Trial Outcomes & Findings for Bleeding Incidence in VWD Patients Undergoing On-Demand Treatment (NCT NCT04053699)
NCT ID: NCT04053699
Last Updated: 2023-12-07
Results Overview
The total annualized bleeding rate (TABR) will be calculated as the total number of spontaneous bleeds, traumatic BEs, and other BEs occurring in the time period between the start of data collection for each patient and the Study Completion Visit, divided by the duration (in years) between the start of data collection and the Study Completion Visit. Surgery periods, and BEs occurring within these surgery periods, will be excluded from the calculation of TABR.
COMPLETED
56 participants
Screening through study completion (6 months)
2023-12-07
Participant Flow
Participant milestones
| Measure |
Patients Undergoing On-demand Treatment With a VWF-containing Product
Patients with type 3, type 2 (except 2N), or severe type 1 Von Willebrand Disease (VWD) undergoing routine on-demand treatment with a VWF-containing product over a period of 6 months
VWF-containing products: Active substances: VWF concentrates, VWF/FVIII concentrates, Cryoprecipitate VWF-containing products licensed in each participating country
Fifty-six patient were screened and enrolled at 15 centers in 8 countries.
14 patients were excluded from the efficacy analyses due to major deviations, resulting in 42 patients in the per protocol (PP) set.
|
|---|---|
|
Full Analysis Set
STARTED
|
56
|
|
Full Analysis Set
COMPLETED
|
51
|
|
Full Analysis Set
NOT COMPLETED
|
5
|
|
Per Protocol Set
STARTED
|
42
|
|
Per Protocol Set
COMPLETED
|
42
|
|
Per Protocol Set
NOT COMPLETED
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Bleeding Incidence in VWD Patients Undergoing On-Demand Treatment
Baseline characteristics by cohort
| Measure |
Patients Undergoing On-demand Treatment With a VWF-containing Product
n=56 Participants
Patients with type 3, type 2 (except 2N), or severe type 1 VWD undergoing routine on-demand treatment with a VWF-containing product over a period of 6 months
VWF-containing products: Active substances: VWF concentrates, VWF/FVIII concentrates, Cryoprecipitate VWF-containing products licensed in each participating country
|
|---|---|
|
Age, Customized
6-11 years
|
15 Participants
n=5 Participants
|
|
Age, Customized
12-16 years
|
16 Participants
n=5 Participants
|
|
Age, Customized
>16 years
|
25 Participants
n=5 Participants
|
|
Sex: Female, Male
Female
|
25 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
31 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
55 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Screening through study completion (6 months)The total annualized bleeding rate (TABR) will be calculated as the total number of spontaneous bleeds, traumatic BEs, and other BEs occurring in the time period between the start of data collection for each patient and the Study Completion Visit, divided by the duration (in years) between the start of data collection and the Study Completion Visit. Surgery periods, and BEs occurring within these surgery periods, will be excluded from the calculation of TABR.
Outcome measures
| Measure |
Patients Undergoing On-demand Treatment With a VWF-containing Product
n=42 Participants
Patients with type 3, type 2 (except 2N), or severe type 1 VWF activity undergoing routine on-demand treatment with a VWF-containing product over a period of 6 months
VWF-containing products: Active substances: VWF concentrates, VWF/FVIII concentrates, Cryoprecipitate VWF-containing products licensed in each participating country
|
|---|---|
|
Total Annualized Bleeding Rate (TABR)
|
29.13 Bleeding events per year
Standard Deviation 22.925
|
SECONDARY outcome
Timeframe: Screening through study completion (6 months)Spontaneous annualized bleeding rate (SABR), calculated in analogy with TABR. This includes all bleeding episodes that occurred spontaneously.
Outcome measures
| Measure |
Patients Undergoing On-demand Treatment With a VWF-containing Product
n=42 Participants
Patients with type 3, type 2 (except 2N), or severe type 1 VWF activity undergoing routine on-demand treatment with a VWF-containing product over a period of 6 months
VWF-containing products: Active substances: VWF concentrates, VWF/FVIII concentrates, Cryoprecipitate VWF-containing products licensed in each participating country
|
|---|---|
|
Spontaneous Annualized Bleeding Rate (SABR)
|
21.19 Bleeding events per year
Standard Deviation 19.337
|
SECONDARY outcome
Timeframe: Screening through study completion (6 months)Population: Four subjects were not treated with VCP, for two subjects the dose administered is unknown for all infusions
Data on the consumption of the VWF-containing product (VWF/FVIII IU/kg per month per patient) used for routine on-demand treatment
Outcome measures
| Measure |
Patients Undergoing On-demand Treatment With a VWF-containing Product
n=50 Participants
Patients with type 3, type 2 (except 2N), or severe type 1 VWF activity undergoing routine on-demand treatment with a VWF-containing product over a period of 6 months
VWF-containing products: Active substances: VWF concentrates, VWF/FVIII concentrates, Cryoprecipitate VWF-containing products licensed in each participating country
|
|---|---|
|
Consumption of the VWF-containing Product
|
77.94 IUs per kg per month per patient
Standard Deviation 67.898
|
SECONDARY outcome
Timeframe: Screening through study completion (6 months)Population: 39 patients who received VWF-containing product in the treatment of BEs
The efficacy assessment of bleeding episodes at the end of a BE was evaluated on a 4 point scale by the patient/legal guardian (together with the Investigator in case of on-site treatment) including the four items 'excellent,' 'good,' moderate,' and 'none.' The assessment was excellent when bleeding was completely stopped within 3 days in case of minor bleed, within 7 days in case of major bleed, and within 10 days in case of gastrointestinal bleed; Good when bleeding was completely stopped, but time and/or dose slightly exceeded expectations ; Moderate when bleeding could be stopped only by significantly exceeding time and/or dose expectations; and None when bleeding could be stopped only by using other VWF-containing products.
