Trial Outcomes & Findings for Efficacy, PK, Immunogenicity and Safety of Wilate in Severe Von Willebrand Disease (VWD) Patients <6 Years of Age (NCT NCT04953884)
NCT ID: NCT04953884
Last Updated: 2026-02-20
Results Overview
TABR is defined as the total number of bleeding episodes (BEs) including spontaneous, traumatic, and other bleeds, occurring during the period from the first prophylactic dose of wilate to the study completion visit, divided by the duration (in years) between these two time points. Bleeding episodes that occurred during surgery periods were excluded from the calculation of TABR. Total BEs refers to all bleeding episodes that occurred during the study period, regardless of whether they were treated with wilate or not. Treated BEs are a subset of total BEs comprising of bleeding episodes that were treated with wilate.
COMPLETED
PHASE3
12 participants
During 12 months of prophylactic treatment
2026-02-20
Participant Flow
Participant milestones
| Measure |
Wilate Treatment
PK: Single dose of 80 IU/kg BW. Prophylactic treatment: 30-50 IU/kg BW administered 2-3 times per week at the recommended dose of over 12 months. Minor haemorrhage: loading dose 30-50 IU/kg BW followed by a maintenance dose of 30-40 IU/kg BW every 12-24 hours to achieve VWF:Ac and FVIII:C trough levels of \>30%. Major haemorrhage: loading dose 50-80 IU/kg BW followed by a maintenance dose of 30-50 IU/kg BW every 12-24 hours to achieve VWF:Ac and FVIII:C trough levels of \>50%. Minor surgery: loading dose of 40-60 IU/kg BW followed by a maintenance dose of 20-30 IU/kg BW every 12-24 hours for up to 3 days, to achieve VWF:Ac peak levels of 50% after loading dose and trough levels \>30% during maintenance. Major surgery: loading dose of 60-80 IU/kg BW followed by a maintenance dose of 30-40 IU/kg BW every 12-24 hours for up to 6 days or longer, to achieve VWF:Ac peak levels of 100% after loading dose and trough levels \>50% during maintenance
Wilate: Wilate is a plasma-derived, stable, highly purified, double virus inactivated concentrate of freeze-dried active VWF and factor VIII (FVIII) prepared from cryoprecipitate and intended for the treatment of patients with von Willebrand disease (VWD) and/or haemophilia A
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|---|---|
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Overall Study
STARTED
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12
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Overall Study
Full analysis set (FAS)
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12
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Overall Study
Safety analysis set (SAF)
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12
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Overall Study
Study population of patients undergoing pharmacokinetic analysis (PK)
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11
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Overall Study
Study population of patients undergoing pharmacokinetic analysis as Per-protocol (PK-PP)
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10
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Overall Study
Per-protocol population (PP)
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8
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Overall Study
Surgery set (SURG)
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1
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Overall Study
COMPLETED
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11
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Overall Study
NOT COMPLETED
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1
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Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Efficacy, PK, Immunogenicity and Safety of Wilate in Severe Von Willebrand Disease (VWD) Patients <6 Years of Age
Baseline characteristics by cohort
| Measure |
Wilate Treatment
n=12 Participants
PK: Single dose of 80 IU/kg body weight (BW). Prophylactic treatment: 30-50 IU/kg BW administered 2-3 times per week at the recommended dose of over 12 months. Minor haemorrhage: loading dose 30-50 IU/kg BW followed by a maintenance dose of 30-40 IU/kg BW every 12-24 hours to achieve von Willebrand factor activity (VWF:Ac) and FVIII:C trough levels of \>30%. Major haemorrhage: loading dose 50-80 IU/kg BW followed by a maintenance dose of 30-50 IU/kg BW every 12-24 hours to achieve VWF:Ac and FVIII:C trough levels of \>50%. Minor surgery: loading dose of 40-60 IU/kg BW followed by a maintenance dose of 20-30 IU/kg BW every 12-24 hours for up to 3 days, to achieve VWF:Ac peak levels of 50% after loading dose and trough levels \>30% during maintenance. Major surgery: loading dose of 60-80 IU/kg BW followed by a maintenance dose of 30-40 IU/kg BW every 12-24 hours for up to 6 days or longer, to achieve VWF:Ac peak levels of 100% after loading dose and trough levels \>50% during maintenance
wilate: wilate is a plasma-derived, stable, highly purified, double virus inactivated concentrate of freeze-dried active VWF and factor VIII (FVIII) prepared from cryoprecipitate and intended for the treatment of patients with von Willebrand disease (VWD) and/or haemophilia A
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Age, Continuous
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2.5 years
STANDARD_DEVIATION 1.2 • n=14 Participants
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Sex: Female, Male
Female
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6 Participants
n=14 Participants
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Sex: Female, Male
Male
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6 Participants
n=14 Participants
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Race/Ethnicity, Customized
White
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10 Participants
n=14 Participants
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Race/Ethnicity, Customized
Arabian
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2 Participants
n=14 Participants
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Blood Group
A
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4 Participants
n=14 Participants
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Blood Group
B
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2 Participants
n=14 Participants
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Blood Group
AB
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2 Participants
n=14 Participants
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Blood Group
O
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3 Participants
n=14 Participants
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Blood Group
Unknown
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1 Participants
n=14 Participants
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VWD type
Type 2
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4 Participants
n=14 Participants
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VWD type
Type 3
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8 Participants
n=14 Participants
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VWF inhibitor history
Yes
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0 Participants
n=14 Participants
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VWF inhibitor history
No
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12 Participants
n=14 Participants
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FVIII inhibitor history
Yes
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0 Participants
n=14 Participants
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FVIII inhibitor history
No
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12 Participants
n=14 Participants
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Family history of VWD
Yes
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6 Participants
n=14 Participants
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Family history of VWD
No
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6 Participants
n=14 Participants
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PRIMARY outcome
Timeframe: During 12 months of prophylactic treatmentPopulation: The analysis population consists of all patients in the full analysis set (FAS)
TABR is defined as the total number of bleeding episodes (BEs) including spontaneous, traumatic, and other bleeds, occurring during the period from the first prophylactic dose of wilate to the study completion visit, divided by the duration (in years) between these two time points. Bleeding episodes that occurred during surgery periods were excluded from the calculation of TABR. Total BEs refers to all bleeding episodes that occurred during the study period, regardless of whether they were treated with wilate or not. Treated BEs are a subset of total BEs comprising of bleeding episodes that were treated with wilate.
