usual activities and may required therapeutic intervention; Severe: Inability to carry out usual activities with sequelae, which required therapeutic intervention. Participants were counted by considering the maximum severity of TEAEs.
Time frame: From first dose of study drug up to end of study (approximately 32 months)
Population: SAS composed of all participants who received any amount of IP (rVWF, vonicog alpha).
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Prior On-demand Participants | Number of Participants Based on Severity of TEAEs | Mild | 7 Participants |
| Prior On-demand Participants | Number of Participants Based on Severity of TEAEs | Moderate | 1 Participants |
| Prior On-demand Participants | Number of Participants Based on Severity of TEAEs | Severe | 2 Participants |
| Switch Participants | Number of Participants Based on Severity of TEAEs | Mild | 4 Participants |
| Switch Participants | Number of Participants Based on Severity of TEAEs | Moderate | 2 Participants |
| Switch Participants | Number of Participants Based on Severity of TEAEs | Severe | 1 Participants |
Secondary
Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs
An adverse event (AE) is defined as any untoward medical occurrence in a participant administered IP that does not necessarily have a causal relationship with the treatment. TEAEs were events which occurred on or after the date and time of administration of the first dose of study medication. TEAEs included both serious AEs and non-serious AEs. Number of participants with TEAEs and serious TEAEs were reported.
Time frame: From first dose of study drug up to end of study (approximately 32 months)
Population: SAS composed of all participants who received any amount of IP (rVWF, vonicog alpha).
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Prior On-demand Participants | Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs | Participants with serious TEAEs | 1 Participants |
| Prior On-demand Participants | Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs | Participants With TEAEs | 10 Participants |
| Switch Participants | Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs | Participants With TEAEs | 7 Participants |
| Switch Participants | Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs | Participants with serious TEAEs | 2 Participants |
Secondary
Number of Participants Who Developed Binding Antibodies to Chinese Hamster Ovary (CHO) Proteins, Mouse Immunoglobulin G (IgG) and/or rFurin
Total Ig antibodies (IgG, IgA, IgM) against CHO protein and human furin was analyzed using ELISA. For detection and quantification of IgG antibodies originating from human plasma that were directed against mouse-IgG (HAMA: human anti- mouse antibodies) was assessed using ELISA (Medac, Hamburg, Germany). Number of participants who developed binding antibodies to CHO proteins, Mouse IgG and/or rFurin was assessed.
Time frame: Baseline through Month 12
Population: SAS composed of all participants who received any amount of IP (rVWF, vonicog alpha).
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Prior On-demand Participants | Number of Participants Who Developed Binding Antibodies to Chinese Hamster Ovary (CHO) Proteins, Mouse Immunoglobulin G (IgG) and/or rFurin | 0 Participants |
| Switch Participants | Number of Participants Who Developed Binding Antibodies to Chinese Hamster Ovary (CHO) Proteins, Mouse Immunoglobulin G (IgG) and/or rFurin | 0 Participants |
Secondary
Number of Participants Who Developed Neutralizing Antibodies to Von Willebrand Factor (rVWF) and Factor VIII (FVIII)
Three functional VWF assays for von Willebrand factor collagen binding (VWF:CB), von Willebrand factor: Ristocetin Cofactor (VWF:RCo) and von Willebrand factor VIII B (VWF:FVIIIB) were used to test the presence of neutralizing anti-VWF antibodies. Neutralizing antibodies to VWF:RCo, VWF:CB and VWF:FVIIIB activities was measured by assays based on the Bethesda assay established for quantitative analysis of FVIII inhibitors (Nijmegen modification of the Bethesda assay). Only confirmed neutralizing anti -VWF antibodies were considered inhibitors. Number of participants who developed neutralizing antibodies to rVWF and FVIII were assessed.
Time frame: Baseline through Month 12
Population: SAS composed of all participants who received any amount of IP (rVWF, vonicog alpha).
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Prior On-demand Participants | Number of Participants Who Developed Neutralizing Antibodies to Von Willebrand Factor (rVWF) and Factor VIII (FVIII) | 0 Participants |
| Switch Participants | Number of Participants Who Developed Neutralizing Antibodies to Von Willebrand Factor (rVWF) and Factor VIII (FVIII) | 0 Participants |
Secondary
Number of Participants Who Developed of Total Binding Antibodies to Von Willebrand Factor (rVWF) and Factor VIII (FVIII)
The presence of total binding anti-VWF antibodies was determined by an enzyme-linked immunosorbent assay (ELISA) employing polyclonal anti-human Immunoglobulin (Ig) antibodies (IgG, IgM and IgA). Binding antibodies against FVIII was analyzed using a proprietary enzyme immunoassay. Number of participants who developed of total binding antibodies to rVWF and FVIII was assessed.
Time frame: Baseline through Month 12
Population: SAS composed of all participants who received any amount of IP (rVWF, vonicog alpha).
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Prior On-demand Participants | Number of Participants Who Developed of Total Binding Antibodies to Von Willebrand Factor (rVWF) and Factor VIII (FVIII) | 0 Participants |
| Switch Participants | Number of Participants Who Developed of Total Binding Antibodies to Von Willebrand Factor (rVWF) and Factor VIII (FVIII) | 0 Participants |
Secondary
Number of Participants With Clinically Significant Change From Baseline in Clinical Laboratory Parameters
Clinical laboratory parameters included hematology and clinical chemistry assessments. Number of participants with clinically significant change from baseline in clinical laboratory parameters was assessed.
Time frame: Baseline up to end of study (approximately 32 months)
Population: SAS composed of all participants who received any amount of IP (rVWF, vonicog alpha).
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Prior On-demand Participants | Number of Participants With Clinically Significant Change From Baseline in Clinical Laboratory Parameters | 0 Participants |
| Switch Participants | Number of Participants With Clinically Significant Change From Baseline in Clinical Laboratory Parameters | 0 Participants |
Secondary
Number of Participants With Clinically Significant Change From Baseline in Vital Signs
Vital signs included blood pressure (systolic and diastolic), pulse rate, respiratory rate and body temperature. Number of participants with clinically significant change from baseline in vital signs was assessed.
Time frame: Baseline up to end of study (approximately 32 months)
Population: SAS composed of all participants who received any amount of IP (rVWF, vonicog alpha).
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Prior On-demand Participants | Number of Participants With Clinically Significant Change From Baseline in Vital Signs | 0 Participants |
| Switch Participants | Number of Participants With Clinically Significant Change From Baseline in Vital Signs | 0 Participants |
Secondary
Number of Participants With Hypersensitivity Reactions
Hypersensitivity (also called hypersensitivity reaction or intolerance) defined as undesirable reactions produced by the normal immune system, including allergies and autoimmunity. Potential hypersensitivity events were identified by broad search criteria and then medically assessed. Number of participants with hypersensitivity reactions as TEAEs of special interest was calculated.
Time frame: From first dose of study drug up to end of study (approximately 32 months)
Population: SAS composed of all participants who received any amount of IP (rVWF, vonicog alpha).
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Prior On-demand Participants | Number of Participants With Hypersensitivity Reactions | 0 Participants |
| Switch Participants | Number of Participants With Hypersensitivity Reactions | 1 Participants |
Secondary
Number of Participants With TEAEs Based Causality
An AE was defined as any untoward medical occurrence in a participant administered IP that does not necessarily have a causal relationship with the treatment. TEAEs were events which occurred on or after the date and time of administration of the first dose of study medication. TEAEs included both serious AEs and non-serious AEs. For each AE, the investigator assessed the causal relationship between the IP and the AE based on clinical expertise and judgment according to the following circumstances of the AE: Not related, Unlikely related, Possibly related, or Probably related. A related TEAE was defined as any TEAE indicated as 'possibly related' or 'probably related'. Number of participants with TEAEs based causality was reported.
