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Pharmacokinetics, Efficacy, Safety, and Immunogenicity of Wilate in Previously Treated Paediatric Patients With Severe Haemophilia A

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03376516
Recruitment Status : Completed
First Posted : December 18, 2017
Results First Posted : December 24, 2019
Last Update Posted : January 19, 2021
Sponsor:
Information provided by (Responsible Party):
Octapharma

Study Type Interventional
Study Design Allocation: N/A;   Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Severe Hemophilia A
Intervention Drug: Wilate
Enrollment 11
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Wilate
Hide Arm/Group Description

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%.

Period Title: Overall Study
Started 11
Received Treatment 10
SAF Population [1] 10
FAS Population [2] 10
PK Population [3] 10
PP Population [4] 9
SURG Population [5] 2
Completed 9
Not Completed 2
Reason Not Completed
Not treated             1
Consent withdrawn             1
[1]
SAF population = study population of patients in safety analysis
[2]
FAS population = full analysis population
[3]
PK population = study population of patients who underwent pharmacokinetic analysis
[4]
PP population = per-protocol population
[5]
SURG population = study population of patients undergoing surgery treated with Wilate
Arm/Group Title Wilate
Hide Arm/Group Description The safety (SAF) population includes all patients who received at least one injection of Wilate during the study (n=10).
Overall Number of Baseline Participants 10
Hide Baseline Analysis Population Description
The safety (SAF) population included all patients who received at least one injection of Wilate during the study (n=10).
Age, Customized   [1] [2] 
Mean (Standard Deviation)
Unit of measure:  Years
1-<6 years Number Analyzed 5 participants
4.0  (1.2)
6-<12 years Number Analyzed 5 participants
9.8  (0.8)
Total Number Analyzed 10 participants
6.9  (3.2)
[1]
Measure Description: Age at screening (years)
[2]
Measure Analysis Population Description: 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] 
Measure Type: Count of Participants
Unit of measure:  Participants
1-<6 years Number Analyzed 5 participants
Female
0
   0.0%
Male
5
 100.0%
6-<12 years Number Analyzed 5 participants
Female
0
   0.0%
Male
5
 100.0%
Total Number Analyzed 10 participants
Female
0
   0.0%
Male
10
 100.0%
[1]
Measure Analysis Population Description: 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] 
Measure Type: Count of Participants
Unit of measure:  Participants
1-<6 years Number Analyzed 5 participants
American Indian or Alaska Native
0
   0.0%
Asian
0
   0.0%
Native Hawaiian or Other Pacific Islander
0
   0.0%
Black or African American
0
   0.0%
White
5
 100.0%
More than one race
0
   0.0%
Unknown or Not Reported
0
   0.0%
6-<12 years Number Analyzed 5 participants
American Indian or Alaska Native
0
   0.0%
Asian
0
   0.0%
Native Hawaiian or Other Pacific Islander
0
   0.0%
Black or African American
0
   0.0%
White
5
 100.0%
More than one race
0
   0.0%
Unknown or Not Reported
