Trial Outcomes & Findings for Pharmacokinetics, Efficacy, Safety, and Immunogenicity of Wilate in Previously Treated Paediatric Patients With Severe Haemophilia A (NCT NCT03376516)
NCT ID: NCT03376516
Last Updated: 2021-01-19
Results Overview
PK assessments of the factor VIII coagulant activity (FVIII:C) for Wilate were determined using the one-stage (OS) assay. The units of measure to calculate AUC is hours (h) x international units (IU)/decilitre (dL).
COMPLETED
PHASE3
11 participants
0h, 0.25h, 1h, 6h, 24h and 48 h following a single dose of Wilate
2021-01-19
Participant Flow
Participant milestones
| Measure |
Wilate
A total of 11 patients were enrolled in this study. For the pharmacokinetic (PK) assessment a single dose of Wilate (50±5 IU/kg BW) was administered to 10 patients.
Prophylactic treatment: Wilate (20-40 IU/kg BW) was administered every 2-3 days for 6 months. In case of unacceptably frequent spontaneous breakthrough bleeding episodes (BEs) the dose of Wilate was to be increased by approximately 5 IU/kg.
The dose (and duration) of treatment for breakthrough BEs was dependent on the location and extent of bleeding and on the clinical condition of the patient; range: 10-50 IU/kg every 12-24 hours or 8-24 hours until resolved.
Two patients underwent surgery treated with Wilate (SURG population). Minor surgeries received 15-30 IU/kg of Wilate every 24 hours until healing was achieved. Major surgeries were treated with 40-50 IU/kg, repeat injection every 8-24 hours until adequate wound healing, then therapy for at least another 7 days to maintain a FVIII activity of 30% to 60%.
|
|---|---|
|
Overall Study
STARTED
|
11
|
|
Overall Study
Received Treatment
|
10
|
|
Overall Study
SAF Population
|
10
|
|
Overall Study
FAS Population
|
10
|
|
Overall Study
PK Population
|
10
|
|
Overall Study
PP Population
|
9
|
|
Overall Study
SURG Population
|
2
|
|
Overall Study
COMPLETED
|
9
|
|
Overall Study
NOT COMPLETED
|
2
|
Reasons for withdrawal
| Measure |
Wilate
A total of 11 patients were enrolled in this study. For the pharmacokinetic (PK) assessment a single dose of Wilate (50±5 IU/kg BW) was administered to 10 patients.
Prophylactic treatment: Wilate (20-40 IU/kg BW) was administered every 2-3 days for 6 months. In case of unacceptably frequent spontaneous breakthrough bleeding episodes (BEs) the dose of Wilate was to be increased by approximately 5 IU/kg.
The dose (and duration) of treatment for breakthrough BEs was dependent on the location and extent of bleeding and on the clinical condition of the patient; range: 10-50 IU/kg every 12-24 hours or 8-24 hours until resolved.
Two patients underwent surgery treated with Wilate (SURG population). Minor surgeries received 15-30 IU/kg of Wilate every 24 hours until healing was achieved. Major surgeries were treated with 40-50 IU/kg, repeat injection every 8-24 hours until adequate wound healing, then therapy for at least another 7 days to maintain a FVIII activity of 30% to 60%.
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|---|---|
|
Overall Study
Not treated
|
1
|
|
Overall Study
Consent withdrawn
|
1
|
Baseline Characteristics
The overall safety (SAF) population included all patients who received at least one injection of Wilate during the study (n=10). Of these, 5 patients aged 1-\<6 years were analyzed, and 5 patients aged 6-\<12 years were analyzed.
Baseline characteristics by cohort
| Measure |
Wilate
n=10 Participants
The safety (SAF) population includes all patients who received at least one injection of Wilate during the study (n=10).
|
|---|---|
|
Age, Customized
1-<6 years
|
4.0 years
STANDARD_DEVIATION 1.2 • n=5 Participants • The overall safety (SAF) population included all patients who received at least one injection of Wilate during the study (n=10). Of these, 5 patients aged 1-\<6 years were analyzed, and 5 patients aged 6-\<12 years were analyzed.
|
|
Age, Customized
6-<12 years
|
9.8 years
STANDARD_DEVIATION 0.8 • n=5 Participants • The overall safety (SAF) population included all patients who received at least one injection of Wilate during the study (n=10). Of these, 5 patients aged 1-\<6 years were analyzed, and 5 patients aged 6-\<12 years were analyzed.
|
|
Age, Customized
Total
|
6.9 years
STANDARD_DEVIATION 3.2 • n=10 Participants • The overall safety (SAF) population included all patients who received at least one injection of Wilate during the study (n=10). Of these, 5 patients aged 1-\<6 years were analyzed, and 5 patients aged 6-\<12 years were analyzed.
|
|
Sex/Gender, Customized
1-<6 years · Female
|
0 Participants
n=5 Participants • The overall safety (SAF) population included all patients who received at least one injection of Wilate during the study (n=10). Of these, 5 patients 1-\<6 years were analyzed, and 5 patients aged 6-\<12 years were analyzed.
|
|
Sex/Gender, Customized
1-<6 years · Male
|
5 Participants
n=5 Participants • The overall safety (SAF) population included all patients who received at least one injection of Wilate during the study (n=10). Of these, 5 patients 1-\<6 years were analyzed, and 5 patients aged 6-\<12 years were analyzed.
|
|
Sex/Gender, Customized
6-<12 years · Female
|
0 Participants
n=5 Participants • The overall safety (SAF) population included all patients who received at least one injection of Wilate during the study (n=10). Of these, 5 patients 1-\<6 years were analyzed, and 5 patients aged 6-\<12 years were analyzed.
|
|
Sex/Gender, Customized
6-<12 years · Male
|
5 Participants
n=5 Participants • The overall safety (SAF) population included all patients who received at least one injection of Wilate during the study (n=10). Of these, 5 patients 1-\<6 years were analyzed, and 5 patients aged 6-\<12 years were analyzed.