Outcome measures
| Measure |
Patients Undergoing On-demand Treatment With a VWF-containing Product
n=457 Number of Bleeding Episodes
Patients with type 3, type 2 (except 2N), or severe type 1 VWF activity undergoing routine on-demand treatment with a VWF-containing product over a period of 6 months
VWF-containing products: Active substances: VWF concentrates, VWF/FVIII concentrates, Cryoprecipitate VWF-containing products licensed in each participating country
|
|---|---|
|
Number of Bleeding Episodes (BEs) Based on a 4-point Efficacy Scale
Excellent
|
450 Number of Bleeding Episodes
|
|
Number of Bleeding Episodes (BEs) Based on a 4-point Efficacy Scale
Good
|
6 Number of Bleeding Episodes
|
|
Number of Bleeding Episodes (BEs) Based on a 4-point Efficacy Scale
Moderate
|
1 Number of Bleeding Episodes
|
|
Number of Bleeding Episodes (BEs) Based on a 4-point Efficacy Scale
None
|
0 Number of Bleeding Episodes
|
SECONDARY outcome
Timeframe: From start of surgery until end of post-operative period (within 8 days after surgery)Population: 6 patients had 7 surgeries that were treated with VWF
Effectiveness of VWF-containing product in surgical prophylaxis based on the proportion of surgeries successfully treated. Overall treatment efficacy will be assessed at the end of the postoperative period by the treating physician using predefined criteria of 'Excellent', 'Good', 'Moderate/Poor' or 'None'.
Outcome measures
| Measure |
Patients Undergoing On-demand Treatment With a VWF-containing Product
n=7 Number of Surgeries
Patients with type 3, type 2 (except 2N), or severe type 1 VWF activity undergoing routine on-demand treatment with a VWF-containing product over a period of 6 months
VWF-containing products: Active substances: VWF concentrates, VWF/FVIII concentrates, Cryoprecipitate VWF-containing products licensed in each participating country
|
|---|---|
|
Number of Surgery With Successful/Unsuccessful Efficacy Assessment
Excellent
|
7 Surgeries
|
|
Number of Surgery With Successful/Unsuccessful Efficacy Assessment
Good
|
0 Surgeries
|
|
Number of Surgery With Successful/Unsuccessful Efficacy Assessment
Moderate
|
0 Surgeries
|
|
Number of Surgery With Successful/Unsuccessful Efficacy Assessment
Poor
|
0 Surgeries
|
SECONDARY outcome
Timeframe: At screening visitQoL assessment based on the results from the PROMIS-29 survey to monitor and evaluate the physical, mental, and social health in all patients, using a scale of a minimum score of 0 and a maximum score of 10, with higher scores representing a better outcome. The survey covers seven domains from the most relevant areas of self-reported health (depression, anxiety, physical function, pain interference, fatigue, sleep disturbance and ability to participate in social roles and activities) for the majority of people with chronic illness. PROMIS scores have a mean of 50 and standard deviation (SD) of 10 in a referent population. Full details of cut off points for each domain can be found here: https://www.healthmeasures.net/score-and-interpret/interpret-scores/promis/promis-score-cut-points
Outcome measures
| Measure |
Patients Undergoing On-demand Treatment With a VWF-containing Product
n=56 Participants
Patients with type 3, type 2 (except 2N), or severe type 1 VWF activity undergoing routine on-demand treatment with a VWF-containing product over a period of 6 months
VWF-containing products: Active substances: VWF concentrates, VWF/FVIII concentrates, Cryoprecipitate VWF-containing products licensed in each participating country
|
|---|---|
|
Quality of Life (QoL) Assessed Using the Patient-Reported Outcomes Measurement Information System (PROMIS-29)
Physical Function
|
47.24 T-Scores
Standard Deviation 7.947
|
|
Quality of Life (QoL) Assessed Using the Patient-Reported Outcomes Measurement Information System (PROMIS-29)
Anxiety/Fear
|
53.57 T-Scores
Standard Deviation 9.941
|
|
Quality of Life (QoL) Assessed Using the Patient-Reported Outcomes Measurement Information System (PROMIS-29)
Depression/Sadness
|
49.96 T-Scores
Standard Deviation 9.265
|
|
Quality of Life (QoL) Assessed Using the Patient-Reported Outcomes Measurement Information System (PROMIS-29)
Fatigue