0
   0.0%
Total Number Analyzed 10 participants
American Indian or Alaska Native
0
   0.0%
Asian
0
   0.0%
Native Hawaiian or Other Pacific Islander
0
   0.0%
Black or African American
0
   0.0%
White
10
 100.0%
More than one race
0
   0.0%
Unknown or Not Reported
0
   0.0%
[1]
Measure Analysis Population Description: 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] 
Mean (Standard Deviation)
Unit of measure:  Kg
1-<6 years Number Analyzed 5 participants
16.9  (3.6)
6-<12 years Number Analyzed 5 participants
37.4  (5.4)
Total Number Analyzed 10 participants
27.2  (11.6)
[1]
Measure Analysis Population Description: 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)   [1] 
Mean (Standard Deviation)
Unit of measure:  Kg/m^2
1-<6 years Number Analyzed 5 participants
15.3  (1.3)
6-<12 years Number Analyzed 5 participants
17.7  (2.2)
Total Number Analyzed 10 participants
16.5  (2.1)
[1]
Measure Analysis Population Description: 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] 
Measure Type: Count of Participants
Unit of measure:  Participants
1-<6 years Number Analyzed 5 participants
O
2
  40.0%
A
1
  20.0%
AB
0
   0.0%
B
2
  40.0%
6-<12 years Number Analyzed 5 participants
O
2
  40.0%
A
3
  60.0%
AB
0
   0.0%
B
0
   0.0%
Total Number Analyzed 10 participants
O
4
  40.0%
A
4
  40.0%
AB
0
   0.0%
B
2
  20.0%
[1]
Measure Analysis Population Description: 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] 
Measure Type: Count of Participants
Unit of measure:  Participants
1-<6 years Number Analyzed 5 participants
On-demand
0
   0.0%
Prophylaxis
3
  60.0%
Combination
2
  40.0%
6-<12 years Number Analyzed 5 participants
On-demand
2
  40.0%
Prophylaxis
0
   0.0%
Combination
3
  60.0%
Total Number Analyzed 10 participants
On-demand
2
  20.0%
Prophylaxis
3
  30.0%
Combination
5
  50.0%
[1]
Measure Analysis Population Description: 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] [2] 
Mean (Standard Deviation)
Unit of measure:  Bleeding events per year (ABR)
1-<6 years Number Analyzed 5 participants
4.8  (3.0)
6-<12 years Number Analyzed 5 participants
13.6  (8.9)
Total Number Analyzed 10 participants
9.2  (7.8)
[1]
Measure Description: Previous ABR is based on the bleeding rate in the 6 months prior to entry into the study.
[2]
Measure Analysis Population Description: 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.
1.Primary Outcome
Title Pharmacokinetic (PK) Assessment (Area Under the Curve (AUC)) of FVIII:C
Hide Description 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).
Time Frame 0h, 0.25h, 1h, 6h, 24h and 48 h following a single dose of Wilate
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Wilate
Hide Arm/Group Description:
PK population
Overall Number of Participants Analyzed 10
Mean (Standard Deviation)
Unit of Measure: h*IU/dL
1-<6 years Number Analyzed 5 participants
768.8  (288.5)
6-<12 years Number Analyzed 5 participants
671.9  (289.7)
Total Number Analyzed 10 participants
720.3  (277.3)
2.Primary Outcome
Title Pharmacokinetic (PK) Assessment (Area Under the Curve [AUC] Normalised (AUCNorm)) of FVIII:C for Wilate
Hide Description