|
|
Sex/Gender, Customized
Total · Female
|
0 Participants
n=10 Participants • The overall safety (SAF) population included all patients who received at least one injection of Wilate during the study (n=10). Of these, 5 patients 1-\<6 years were analyzed, and 5 patients aged 6-\<12 years were analyzed.
|
|
Sex/Gender, Customized
Total · Male
|
10 Participants
n=10 Participants • The overall safety (SAF) population included all patients who received at least one injection of Wilate during the study (n=10). Of these, 5 patients 1-\<6 years were analyzed, and 5 patients aged 6-\<12 years were analyzed.
|
|
Race (NIH/OMB)
1-<6 years · American Indian or Alaska Native
|
0 Participants
n=5 Participants • The overall safety (SAF) population included all patients who received at least one injection of Wilate during the study (n=10). Of these, 5 patients 1-\<6 years were analyzed, and 5 patients aged 6-\<12 years were analyzed.
|
|
Race (NIH/OMB)
1-<6 years · Asian
|
0 Participants
n=5 Participants • The overall safety (SAF) population included all patients who received at least one injection of Wilate during the study (n=10). Of these, 5 patients 1-\<6 years were analyzed, and 5 patients aged 6-\<12 years were analyzed.
|
|
Race (NIH/OMB)
1-<6 years · Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants • The overall safety (SAF) population included all patients who received at least one injection of Wilate during the study (n=10). Of these, 5 patients 1-\<6 years were analyzed, and 5 patients aged 6-\<12 years were analyzed.
|
|
Race (NIH/OMB)
1-<6 years · Black or African American
|
0 Participants
n=5 Participants • The overall safety (SAF) population included all patients who received at least one injection of Wilate during the study (n=10). Of these, 5 patients 1-\<6 years were analyzed, and 5 patients aged 6-\<12 years were analyzed.
|
|
Race (NIH/OMB)
1-<6 years · White
|
5 Participants
n=5 Participants • The overall safety (SAF) population included all patients who received at least one injection of Wilate during the study (n=10). Of these, 5 patients 1-\<6 years were analyzed, and 5 patients aged 6-\<12 years were analyzed.
|
|
Race (NIH/OMB)
1-<6 years · More than one race
|
0 Participants
n=5 Participants • The overall safety (SAF) population included all patients who received at least one injection of Wilate during the study (n=10). Of these, 5 patients 1-\<6 years were analyzed, and 5 patients aged 6-\<12 years were analyzed.
|
|
Race (NIH/OMB)
1-<6 years · Unknown or Not Reported
|
0 Participants
n=5 Participants • The overall safety (SAF) population included all patients who received at least one injection of Wilate during the study (n=10). Of these, 5 patients 1-\<6 years were analyzed, and 5 patients aged 6-\<12 years were analyzed.
|
|
Race (NIH/OMB)
6-<12 years · American Indian or Alaska Native
|
0 Participants
n=5 Participants • The overall safety (SAF) population included all patients who received at least one injection of Wilate during the study (n=10). Of these, 5 patients 1-\<6 years were analyzed, and 5 patients aged 6-\<12 years were analyzed.
|
|
Race (NIH/OMB)
6-<12 years · Asian
|
0 Participants
n=5 Participants • The overall safety (SAF) population included all patients who received at least one injection of Wilate during the study (n=10). Of these, 5 patients 1-\<6 years were analyzed, and 5 patients aged 6-\<12 years were analyzed.
|
|
Race (NIH/OMB)
6-<12 years · Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants • The overall safety (SAF) population included all patients who received at least one injection of Wilate during the study (n=10). Of these, 5 patients 1-\<6 years were analyzed, and 5 patients aged 6-\<12 years were analyzed.
|
|
Race (NIH/OMB)
6-<12 years · Black or African American
|
0 Participants
n=5 Participants • The overall safety (SAF) population included all patients who received at least one injection of Wilate during the study (n=10). Of these, 5 patients 1-\<6 years were analyzed, and 5 patients aged 6-\<12 years were analyzed.
|
|
Race (NIH/OMB)
6-<12 years · White
|
5 Participants
n=5 Participants • The overall safety (SAF) population included all patients who received at least one injection of Wilate during the study (n=10). Of these, 5 patients 1-\<6 years were analyzed, and 5 patients aged 6-\<12 years were analyzed.
|
|
Race (NIH/OMB)
6-<12 years · More than one race
|
0 Participants
n=5 Participants • The overall safety (SAF) population included all patients who received at least one injection of Wilate during the study (n=10). Of these, 5 patients 1-\<6 years were analyzed, and 5 patients aged 6-\<12 years were analyzed.
|
|
Race (NIH/OMB)
6-<12 years · Unknown or Not Reported
|
0 Participants
n=5 Participants • The overall safety (SAF) population included all patients who received at least one injection of Wilate during the study (n=10). Of these, 5 patients 1-\<6 years were analyzed, and 5 patients aged 6-\<12 years were analyzed.
|
|
Race (NIH/OMB)
Total · American Indian or Alaska Native
|
0 Participants
n=10 Participants • The overall safety (SAF) population included all patients who received at least one injection of Wilate during the study (n=10). Of these, 5 patients 1-\<6 years were analyzed, and 5 patients aged 6-\<12 years were analyzed.
|
|
Race (NIH/OMB)
Total · Asian
|
0 Participants
n=10 Participants • The overall safety (SAF) population included all patients who received at least one injection of Wilate during the study (n=10). Of these, 5 patients 1-\<6 years were analyzed, and 5 patients aged 6-\<12 years were analyzed.
|
|
Race (NIH/OMB)
Total · Native Hawaiian or Other Pacific Islander
|
0 Participants
n=10 Participants • The overall safety (SAF) population included all patients who received at least one injection of Wilate during the study (n=10). Of these, 5 patients 1-\<6 years were analyzed, and 5 patients aged 6-\<12 years were analyzed.