Time frame: From first dose of study drug up to end of study (approximately 32 months)
Population: SAS composed of all participants who received any amount of IP (rVWF, vonicog alpha).
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Prior On-demand Participants | Number of Participants With TEAEs Based Causality | 1 Participants |
| Switch Participants | Number of Participants With TEAEs Based Causality | 0 Participants |
Secondary
Number of Participants With Thromboembolic Events
Thromboembolism defined as formation in a blood vessel of a clot (thrombus) that breaks loose and carried by the blood stream and could plug another vessel. Number of participants with thromboembolic events as TEAEs of special interest was reported. A broad standard search query approach was used (broad SMQ) to identify all potential thromboembolic events of interest which were then medically assessed. Number of participants with thromboembolic events as TEAEs of special interest was reported.
Time frame: From first dose of study drug up to end of study (approximately 32 months)
Population: SAS composed of all participants who received any amount of IP (rVWF, vonicog alpha).
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Prior On-demand Participants | Number of Participants With Thromboembolic Events | 1 Participants |
| Switch Participants | Number of Participants With Thromboembolic Events | 0 Participants |
Secondary
Number of Treated Spontaneous BEs by Location of Bleeding While on Prophylactic Treatment With rVWF Through Month 12
Number of treated spontaneous BEs by location of bleeding (for example: oral and other mucosa, menorrhagia, hemarthrosis, etc.) while on prophylactic treatment with rVWF was reported.
Time frame: Up to 12 months
Population: FAS composed of all participants who received prophylactic IP treatment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Prior On-demand Participants | Number of Treated Spontaneous BEs by Location of Bleeding While on Prophylactic Treatment With rVWF Through Month 12 | Menorrhagia | 3 number of BEs |
| Prior On-demand Participants | Number of Treated Spontaneous BEs by Location of Bleeding While on Prophylactic Treatment With rVWF Through Month 12 | Unknown | 0 number of BEs |
| Prior On-demand Participants | Number of Treated Spontaneous BEs by Location of Bleeding While on Prophylactic Treatment With rVWF Through Month 12 | Hemarthrosis | 0 number of BEs |
| Prior On-demand Participants | Number of Treated Spontaneous BEs by Location of Bleeding While on Prophylactic Treatment With rVWF Through Month 12 | Other | 1 number of BEs |
| Prior On-demand Participants | Number of Treated Spontaneous BEs by Location of Bleeding While on Prophylactic Treatment With rVWF Through Month 12 | Oral and other mucosa | 5 number of BEs |
| Switch Participants | Number of Treated Spontaneous BEs by Location of Bleeding While on Prophylactic Treatment With rVWF Through Month 12 | Unknown | 3 number of BEs |
| Switch Participants | Number of Treated Spontaneous BEs by Location of Bleeding While on Prophylactic Treatment With rVWF Through Month 12 | Oral and other mucosa | 14 number of BEs |
| Switch Participants | Number of Treated Spontaneous BEs by Location of Bleeding While on Prophylactic Treatment With rVWF Through Month 12 | Menorrhagia | 0 number of BEs |
| Switch Participants | Number of Treated Spontaneous BEs by Location of Bleeding While on Prophylactic Treatment With rVWF Through Month 12 | Other | 0 number of BEs |
| Switch Participants | Number of Treated Spontaneous BEs by Location of Bleeding While on Prophylactic Treatment With rVWF Through Month 12 | Hemarthrosis | 1 number of BEs |
Secondary
Percentage of Prior On-demand Participants Achieved Spontaneous ABR Percent Reduction Success Through Month 12
For prior on-demand participants, spontaneous ABR percent reduction success was defined as at least 25% reduction of the ABR for treated spontaneous (not related to trauma) BEs during the first 12 months of rVWF (vonicog alfa) prophylaxis relative to the participant's own historical treated spontaneous ABR. Percentage of participants with ABR percent reduction success for on-demand cohort was reported.
Time frame: Up to 12 months
Population: FAS composed of all participants who received prophylactic IP treatment. This outcome measure was analyzed only for prior on-demand participants treated for spontaneous BEs.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Prior On-demand Participants | Percentage of Prior On-demand Participants Achieved Spontaneous ABR Percent Reduction Success Through Month 12 | 92.3 percentage of participants |
Secondary
Percentage of Switch Participants With Spontaneous ABR Preservation Success Through Month 12
For switch participants, spontaneous ABR preservation success was defined as achieving an ABR for treated spontaneous BEs during first 12 months of rVWF (vonicog alfa) prophylaxis that was no greater than the participant's own historical ABR for treated spontaneous BEs during prophylactic treatment with pdVWF. Percentage of participants with ABR preservation success in switch cohort was reported.
Time frame: Up to 12 months
Population: FAS composed of all participants who received prophylactic IP treatment. This outcome measure was analyzed only for switch participants treated for spontaneous BEs.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Prior On-demand Participants | Percentage of Switch Participants With Spontaneous ABR Preservation Success Through Month 12 | 90.0 percentage of participants |
Secondary
Pharmacodynamic Assessment: Area Under the Plasma Concentration Versus Time Curve From Time 0 to the Last Measurable Concentration (AUC0-tlast) Based on Factor VIII Clotting (FVIII:C) Activity
AUC0-tlast based on FVIII:C activity at initial PD assessment by the 1-stage clotting assay was reported.
Time frame: At baseline: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours
Population: PKFAS composed of all participants who received at least one IP infusion and who provided at least one quantifiable pharmacokinetic or pharmacodynamic post dose measurement for pharmacokinetic and/or pharmacodynamics analysis. Here overall number of participants analyzed were participants who were evaluable for this outcome measure. As planned, this outcome measure was assessed only for prior on-demand participants.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Prior On-demand Participants | Pharmacodynamic Assessment: Area Under the Plasma Concentration Versus Time Curve From Time 0 to the Last Measurable Concentration (AUC0-tlast) Based on Factor VIII Clotting (FVIII:C) Activity | 4949 IU*h/dL | Standard Deviation 2436 |
Secondary
Pharmacodynamic Assessment at Steady State: Area Under the Plasma Concentration Versus Time Curve From Time 0 to End of the Partial Dosing Interval (AUC0- Tau;ss) Based on Factor VIII Clotting (FVIII:C) Activity
AUC0-tau;ss based on FVIII:C activity at steady state during end of study (Month 12) was reported.
Time frame: At Month 12: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours
Population: PKFAS composed of all participants who received at least one IP infusion and who provided at least one quantifiable pharmacokinetic or pharmacodynamic post dose measurement for pharmacokinetic and/or pharmacodynamics analysis. Here overall number of participants analyzed were participants who were evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Prior On-demand Participants | Pharmacodynamic Assessment at Steady State: Area Under the Plasma Concentration Versus Time Curve From Time 0 to End of the Partial Dosing Interval (AUC0- Tau;ss) Based on Factor VIII Clotting (FVIII:C) Activity | 5984 IU*h/dL | Standard Deviation 2490 |
| Switch Participants | Pharmacodynamic Assessment at Steady State: Area Under the Plasma Concentration Versus Time Curve From Time 0 to End of the Partial Dosing Interval (AUC0- Tau;ss) Based on Factor VIII Clotting (FVIII:C) Activity | 5836 IU*h/dL | Standard Deviation 1735 |
Secondary
Pharmacodynamic Assessment at Steady State: Maximum Plasma Concentration During the Partial Dosing Interval at Steady State (Cmax;ss) Based on Factor VIII Clotting (FVIII:C) Activity
Cmax;ss based on FVIII:C activity was assessed at steady state during end of study (Month 12) was reported.