Outcome measures
| Measure |
Wilate Treatment
n=12 Participants
TABR was assessed in the FAS.
Prophylactic treatment: 30-50 IU/kg BW administered 2-3 times per week at the recommended dose of over 12 months.
wilate: wilate is a plasma-derived, stable, highly purified, double virus inactivated concentrate of freeze-dried active VWF and factor VIII (FVIII) prepared from cryoprecipitate and intended for the treatment of patients with von Willebrand disease (VWD) and/or haemophilia A
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|---|---|
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Total Annualised Bleeding Rate (TABR) During Prophylactic Treatment With Wilate.
Total BEs
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4.6 Annualized number of bleeding episodes
Standard Deviation 6.1
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Total Annualised Bleeding Rate (TABR) During Prophylactic Treatment With Wilate.
Treated BEs
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3.7 Annualized number of bleeding episodes
Standard Deviation 5.1
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SECONDARY outcome
Timeframe: At baseline, 15 minutes, 3, 9, 24, 48 and 72 hours after dosing of 80 IU/kg BW wilatePopulation: The analysis population consists of all patients in the PK per protocol population (PK-PP).
Mean AUC of VWF:Ac after PK injection of wilate as measured by chromogenic assay.
Outcome measures
| Measure |
Wilate Treatment
n=10 Participants
TABR was assessed in the FAS.
Prophylactic treatment: 30-50 IU/kg BW administered 2-3 times per week at the recommended dose of over 12 months.
wilate: wilate is a plasma-derived, stable, highly purified, double virus inactivated concentrate of freeze-dried active VWF and factor VIII (FVIII) prepared from cryoprecipitate and intended for the treatment of patients with von Willebrand disease (VWD) and/or haemophilia A
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|---|---|
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Area Under the Curve (AUC) of Wilate for VWF:Ac (VWF:RCo) Over Time
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1100 h*IU/dL
Standard Deviation 532
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SECONDARY outcome
Timeframe: At baseline, 15 minutes, 3, 9, 24, 48 and 72 hours after dosing of 80 IU/kg BW wilatePopulation: Of the 10 patients in the PK per protocol population (PK-PP), evaluable data for FVIII measurements was available for only 8 patients.
Mean AUC of FVIII after PK injection of wilate as measured by chromogenic assay.
Outcome measures
| Measure |
Wilate Treatment
n=8 Participants
TABR was assessed in the FAS.
Prophylactic treatment: 30-50 IU/kg BW administered 2-3 times per week at the recommended dose of over 12 months.
wilate: wilate is a plasma-derived, stable, highly purified, double virus inactivated concentrate of freeze-dried active VWF and factor VIII (FVIII) prepared from cryoprecipitate and intended for the treatment of patients with von Willebrand disease (VWD) and/or haemophilia A
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|---|---|
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Area Under the Curve (AUC) of Wilate for FVIII (OS) Over Time
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2410 h*IU/dL
Standard Deviation 1122
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SECONDARY outcome
Timeframe: At baseline, 15 minutes, 3, 9, 24, 48 and 72 hours after dosing of 80 IU/kg BW wilatePopulation: The analysis population consists of all 10 patients in the PK per protocol population (PK-PP).
Mean AUC of VWF:Ac after PK injection of wilate, normalised for the actual administered dose (IU/kg), over time. AUC norm was measured and reported as \[h\*kg/IU\]/(dL/IU) which could also be reported as h\*kg/dL.
Outcome measures
| Measure |
Wilate Treatment
n=10 Participants
TABR was assessed in the FAS.
Prophylactic treatment: 30-50 IU/kg BW administered 2-3 times per week at the recommended dose of over 12 months.
wilate: wilate is a plasma-derived, stable, highly purified, double virus inactivated concentrate of freeze-dried active VWF and factor VIII (FVIII) prepared from cryoprecipitate and intended for the treatment of patients with von Willebrand disease (VWD) and/or haemophilia A
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|---|---|
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AUC Normalised for the Administered Dose (AUCnorm) of Wilate for VWF:Ac (VWF:RCo) Over Time
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13.7 h*kg/dL
Standard Deviation 6.7
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SECONDARY outcome
Timeframe: At baseline, 15 minutes, 3, 9, 24, 48 and 72 hours after dosing of 80 IU/kg BW wilatePopulation: Of the 10 patients in the PK per protocol population (PK-PP), evaluable data for FVIII measurements was available for only 8 patients.
Mean AUC of FVIII after PK injection of wilate, normalised for the actual administered dose (IU/kg), over time. AUC norm was measured and reported as \[h\*kg/IU\]/(dL/IU) which could also be reported as h\*kg/dL.
Outcome measures
| Measure |
Wilate Treatment
n=8 Participants
TABR was assessed in the FAS.
Prophylactic treatment: 30-50 IU/kg BW administered 2-3 times per week at the recommended dose of over 12 months.
wilate: wilate is a plasma-derived, stable, highly purified, double virus inactivated concentrate of freeze-dried active VWF and factor VIII (FVIII) prepared from cryoprecipitate and intended for the treatment of patients with von Willebrand disease (VWD) and/or haemophilia A
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|---|---|
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AUC Normalised for the Administered Dose (AUCnorm) of Wilate for FVIII:C (OS) Over Time
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30.1 h*kg/dL
Standard Deviation 14.2
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SECONDARY outcome
Timeframe: At baseline, 15 minutes, 3, 9, 24, 48 and 72 hours after dosing of 80 IU/kg BW wilatePopulation: The analysis population consists of all 10 patients in the PK per protocol population (PK-PP).
Mean clearance (CL) of VWF:Ac, measured by ristocetin cofactor assay \[VWF:RCo\]) after PK injection of wilate, calculated as the ratio of dose administered to the area under the plasma concentration-time curve (AUC), over time. Clearance was defined as the rate of drug elimination divided by plasma concentration, giving a volume of plasma from which drug is completely removed per unit of time.
Outcome measures
| Measure |
Wilate Treatment
n=10 Participants
TABR was assessed in the FAS.