|
|
Race (NIH/OMB)
Total · Black or African American
|
0 Participants
n=10 Participants • The overall safety (SAF) population included all patients who received at least one injection of Wilate during the study (n=10). Of these, 5 patients 1-\<6 years were analyzed, and 5 patients aged 6-\<12 years were analyzed.
|
|
Race (NIH/OMB)
Total · White
|
10 Participants
n=10 Participants • The overall safety (SAF) population included all patients who received at least one injection of Wilate during the study (n=10). Of these, 5 patients 1-\<6 years were analyzed, and 5 patients aged 6-\<12 years were analyzed.
|
|
Race (NIH/OMB)
Total · More than one race
|
0 Participants
n=10 Participants • The overall safety (SAF) population included all patients who received at least one injection of Wilate during the study (n=10). Of these, 5 patients 1-\<6 years were analyzed, and 5 patients aged 6-\<12 years were analyzed.
|
|
Race (NIH/OMB)
Total · Unknown or Not Reported
|
0 Participants
n=10 Participants • The overall safety (SAF) population included all patients who received at least one injection of Wilate during the study (n=10). Of these, 5 patients 1-\<6 years were analyzed, and 5 patients aged 6-\<12 years were analyzed.
|
|
Weight
1-<6 years
|
16.9 kg
STANDARD_DEVIATION 3.6 • n=5 Participants • The overall safety (SAF) population included all patients who received at least one injection of Wilate during the study (n=10). Of these, 5 patients 1-\<6 years were analyzed, and 5 patients aged 6-\<12 years were analyzed.
|
|
Weight
6-<12 years
|
37.4 kg
STANDARD_DEVIATION 5.4 • n=5 Participants • The overall safety (SAF) population included all patients who received at least one injection of Wilate during the study (n=10). Of these, 5 patients 1-\<6 years were analyzed, and 5 patients aged 6-\<12 years were analyzed.
|
|
Weight
Total
|
27.2 kg
STANDARD_DEVIATION 11.6 • n=10 Participants • The overall safety (SAF) population included all patients who received at least one injection of Wilate during the study (n=10). Of these, 5 patients 1-\<6 years were analyzed, and 5 patients aged 6-\<12 years were analyzed.
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|
Body Mass Index (BMI)
1-<6 years
|
15.3 kg/m^2
STANDARD_DEVIATION 1.3 • n=5 Participants • The overall safety (SAF) population included all patients who received at least one injection of Wilate during the study (n=10). Of these, 5 patients 1-\<6 years were analyzed, and 5 patients aged 6-\<12 years were analyzed.
|
|
Body Mass Index (BMI)
6-<12 years
|
17.7 kg/m^2
STANDARD_DEVIATION 2.2 • n=5 Participants • The overall safety (SAF) population included all patients who received at least one injection of Wilate during the study (n=10). Of these, 5 patients 1-\<6 years were analyzed, and 5 patients aged 6-\<12 years were analyzed.
|
|
Body Mass Index (BMI)
Total
|
16.5 kg/m^2
STANDARD_DEVIATION 2.1 • n=10 Participants • The overall safety (SAF) population included all patients who received at least one injection of Wilate during the study (n=10). Of these, 5 patients 1-\<6 years were analyzed, and 5 patients aged 6-\<12 years were analyzed.
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|
Blood groups
1-<6 years · O
|
2 Participants
n=5 Participants • The overall safety (SAF) population included all patients who received at least one injection of Wilate during the study (n=10). Of these, 5 patients 1-\<6 years were analyzed, and 5 patients aged 6-\<12 years were analyzed.
|
|
Blood groups
1-<6 years · A
|
1 Participants
n=5 Participants • The overall safety (SAF) population included all patients who received at least one injection of Wilate during the study (n=10). Of these, 5 patients 1-\<6 years were analyzed, and 5 patients aged 6-\<12 years were analyzed.
|
|
Blood groups
1-<6 years · AB
|
0 Participants
n=5 Participants • The overall safety (SAF) population included all patients who received at least one injection of Wilate during the study (n=10). Of these, 5 patients 1-\<6 years were analyzed, and 5 patients aged 6-\<12 years were analyzed.
|
|
Blood groups
1-<6 years · B
|
2 Participants
n=5 Participants • The overall safety (SAF) population included all patients who received at least one injection of Wilate during the study (n=10). Of these, 5 patients 1-\<6 years were analyzed, and 5 patients aged 6-\<12 years were analyzed.
|
|
Blood groups
6-<12 years · O
|
2 Participants
n=5 Participants • The overall safety (SAF) population included all patients who received at least one injection of Wilate during the study (n=10). Of these, 5 patients 1-\<6 years were analyzed, and 5 patients aged 6-\<12 years were analyzed.
|
|
Blood groups
6-<12 years · A
|
3 Participants
n=5 Participants • The overall safety (SAF) population included all patients who received at least one injection of Wilate during the study (n=10). Of these, 5 patients 1-\<6 years were analyzed, and 5 patients aged 6-\<12 years were analyzed.
|
|
Blood groups
6-<12 years · AB
|
0 Participants
n=5 Participants • The overall safety (SAF) population included all patients who received at least one injection of Wilate during the study (n=10). Of these, 5 patients 1-\<6 years were analyzed, and 5 patients aged 6-\<12 years were analyzed.
|
|
Blood groups
6-<12 years · B
|
0 Participants
n=5 Participants • The overall safety (SAF) population included all patients who received at least one injection of Wilate during the study (n=10). Of these, 5 patients 1-\<6 years were analyzed, and 5 patients aged 6-\<12 years were analyzed.
|
|
Blood groups
Total · O
|
4 Participants
n=10 Participants • The overall safety (SAF) population included all patients who received at least one injection of Wilate during the study (n=10). Of these, 5 patients 1-\<6 years were analyzed, and 5 patients aged 6-\<12 years were analyzed.
|
|
Blood groups
Total · A
|
4 Participants
n=10 Participants • The overall safety (SAF) population included all patients who received at least one injection of Wilate during the study (n=10). Of these, 5 patients 1-\<6 years were analyzed, and 5 patients aged 6-\<12 years were analyzed.