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.

Time Frame 0h, 0.25h, 1h, 6h, 24h and 48 h following a single dose of Wilate
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Wilate
Hide Arm/Group Description:
PK population
Overall Number of Participants Analyzed 10
Mean (Standard Deviation)
Unit of Measure: h*kg/dL
1-<6 years Number Analyzed 5 participants
15.38  (5.77)
6-<12 years Number Analyzed 5 participants
13.44  (5.79)
Total Number Analyzed 10 participants
14.41  (5.55)
3.Primary Outcome
Title Pharmacokinetic (PK) Assessment (Half-life (h)) of FVIII:C
Hide Description 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.
Time Frame 0h, 0.25h, 1h, 6h, 24h and 48 h following a single dose of Wilate
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Wilate
Hide Arm/Group Description:
PK population
Overall Number of Participants Analyzed 10
Mean (Standard Deviation)
Unit of Measure: hours
1-<6 years Number Analyzed 5 participants
8.28  (1.51)
6-<12 years Number Analyzed 5 participants
9.35  (2.40)
Total Number Analyzed 10 participants
8.82  (1.97)
4.Primary Outcome
Title Pharmacokinetic (PK) Assessment (Maximum Plasma Concentration) for FVIII:C
Hide Description

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)

Time Frame 0h, 0.25h, 1h, 6h, 24h and 48 h following a single dose of Wilate
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Wilate
Hide Arm/Group Description:
PK population
Overall Number of Participants Analyzed 10
Mean (Standard Deviation)
Unit of Measure: IU/dL
1-<6 years Number Analyzed 5 participants
83.0  (16.5)
6-<12 years Number Analyzed 5 participants
78.94  (26.56)
Total Number Analyzed 10 participants
80.99  (20.94)
5.Primary Outcome
Title Pharmacokinetic (PK) Assessment (Time to Reach Maximum Plasma Concentration (Tmax)) of FVIII:C
Hide Description 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).
Time Frame 48 h following a single dose of Wilate
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Wilate
Hide Arm/Group Description:
PK population
Overall Number of Participants Analyzed 10
Mean (Standard Deviation)
Unit of Measure: hours
1-<6 years Number Analyzed 5 participants
0.25  (0.00)
6-<12 years Number Analyzed 5 participants
0.25  (0.00)
Total Number Analyzed 10 participants
0.25  (0.00)
6.Primary Outcome
Title Pharmacokinetic (PK) Assessment (Mean Residence Time (MRT)) of FVIII:C
Hide Description 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.
Time Frame 48 h following a single dose of Wilate
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Wilate
Hide Arm/Group Description:
PK population
Overall Number of Participants Analyzed 10
Mean (Standard Deviation)
Unit of Measure: hours
1-<6 years Number Analyzed 5 participants
11.47  (2.34)
6-<12 years Number Analyzed 5 participants
12.56  (3.53)
Total Number Analyzed 10 participants
12.01  (2.88)
7.Primary Outcome
Title Pharmacokinetic (PK) Assessment (Volume of Distribution (Vd)) of FVIII:C
Hide Description 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).
Time Frame 0h, 0.25h, 1h, 6h, 24h and 48 h following a single dose of Wilate
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Wilate
Hide Arm/Group Description:
PK population
Overall Number of Participants Analyzed 10
Mean (Standard Deviation)
Unit of Measure: dL/kg
1-<6 years Number Analyzed 5 participants
0.784  (0.177)
6-<12 years Number Analyzed 5 participants
1.081  (0.494)
Total Number Analyzed 10 participants
0.933  (0.384)
8.Primary Outcome
Title Pharmacokinetic (PK) Assessment (Clearance) of FVIII:C
Hide Description 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).
Time Frame 0h, 0.25h, 1h, 6h, 24h and 48 h following a single dose of Wilate
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Wilate
Hide Arm/Group Description:
PK population
Overall Number of Participants Analyzed 10
Mean (Standard Deviation)
Unit of Measure: dL/h/kg
1-<6 years Number Analyzed 5 participants
0.071  (0.019)
6-<12 years Number Analyzed 5 participants
0.098  (0.074)
Total Number Analyzed 10 participants
0.084  (0.053)
9.Primary Outcome
Title Incremental In Vivo Recovery (IVR) of FVIII:C
Hide Description

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)

Time Frame 48 h following a single dose of Wilate
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title 1-<6 Years 6-<12 Years Total
Hide Arm/Group Description:
FAS population patients aged 1-<6 years
FAS population patients aged 6-<12 years
All patients in the FAS population.
Overall Number of Participants Analyzed 5 5 10
Mean (Standard Deviation)
Unit of Measure: kg/dL
1.65  (0.33) 1.57  (0.53) 1.61  (0.42)
10.Secondary Outcome
Title Total Annualized Bleeding Rate (TABR)
Hide Description

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.

Time Frame 6 months
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Wilate
Hide Arm/Group Description:
FAS population
Overall Number of Participants Analyzed 10
Mean (Standard Deviation)
Unit of Measure: Bleeding events per year (TABR)
1-<6 years Number Analyzed 5 participants
6.47  (6.61)
6-<12 years Number Analyzed 5 participants
10.62  (9.06)
Total Number Analyzed 10 participants
8.54  (7.79)
11.Secondary Outcome
Title Spontaneous Annualized Bleeding Rate (SABR)
Hide Description

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.