Prophylactic treatment: 30-50 IU/kg BW administered 2-3 times per week at the recommended dose of over 12 months.
wilate: wilate is a plasma-derived, stable, highly purified, double virus inactivated concentrate of freeze-dried active VWF and factor VIII (FVIII) prepared from cryoprecipitate and intended for the treatment of patients with von Willebrand disease (VWD) and/or haemophilia A
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|---|---|
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Clearance (CL) of Wilate for VWF:Ac (VWF:RCo) Over Time
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0.09 dL/h/kg
Standard Deviation 0.04
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SECONDARY outcome
Timeframe: At baseline, 15 minutes, 3, 9, 24, 48 and 72 hours after dosing of 80 IU/kg BW wilatePopulation: Of the 10 patients in the PK per protocol population (PK-PP), evaluable data for FVIII measurements was available for only 8 patients.
Mean clearance (CL) of FVIII:C, measured by one-stage assay \[OS\]) after PK injection of wilate, calculated as the ratio of dose administered to the area under the plasma concentration-time curve (AUC), over time.
Outcome measures
| Measure |
Wilate Treatment
n=8 Participants
TABR was assessed in the FAS.
Prophylactic treatment: 30-50 IU/kg BW administered 2-3 times per week at the recommended dose of over 12 months.
wilate: wilate is a plasma-derived, stable, highly purified, double virus inactivated concentrate of freeze-dried active VWF and factor VIII (FVIII) prepared from cryoprecipitate and intended for the treatment of patients with von Willebrand disease (VWD) and/or haemophilia A
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|---|---|
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Clearance (CL) of Wilate for FVIII:C (OS) Over Time
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0.04 dL/h/kg
Standard Deviation 0.03
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SECONDARY outcome
Timeframe: At baseline, 15 minutes, 3, 9, 24, 48 and 72 hours after dosing of 80 IU/kg BW wilatePopulation: The analysis population consists of all 10 patients in the PK per protocol population (PK-PP).
Mean maximum plasma concentration (Cmax) of VWF:Ac, measured by ristocetin cofactor assay \[VWF:RCo\]) after PK injection of wilate, as determined from the observed peak value in the plasma concentration-time profile.
Outcome measures
| Measure |
Wilate Treatment
n=10 Participants
TABR was assessed in the FAS.
Prophylactic treatment: 30-50 IU/kg BW administered 2-3 times per week at the recommended dose of over 12 months.
wilate: wilate is a plasma-derived, stable, highly purified, double virus inactivated concentrate of freeze-dried active VWF and factor VIII (FVIII) prepared from cryoprecipitate and intended for the treatment of patients with von Willebrand disease (VWD) and/or haemophilia A
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|---|---|
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Maximum Plasma Concentration (Cmax) of Wilate for VWF:Ac (VWF:RCo) Over Time
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105 IU/dL
Standard Deviation 19.7
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SECONDARY outcome
Timeframe: At baseline, 15 minutes, 3, 9, 24, 48 and 72 hours after dosing of 80 IU/kg BW wilatePopulation: Of the 10 patients in the PK per protocol population (PK-PP), evaluable data for FVIII measurements was available for only 8 patients.
Mean maximum plasma concentration (Cmax) of FVIII:C, measured by one-stage assay \[OS\]) after PK injection of wilate, as determined from the observed peak value in the plasma concentration-time profile.
Outcome measures
| Measure |
Wilate Treatment
n=8 Participants
TABR was assessed in the FAS.
Prophylactic treatment: 30-50 IU/kg BW administered 2-3 times per week at the recommended dose of over 12 months.
wilate: wilate is a plasma-derived, stable, highly purified, double virus inactivated concentrate of freeze-dried active VWF and factor VIII (FVIII) prepared from cryoprecipitate and intended for the treatment of patients with von Willebrand disease (VWD) and/or haemophilia A
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|---|---|
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Maximum Plasma Concentration (Cmax) of Wilate for FVIII:C (OS) Over Time
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114.1 IU/dL
Standard Deviation 27.1
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SECONDARY outcome
Timeframe: At baseline, 15 minutes, 3, 9, 24, 48 and 72 hours after dosing of 80 IU/kg BW wilatePopulation: The analysis population consists of all 10 patients in the PK per protocol population (PK-PP).
Mean residence time (MRT) of VWF:Ac, measured by ristocetin cofactor assay \[VWF:RCo\]) after PK injection of wilate, calculated as the average time a VWF:Ac molecule remains in the body, derived from the ratio of area under the first moment curve (AUMC) to AUC.
Outcome measures
| Measure |
Wilate Treatment
n=10 Participants
TABR was assessed in the FAS.
Prophylactic treatment: 30-50 IU/kg BW administered 2-3 times per week at the recommended dose of over 12 months.
wilate: wilate is a plasma-derived, stable, highly purified, double virus inactivated concentrate of freeze-dried active VWF and factor VIII (FVIII) prepared from cryoprecipitate and intended for the treatment of patients with von Willebrand disease (VWD) and/or haemophilia A
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|---|---|
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Mean Residence Time (MRT) of Wilate for VWF:Ac (VWF:RCo) Over Time
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15.6 hours
Standard Deviation 9.5
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SECONDARY outcome
Timeframe: At baseline, 15 minutes, 3, 9, 24, 48 and 72 hours after dosing of 80 IU/kg BW wilatePopulation: Of the 10 patients in the PK per protocol population (PK-PP), evaluable data for FVIII was available for only 8 patients.
Mean residence time (MRT) of FVIII:C, measured by one-stage assay \[OS\]) after PK injection of wilate, calculated as the average time a FVIII:C molecule remains in the body, derived from the ratio of area under the first moment curve (AUMC) to AUC.
Outcome measures
| Measure |
Wilate Treatment
n=8 Participants
TABR was assessed in the FAS.