|
|
Blood groups
Total · AB
|
0 Participants
n=10 Participants • The overall safety (SAF) population included all patients who received at least one injection of Wilate during the study (n=10). Of these, 5 patients 1-\<6 years were analyzed, and 5 patients aged 6-\<12 years were analyzed.
|
|
Blood groups
Total · B
|
2 Participants
n=10 Participants • The overall safety (SAF) population included all patients who received at least one injection of Wilate during the study (n=10). Of these, 5 patients 1-\<6 years were analyzed, and 5 patients aged 6-\<12 years were analyzed.
|
|
Previous Factor (F)VIII treatment
1-<6 years · On-demand
|
0 Participants
n=5 Participants • The overall safety (SAF) population included all patients who received at least one injection of Wilate during the study (n=10). Of these, 5 patients 1-\<6 years were analyzed, and 5 patients aged 6-\<12 years were analyzed.
|
|
Previous Factor (F)VIII treatment
1-<6 years · Prophylaxis
|
3 Participants
n=5 Participants • The overall safety (SAF) population included all patients who received at least one injection of Wilate during the study (n=10). Of these, 5 patients 1-\<6 years were analyzed, and 5 patients aged 6-\<12 years were analyzed.
|
|
Previous Factor (F)VIII treatment
1-<6 years · Combination
|
2 Participants
n=5 Participants • The overall safety (SAF) population included all patients who received at least one injection of Wilate during the study (n=10). Of these, 5 patients 1-\<6 years were analyzed, and 5 patients aged 6-\<12 years were analyzed.
|
|
Previous Factor (F)VIII treatment
6-<12 years · On-demand
|
2 Participants
n=5 Participants • The overall safety (SAF) population included all patients who received at least one injection of Wilate during the study (n=10). Of these, 5 patients 1-\<6 years were analyzed, and 5 patients aged 6-\<12 years were analyzed.
|
|
Previous Factor (F)VIII treatment
6-<12 years · Prophylaxis
|
0 Participants
n=5 Participants • The overall safety (SAF) population included all patients who received at least one injection of Wilate during the study (n=10). Of these, 5 patients 1-\<6 years were analyzed, and 5 patients aged 6-\<12 years were analyzed.
|
|
Previous Factor (F)VIII treatment
6-<12 years · Combination
|
3 Participants
n=5 Participants • The overall safety (SAF) population included all patients who received at least one injection of Wilate during the study (n=10). Of these, 5 patients 1-\<6 years were analyzed, and 5 patients aged 6-\<12 years were analyzed.
|
|
Previous Factor (F)VIII treatment
Total · On-demand
|
2 Participants
n=10 Participants • The overall safety (SAF) population included all patients who received at least one injection of Wilate during the study (n=10). Of these, 5 patients 1-\<6 years were analyzed, and 5 patients aged 6-\<12 years were analyzed.
|
|
Previous Factor (F)VIII treatment
Total · Prophylaxis
|
3 Participants
n=10 Participants • The overall safety (SAF) population included all patients who received at least one injection of Wilate during the study (n=10). Of these, 5 patients 1-\<6 years were analyzed, and 5 patients aged 6-\<12 years were analyzed.
|
|
Previous Factor (F)VIII treatment
Total · Combination
|
5 Participants
n=10 Participants • The overall safety (SAF) population included all patients who received at least one injection of Wilate during the study (n=10). Of these, 5 patients 1-\<6 years were analyzed, and 5 patients aged 6-\<12 years were analyzed.
|
|
Previous annualised bleeding rate (ABR)
1-<6 years
|
4.8 Bleeding events per year (ABR)
STANDARD_DEVIATION 3.0 • n=5 Participants • The overall safety (SAF) population included all patients who received at least one injection of Wilate during the study (n=10). Of these, 5 patients 1-\<6 years were analyzed, and 5 patients aged 6-\<12 years were analyzed.
|
|
Previous annualised bleeding rate (ABR)
6-<12 years
|
13.6 Bleeding events per year (ABR)
STANDARD_DEVIATION 8.9 • n=5 Participants • The overall safety (SAF) population included all patients who received at least one injection of Wilate during the study (n=10). Of these, 5 patients 1-\<6 years were analyzed, and 5 patients aged 6-\<12 years were analyzed.
|
|
Previous annualised bleeding rate (ABR)
Total
|
9.2 Bleeding events per year (ABR)
STANDARD_DEVIATION 7.8 • n=10 Participants • The overall safety (SAF) population included all patients who received at least one injection of Wilate during the study (n=10). Of these, 5 patients 1-\<6 years were analyzed, and 5 patients aged 6-\<12 years were analyzed.
|
PRIMARY outcome
Timeframe: 0h, 0.25h, 1h, 6h, 24h and 48 h following a single dose of WilatePopulation: The analysis was performed in the PK population which included all patients who underwent PK assessment during the study (total: n=10). The PK population comprised 5 patients aged 1-\<6 years and 5 patients aged 6-\<12 years.
PK assessments of the factor VIII coagulant activity (FVIII:C) for Wilate were determined using the one-stage (OS) assay. The units of measure to calculate AUC is hours (h) x international units (IU)/decilitre (dL).
Outcome measures
| Measure |
Wilate
n=10 Participants
PK population
|
6-<12 Years
FAS population patients aged 6-\<12 years
|
Total
All patients in the FAS population.
|
|---|---|---|---|
|
Pharmacokinetic (PK) Assessment (Area Under the Curve (AUC)) of FVIII:C
1-<6 years
|
768.8 h*IU/dL
Standard Deviation 288.5
|
—
|
—
|
|
Pharmacokinetic (PK) Assessment (Area Under the Curve (AUC)) of FVIII:C
6-<12 years
|
671.9 h*IU/dL
Standard Deviation 289.7
|
—
|
—
|
|
Pharmacokinetic (PK) Assessment (Area Under the Curve (AUC)) of FVIII:C
Total
|
720.3 h*IU/dL
Standard Deviation 277.3
|
—
|
—
|
PRIMARY outcome
Timeframe: 0h, 0.25h, 1h, 6h, 24h and 48 h following a single dose of WilatePopulation: The analysis was performed in the PK population which included all patients who underwent PK assessment during the study (total: n=10). The PK population comprised 5 patients aged 1-\<6 years and 5 patients aged 6-\<12 years.