Time frame: At Month 12: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours
Population: PKFAS composed of all participants who received at least one IP infusion and who provided at least one quantifiable pharmacokinetic or pharmacodynamic post dose measurement for pharmacokinetic and/or pharmacodynamics analysis. Here overall number of participants analyzed were participants who were evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Prior On-demand Participants | Pharmacodynamic Assessment at Steady State: Maximum Plasma Concentration During the Partial Dosing Interval at Steady State (Cmax;ss) Based on Factor VIII Clotting (FVIII:C) Activity | 104.1 IU/dL | Standard Deviation 35.1 |
| Switch Participants | Pharmacodynamic Assessment at Steady State: Maximum Plasma Concentration During the Partial Dosing Interval at Steady State (Cmax;ss) Based on Factor VIII Clotting (FVIII:C) Activity | 75.7 IU/dL | Standard Deviation 37.3 |
Secondary
Pharmacodynamic Assessment at Steady State: Minimum Plasma Concentration During the Partial Dosing Interval at Steady State (Cmin;ss) Based on Factor VIII Clotting (FVIII:C) Activity
Cmin;ss based on FVIII:C activity at steady state during end of study (Month 12) was reported.
Time frame: At Month 12: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours
Population: PKFAS composed of all participants who received at least one IP infusion and who provided at least one quantifiable pharmacokinetic or pharmacodynamic post dose measurement for pharmacokinetic and/or pharmacodynamics analysis. Here overall number of participants analyzed were participants who were evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Prior On-demand Participants | Pharmacodynamic Assessment at Steady State: Minimum Plasma Concentration During the Partial Dosing Interval at Steady State (Cmin;ss) Based on Factor VIII Clotting (FVIII:C) Activity | 15.8 IU/dL | Standard Deviation 8.6 |
| Switch Participants | Pharmacodynamic Assessment at Steady State: Minimum Plasma Concentration During the Partial Dosing Interval at Steady State (Cmin;ss) Based on Factor VIII Clotting (FVIII:C) Activity | 22.9 IU/dL | Standard Deviation 11.3 |
Secondary
Pharmacodynamic Assessment at Steady State: Minimum Time to Reach the Maximum Plasma Concentration at Steady State (Tmax;ss) Based on Factor VIII Clotting (FVIII:C) Activity
Tmax;ss based on FVIII:C activity at steady state during end of study (Month 12) was reported.
Time frame: At Month 12: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours
Population: PKFAS composed of all participants who received at least one IP infusion and who provided at least one quantifiable pharmacokinetic or pharmacodynamic post dose measurement for pharmacokinetic and/or pharmacodynamics analysis. Here overall number of participants analyzed were participants who were evaluable for this outcome measure.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Prior On-demand Participants | Pharmacodynamic Assessment at Steady State: Minimum Time to Reach the Maximum Plasma Concentration at Steady State (Tmax;ss) Based on Factor VIII Clotting (FVIII:C) Activity | 24.500 hours |
| Switch Participants | Pharmacodynamic Assessment at Steady State: Minimum Time to Reach the Maximum Plasma Concentration at Steady State (Tmax;ss) Based on Factor VIII Clotting (FVIII:C) Activity | 24.070 hours |
Secondary
Pharmacodynamic Assessment: Minimum Time to Reach the Maximum Plasma Concentration (Tmax) Based on Factor VIII Clotting (FVIII:C) Activity
Tmax based on FVIII:C activity at initial PD assessment by the 1-stage clotting assay was reported.
Time frame: At baseline: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours
Population: PKFAS composed of all participants who received at least one IP infusion and who provided at least one quantifiable pharmacokinetic or pharmacodynamic post dose measurement for pharmacokinetic and/or pharmacodynamics analysis. Here overall number of participants analyzed were participants who were evaluable for this outcome measure. As planned, this outcome measure was assessed only for prior on-demand participants.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Prior On-demand Participants | Pharmacodynamic Assessment: Minimum Time to Reach the Maximum Plasma Concentration (Tmax) Based on Factor VIII Clotting (FVIII:C) Activity | 24.055 hours |
Secondary
Pharmacodynamic (PD) Assessment: Maximum Plasma Concentration (Cmax) Based on Factor VIII Clotting (FVIII:C) Activity
Cmax based on FVIII:C activity at initial PD assessment by the 1-stage clotting assay was reported.
Time frame: At baseline: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours
Population: PKFAS composed of all participants who received at least one IP infusion and who provided at least one quantifiable pharmacokinetic or pharmacodynamic post dose measurement for pharmacokinetic and/or pharmacodynamics analysis. Here overall number of participants analyzed were participants who were evaluable for this outcome measure. As planned, this outcome measure was assessed only for prior on-demand participants.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Prior On-demand Participants | Pharmacodynamic (PD) Assessment: Maximum Plasma Concentration (Cmax) Based on Factor VIII Clotting (FVIII:C) Activity | 90.8 IU/dL | Standard Deviation 32.1 |
Secondary
Pharmacokinetic Assessment: Area Under the Plasma Concentration Versus Time Curve From Time 0 Extrapolated to Infinity (AUC0-∞) Based on Von Willebrand Factor Antigen (VWF:Ag) Activity
AUC0-∞ based on VWF:Ag activity at initial PK assessment was reported.
Time frame: At baseline: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours
Population: PKFAS composed of all participants who received at least one IP infusion and who provided at least one quantifiable pharmacokinetic or pharmacodynamic post dose measurement for pharmacokinetic and/or pharmacodynamics analysis. Here overall number of participants analyzed were participants who were evaluable for this outcome measure. As planned, this outcome measure was assessed only for prior on-demand participants.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Prior On-demand Participants | Pharmacokinetic Assessment: Area Under the Plasma Concentration Versus Time Curve From Time 0 Extrapolated to Infinity (AUC0-∞) Based on Von Willebrand Factor Antigen (VWF:Ag) Activity | 2578 IU*h/dL | Standard Deviation 1067 |
Secondary
Pharmacokinetic Assessment: Area Under the Plasma Concentration Versus Time Curve From Time 0 Extrapolated to Infinity (AUC0-∞) Based on Von Willebrand Factor Collagen Binding (VWF:CB) Activity
AUC0-∞ based on VWF:CB activity at initial PK assessment was reported.
Time frame: At baseline: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours
Population: PKFAS composed of all participants who received at least one IP infusion and who provided at least one quantifiable pharmacokinetic or pharmacodynamic post dose measurement for pharmacokinetic and/or pharmacodynamics analysis. Here overall number of participants analyzed were participants who were evaluable for this outcome measure. As planned, this outcome measure was assessed only for prior on-demand participants.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Prior On-demand Participants | Pharmacokinetic Assessment: Area Under the Plasma Concentration Versus Time Curve From Time 0 Extrapolated to Infinity (AUC0-∞) Based on Von Willebrand Factor Collagen Binding (VWF:CB) Activity | 3010 IU*h/dL | Standard Deviation 1221 |
Secondary
Pharmacokinetic Assessment: Area Under the Plasma Concentration Versus Time Curve From Time 0 Extrapolated to Infinity (AUC0-∞) Based on Von Willebrand Factor: Ristocetin Cofactor (VWF:Rco) Activity
AUC0-∞ based on VWF:Rco activity at initial PK assessment was reported. Unit of measure: International Units\*hour per deciliter (IU\*h/dL).
Time frame: At baseline: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours
Population: PKFAS composed of all participants who received at least one IP infusion and who provided at least one quantifiable pharmacokinetic or pharmacodynamic post dose measurement for pharmacokinetic and/or pharmacodynamics analysis. Here overall number of participants analyzed were participants who were evaluable for this outcome measure. As planned, this outcome measure was assessed only for prior on-demand participants.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Prior On-demand Participants | Pharmacokinetic Assessment: Area Under the Plasma Concentration Versus Time Curve From Time 0 Extrapolated to Infinity (AUC0-∞) Based on Von Willebrand Factor: Ristocetin Cofactor (VWF:Rco) Activity | 1199 IU*h/dL | Standard Deviation 467.8 |
Secondary
Pharmacokinetic Assessment: Area Under the Plasma Concentration Versus Time Curve From Time 0 to the Last Measurable Concentration (AUC0-tlast) Based on Von Willebrand Factor Antigen (VWF:Ag) Activity
AUC0-tlast based on VWF:Ag activity at initial PK assessment was reported.