Prophylactic treatment: 30-50 IU/kg BW administered 2-3 times per week at the recommended dose of over 12 months.
wilate: wilate is a plasma-derived, stable, highly purified, double virus inactivated concentrate of freeze-dried active VWF and factor VIII (FVIII) prepared from cryoprecipitate and intended for the treatment of patients with von Willebrand disease (VWD) and/or haemophilia A
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|---|---|
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Mean Residence Time (MRT) of Wilate for FVIII:C (OS) Over Time
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22.5 hours
Standard Deviation 9.4
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SECONDARY outcome
Timeframe: At baseline, 15 minutes, 3, 9, 24, 48 and 72 hours after dosing of 80 IU/kg BW wilatePopulation: The analysis population consists of all 10 patients in the PK per protocol population (PK-PP).
Mean in vivo half-life (T1/2) VWF:Ac, measured by ristocetin cofactor assay \[VWF:RCo\]) after PK injection of wilate, calculated as the time required for the plasma concentration to decrease by half during the terminal elimination phase.
Outcome measures
| Measure |
Wilate Treatment
n=10 Participants
TABR was assessed in the FAS.
Prophylactic treatment: 30-50 IU/kg BW administered 2-3 times per week at the recommended dose of over 12 months.
wilate: wilate is a plasma-derived, stable, highly purified, double virus inactivated concentrate of freeze-dried active VWF and factor VIII (FVIII) prepared from cryoprecipitate and intended for the treatment of patients with von Willebrand disease (VWD) and/or haemophilia A
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|---|---|
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In Vivo Half-life (T1/2) of Wilate for VWF:Ac (VWF:RCo) Over Time
|
11.7 hours
Standard Deviation 9.6
|
SECONDARY outcome
Timeframe: At baseline, 15 minutes, 3, 9, 24, 48 and 72 hours after dosing of 80 IU/kg BW wilatePopulation: Of the 10 patients in the PK per protocol population (PK-PP), evaluable data for FVIII measurements was available for only 8 patients.
Mean in vivo half-life (T1/2) of FVIII:C, measured by one-stage assay \[OS\]) after PK injection of wilate, calculated as the time required for the plasma concentration to decrease by half during the terminal elimination phase.
Outcome measures
| Measure |
Wilate Treatment
n=8 Participants
TABR was assessed in the FAS.
Prophylactic treatment: 30-50 IU/kg BW administered 2-3 times per week at the recommended dose of over 12 months.
wilate: wilate is a plasma-derived, stable, highly purified, double virus inactivated concentrate of freeze-dried active VWF and factor VIII (FVIII) prepared from cryoprecipitate and intended for the treatment of patients with von Willebrand disease (VWD) and/or haemophilia A
|
|---|---|
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In Vivo Half-life (T1/2) of Wilate for FVIII:C (OS) Over Time
|
15 hours
Standard Deviation 7.5
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SECONDARY outcome
Timeframe: At baseline, 15 minutes, 3, 9, 24, 48 and 72 hours after dosing of 80 IU/kg BW wilatePopulation: The analysis population consists of all 10 patients in the PK per protocol population (PK-PP).
Mean time to reach maximum plasma concentration (Tmax) of VWF:Ac, measured by ristocetin cofactor assay \[VWF:RCo\]) after PK injection of wilate, defined as the time from dosing to the observed peak plasma concentration.
Outcome measures
| Measure |
Wilate Treatment
n=10 Participants
TABR was assessed in the FAS.
Prophylactic treatment: 30-50 IU/kg BW administered 2-3 times per week at the recommended dose of over 12 months.
wilate: wilate is a plasma-derived, stable, highly purified, double virus inactivated concentrate of freeze-dried active VWF and factor VIII (FVIII) prepared from cryoprecipitate and intended for the treatment of patients with von Willebrand disease (VWD) and/or haemophilia A
|
|---|---|
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Time to Reach Maximum Plasma Concentration (Tmax) of Wilate for VWF:Ac (VWF:RCo) Over Time
|
0.27 hours
Standard Deviation 0.04
|
SECONDARY outcome
Timeframe: At baseline, 15 minutes, 3, 9, 24, 48 and 72 hours after dosing of 80 IU/kg BW wilatePopulation: Of the 10 patients in the PK per protocol population (PK-PP), evaluable data for FVIII measurements was available for only 8 patients.
Mean time to reach maximum plasma concentration (Tmax) of FVIII:C, measured by one-stage assay \[OS\]) after PK injection of wilate, defined as the time from dosing to the observed peak plasma concentration.
Outcome measures
| Measure |
Wilate Treatment
n=8 Participants
TABR was assessed in the FAS.
Prophylactic treatment: 30-50 IU/kg BW administered 2-3 times per week at the recommended dose of over 12 months.
wilate: wilate is a plasma-derived, stable, highly purified, double virus inactivated concentrate of freeze-dried active VWF and factor VIII (FVIII) prepared from cryoprecipitate and intended for the treatment of patients with von Willebrand disease (VWD) and/or haemophilia A
|
|---|---|
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Time to Reach Maximum Plasma Concentration (Tmax) of Wilate for FVIII:C (OS) Over Time
|
0.26 hours
Standard Deviation 0.05
|
SECONDARY outcome
Timeframe: At baseline, 15 minutes, 3, 9, 24, 48 and 72 hours after dosing of 80 IU/kg BW wilatePopulation: The analysis population consists of all 10 patients in the PK per protocol population (PK-PP).
Mean volume of distribution at steady state (Vd) of VWF:Ac, measured by ristocetin cofactor assay \[VWF:RCo\]) after PK injection of wilate, calculated as clearance (CL) multiplied by mean residence time (MRT).
Outcome measures
| Measure |
Wilate Treatment
n=10 Participants
TABR was assessed in the FAS.
Prophylactic treatment: 30-50 IU/kg BW administered 2-3 times per week at the recommended dose of over 12 months.
wilate: wilate is a plasma-derived, stable, highly purified, double virus inactivated concentrate of freeze-dried active VWF and factor VIII (FVIII) prepared from cryoprecipitate and intended for the treatment of patients with von Willebrand disease (VWD) and/or haemophilia A
|
|---|---|
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Volume of Distribution (Vd) of Wilate for VWF:Ac (VWF:RCo) Over Time
|
1.12 dL/kg
Standard Deviation 0.24
|
SECONDARY outcome
Timeframe: At baseline, 15 minutes, 3, 9, 24, 48 and 72 hours after dosing of 80 IU/kg BW wilatePopulation: Of the 10 patients in the PK per protocol population (PK-PP), evaluable data for FVIII measurements was available for only 8 patients.