PK assessments of the factor VIII coagulant activity (FVIII:C) for Wilate were determined using the one-stage (OS) assay. The mean area under the curve normalised for the administered dose (AUCnorm) was calculated for Wilate. The units of measure used were AUC divided by dose.
Outcome measures
| Measure |
Wilate
n=10 Participants
PK population
|
6-<12 Years
FAS population patients aged 6-\<12 years
|
Total
All patients in the FAS population.
|
|---|---|---|---|
|
Pharmacokinetic (PK) Assessment (Area Under the Curve [AUC] Normalised (AUCNorm)) of FVIII:C for Wilate
1-<6 years
|
15.38 h*kg/dL
Standard Deviation 5.77
|
—
|
—
|
|
Pharmacokinetic (PK) Assessment (Area Under the Curve [AUC] Normalised (AUCNorm)) of FVIII:C for Wilate
6-<12 years
|
13.44 h*kg/dL
Standard Deviation 5.79
|
—
|
—
|
|
Pharmacokinetic (PK) Assessment (Area Under the Curve [AUC] Normalised (AUCNorm)) of FVIII:C for Wilate
Total
|
14.41 h*kg/dL
Standard Deviation 5.55
|
—
|
—
|
PRIMARY outcome
Timeframe: 0h, 0.25h, 1h, 6h, 24h and 48 h following a single dose of WilatePopulation: The analysis was performed in the PK population which included all patients who underwent PK assessment during the study (total: n=10). The PK population comprised 5 patients aged 1-\<6 years and 5 patients aged 6-\<12 years.
PK assessments of the factor VIII coagulant activity (FVIII:C) for Wilate were determined using the one-stage (OS) assay. The units of measure to calculate half-life is hours.
Outcome measures
| Measure |
Wilate
n=10 Participants
PK population
|
6-<12 Years
FAS population patients aged 6-\<12 years
|
Total
All patients in the FAS population.
|
|---|---|---|---|
|
Pharmacokinetic (PK) Assessment (Half-life (h)) of FVIII:C
1-<6 years
|
8.28 hours
Standard Deviation 1.51
|
—
|
—
|
|
Pharmacokinetic (PK) Assessment (Half-life (h)) of FVIII:C
6-<12 years
|
9.35 hours
Standard Deviation 2.40
|
—
|
—
|
|
Pharmacokinetic (PK) Assessment (Half-life (h)) of FVIII:C
Total
|
8.82 hours
Standard Deviation 1.97
|
—
|
—
|
PRIMARY outcome
Timeframe: 0h, 0.25h, 1h, 6h, 24h and 48 h following a single dose of WilatePopulation: The analysis was performed in the PK population which included all patients who underwent PK assessment during the study (total: n=10). The PK population comprised 5 patients aged 1-\<6 years and 5 patients aged 6-\<12 years.
PK assessments of FVIII:C were determined using the one-stage (OS) assays. The maximum plasma concentration of FVIII:C was calculated based on the FVIII:C values measured in the patients participating in the PK study. Units of measure for maximum plasma concentration are international units (IU)/ decilitre (dL)
Outcome measures
| Measure |
Wilate
n=10 Participants
PK population
|
6-<12 Years
FAS population patients aged 6-\<12 years
|
Total
All patients in the FAS population.
|
|---|---|---|---|
|
Pharmacokinetic (PK) Assessment (Maximum Plasma Concentration) for FVIII:C
1-<6 years
|
83.0 IU/dL
Standard Deviation 16.5
|
—
|
—
|
|
Pharmacokinetic (PK) Assessment (Maximum Plasma Concentration) for FVIII:C
6-<12 years
|
78.94 IU/dL
Standard Deviation 26.56
|
—
|
—
|
|
Pharmacokinetic (PK) Assessment (Maximum Plasma Concentration) for FVIII:C
Total
|
80.99 IU/dL
Standard Deviation 20.94
|
—
|
—
|
PRIMARY outcome
Timeframe: 48 h following a single dose of WilatePopulation: The analysis was performed in the PK population which included all patients who underwent PK assessment during the study (total: n=10). The PK population comprised 5 patients aged 1-\<6 years and 5 patients aged 6-\<12 years.
PK assessments of the factor VIII coagulant activity (FVIII:C) for Wilate were determined using the one-stage (OS) assay. The units of measure to calculate Tmax is hours (h).
Outcome measures
| Measure |
Wilate
n=10 Participants
PK population
|
6-<12 Years
FAS population patients aged 6-\<12 years
|
Total
All patients in the FAS population.
|
|---|---|---|---|
|
Pharmacokinetic (PK) Assessment (Time to Reach Maximum Plasma Concentration (Tmax)) of FVIII:C
1-<6 years
|
0.25 hours
Standard Deviation 0.00
|
—
|
—
|
|
Pharmacokinetic (PK) Assessment (Time to Reach Maximum Plasma Concentration (Tmax)) of FVIII:C
6-<12 years
|
0.25 hours
Standard Deviation 0.00
|
—
|
—
|
|
Pharmacokinetic (PK) Assessment (Time to Reach Maximum Plasma Concentration (Tmax)) of FVIII:C
Total
|
0.25 hours
Standard Deviation 0.00
|
—
|
—
|
PRIMARY outcome
Timeframe: 48 h following a single dose of WilatePopulation: The analysis was performed in the PK population which included all patients who underwent PK assessment during the study (total: n=10). The PK population comprised 5 patients aged 1-\<6 years and 5 patients aged 6-\<12 years.