Time frame: At baseline: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours
Population: PKFAS composed of all participants who received at least one IP infusion and who provided at least one quantifiable pharmacokinetic or pharmacodynamic post dose measurement for pharmacokinetic and/or pharmacodynamics analysis. Here overall number of participants analyzed were participants who were evaluable for this outcome measure. As planned, this outcome measure was assessed only for prior on-demand participants.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Prior On-demand Participants | Pharmacokinetic Assessment: Area Under the Plasma Concentration Versus Time Curve From Time 0 to the Last Measurable Concentration (AUC0-tlast) Based on Von Willebrand Factor Antigen (VWF:Ag) Activity | 2357 IU*h/dL | Standard Deviation 848.6 |
Secondary
Pharmacokinetic Assessment: Area Under the Plasma Concentration Versus Time Curve From Time 0 to the Last Measurable Concentration (AUC0-tlast) Based on Von Willebrand Factor Collagen Binding (VWF:CB) Activity
AUC0-tlast based on VWF:CB activity at initial PK assessment was reported.
Time frame: At baseline: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours
Population: PKFAS composed of all participants who received at least one IP infusion and who provided at least one quantifiable pharmacokinetic or pharmacodynamic post dose measurement for pharmacokinetic and/or pharmacodynamics analysis. Here overall number of participants analyzed were participants who were evaluable for this outcome measure. As planned, this outcome measure was assessed only for prior on-demand participants.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Prior On-demand Participants | Pharmacokinetic Assessment: Area Under the Plasma Concentration Versus Time Curve From Time 0 to the Last Measurable Concentration (AUC0-tlast) Based on Von Willebrand Factor Collagen Binding (VWF:CB) Activity | 2824 IU*h/dL | Standard Deviation 1112 |
Secondary
Pharmacokinetic Assessment: Area Under the Plasma Concentration Versus Time Curve From Time 0 to the Last Measurable Concentration (AUC0-tlast) Based on Von Willebrand Factor: Ristocetin Cofactor (VWF:Rco) Activity
AUC0-tlast based on VWF:Rco activity at initial PK assessment was reported.
Time frame: At baseline: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours
Population: PKFAS composed of all participants who received at least one IP infusion and who provided at least one quantifiable pharmacokinetic or pharmacodynamic post dose measurement for pharmacokinetic and/or pharmacodynamics analysis. Here overall number of participants analyzed were participants who were evaluable for this outcome measure. As planned, this outcome measure was assessed only for prior on-demand participants.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Prior On-demand Participants | Pharmacokinetic Assessment: Area Under the Plasma Concentration Versus Time Curve From Time 0 to the Last Measurable Concentration (AUC0-tlast) Based on Von Willebrand Factor: Ristocetin Cofactor (VWF:Rco) Activity | 919.8 IU*h/dL | Standard Deviation 378.4 |
Secondary
Pharmacokinetic Assessment at Steady State: Area Under the Plasma Concentration Versus Time Curve From Time 0 to End of the Partial Dosing Interval (AUC0- Tau;ss) Based on Von Willebrand Factor Antigen (VWF:Ag) Activity
AUC0-tau;ss based on VWF:Ag activity at steady state during end of study (Month 12) was reported.
Time frame: At Month 12: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours
Population: PKFAS composed of all participants who received at least one IP infusion and who provided at least one quantifiable pharmacokinetic or pharmacodynamic post dose measurement for pharmacokinetic and/or pharmacodynamics analysis. Here overall number of participants analyzed were participants who were evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Prior On-demand Participants | Pharmacokinetic Assessment at Steady State: Area Under the Plasma Concentration Versus Time Curve From Time 0 to End of the Partial Dosing Interval (AUC0- Tau;ss) Based on Von Willebrand Factor Antigen (VWF:Ag) Activity | 2908 IU*h/dL | Standard Deviation 1372 |
| Switch Participants | Pharmacokinetic Assessment at Steady State: Area Under the Plasma Concentration Versus Time Curve From Time 0 to End of the Partial Dosing Interval (AUC0- Tau;ss) Based on Von Willebrand Factor Antigen (VWF:Ag) Activity | 3196 IU*h/dL | Standard Deviation 838 |
Secondary
Pharmacokinetic Assessment at Steady State: Area Under the Plasma Concentration Versus Time Curve From Time 0 to End of the Partial Dosing Interval (AUC0- Tau;ss) Based on Von Willebrand Factor Collagen Binding (VWF:CB) Activity
AUC0-tau;ss based on VWF:CB activity at steady state during end of study (Month 12) was reported.
Time frame: At Month 12: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours
Population: PKFAS composed of all participants who received at least one IP infusion and who provided at least one quantifiable pharmacokinetic or pharmacodynamic post dose measurement for pharmacokinetic and/or pharmacodynamics analysis. Here overall number of participants analyzed were participants who were evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Prior On-demand Participants | Pharmacokinetic Assessment at Steady State: Area Under the Plasma Concentration Versus Time Curve From Time 0 to End of the Partial Dosing Interval (AUC0- Tau;ss) Based on Von Willebrand Factor Collagen Binding (VWF:CB) Activity | 3445 IU*h/dL | Standard Deviation 1914 |
| Switch Participants | Pharmacokinetic Assessment at Steady State: Area Under the Plasma Concentration Versus Time Curve From Time 0 to End of the Partial Dosing Interval (AUC0- Tau;ss) Based on Von Willebrand Factor Collagen Binding (VWF:CB) Activity | 4276 IU*h/dL | Standard Deviation 1471 |
Secondary
Pharmacokinetic Assessment at Steady State: Area Under the Plasma Concentration Versus Time Curve From Time 0 to End of the Partial Dosing Interval (AUC0- Tau;ss) Based on Von Willebrand Factor: Ristocetin Cofactor (VWF:Rco) Activity
AUC0-tau;ss based on VWF:Rco activity at steady state during end of study (Month 12) was reported.
Time frame: At Month 12: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours
Population: PKFAS composed of all participants who received at least one IP infusion and who provided at least one quantifiable pharmacokinetic or pharmacodynamic post dose measurement for pharmacokinetic and/or pharmacodynamics analysis. Here overall number of participants analyzed were participants who were evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Prior On-demand Participants | Pharmacokinetic Assessment at Steady State: Area Under the Plasma Concentration Versus Time Curve From Time 0 to End of the Partial Dosing Interval (AUC0- Tau;ss) Based on Von Willebrand Factor: Ristocetin Cofactor (VWF:Rco) Activity | 1561 IU*h/dL | Standard Deviation 1298 |
| Switch Participants | Pharmacokinetic Assessment at Steady State: Area Under the Plasma Concentration Versus Time Curve From Time 0 to End of the Partial Dosing Interval (AUC0- Tau;ss) Based on Von Willebrand Factor: Ristocetin Cofactor (VWF:Rco) Activity | 1662 IU*h/dL | Standard Deviation 675 |
Secondary
Pharmacokinetic Assessment: Clearance (CL) Based on Von Willebrand Factor Antigen (VWF:Ag) Activity
Clearance is defined as a quantitative measure of the rate at which a drug substance is removed from the body. CL based on VWF:Ag activity at initial PK assessment was reported.