Mean volume of distribution at steady state (Vd) of FVIII:C, measured by one-stage assay \[OS\]) after PK injection of wilate, calculated as clearance (CL) multiplied by mean residence time (MRT).
Outcome measures
| Measure |
Wilate Treatment
n=8 Participants
TABR was assessed in the FAS.
Prophylactic treatment: 30-50 IU/kg BW administered 2-3 times per week at the recommended dose of over 12 months.
wilate: wilate is a plasma-derived, stable, highly purified, double virus inactivated concentrate of freeze-dried active VWF and factor VIII (FVIII) prepared from cryoprecipitate and intended for the treatment of patients with von Willebrand disease (VWD) and/or haemophilia A
|
|---|---|
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Volume of Distribution (Vd) of Wilate for FVIII:C (OS) Over Time
|
0.82 dL/kg
Standard Deviation 0.28
|
SECONDARY outcome
Timeframe: Measures were taken at the following timepoints: baseline and 1, 2, 3, 6, 9, and 12 months of treatment with IVR values reported at baseline and 12 months.Population: Analysis was performed on the full analysis set (FAS). At 12 months, data was available for only 11 patients as 1 patient terminated the study early due to an AE.
Mean incremental in vivo recovery (IVR) of VWF:Ac, measured by ristocetin cofactor assay \[VWF:RCo\]) after PK injection of wilate, calculated as the increase in plasma VWF:Ac concentration per IU/kg of wilate administered.
Outcome measures
| Measure |
Wilate Treatment
n=12 Participants
TABR was assessed in the FAS.
Prophylactic treatment: 30-50 IU/kg BW administered 2-3 times per week at the recommended dose of over 12 months.
wilate: wilate is a plasma-derived, stable, highly purified, double virus inactivated concentrate of freeze-dried active VWF and factor VIII (FVIII) prepared from cryoprecipitate and intended for the treatment of patients with von Willebrand disease (VWD) and/or haemophilia A
|
|---|---|
|
Incremental In-vivo Recovery (IVR) of Wilate for VWF:Ac (VWF:RCo) Over Time
Baseline
|
1.26 kg/dL
Interval 1.0 to 1.53
|
|
Incremental In-vivo Recovery (IVR) of Wilate for VWF:Ac (VWF:RCo) Over Time
12-month visit
|
1.75 kg/dL
Interval 1.58 to 1.92
|
SECONDARY outcome
Timeframe: Measures were taken at the following timepoints: baseline and 1, 2, 3, 6, 9, and 12 months of treatment with IVR values reported at baseline and 12 months.Population: Analysis was performed on the full analysis set; however, at baseline there were only 9 patients with valid FVIII data. At 12 months, valid FVIII data was available for only 8 patients as 1 patient terminated the study early due to an AE.
Mean incremental in vivo recovery (IVR) of FVIII:C, measured by one-stage assay \[OS\]) after PK injection of wilate, calculated as the increase in plasma FVIII:C concentration per IU/kg of wilate administered.
Outcome measures
| Measure |
Wilate Treatment
n=9 Participants
TABR was assessed in the FAS.
Prophylactic treatment: 30-50 IU/kg BW administered 2-3 times per week at the recommended dose of over 12 months.
wilate: wilate is a plasma-derived, stable, highly purified, double virus inactivated concentrate of freeze-dried active VWF and factor VIII (FVIII) prepared from cryoprecipitate and intended for the treatment of patients with von Willebrand disease (VWD) and/or haemophilia A
|
|---|---|
|
Incremental In-vivo Recovery (IVR) of Wilate for FVIII:C (OS) Over Time
Baseline
|
1.48 kg/dL
Interval 1.23 to 1.73
|
|
Incremental In-vivo Recovery (IVR) of Wilate for FVIII:C (OS) Over Time
12-month visit
|
1.69 kg/dL
Interval 1.33 to 2.05
|
SECONDARY outcome
Timeframe: Up to 12 months of treatmentPopulation: BEs were recorded in the FAS set. Of the 12 patients, a total of 59 BEs were recorded in 10 of the 12 patients. OF these 59 BEs, 47 were treated with wilate.
Proportion of BEs successfully treated with wilate, as assessed using a predefined 4-point ordinal haemostatic efficacy scale. Each BE was rated at the end of treatment as "excellent", "good", "moderate", or "none" based on the time to bleeding cessation and the dose required. A BE is considered successfully treated if the efficacy rating is "excellent" (bleeding stopped within 3 days for minor bleeds, within 7 days for major bleeds, or within 10 days for gastrointestinal bleeds) or "good" (bleeding stopped, but time and/or dose slightly exceeded expectations). The outcome is reported as the percentage of BEs with a rating of "excellent" or "good" out of all treated BEs
Outcome measures
| Measure |
Wilate Treatment
n=47 BEs
TABR was assessed in the FAS.
Prophylactic treatment: 30-50 IU/kg BW administered 2-3 times per week at the recommended dose of over 12 months.
wilate: wilate is a plasma-derived, stable, highly purified, double virus inactivated concentrate of freeze-dried active VWF and factor VIII (FVIII) prepared from cryoprecipitate and intended for the treatment of patients with von Willebrand disease (VWD) and/or haemophilia A
|
|---|---|
|
Efficacy of Wilate Measured by the Proportion of BEs Successfully Treated With Wilate
Good
|
1 number of treated BEs
|
|
Efficacy of Wilate Measured by the Proportion of BEs Successfully Treated With Wilate
Excellent
|
46 number of treated BEs
|
|
Efficacy of Wilate Measured by the Proportion of BEs Successfully Treated With Wilate
Moderate
|
0 number of treated BEs
|
|
Efficacy of Wilate Measured by the Proportion of BEs Successfully Treated With Wilate
None
|
0 number of treated BEs
|
SECONDARY outcome
Timeframe: Up to 12 months of treatmentPopulation: Analysis was measured in the SURG population.