PK assessments of the factor VIII coagulant activity (FVIII:C) for Wilate were determined using the one-stage (OS) assay. The units of measure to calculate MRT is hours.
Outcome measures
| Measure |
Wilate
n=10 Participants
PK population
|
6-<12 Years
FAS population patients aged 6-\<12 years
|
Total
All patients in the FAS population.
|
|---|---|---|---|
|
Pharmacokinetic (PK) Assessment (Mean Residence Time (MRT)) of FVIII:C
1-<6 years
|
11.47 hours
Standard Deviation 2.34
|
—
|
—
|
|
Pharmacokinetic (PK) Assessment (Mean Residence Time (MRT)) of FVIII:C
6-<12 years
|
12.56 hours
Standard Deviation 3.53
|
—
|
—
|
|
Pharmacokinetic (PK) Assessment (Mean Residence Time (MRT)) of FVIII:C
Total
|
12.01 hours
Standard Deviation 2.88
|
—
|
—
|
PRIMARY outcome
Timeframe: 0h, 0.25h, 1h, 6h, 24h and 48 h following a single dose of WilatePopulation: The analysis was performed in the PK population which included all patients who underwent PK assessment during the study (total: n=10). The PK population comprised 5 patients aged 1-\<6 years and 5 patients aged 6-\<12 years.
PK assessments of the factor VIII coagulant activity (FVIII:C) for Wilate were determined using the one-stage (OS) assay. The units of measure to calculate Vd is decilitre (dL)/ kilograms (kg).
Outcome measures
| Measure |
Wilate
n=10 Participants
PK population
|
6-<12 Years
FAS population patients aged 6-\<12 years
|
Total
All patients in the FAS population.
|
|---|---|---|---|
|
Pharmacokinetic (PK) Assessment (Volume of Distribution (Vd)) of FVIII:C
1-<6 years
|
0.784 dL/kg
Standard Deviation 0.177
|
—
|
—
|
|
Pharmacokinetic (PK) Assessment (Volume of Distribution (Vd)) of FVIII:C
6-<12 years
|
1.081 dL/kg
Standard Deviation 0.494
|
—
|
—
|
|
Pharmacokinetic (PK) Assessment (Volume of Distribution (Vd)) of FVIII:C
Total
|
0.933 dL/kg
Standard Deviation 0.384
|
—
|
—
|
PRIMARY outcome
Timeframe: 0h, 0.25h, 1h, 6h, 24h and 48 h following a single dose of WilatePopulation: The analysis was performed in the PK population which included all patients who underwent PK assessment during the study (total: n=10). The PK population comprised 5 patients aged 1-\<6 years and 5 patients aged 6-\<12 years.
PK assessments of the factor VIII coagulant activity (FVIII:C) for Wilate were determined using the one-stage (OS) assay. The units of measure to calculate clearance are decilitre (dL)/ hours (h)/ kilograms (kg).
Outcome measures
| Measure |
Wilate
n=10 Participants
PK population
|
6-<12 Years
FAS population patients aged 6-\<12 years
|
Total
All patients in the FAS population.
|
|---|---|---|---|
|
Pharmacokinetic (PK) Assessment (Clearance) of FVIII:C
1-<6 years
|
0.071 dL/h/kg
Standard Deviation 0.019
|
—
|
—
|
|
Pharmacokinetic (PK) Assessment (Clearance) of FVIII:C
6-<12 years
|
0.098 dL/h/kg
Standard Deviation 0.074
|
—
|
—
|
|
Pharmacokinetic (PK) Assessment (Clearance) of FVIII:C
Total
|
0.084 dL/h/kg
Standard Deviation 0.053
|
—
|
—
|
PRIMARY outcome
Timeframe: 48 h following a single dose of WilatePopulation: This analysis was performed for the full-analysis (FAS) population which included all patients who has at least one injection of Wilate (n=10). The FAS population comprised 5 patients aged 1-\<6 years and 5 patients aged 6-\<12 years.
The incremental IVR was determined from all patients at baseline was determined using the one-stage (OS) assay (standardised to 50 IU/kg). The units of measure to calculate IVR is kilograms (kg) / deciliter (dL)
Outcome measures
| Measure |
Wilate
n=5 Participants
PK population
|
6-<12 Years
n=5 Participants
FAS population patients aged 6-\<12 years
|
Total
n=10 Participants
All patients in the FAS population.
|
|---|---|---|---|
|
Incremental In Vivo Recovery (IVR) of FVIII:C
|
1.65 kg/dL
Standard Deviation 0.33
|
1.57 kg/dL
Standard Deviation 0.53
|
1.61 kg/dL
Standard Deviation 0.42
|
SECONDARY outcome
Timeframe: 6 monthsPopulation: This analysis was performed for the full-analysis (FAS) population which included all patients who has at least one injection of Wilate (n=10). The FAS population comprised 5 patients aged 1-\<6 years and 5 patients aged 6-\<12 years.
The total number of bleeding events (BEs) in the time period between the first dose of IMP and the study completion visit, divided by the duration (in years) between the first dose of IMP and the study completion visit. Surgery periods, and BEs occurring within these periods, will be excluded from the calculation of TABR.
Outcome measures
| Measure |
Wilate
n=10 Participants
PK population
|
6-<12 Years
FAS population patients aged 6-\<12 years
|
Total
All patients in the FAS population.
|
|---|---|---|---|
|
Total Annualized Bleeding Rate (TABR)
1-<6 years
|
6.47 Bleeding events per year (TABR)
Standard Deviation 6.61
|
—
|
—
|
|
Total Annualized Bleeding Rate (TABR)
6-<12 years
|
10.62 Bleeding events per year (TABR)
Standard Deviation 9.06
|
—
|
—
|
|
Total Annualized Bleeding Rate (TABR)
Total
|
8.54 Bleeding events per year (TABR)
Standard Deviation 7.79
|
—
|
—
|
SECONDARY outcome
Timeframe: 6 monthsPopulation: This analysis was performed for the full-analysis (FAS) population which included all patients who has at least one injection of Wilate (n=10). The FAS population comprised 5 patients aged 1-\<6 years and 5 patients aged 6-\<12 years.