Time Frame 6 months
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Wilate
Hide Arm/Group Description:
FAS population
Overall Number of Participants Analyzed 10
Mean (Standard Deviation)
Unit of Measure: Spontaneous bleeding events per year
1-<6 years Number Analyzed 5 participants
2.70  (2.93)
6-<12 years Number Analyzed 5 participants
1.20  (2.68)
Total Number Analyzed 10 participants
1.95  (2.76)
12.Secondary Outcome
Title Efficacy of Wilate in the Treatment of Breakthrough Bleeding Events (BEs)
Hide Description 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".
Time Frame 6 months
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title 1-<6 Years 6-<12 Years Total
Hide Arm/Group Description:
All patients in the PP population aged 1-<6 years.
All patients in the PP population aged 6-<12 years.
All patients in the PP population
Overall Number of Participants Analyzed 5 3 8
Overall Number of Units Analyzed
Type of Units Analyzed: Bleeding Events (BEs)
17 18 35
Count of Units
Unit of Measure: Bleeding Events (BEs)
Excellent
7
  41.2%
9
  50.0%
16
  45.7%
Good
9
  52.9%
8
  44.4%
17
  48.6%
Moderate
1
   5.9%
1
   5.6%
2
   5.7%
None
0
   0.0%
0
   0.0%
0
   0.0%
13.Secondary Outcome
Title Wilate Consumption Data: Average Dose of Wilate Per Week of Study
Hide Description The average consumption of Wilate per week of the study (IU/kg) for all patients receiving prophylaxis
Time Frame 6 months
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title 1-<6 Years 6-<12 Years Total
Hide Arm/Group Description:
All patients in the FAS population aged 1-<6 years.
All patients in the FAS population aged 6-<12 years.
Total patients in the FAS population
Overall Number of Participants Analyzed 5 5 10
Mean (Standard Deviation)
Unit of Measure: IU/kg per week
58.52  (14.85) 68.08  (19.02) 63.30  (16.86)
14.Secondary Outcome
Title Incremental in Vivo Recovery (IVR) of Wilate Over Time
Hide Description 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.
Time Frame Baseline, and 3 and 6 months of treatment
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title 1-<6 Years 6-<12 Years Total
Hide Arm/Group Description:
All patients in the FAS population aged 1-<6 years.
All patients in the FAS population aged 6-<12 years.
Total patients in the FAS population
Overall Number of Participants Analyzed 5 5 10
Mean (Standard Deviation)
Unit of Measure: kg/dL
Baseline 1.65  (0.33) 1.57  (0.53) 1.61  (0.42)
3 months 1.55  (0.14) 1.56  (0.57) 1.56  (0.39)
6 months 1.63  (0.24) 1.32  (0.45) 1.48  (0.38)
15.Secondary Outcome
Title Association Between ABO Blood Type and the FVIII:C Half-life of Wilate (OS Assay)
Hide Description 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.
Time Frame 6 months
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Wilate
Hide Arm/Group Description:
PK population
Overall Number of Participants Analyzed 10
Measure Type: Number
Unit of Measure: Correlation coefficient
1-<6 years Number Analyzed 5 participants
0.185
6-<12 years Number Analyzed 5 participants
6.100
Total Number Analyzed 10 participants
0.922
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Wilate
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9593
Comments P-Value for patients aged 1-<6 years (N=5)
Method ANOVA
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Wilate
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3752
Comments P-Value for patients aged 6-<12 years (N=5)
Method ANOVA
Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Wilate
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.8273
Comments P-Value for total PK population (N=10)
Method ANOVA
Comments [Not Specified]
16.Secondary Outcome
Title Association Between VWF:Ag Concentration and the FVIII:C Half-life of Wilate
Hide Description 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.
Time Frame 6 months
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis was performed for the PK population which included all patients who underwent PK assessment during the study (total: n=10).
Arm/Group Title Wilate
Hide Arm/Group Description:
PK population
Overall Number of Participants Analyzed 10
Measure Type: Number
Unit of Measure: Correlation coefficient
1-<6 years Number Analyzed 5 participants
0.121