Overall efficacy of wilate in perioperative prophylaxis against excessive bleeding, as assessed at the end of the postoperative period by the responsible treating investigator using a predefined 4-point ordinal haemostatic efficacy scale. The assessment is based on the presence or absence of postoperative bleeding or oozing, the need for additional dosing, and the ability to control bleeding with wilate. Excellent: No postoperative bleeding or oozing not due to surgical complications; all postoperative bleeding due to complications controlled with wilate as anticipated for the procedure. Good: No postoperative bleeding or oozing not due to surgical complications; control of postoperative bleeding due to complications required increased dosing or additional injections of wilate not originally anticipated. Moderate: Some postoperative bleeding or oozing not due to surgical complications; control required increased dosing or additional injections of wilate not originally anticipated
Outcome measures
| Measure |
Wilate Treatment
n=1 Participants
TABR was assessed in the FAS.
Prophylactic treatment: 30-50 IU/kg BW administered 2-3 times per week at the recommended dose of over 12 months.
wilate: wilate is a plasma-derived, stable, highly purified, double virus inactivated concentrate of freeze-dried active VWF and factor VIII (FVIII) prepared from cryoprecipitate and intended for the treatment of patients with von Willebrand disease (VWD) and/or haemophilia A
|
|---|---|
|
The Overall Efficacy of Wilate in Perioperative Prophylaxis Against Excessive Bleeding as Assessed at the End of the Postoperative Period by the Responsible Treating Investigator
Excellent
|
1 Participants
|
|
The Overall Efficacy of Wilate in Perioperative Prophylaxis Against Excessive Bleeding as Assessed at the End of the Postoperative Period by the Responsible Treating Investigator
Good
|
0 Participants
|
|
The Overall Efficacy of Wilate in Perioperative Prophylaxis Against Excessive Bleeding as Assessed at the End of the Postoperative Period by the Responsible Treating Investigator
Moderate
|
0 Participants
|
|
The Overall Efficacy of Wilate in Perioperative Prophylaxis Against Excessive Bleeding as Assessed at the End of the Postoperative Period by the Responsible Treating Investigator
None
|
0 Participants
|
SECONDARY outcome
Timeframe: Up to 12 months of treatmentPopulation: Analysis was measured in the FAS population.
Mean dose of wilate administered for routine prophylactic treatment, reported as (a) mean dose per injection (IU/kg) and (b) mean dose per week (IU/kg). Dose per injection is calculated as the total amount of wilate (IU) administered per injection divided by the patient's body weight (kg). Dose per week was calculated as the total amount of wilate (IU) administered for prophylaxis in a week, divided by the patient's body weight (kg). Both measures were averaged across all prophylactic infusions during the study period
Outcome measures
| Measure |
Wilate Treatment
n=12 Participants
TABR was assessed in the FAS.
Prophylactic treatment: 30-50 IU/kg BW administered 2-3 times per week at the recommended dose of over 12 months.
wilate: wilate is a plasma-derived, stable, highly purified, double virus inactivated concentrate of freeze-dried active VWF and factor VIII (FVIII) prepared from cryoprecipitate and intended for the treatment of patients with von Willebrand disease (VWD) and/or haemophilia A
|
|---|---|
|
Consumption of Wilate for Prophylactic Treatment
Dose per injection
|
54 IU/kg
Standard Deviation 27.5
|
|
Consumption of Wilate for Prophylactic Treatment
Dose per week
|
120.1 IU/kg
Standard Deviation 65
|
SECONDARY outcome
Timeframe: Up to 12 months of treatmentPopulation: The study population consists of all the patients in the FAS.
Mean dose of wilate administered for the on-demand treatment of BEs, reported as (a) mean dose per BE (IU/kg) and (b) mean dose per injection (IU/kg). Dose per BE is calculated as the total amount of wilate (IU) administered per BE treatment divided by the patient's body weight (kg). Dose per injection is calculated as the total amount of wilate (IU) administered for BE treatment in a week, divided by the patient's body weight (kg). Both measures are averaged across all treated BEs during the study period
Outcome measures
| Measure |
Wilate Treatment
n=12 Participants
TABR was assessed in the FAS.
Prophylactic treatment: 30-50 IU/kg BW administered 2-3 times per week at the recommended dose of over 12 months.
wilate: wilate is a plasma-derived, stable, highly purified, double virus inactivated concentrate of freeze-dried active VWF and factor VIII (FVIII) prepared from cryoprecipitate and intended for the treatment of patients with von Willebrand disease (VWD) and/or haemophilia A
|
|---|---|
|
Consumption of Wilate for the Treatment of BEs (On-demand Treatment)
Dose per BE
|
58.7 IU/kg
Standard Deviation 27.6
|
|
Consumption of Wilate for the Treatment of BEs (On-demand Treatment)
Dose per injection
|
55 IU/kg
Standard Deviation 22.3
|
SECONDARY outcome
Timeframe: Up to 12 months of treatmentPopulation: Analysis measured in SURG population.
Mean dose of wilate administered for surgical prophylaxis, reported as dose per exposure day (ED) in IU/kg. Dose per exposure day is calculated as the total amount of wilate (IU) administered for surgical prophylaxis on each day, divided by the patient's body weight (kg). The measure is averaged across all exposure days during the perioperative period
Outcome measures
| Measure |
Wilate Treatment
n=1 Participants
TABR was assessed in the FAS.
Prophylactic treatment: 30-50 IU/kg BW administered 2-3 times per week at the recommended dose of over 12 months.
wilate: wilate is a plasma-derived, stable, highly purified, double virus inactivated concentrate of freeze-dried active VWF and factor VIII (FVIII) prepared from cryoprecipitate and intended for the treatment of patients with von Willebrand disease (VWD) and/or haemophilia A
|
|---|---|
|
Consumption of Wilate During Surgical Prophylaxis
|
62.1 IU/kg
Standard Deviation 0
|
SECONDARY outcome
Timeframe: Up to 12 months of treatmentPopulation: Analysis was performed on the FAS.
Number of patients with detectable inhibitory antibodies to von Willebrand factor (VWF) and factor VIII (FVIII) during the study testing. Inhibitor testing is performed at baseline, every 3 months, and at any time if inhibitor development is suspected.
Outcome measures
| Measure |
Wilate Treatment
n=12 Participants
TABR was assessed in the FAS.