The SABR was calculated in analogy to the TABR. The total number of spontaneous bleeding events (BEs) in the time period between the first dose of IMP and the study completion visit, divided by the duration (in years) between the first dose of IMP and the study completion visit. Surgery periods, and BEs occurring within these periods, will be excluded from the calculation of the SABR.
Outcome measures
| Measure |
Wilate
n=10 Participants
PK population
|
6-<12 Years
FAS population patients aged 6-\<12 years
|
Total
All patients in the FAS population.
|
|---|---|---|---|
|
Spontaneous Annualized Bleeding Rate (SABR)
1-<6 years
|
2.70 Spontaneous bleeding events per year
Standard Deviation 2.93
|
—
|
—
|
|
Spontaneous Annualized Bleeding Rate (SABR)
6-<12 years
|
1.20 Spontaneous bleeding events per year
Standard Deviation 2.68
|
—
|
—
|
|
Spontaneous Annualized Bleeding Rate (SABR)
Total
|
1.95 Spontaneous bleeding events per year
Standard Deviation 2.76
|
—
|
—
|
SECONDARY outcome
Timeframe: 6 monthsPopulation: Analysis was performed in the per-protocol (PP) population. Of the patients in the PP population, only 8 patients had evaluable bleeding events. Five of these patients were aged 1-\<6 years, and 3 aged 6-\<12 years.
The proportion of BEs successfully treated with Wilate was assessed by the patient (together with the investigator in case of on-site treatment) in a patient diary. The treatment efficacy for all BEs was assessed using a pre-defined four-point scale: 'excellent', 'good', 'moderate', 'none'. 'Excellent' was defined as "Abrupt pain relief and/or unequivocal improvement in objective signs of bleeding within approximately 8 hours after a single injection" (best outcome); 'good 'was defined as "definite pain relief and/or improvement in signs of bleeding within approximately 8-12 hours after an injection, requiring up to 2 injections for complete resolution". All efficacy ratings assessed as either 'excellent' or 'good' were considered 'successfully treated'. 'Moderate' was defined as "probable or slight beneficial effect within approximately 12 hours after the first injection" and 'none' defined as "no improvement within 12 hours, or worsening of symptoms".
Outcome measures
| Measure |
Wilate
n=17 Bleeding Events (BEs)
PK population
|
6-<12 Years
n=18 Bleeding Events (BEs)
FAS population patients aged 6-\<12 years
|
Total
n=35 Bleeding Events (BEs)
All patients in the FAS population.
|
|---|---|---|---|
|
Efficacy of Wilate in the Treatment of Breakthrough Bleeding Events (BEs)
Excellent
|
7 Bleeding Events (BEs)
|
9 Bleeding Events (BEs)
|
16 Bleeding Events (BEs)
|
|
Efficacy of Wilate in the Treatment of Breakthrough Bleeding Events (BEs)
Good
|
9 Bleeding Events (BEs)
|
8 Bleeding Events (BEs)
|
17 Bleeding Events (BEs)
|
|
Efficacy of Wilate in the Treatment of Breakthrough Bleeding Events (BEs)
Moderate
|
1 Bleeding Events (BEs)
|
1 Bleeding Events (BEs)
|
2 Bleeding Events (BEs)
|
|
Efficacy of Wilate in the Treatment of Breakthrough Bleeding Events (BEs)
None
|
0 Bleeding Events (BEs)
|
0 Bleeding Events (BEs)
|
0 Bleeding Events (BEs)
|
SECONDARY outcome
Timeframe: 6 monthsPopulation: The analysis was performed in the full analysis (FAS) population (total: n=10). The FAS comprised 5 patients were aged 1-\<6 years and 5 were aged 6-\<12 years.
The average consumption of Wilate per week of the study (IU/kg) for all patients receiving prophylaxis
Outcome measures
| Measure |
Wilate
n=5 Participants
PK population
|
6-<12 Years
n=5 Participants
FAS population patients aged 6-\<12 years
|
Total
n=10 Participants
All patients in the FAS population.
|
|---|---|---|---|
|
Wilate Consumption Data: Average Dose of Wilate Per Week of Study
|
58.52 IU/kg per week
Standard Deviation 14.85
|
68.08 IU/kg per week
Standard Deviation 19.02
|
63.30 IU/kg per week
Standard Deviation 16.86
|
SECONDARY outcome
Timeframe: Baseline, and 3 and 6 months of treatmentPopulation: The analysis was performed in the full analysis (FAS) population (total: n=10). The FAS comprised 5 patients were aged 1-\<6 years and 5 were aged 6-\<12 years.
The rise in FVIII:C activity in IU/dl per unit dose administered in IU/kg was determined for all patients at baseline, 3 and 6 months, using the one-stage (OS) assay.
Outcome measures
| Measure |
Wilate
n=5 Participants
PK population
|
6-<12 Years
n=5 Participants
FAS population patients aged 6-\<12 years
|
Total
n=10 Participants
All patients in the FAS population.
|
|---|---|---|---|
|
Incremental in Vivo Recovery (IVR) of Wilate Over Time
Baseline
|
1.65 kg/dL
Standard Deviation 0.33
|
1.57 kg/dL
Standard Deviation 0.53
|
1.61 kg/dL
Standard Deviation 0.42
|
|
Incremental in Vivo Recovery (IVR) of Wilate Over Time
3 months
|
1.55 kg/dL
Standard Deviation 0.14
|
1.56 kg/dL
Standard Deviation 0.57
|
1.56 kg/dL
Standard Deviation 0.39
|
|
Incremental in Vivo Recovery (IVR) of Wilate Over Time
6 months
|
1.63 kg/dL
Standard Deviation 0.24
|
1.32 kg/dL
Standard Deviation 0.45
|
1.48 kg/dL
Standard Deviation 0.38
|
SECONDARY outcome
Timeframe: 6 monthsPopulation: The analysis was performed for the PK population which included all patients who underwent PK assessment during the study (total: n=10). The PK population comprised 5 patients aged 1-\<6 years and 5 aged 6-\<12 years.