Time frame: At baseline: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours
Population: PKFAS composed of all participants who received at least one IP infusion and who provided at least one quantifiable pharmacokinetic or pharmacodynamic post dose measurement for pharmacokinetic and/or pharmacodynamics analysis. Here overall number of participants analyzed were participants who were evaluable for this outcome measure. As planned, this outcome measure was assessed only for prior on-demand participants.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Prior On-demand Participants | Pharmacokinetic Assessment: Clearance (CL) Based on Von Willebrand Factor Antigen (VWF:Ag) Activity | 0.02185 dL/kg/h | Standard Deviation 0.006821 |
Secondary
Pharmacokinetic Assessment: Clearance (CL) Based on Von Willebrand Factor Collagen Binding (VWF:CB) Activity
Clearance is defined as a quantitative measure of the rate at which a drug substance is removed from the body. CL based on VWF:CB activity at initial PK assessment was reported.
Time frame: At baseline: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours
Population: PKFAS composed of all participants who received at least one IP infusion and who provided at least one quantifiable pharmacokinetic or pharmacodynamic post dose measurement for pharmacokinetic and/or pharmacodynamics analysis. Here overall number of participants analyzed were participants who were evaluable for this outcome measure. As planned, this outcome measure was assessed only for prior on-demand participants.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Prior On-demand Participants | Pharmacokinetic Assessment: Clearance (CL) Based on Von Willebrand Factor Collagen Binding (VWF:CB) Activity | 0.01872 dL/kg/h | Standard Deviation 0.005946 |
Secondary
Pharmacokinetic Assessment: Clearance (CL) Based on Von Willebrand Factor: Ristocetin Cofactor (VWF:Rco) Activity
Clearance is defined as a quantitative measure of the rate at which a drug substance is removed from the body. CL based on VWF:Rco activity at initial PK assessment was reported. Unit of measure: deciliter per kilogram per hour (dL/kg/h).
Time frame: At baseline: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours
Population: PKFAS composed of all participants who received at least one IP infusion and who provided at least one quantifiable pharmacokinetic or pharmacodynamic post dose measurement for pharmacokinetic and/or pharmacodynamics analysis. Here overall number of participants analyzed were participants who were evaluable for this outcome measure. As planned, this outcome measure was assessed only for prior on-demand participants.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Prior On-demand Participants | Pharmacokinetic Assessment: Clearance (CL) Based on Von Willebrand Factor: Ristocetin Cofactor (VWF:Rco) Activity | 0.04765 dL/kg/h | Standard Deviation 0.0162 |
Secondary
Pharmacokinetic Assessment: Incremental Recovery (IR) Based on Von Willebrand Factor Antigen (VWF:Ag) Activity
IR based on VWF:Ag activity at initial PK assessment was reported.
Time frame: At baseline: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours
Population: PKFAS composed of all participants who received at least one IP infusion and who provided at least one quantifiable pharmacokinetic or pharmacodynamic post dose measurement for pharmacokinetic and/or pharmacodynamics analysis. Here overall number of participants analyzed were participants who were evaluable for this outcome measure. As planned, this outcome measure was assessed only for prior on-demand participants.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Prior On-demand Participants | Pharmacokinetic Assessment: Incremental Recovery (IR) Based on Von Willebrand Factor Antigen (VWF:Ag) Activity | 1.699 (IU/dL)/(IU/kg) | Standard Deviation 0.3488 |
Secondary
Pharmacokinetic Assessment: Incremental Recovery (IR) Based on Von Willebrand Factor Collagen Binding (VWF:CB) Activity
IR at the maximum plasma concentration of VWF:CB activity at initial PK assessment was reported.
Time frame: At baseline: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours
Population: PKFAS composed of all participants who received at least one IP infusion and who provided at least one quantifiable pharmacokinetic or pharmacodynamic post dose measurement for pharmacokinetic and/or pharmacodynamics analysis. Here overall number of participants analyzed were participants who were evaluable for this outcome measure. As planned, this outcome measure was assessed only for prior on-demand participants.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Prior On-demand Participants | Pharmacokinetic Assessment: Incremental Recovery (IR) Based on Von Willebrand Factor Collagen Binding (VWF:CB) Activity | 2.405 (IU/dL)/(IU/kg) | Standard Deviation 0.5737 |
Secondary
Pharmacokinetic Assessment: Maximum Plasma Concentration (Cmax) Based on Von Willebrand Factor Antigen (VWF:Ag) Activity
Cmax based on VWF:Ag activity at initial PK assessment was reported.
Time frame: At baseline: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours
Population: PKFAS composed of all participants who received at least one IP infusion and who provided at least one quantifiable pharmacokinetic or pharmacodynamic post dose measurement for pharmacokinetic and/or pharmacodynamics analysis. Here overall number of participants analyzed were participants who were evaluable for this outcome measure. As planned, this outcome measure was assessed only for prior on-demand participants.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Prior On-demand Participants | Pharmacokinetic Assessment: Maximum Plasma Concentration (Cmax) Based on Von Willebrand Factor Antigen (VWF:Ag) Activity | 85.1 IU/dL | Standard Deviation 19.2 |
Secondary
Pharmacokinetic Assessment: Maximum Plasma Concentration (Cmax) Based on Von Willebrand Factor Collagen Binding (VWF:CB) Activity
Cmax based on VWF:CB activity at initial PK assessment was reported.
Time frame: At baseline: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours
Population: PKFAS composed of all participants who received at least one IP infusion and who provided at least one quantifiable pharmacokinetic or pharmacodynamic post dose measurement for pharmacokinetic and/or pharmacodynamics analysis. Here overall number of participants analyzed were participants who were evaluable for this outcome measure. As planned, this outcome measure was assessed only for prior on-demand participants.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Prior On-demand Participants | Pharmacokinetic Assessment: Maximum Plasma Concentration (Cmax) Based on Von Willebrand Factor Collagen Binding (VWF:CB) Activity | 120.74 IU/dL | Standard Deviation 29.83 |
Secondary
Pharmacokinetic Assessment: Maximum Plasma Concentration (Cmax) Based on Von Willebrand Factor: Ristocetin Cofactor (VWF:Rco) Activity
Cmax based on VWF:Rco at initial PK assessment was reported. Unit of measure: International Units per deciliter (IU/dL).
Time frame: At baseline: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours
Population: PKFAS composed of all participants who received at least one IP infusion and who provided at least one quantifiable pharmacokinetic or pharmacodynamic post dose measurement for pharmacokinetic and/or pharmacodynamics analysis. Here overall number of participants analyzed were participants who were evaluable for this outcome measure. As planned, this outcome measure was assessed only for prior on-demand participants.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Prior On-demand Participants | Pharmacokinetic Assessment: Maximum Plasma Concentration (Cmax) Based on Von Willebrand Factor: Ristocetin Cofactor (VWF:Rco) Activity | 74.62 IU/dL | Standard Deviation 16.09 |
Secondary
Pharmacokinetic Assessment: Mean Residence Time (MRT) Based on Von Willebrand Factor Antigen (VWF:Ag) Activity
MRT was calculated as (AUMC0-∞/AUC0-∞) - T1/2 where T1 represented the time duration of infusion, where AUMC represented the area under the first moment curve. MRT based on VWF:Ag activity at initial PK assessment was reported.
Time frame: At baseline: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours
Population: PKFAS composed of all participants who received at least one IP infusion and who provided at least one quantifiable pharmacokinetic or pharmacodynamic post dose measurement for pharmacokinetic and/or pharmacodynamics analysis. Here overall number of participants analyzed were participants who were evaluable for this outcome measure. As planned, this outcome measure was assessed only for prior on-demand participants.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Prior On-demand Participants | Pharmacokinetic Assessment: Mean Residence Time (MRT) Based on Von Willebrand Factor Antigen (VWF:Ag) Activity | 33.55 hours | Standard Deviation 9.777 |
Secondary
Pharmacokinetic Assessment: Mean Residence Time (MRT) Based on Von Willebrand Factor Collagen Binding (VWF:CB) Activity
MRT was calculated as (AUMC0-∞/AUC0-∞) - T1/2 where T1 represented the time duration of infusion, where AUMC represented the area under the first moment curve. MRT based on VWF:CB activity at initial PK assessment was reported.