Prophylactic treatment: 30-50 IU/kg BW administered 2-3 times per week at the recommended dose of over 12 months.
wilate: wilate is a plasma-derived, stable, highly purified, double virus inactivated concentrate of freeze-dried active VWF and factor VIII (FVIII) prepared from cryoprecipitate and intended for the treatment of patients with von Willebrand disease (VWD) and/or haemophilia A
|
|---|---|
|
Number of Participants With Detectable Inhibitory Antibodies Against VWF and/or FVIII
|
1 Participants
|
SECONDARY outcome
Timeframe: Up to 12 months of treatmentPopulation: Analysis measured in the SAF.
Incidence of thromboembolic events, defined as the proportion of patients who experience one or more thromboembolic events (such as deep vein thrombosis, pulmonary embolism, or other clinically relevant thromboses) during the study period. Thromboembolic events are monitored and recorded as adverse events throughout the study, and are confirmed by clinical assessment and/or diagnostic imaging as appropriate. The outcome is reported as the number and percentage of patients with at least one thromboembolic event during the study
Outcome measures
| Measure |
Wilate Treatment
n=12 Participants
TABR was assessed in the FAS.
Prophylactic treatment: 30-50 IU/kg BW administered 2-3 times per week at the recommended dose of over 12 months.
wilate: wilate is a plasma-derived, stable, highly purified, double virus inactivated concentrate of freeze-dried active VWF and factor VIII (FVIII) prepared from cryoprecipitate and intended for the treatment of patients with von Willebrand disease (VWD) and/or haemophilia A
|
|---|---|
|
Number of Participants With Detectable Thromboembolic Events
|
0 Participants
|
SECONDARY outcome
Timeframe: At baseline and at 12 months of treatmentPopulation: Analysis measured in FAS and of 12 patients, only 11 patients with evaluable data.
Change from baseline in the Haemophilia Joint Health Score (HJHS) total score, assessed at baseline and at the end of the study (12 months). The HJHS is a validated clinical tool used to evaluate joint health in patients with bleeding disorders, measured over a scale of 0-124, with higher scores indicating worse joint health. This score is comprised of the assessments of 6 joints according to 8 criteria (each joint is scored from 0 to 20, giving a possible assessment range for all joints of 0 to 120) plus the Global Gait Score (measured from 0 to 4). The outcome is reported as the mean change in total HJHS score from baseline to study completion for each participant. An increase (positive value) indicates an increase in HJHS over the course of the study and worsening of joint health. A decrease (negative value) reflects a reduction in HJHS over the study duration and improvements in joint health. Assessments are performed by trained investigators using the standard HJHS protocol.
Outcome measures
| Measure |
Wilate Treatment
n=11 Participants
TABR was assessed in the FAS.
Prophylactic treatment: 30-50 IU/kg BW administered 2-3 times per week at the recommended dose of over 12 months.
wilate: wilate is a plasma-derived, stable, highly purified, double virus inactivated concentrate of freeze-dried active VWF and factor VIII (FVIII) prepared from cryoprecipitate and intended for the treatment of patients with von Willebrand disease (VWD) and/or haemophilia A
|
|---|---|
|
Change in Haemophilia Joint Health Score
Baseline
|
1.55 score on a scale
Standard Deviation 3.01
|
|
Change in Haemophilia Joint Health Score
12-months
|
0.80 score on a scale
Standard Deviation 1.93
|
|
Change in Haemophilia Joint Health Score
Change from baseline
|
-0.90 score on a scale
Standard Deviation 1.37
|
Adverse Events
Wilate Treatment
Serious adverse events
| Measure |
Wilate Treatment
n=12 participants at risk
PK: Single dose of 80 IU/kg body weight (BW). Prophylactic treatment: 30-50 IU/kg BW administered 2-3 times per week at the recommended dose of over 12 months. Minor haemorrhage: loading dose 30-50 IU/kg BW followed by a maintenance dose of 30-40 IU/kg BW every 12-24 hours to achieve von Willebrand factor activity (VWF:Ac) and FVIII:C trough levels of \>30%. Major haemorrhage: loading dose 50-80 IU/kg BW followed by a maintenance dose of 30-50 IU/kg BW every 12-24 hours to achieve VWF:Ac and FVIII:C trough levels of \>50%. Minor surgery: loading dose of 40-60 IU/kg BW followed by a maintenance dose of 20-30 IU/kg BW every 12-24 hours for up to 3 days, to achieve VWF:Ac peak levels of 50% after loading dose and trough levels \>30% during maintenance. Major surgery: loading dose of 60-80 IU/kg BW followed by a maintenance dose of 30-40 IU/kg BW every 12-24 hours for up to 6 days or longer, to achieve VWF:Ac peak levels of 100% after loading dose and trough levels \>50% during maintenance
wilate: wilate is a plasma-derived, stable, highly purified, double virus inactivated concentrate of freeze-dried active VWF and factor VIII (FVIII) prepared from cryoprecipitate and intended for the treatment of patients with von Willebrand disease (VWD) and/or haemophilia A
|
|---|---|
|
General disorders
Pyrexia
|
8.3%
1/12 • Number of events 1 • From the first administration of study drug and continuing until study a completion which was up to 12 months +2 weeks.
|
|
Infections and infestations
Soft tissue infection
|
8.3%
1/12 • Number of events 1 • From the first administration of study drug and continuing until study a completion which was up to 12 months +2 weeks.
|
|
Infections and infestations
Pneumonia
|
8.3%
1/12 • Number of events 1 • From the first administration of study drug and continuing until study a completion which was up to 12 months +2 weeks.
|
|
Blood and lymphatic system disorders
Iron deficiency anaemia
|
8.3%
1/12 • Number of events 1 • From the first administration of study drug and continuing until study a completion which was up to 12 months +2 weeks.