Analysis of variance (ANOVA) was used in an exploratory sense to assess a possible association between the ABO blood type and the FVIII:C half-life of Wilate. This was analysed by calculating the mean square in a one-stage (OS) assay.
Outcome measures
| Measure |
Wilate
n=10 Participants
PK population
|
6-<12 Years
FAS population patients aged 6-\<12 years
|
Total
All patients in the FAS population.
|
|---|---|---|---|
|
Association Between ABO Blood Type and the FVIII:C Half-life of Wilate (OS Assay)
1-<6 years
|
0.185 Correlation coefficient
|
—
|
—
|
|
Association Between ABO Blood Type and the FVIII:C Half-life of Wilate (OS Assay)
6-<12 years
|
6.100 Correlation coefficient
|
—
|
—
|
|
Association Between ABO Blood Type and the FVIII:C Half-life of Wilate (OS Assay)
Total
|
0.922 Correlation coefficient
|
—
|
—
|
SECONDARY outcome
Timeframe: 6 monthsPopulation: The analysis was performed for the PK population which included all patients who underwent PK assessment during the study (total: n=10).
Analysis of variance (ANOVA) was used in an exploratory sense to assess a possible association between VWF:Ag with the FVIII:C half-life of Wilate. This was analysed by calculating the mean square in a one-stage (OS) assay.
Outcome measures
| Measure |
Wilate
n=10 Participants
PK population
|
6-<12 Years
FAS population patients aged 6-\<12 years
|
Total
All patients in the FAS population.
|
|---|---|---|---|
|
Association Between VWF:Ag Concentration and the FVIII:C Half-life of Wilate
1-<6 years
|
0.121 Correlation coefficient
|
—
|
—
|
|
Association Between VWF:Ag Concentration and the FVIII:C Half-life of Wilate
6-<12 years
|
0.006 Correlation coefficient
|
—
|
—
|
|
Association Between VWF:Ag Concentration and the FVIII:C Half-life of Wilate
Total
|
0.003 Correlation coefficient
|
—
|
—
|
SECONDARY outcome
Timeframe: 6 monthsPopulation: The safety (SAF) population included all patients who received at least one injection of Wilate during the study (n=10).
At each visit (whether scheduled or unscheduled) , AEs will be documented by the investigator throughout the study. In addition, the investigator will check the patient diaries for any documented event.
Outcome measures
| Measure |
Wilate
n=10 Participants
PK population
|
6-<12 Years
FAS population patients aged 6-\<12 years
|
Total
All patients in the FAS population.
|
|---|---|---|---|
|
Safety and Tolerability of Wilate by Monitoring The Number of Adverse Events (AEs) Throughout the Study
|
6 Adverse events
|
—
|
—
|
SECONDARY outcome
Timeframe: 6 monthsPopulation: The analysis was performed in the overall safety (SAF) population included all patients who received at least one injection of Wilate during the study (n=10). Of these, 5 patients 1-\<6 years were analyzed, and 5 patients aged 6-\<12 years were analyzed.
FVIII inhibitor activity was determined at each study visit: screening, PK, Day 14 visit, Day 30 visit, 3 Months visit and 6 Months visit before injection.
Outcome measures
| Measure |
Wilate
n=10 Participants
PK population
|
6-<12 Years
FAS population patients aged 6-\<12 years
|
Total
All patients in the FAS population.
|
|---|---|---|---|
|
Immunogenicity of Wilate: Number of Participants With FVIII Inhibitor Activity at 6 Months
|
0 Participants
|
—
|
—
|
SECONDARY outcome
Timeframe: 6 monthsPopulation: Analysis was performed in all patients who underwent full analysis (FAS population) (n=10).
Virus safety was evaluated by taking a plasma sample for parvovirus B19 antibody testing before the first injection of Wilate at the PK visit. All patients negative at screening were tested again at the Study Completion visit. The number of Parvovirus B19 seroconversions between BL and end of study was recorded
Outcome measures
| Measure |
Wilate
n=10 Participants
PK population
|
6-<12 Years
FAS population patients aged 6-\<12 years
|
Total
All patients in the FAS population.
|
|---|---|---|---|
|
Virus Safety Measured by the Number With Parvovirus B19 Seroconversions Between Baseline (BL) and End of Study
|
1 Participants with seroconversions
|
—
|
—
|
Adverse Events
Wilate
Serious adverse events
| Measure |
Wilate
n=10 participants at risk
The safety (SAF) population includes all patients who received at least one injection of Wilate during the study (n=10).
|
|---|---|
|
Congenital, familial and genetic disorders
Cryptochidism
|
10.0%
1/10 • Number of events 1 • Between the screening visit and the follow up contact visit (30 days after the 6-month study completion visit)
|
Other adverse events
| Measure |
Wilate
n=10 participants at risk
The safety (SAF) population includes all patients who received at least one injection of Wilate during the study (n=10).
|
|---|---|
|
Infections and infestations
Respiratory tract infection
|
10.0%
1/10 • Number of events 1 • Between the screening visit and the follow up contact visit (30 days after the 6-month study completion visit)
|
|
Infections and infestations
Varicella
|
10.0%
1/10 • Number of events 1 • Between the screening visit and the follow up contact visit (30 days after the 6-month study completion visit)
|
|
Infections and infestations
Viral upper respiratory tract infection
|
10.0%
1/10 • Number of events 1 • Between the screening visit and the follow up contact visit (30 days after the 6-month study completion visit)
|
|
Nervous system disorders
Headache
|
10.0%
1/10 • Number of events 1 • Between the screening visit and the follow up contact visit (30 days after the 6-month study completion visit)
|
|
Investigations
Parvovirus B19 test positive
|
10.0%
1/10 • Number of events 1 • Between the screening visit and the follow up contact visit (30 days after the 6-month study completion visit)
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place