6-<12 years Number Analyzed 5 participants
0.006
Total Number Analyzed 10 participants
0.003
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Wilate
Comments [Not Specified]
Type of Statistical Test Other
Comments P-Value for patients aged 1-<6 years (N=5)
Statistical Test of Hypothesis P-Value 0.8536
Comments [Not Specified]
Method ANOVA
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Wilate
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9791
Comments P-Value for patients aged 6-<12 years (N=5)
Method ANOVA
Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Wilate
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9791
Comments P-Value for total PK population (N=10)
Method ANOVA
Comments [Not Specified]
17.Secondary Outcome
Title Safety and Tolerability of Wilate by Monitoring The Number of Adverse Events (AEs) Throughout the Study
Hide Description 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.
Time Frame 6 months
Hide Outcome Measure Data
Hide Analysis Population Description
The safety (SAF) population included all patients who received at least one injection of Wilate during the study (n=10).
Arm/Group Title Wilate
Hide Arm/Group Description:
The safety (SAF) population
Overall Number of Participants Analyzed 10
Measure Type: Number
Unit of Measure: Adverse events
6
18.Secondary Outcome
Title Immunogenicity of Wilate: Number of Participants With FVIII Inhibitor Activity at 6 Months
Hide Description 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.
Time Frame 6 months
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Wilate
Hide Arm/Group Description:
FAS population
Overall Number of Participants Analyzed 10
Measure Type: Count of Participants
Unit of Measure: Participants
0
   0.0%
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Wilate
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Pearson-Copper
Estimated Value 0
Confidence Interval (2-Sided) 95%
0 to 30.85
Estimation Comments [Not Specified]
19.Secondary Outcome
Title Virus Safety Measured by the Number With Parvovirus B19 Seroconversions Between Baseline (BL) and End of Study
Hide Description 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
Time Frame 6 months
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed in all patients who underwent full analysis (FAS population) (n=10).
Arm/Group Title Wilate
Hide Arm/Group Description:
FAS population
Overall Number of Participants Analyzed 10
Measure Type: Number
Unit of Measure: Participants with seroconversions
1
Time Frame Between the screening visit and the follow up contact visit (30 days after the 6-month study completion visit)
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Wilate
Hide Arm/Group Description The safety (SAF) population includes all patients who received at least one injection of Wilate during the study (n=10).
All-Cause Mortality
Wilate
Affected / at Risk (%)
Total   0/10 (0.00%)    
Hide Serious Adverse Events
Wilate
Affected / at Risk (%) # Events
Total   1/10 (10.00%)    
Congenital, familial and genetic disorders   
Cryptochidism  [1]  1/10 (10.00%)  1
Indicates events were collected by systematic assessment
[1]
One patient had a treatment emergent adverse event (TEAE) that was classified as serious because it required hospitalisation for surgery. The adverse event was judged as moderate and not related to Wilate.
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Wilate
Affected / at Risk (%) # Events
Total   3/10 (30.00%)    
Infections and infestations   
Respiratory tract infection   1/10 (10.00%)  1
Varicella   1/10 (10.00%)  1
Viral upper respiratory tract infection   1/10 (10.00%)  1
Investigations   
Parvovirus B19 test positive   1/10 (10.00%)  1
Nervous system disorders   
Headache   1/10 (10.00%)  1
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Sylvia Werner
Organization: Octapharma AG
Phone: 604-1149 ext +1 (201)
EMail: sylvia.werner@octapharma.com
Layout table for additonal information
Responsible Party: Octapharma
ClinicalTrials.gov Identifier: NCT03376516    
Other Study ID Numbers: WIL-30
First Submitted: December 13, 2017
First Posted: December 18, 2017
Results First Submitted: October 23, 2019
Results First Posted: December 24, 2019
Last Update Posted: January 19, 2021