|
Other adverse events
| Measure |
Wilate Treatment
n=12 participants at risk
PK: Single dose of 80 IU/kg body weight (BW). Prophylactic treatment: 30-50 IU/kg BW administered 2-3 times per week at the recommended dose of over 12 months. Minor haemorrhage: loading dose 30-50 IU/kg BW followed by a maintenance dose of 30-40 IU/kg BW every 12-24 hours to achieve von Willebrand factor activity (VWF:Ac) and FVIII:C trough levels of \>30%. Major haemorrhage: loading dose 50-80 IU/kg BW followed by a maintenance dose of 30-50 IU/kg BW every 12-24 hours to achieve VWF:Ac and FVIII:C trough levels of \>50%. Minor surgery: loading dose of 40-60 IU/kg BW followed by a maintenance dose of 20-30 IU/kg BW every 12-24 hours for up to 3 days, to achieve VWF:Ac peak levels of 50% after loading dose and trough levels \>30% during maintenance. Major surgery: loading dose of 60-80 IU/kg BW followed by a maintenance dose of 30-40 IU/kg BW every 12-24 hours for up to 6 days or longer, to achieve VWF:Ac peak levels of 100% after loading dose and trough levels \>50% during maintenance
wilate: wilate is a plasma-derived, stable, highly purified, double virus inactivated concentrate of freeze-dried active VWF and factor VIII (FVIII) prepared from cryoprecipitate and intended for the treatment of patients with von Willebrand disease (VWD) and/or haemophilia A
|
|---|---|
|
Infections and infestations
Respiratory tract infection viral
|
8.3%
1/12 • Number of events 1 • From the first administration of study drug and continuing until study a completion which was up to 12 months +2 weeks.
|
|
Infections and infestations
Rhinitis
|
8.3%
1/12 • Number of events 1 • From the first administration of study drug and continuing until study a completion which was up to 12 months +2 weeks.
|
|
Infections and infestations
Scarlet fever
|
8.3%
1/12 • Number of events 1 • From the first administration of study drug and continuing until study a completion which was up to 12 months +2 weeks.
|
|
Infections and infestations
Soft tissue infection
|
8.3%
1/12 • Number of events 2 • From the first administration of study drug and continuing until study a completion which was up to 12 months +2 weeks.
|
|
Infections and infestations
Upper respiratory tract infection
|
8.3%
1/12 • Number of events 1 • From the first administration of study drug and continuing until study a completion which was up to 12 months +2 weeks.
|
|
Blood and lymphatic system disorders
Iron deficiency anaemia
|
25.0%
3/12 • Number of events 4 • From the first administration of study drug and continuing until study a completion which was up to 12 months +2 weeks.
|
|
Metabolism and nutrition disorders
Vitamin D deficiency
|
8.3%
1/12 • Number of events 1 • From the first administration of study drug and continuing until study a completion which was up to 12 months +2 weeks.
|
|
Psychiatric disorders
Attention deficit hyperactivity disorder
|
8.3%
1/12 • Number of events 1 • From the first administration of study drug and continuing until study a completion which was up to 12 months +2 weeks.
|
|
Vascular disorders
Hypertension
|
8.3%
1/12 • Number of events 1 • From the first administration of study drug and continuing until study a completion which was up to 12 months +2 weeks.
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
16.7%
2/12 • Number of events 2 • From the first administration of study drug and continuing until study a completion which was up to 12 months +2 weeks.
|
|
Gastrointestinal disorders
Dental caries
|
8.3%
1/12 • Number of events 1 • From the first administration of study drug and continuing until study a completion which was up to 12 months +2 weeks.
|
|
Gastrointestinal disorders
Mouth swelling
|
8.3%
1/12 • Number of events 3 • From the first administration of study drug and continuing until study a completion which was up to 12 months +2 weeks.
|
|
Gastrointestinal disorders
Toothache
|
8.3%
1/12 • Number of events 6 • From the first administration of study drug and continuing until study a completion which was up to 12 months +2 weeks.
|
|
Skin and subcutaneous tissue disorders
Dermatitis contact
|
8.3%
1/12 • Number of events 1 • From the first administration of study drug and continuing until study a completion which was up to 12 months +2 weeks.
|
|
General disorders
Pain
|
8.3%
1/12 • Number of events 1 • From the first administration of study drug and continuing until study a completion which was up to 12 months +2 weeks.
|
|
General disorders
Pyrexia
|
16.7%
2/12 • Number of events 6 • From the first administration of study drug and continuing until study a completion which was up to 12 months +2 weeks.
|
|
Injury, poisoning and procedural complications
Limb injury
|
8.3%
1/12 • Number of events 1 • From the first administration of study drug and continuing until study a completion which was up to 12 months +2 weeks.
|
|
Injury, poisoning and procedural complications
Lip injury
|
8.3%
1/12 • Number of events 1 • From the first administration of study drug and continuing until study a completion which was up to 12 months +2 weeks.
|
|
Injury, poisoning and procedural complications
Skin laceration
|
8.3%
1/12 • Number of events 1 • From the first administration of study drug and continuing until study a completion which was up to 12 months +2 weeks.
|
|
Infections and infestations
Bronchitis
|
8.3%
1/12 • Number of events 1 • From the first administration of study drug and continuing until study a completion which was up to 12 months +2 weeks.
|
|
Infections and infestations
Conjunctivitis
|
8.3%
1/12 • Number of events 1 • From the first administration of study drug and continuing until study a completion which was up to 12 months +2 weeks.
|
|
Infections and infestations
Ear infection
|
8.3%
1/12 • Number of events 1 • From the first administration of study drug and continuing until study a completion which was up to 12 months +2 weeks.
|
|
Infections and infestations
Gastroenteritis
|
8.3%
1/12 • Number of events 1 • From the first administration of study drug and continuing until study a completion which was up to 12 months +2 weeks.
|
|
Infections and infestations
Nasopharyngitis
|
16.7%
2/12 • Number of events 2 • From the first administration of study drug and continuing until study a completion which was up to 12 months +2 weeks.
|
|
Infections and infestations
Pharyngitis
|
8.3%
1/12 • Number of events 1 • From the first administration of study drug and continuing until study a completion which was up to 12 months +2 weeks.
|
|
Infections and infestations
Pneumonia
|
8.3%
1/12 • Number of events 1 • From the first administration of study drug and continuing until study a completion which was up to 12 months +2 weeks.
|
|
Infections and infestations
Pulpitis dental
|
8.3%
1/12 • Number of events 1 • From the first administration of study drug and continuing until study a completion which was up to 12 months +2 weeks.
|
|
Infections and infestations
Respiratory tract infection
|
8.3%
1/12 • Number of events 1 • From the first administration of study drug and continuing until study a completion which was up to 12 months +2 weeks.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place