Time frame: At baseline: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours
Population: PKFAS composed of all participants who received at least one IP infusion and who provided at least one quantifiable pharmacokinetic or pharmacodynamic post dose measurement for pharmacokinetic and/or pharmacodynamics analysis. Here overall number of participants analyzed were participants who were evaluable for this outcome measure. As planned, this outcome measure was assessed only for prior on-demand participants.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Prior On-demand Participants | Pharmacokinetic Assessment: Mean Residence Time (MRT) Based on Von Willebrand Factor Collagen Binding (VWF:CB) Activity | 27.39 hours | Standard Deviation 6.86 |
Secondary
Pharmacokinetic Assessment: Mean Residence Time (MRT) Based on Von Willebrand Factor: Ristocetin Cofactor (VWF:Rco) Activity
MRT was calculated as (AUMC0-∞/AUC0-∞) - T1/2 where T1 represented the time duration of infusion, where AUMC represented the area under the first moment curve. MRT based on VWF:Rco activity at initial PK assessment was reported.
Time frame: At baseline: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours
Population: PKFAS composed of all participants who received at least one IP infusion and who provided at least one quantifiable pharmacokinetic or pharmacodynamic post dose measurement for pharmacokinetic and/or pharmacodynamics analysis. Here overall number of participants analyzed were participants who were evaluable for this outcome measure. As planned, this outcome measure was assessed only for prior on-demand participants.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Prior On-demand Participants | Pharmacokinetic Assessment: Mean Residence Time (MRT) Based on Von Willebrand Factor: Ristocetin Cofactor (VWF:Rco) Activity | 23.27 hours | Standard Deviation 11 |
Secondary
Pharmacokinetic Assessment: Minimum Time to Reach the Maximum Plasma Concentration (Tmax) Based on Von Willebrand Factor Antigen (VWF:Ag) Activity
Tmax based on VWF:Ag activity at initial PK assessment was reported.
Time frame: At baseline: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours
Population: PKFAS composed of all participants who received at least one IP infusion and who provided at least one quantifiable pharmacokinetic or pharmacodynamic post dose measurement for pharmacokinetic and/or pharmacodynamics analysis. Here overall number of participants analyzed were participants who were evaluable for this outcome measure. As planned, this outcome measure was assessed only for prior on-demand participants.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Prior On-demand Participants | Pharmacokinetic Assessment: Minimum Time to Reach the Maximum Plasma Concentration (Tmax) Based on Von Willebrand Factor Antigen (VWF:Ag) Activity | 1 hours |
Secondary
Pharmacokinetic Assessment: Minimum Time to Reach the Maximum Plasma Concentration (Tmax) Based on Von Willebrand Factor Collagen Binding (VWF:CB) Activity
Tmax based on VWF:CB activity at initial PK assessment was reported.
Time frame: At baseline: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours
Population: PKFAS composed of all participants who received at least one IP infusion and who provided at least one quantifiable pharmacokinetic or pharmacodynamic post dose measurement for pharmacokinetic and/or pharmacodynamics analysis. Here overall number of participants analyzed were participants who were evaluable for this outcome measure. As planned, this outcome measure was assessed only for prior on-demand participants.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Prior On-demand Participants | Pharmacokinetic Assessment: Minimum Time to Reach the Maximum Plasma Concentration (Tmax) Based on Von Willebrand Factor Collagen Binding (VWF:CB) Activity | 0.500 hours |
Secondary
Pharmacokinetic Assessment: Minimum Time to Reach the Maximum Plasma Concentration (Tmax) Based on Von Willebrand Factor: Ristocetin Cofactor (VWF:Rco) Activity
Tmax based on VWF:Rco activity at initial PK assessment was reported.
Time frame: At baseline: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours
Population: PKFAS composed of all participants who received at least one IP infusion and who provided at least one quantifiable pharmacokinetic or pharmacodynamic post dose measurement for pharmacokinetic and/or pharmacodynamics analysis. Here overall number of participants analyzed were participants who were evaluable for this outcome measure. As planned, this outcome measure was assessed only for prior on-demand participants.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Prior On-demand Participants | Pharmacokinetic Assessment: Minimum Time to Reach the Maximum Plasma Concentration (Tmax) Based on Von Willebrand Factor: Ristocetin Cofactor (VWF:Rco) Activity | 0.540 hours |
Secondary
Pharmacokinetic Assessment: Terminal Half-life (T1/2) Based on Von Willebrand Factor Antigen (VWF:Ag) Activity
T1/2 defined as the time in hours required for the concentration of the drug to reach half of its original value. T1/2 based on VWF:Ag activity at initial PK assessment was reported.
Time frame: At baseline: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours
Population: PKFAS composed of all participants who received at least one IP infusion and who provided at least one quantifiable pharmacokinetic or pharmacodynamic post dose measurement for pharmacokinetic and/or pharmacodynamics analysis. Here overall number of participants analyzed were participants who were evaluable for this outcome measure. As planned, this outcome measure was assessed only for prior on-demand participants.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Prior On-demand Participants | Pharmacokinetic Assessment: Terminal Half-life (T1/2) Based on Von Willebrand Factor Antigen (VWF:Ag) Activity | 21.81 hours |
Secondary
Pharmacokinetic Assessment: Terminal Half-life (T1/2) Based on Von Willebrand Factor Collagen Binding (VWF:CB) Activity
T1/2 defined as the time in hours required for the concentration of the drug to reach half of its original value. T1/2 based on VWF:CB activity at initial PK assessment was reported.
Time frame: At baseline: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours
Population: PKFAS composed of all participants who received at least one IP infusion and who provided at least one quantifiable pharmacokinetic or pharmacodynamic post dose measurement for pharmacokinetic and/or pharmacodynamics analysis. Here overall number of participants analyzed were participants who were evaluable for this outcome measure. As planned, this outcome measure was assessed only for prior on-demand participants.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Prior On-demand Participants | Pharmacokinetic Assessment: Terminal Half-life (T1/2) Based on Von Willebrand Factor Collagen Binding (VWF:CB) Activity | 18.64 hours |
Secondary
Pharmacokinetic Assessment: Terminal Half-life (T1/2) Based on Von Willebrand Factor: Ristocetin Cofactor (VWF:Rco) Activity
T1/2 defined as the time in hours required for the concentration of the drug to reach half of its original value. T1/2 based on VWF:Rco activity at initial PK assessment was reported.
Time frame: At baseline: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours
Population: PKFAS composed of all participants who received at least one IP infusion and who provided at least one quantifiable pharmacokinetic or pharmacodynamic post dose measurement for pharmacokinetic and/or pharmacodynamics analysis. Here overall number of participants analyzed were participants who were evaluable for this outcome measure. As planned, this outcome measure was assessed only for prior on-demand participants.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Prior On-demand Participants | Pharmacokinetic Assessment: Terminal Half-life (T1/2) Based on Von Willebrand Factor: Ristocetin Cofactor (VWF:Rco) Activity | 15.98 hours |
Secondary
Pharmacokinetic Assessment: Volume of Distribution at Steady State (Vss) Based on Von Willebrand Factor Antigen (VWF:Ag) Activity
Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. Vss based on VWF:Ag activity at initial assessment was reported.
Time frame: At baseline: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours
Population: PKFAS composed of all participants who received at least one IP infusion and who provided at least one quantifiable pharmacokinetic or pharmacodynamic post dose measurement for pharmacokinetic and/or pharmacodynamics analysis. Here overall number of participants analyzed were participants who were evaluable for this outcome measure. As planned, this outcome measure was assessed only for prior on-demand participants.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Prior On-demand Participants | Pharmacokinetic Assessment: Volume of Distribution at Steady State (Vss) Based on Von Willebrand Factor Antigen (VWF:Ag) Activity | 0.6860 dL/kg | Standard Deviation 0.1556 |
Secondary
Pharmacokinetic Assessment: Volume of Distribution at Steady State (Vss) Based on Von Willebrand Factor Collagen Binding (VWF:CB) Activity
Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. Vss based on VWF:CB activity at initial assessment was reported.
Time frame: At baseline: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours
Population: PKFAS composed of all participants who received at least one IP infusion and who provided at least one quantifiable pharmacokinetic or pharmacodynamic post dose measurement for pharmacokinetic and/or pharmacodynamics analysis. Here overall number of participants analyzed were participants who were evaluable for this outcome measure. As planned, this outcome measure was assessed only for prior on-demand participants.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Prior On-demand Participants | Pharmacokinetic Assessment: Volume of Distribution at Steady State (Vss) Based on Von Willebrand Factor Collagen Binding (VWF:CB) Activity | 0.4889 dL/kg | Standard Deviation 0.1371 |
Secondary
Pharmacokinetic Assessment: Volume of Distribution at Steady State (Vss) Based on Von Willebrand Factor: Ristocetin Cofactor (VWF:Rco) Activity
Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. Vss based on VWF:Rco activity at initial assessment was reported.
Time frame: At baseline: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours
Population: PKFAS composed of all participants who received at least one IP infusion and who provided at least one quantifiable pharmacokinetic or pharmacodynamic post dose measurement for pharmacokinetic and/or pharmacodynamics analysis. Here overall number of participants analyzed were participants who were evaluable for this outcome measure. As planned, this outcome measure was assessed only for prior on-demand participants.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Prior On-demand Participants | Pharmacokinetic Assessment: Volume of Distribution at Steady State (Vss) Based on Von Willebrand Factor: Ristocetin Cofactor (VWF:Rco) Activity | 1.052 deciliter per kilogram (dL/kg) | Standard Deviation 0.4981 |
Secondary
Pharmacokinetic (PK) Assessment: Incremental Recovery (IR) Based on Von Willebrand Factor: Ristocetin Cofactor (VWF:Rco) Activity
IR at the maximum plasma concentration of VWF:RCo activity at initial PK assessment was reported. Unit of measure: International Units per deciliter/International Units per kilogram (\[IU/dL\]/\[IU/kg\]).
Time frame: At baseline: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours
Population: PK full analysis set (PKFAS) composed of all participants who received at least one IP infusion and who provided at least one quantifiable pharmacokinetic or pharmacodynamic post dose measurement for pharmacokinetic and/or pharmacodynamics analysis. Here overall number of participants analyzed were participants who were evaluable for this outcome measure. As planned, this outcome measure was assessed only for prior on-demand participants.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Prior On-demand Participants | Pharmacokinetic (PK) Assessment: Incremental Recovery (IR) Based on Von Willebrand Factor: Ristocetin Cofactor (VWF:Rco) Activity | 1.463 (IU/dL)/(IU/kg) | Standard Deviation 0.3205 |
Secondary
Pharmacokinetics Assessment at Steady State: Maximum Plasma Concentration During the Partial Dosing Interval at Steady State (Cmax;ss) Based on Von Willebrand Factor Antigen (VWF:Ag) Activity
Cmax;ss based on VWF:Ag activity at steady state during end of study (Month 12) was reported.
Time frame: At Month 12: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours
Population: PKFAS composed of all participants who received at least one IP infusion and who provided at least one quantifiable pharmacokinetic or pharmacodynamic post dose measurement for pharmacokinetic and/or pharmacodynamics analysis. Here overall number of participants analyzed were participants who were evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Prior On-demand Participants | Pharmacokinetics Assessment at Steady State: Maximum Plasma Concentration During the Partial Dosing Interval at Steady State (Cmax;ss) Based on Von Willebrand Factor Antigen (VWF:Ag) Activity | 108.1 IU/dL | Standard Deviation 39.6 |
| Switch Participants | Pharmacokinetics Assessment at Steady State: Maximum Plasma Concentration During the Partial Dosing Interval at Steady State (Cmax;ss) Based on Von Willebrand Factor Antigen (VWF:Ag) Activity | 107.1 IU/dL | Standard Deviation 37.4 |
Secondary
Pharmacokinetics Assessment at Steady State: Maximum Plasma Concentration During the Partial Dosing Interval at Steady State (Cmax;ss) Based on Von Willebrand Factor Collagen Binding (VWF:CB) Activity
Cmax;ss based on VWF:CB activity at steady state during end of study (Month 12) was reported.
Time frame: At Month 12: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours
Population: PKFAS composed of all participants who received at least one IP infusion and who provided at least one quantifiable pharmacokinetic or pharmacodynamic post dose measurement for pharmacokinetic and/or pharmacodynamics analysis. Here overall number of participants analyzed were participants who were evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Prior On-demand Participants | Pharmacokinetics Assessment at Steady State: Maximum Plasma Concentration During the Partial Dosing Interval at Steady State (Cmax;ss) Based on Von Willebrand Factor Collagen Binding (VWF:CB) Activity | 137.48 IU/dL | Standard Deviation 44.97 |
| Switch Participants | Pharmacokinetics Assessment at Steady State: Maximum Plasma Concentration During the Partial Dosing Interval at Steady State (Cmax;ss) Based on Von Willebrand Factor Collagen Binding (VWF:CB) Activity | 162.19 IU/dL | Standard Deviation 60.04 |
Secondary
Pharmacokinetics Assessment at Steady State: Maximum Plasma Concentration During the Partial Dosing Interval at Steady State (Cmax;ss) Based on Von Willebrand Factor: Ristocetin Cofactor (VWF:Rco) Activity
Cmax;ss based on VWF:Rco activity at steady state during end of study (Month 12) was reported.
Time frame: At Month 12: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours
Population: PKFAS composed of all participants who received at least one IP infusion and who provided at least one quantifiable pharmacokinetic or pharmacodynamic post dose measurement for pharmacokinetic and/or pharmacodynamics analysis. Here overall number of participants analyzed were participants who were evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Prior On-demand Participants | Pharmacokinetics Assessment at Steady State: Maximum Plasma Concentration During the Partial Dosing Interval at Steady State (Cmax;ss) Based on Von Willebrand Factor: Ristocetin Cofactor (VWF:Rco) Activity | 92.63 IU/dL | Standard Deviation 37.05 |
| Switch Participants | Pharmacokinetics Assessment at Steady State: Maximum Plasma Concentration During the Partial Dosing Interval at Steady State (Cmax;ss) Based on Von Willebrand Factor: Ristocetin Cofactor (VWF:Rco) Activity | 102.89 IU/dL | Standard Deviation 44.74 |
Secondary
Pharmacokinetics Assessment at Steady State: Minimum Plasma Concentration During the Partial Dosing Interval at Steady State (Cmin;ss) Based on Von Willebrand Factor Antigen (VWF:Ag) Activity
Cmin;ss based on VWF:Rco activity at steady state during end of study (Month 12) was reported.
Time frame: At Month 12: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours
Population: PKFAS composed of all participants who received at least one IP infusion and who provided at least one quantifiable pharmacokinetic or pharmacodynamic post dose measurement for pharmacokinetic and/or pharmacodynamics analysis. Here overall number of participants analyzed were participants who were evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Prior On-demand Participants | Pharmacokinetics Assessment at Steady State: Minimum Plasma Concentration During the Partial Dosing Interval at Steady State (Cmin;ss) Based on Von Willebrand Factor Antigen (VWF:Ag) Activity | 6.3 IU/dL | Standard Deviation 4.8 |
| Switch Participants | Pharmacokinetics Assessment at Steady State: Minimum Plasma Concentration During the Partial Dosing Interval at Steady State (Cmin;ss) Based on Von Willebrand Factor Antigen (VWF:Ag) Activity | 11.7 IU/dL | Standard Deviation 8.9 |
Secondary
Pharmacokinetics Assessment at Steady State: Minimum Plasma Concentration During the Partial Dosing Interval at Steady State (Cmin;ss) Based on Von Willebrand Factor Collagen Binding (VWF:CB) Activity
Cmin;ss based on VWF:CB activity at steady state during end of study (Month 12) was reported.
Time frame: At Month 12: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours
Population: PKFAS composed of all participants who received at least one IP infusion and who provided at least one quantifiable pharmacokinetic or pharmacodynamic post dose measurement for pharmacokinetic and/or pharmacodynamics analysis. Here overall number of participants analyzed were participants who were evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Prior On-demand Participants | Pharmacokinetics Assessment at Steady State: Minimum Plasma Concentration During the Partial Dosing Interval at Steady State (Cmin;ss) Based on Von Willebrand Factor Collagen Binding (VWF:CB) Activity | 3.82 IU/dL | Standard Deviation 6.86 |
| Switch Participants | Pharmacokinetics Assessment at Steady State: Minimum Plasma Concentration During the Partial Dosing Interval at Steady State (Cmin;ss) Based on Von Willebrand Factor Collagen Binding (VWF:CB) Activity | 9.94 IU/dL | Standard Deviation 8.46 |
Secondary
Pharmacokinetics Assessment at Steady State: Minimum Plasma Concentration During the Partial Dosing Interval at Steady State (Cmin;ss) Based on Von Willebrand Factor: Ristocetin Cofactor (VWF:Rco) Activity
Cmin;ss based on VWF:Rco activity at steady state during end of study (Month 12) was reported.
Time frame: At Month 12: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours
Population: PKFAS composed of all participants who received at least one IP infusion and who provided at least one quantifiable pharmacokinetic or pharmacodynamic post dose measurement for pharmacokinetic and/or pharmacodynamics analysis. Here overall number of participants analyzed were participants who were evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Prior On-demand Participants | Pharmacokinetics Assessment at Steady State: Minimum Plasma Concentration During the Partial Dosing Interval at Steady State (Cmin;ss) Based on Von Willebrand Factor: Ristocetin Cofactor (VWF:Rco) Activity | NA IU/dL |
| Switch Participants | Pharmacokinetics Assessment at Steady State: Minimum Plasma Concentration During the Partial Dosing Interval at Steady State (Cmin;ss) Based on Von Willebrand Factor: Ristocetin Cofactor (VWF:Rco) Activity | NA IU/dL |
Secondary
Pharmacokinetics Assessment at Steady State: Minimum Time to Reach the Maximum Plasma Concentration at Steady State (Tmax;ss) Based on Von Willebrand Factor Antigen (VWF:Ag) Activity
Tmax;ss based on VWF:Ag activity at steady state during end of study (Month 12) was reported.
Time frame: At Month 12: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours
Population: PKFAS composed of all participants who received at least one IP infusion and who provided at least one quantifiable pharmacokinetic or pharmacodynamic post dose measurement for pharmacokinetic and/or pharmacodynamics analysis. Here overall number of participants analyzed were participants who were evaluable for this outcome measure.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Prior On-demand Participants | Pharmacokinetics Assessment at Steady State: Minimum Time to Reach the Maximum Plasma Concentration at Steady State (Tmax;ss) Based on Von Willebrand Factor Antigen (VWF:Ag) Activity | 0.580 hours |
| Switch Participants | Pharmacokinetics Assessment at Steady State: Minimum Time to Reach the Maximum Plasma Concentration at Steady State (Tmax;ss) Based on Von Willebrand Factor Antigen (VWF:Ag) Activity | 0.330 hours |
Secondary
Pharmacokinetics Assessment at Steady State: Minimum Time to Reach the Maximum Plasma Concentration at Steady State (Tmax;ss) Based on Von Willebrand Factor Collagen Binding (VWF:CB) Activity
Tmax;ss based on VWF:CB activity at steady state during end of study (Month 12) was reported.
Time frame: At Month 12: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours
Population: PKFAS composed of all participants who received at least one IP infusion and who provided at least one quantifiable pharmacokinetic or pharmacodynamic post dose measurement for pharmacokinetic and/or pharmacodynamics analysis. Here overall number of participants analyzed were participants who were evaluable for this outcome measure.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Prior On-demand Participants | Pharmacokinetics Assessment at Steady State: Minimum Time to Reach the Maximum Plasma Concentration at Steady State (Tmax;ss) Based on Von Willebrand Factor Collagen Binding (VWF:CB) Activity | 0.420 hours |
| Switch Participants | Pharmacokinetics Assessment at Steady State: Minimum Time to Reach the Maximum Plasma Concentration at Steady State (Tmax;ss) Based on Von Willebrand Factor Collagen Binding (VWF:CB) Activity | 0.670 hours |
Secondary
Pharmacokinetics Assessment at Steady State: Minimum Time to Reach the Maximum Plasma Concentration at Steady State (Tmax;ss) Based on Von Willebrand Factor: Ristocetin Cofactor (VWF:Rco) Activity
Tmax;ss based on VWF:Rco activity at steady state during end of study (Month 12) was reported.
Time frame: At Month 12: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours
Population: PKFAS composed of all participants who received at least one IP infusion and who provided at least one quantifiable pharmacokinetic or pharmacodynamic post dose measurement for pharmacokinetic and/or pharmacodynamics analysis. Here overall number of participants analyzed were participants who were evaluable for this outcome measure.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Prior On-demand Participants | Pharmacokinetics Assessment at Steady State: Minimum Time to Reach the Maximum Plasma Concentration at Steady State (Tmax;ss) Based on Von Willebrand Factor: Ristocetin Cofactor (VWF:Rco) Activity | 0.330 hours |
| Switch Participants | Pharmacokinetics Assessment at Steady State: Minimum Time to Reach the Maximum Plasma Concentration at Steady State (Tmax;ss) Based on Von Willebrand Factor: Ristocetin Cofactor (VWF:Rco) Activity | 0.400 hours |
Secondary
Total Number of Infusions Administered Per Participant During Prophylactic Treatment With rVWF Through Month 12
For each participant, the total number of infusions was counted as the total number of unique infusions of rVWF which were administered between the dates of informed consent and termination from the study, inclusive, regardless of the date and time of administration. The total number of infusions administered during the study was entered in electronic case record form (eCRF), and recorded in ERT system. Total number of infusions administered per participant during prophylactic treatment With rVWF through 12 months was calculated.
Time frame: Up to 12 months
Population: FAS composed of all participants who received prophylactic IP treatment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Prior On-demand Participants | Total Number of Infusions Administered Per Participant During Prophylactic Treatment With rVWF Through Month 12 | 65.1 infusions | Standard Deviation 38.4 |
| Switch Participants | Total Number of Infusions Administered Per Participant During Prophylactic Treatment With rVWF Through Month 12 | 87.8 infusions | Standard Deviation 30.2 |
Secondary
Total Weight Adjusted Consumption of rVWF Per Participant During Prophylactic Treatment Through Month 12
For each participant, the body weight-adjusted dose (IU/kg) was derived as the number of units of rVWF infused (IU) divided by the last available body weight (kilogram \[kg\]) prior to the infusion. Total weight adjusted consumption of rVWF (vonicog alfa) per participant during prophylactic treatment was reported.
Time frame: Up to 12 months
Population: FAS composed of all participants who received prophylactic IP treatment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Prior On-demand Participants | Total Weight Adjusted Consumption of rVWF Per Participant During Prophylactic Treatment Through Month 12 | 3431.584 IU/kg | Standard Deviation 2117.6562 |
| Switch Participants | Total Weight Adjusted Consumption of rVWF Per Participant During Prophylactic Treatment Through Month 12 | 4433.752 IU/kg | Standard Deviation 1844.8761 |