|
49.77 T-Scores
Standard Deviation 11.202
|
|
Quality of Life (QoL) Assessed Using the Patient-Reported Outcomes Measurement Information System (PROMIS-29)
Sleep Disturbance
|
49.81 T-Scores
Standard Deviation 10.373
|
|
Quality of Life (QoL) Assessed Using the Patient-Reported Outcomes Measurement Information System (PROMIS-29)
Ability to Participate in Social Roles/Activities
|
52.78 T-Scores
Standard Deviation 9.817
|
|
Quality of Life (QoL) Assessed Using the Patient-Reported Outcomes Measurement Information System (PROMIS-29)
Pain Interference
|
53.87 T-Scores
Standard Deviation 11.134
|
SECONDARY outcome
Timeframe: At screening visitPopulation: 31 patients complete SF-36 questionnaire
QoL assessment based on the results from the SF-36v2 questionnaire to measure functional health and well-being in patients ≥16 years. SF-36v2 ranks 8 different domains using a scale standardized with a scoring algorithm to obtain a score ranging from 0 to 100.The eight health domains include physical functioning (PF), role physical (RP), bodily pain (BP), general health problems (GH), vitality (VT), social functioning (SF), role emotional (RE) and general mental health (MH). Higher scores indicate better health status, and a mean score of 50 has been articulated as a normative value for all scales.
Outcome measures
| Measure |
Patients Undergoing On-demand Treatment With a VWF-containing Product
n=31 Participants
Patients with type 3, type 2 (except 2N), or severe type 1 VWF activity undergoing routine on-demand treatment with a VWF-containing product over a period of 6 months
VWF-containing products: Active substances: VWF concentrates, VWF/FVIII concentrates, Cryoprecipitate VWF-containing products licensed in each participating country
|
|---|---|
|
Quality of Life (QoL) Assessed Using a 36-Item Short Form Health Survey, Version 2 (SF-36v2)
Bodily Pain
|
49.87 Units on a scale
Standard Deviation 27.304
|
|
Quality of Life (QoL) Assessed Using a 36-Item Short Form Health Survey, Version 2 (SF-36v2)
General Health
|
49.45 Units on a scale
Standard Deviation 21.857
|
|
Quality of Life (QoL) Assessed Using a 36-Item Short Form Health Survey, Version 2 (SF-36v2)
Mental Health
|
62.74 Units on a scale
Standard Deviation 16.923
|
|
Quality of Life (QoL) Assessed Using a 36-Item Short Form Health Survey, Version 2 (SF-36v2)
Physical Functioning
|
64.03 Units on a scale
Standard Deviation 24.509
|
|
Quality of Life (QoL) Assessed Using a 36-Item Short Form Health Survey, Version 2 (SF-36v2)
Role Emotional
|
62.63 Units on a scale
Standard Deviation 27.035
|
|
Quality of Life (QoL) Assessed Using a 36-Item Short Form Health Survey, Version 2 (SF-36v2)
Role Physical
|
51.21 Units on a scale
Standard Deviation 25.435
|
|
Quality of Life (QoL) Assessed Using a 36-Item Short Form Health Survey, Version 2 (SF-36v2)
Social Functioning
|
64.52 Units on a scale
Standard Deviation 24.173
|
|
Quality of Life (QoL) Assessed Using a 36-Item Short Form Health Survey, Version 2 (SF-36v2)
Vitality
|
58.06 Units on a scale
Standard Deviation 18.128
|
SECONDARY outcome
Timeframe: At screeningPopulation: 25 subjects completed SF-10 questionnaire
QoL assessment based on the results from a SF-10 parent-completed questionnaire for patients ≥5.5 and \<16 years of age, in order to score physical and psychosocial health. SF-10 uses norm-based scoring where scales have a standardized mean value of 50 and standard deviation of 10.
Outcome measures
| Measure |
Patients Undergoing On-demand Treatment With a VWF-containing Product
n=25 Participants
Patients with type 3, type 2 (except 2N), or severe type 1 VWF activity undergoing routine on-demand treatment with a VWF-containing product over a period of 6 months
VWF-containing products: Active substances: VWF concentrates, VWF/FVIII concentrates, Cryoprecipitate VWF-containing products licensed in each participating country
|
|---|---|
|
Quality of Life (QoL) Assessed Using a 10-item Short Form Health Survey (SF-10)
Physical Summary Score
|
28.60 Units on a scale
Standard Deviation 14.961
|
|
Quality of Life (QoL) Assessed Using a 10-item Short Form Health Survey (SF-10)
Psychosocial Summary Score
|
46.56 Units on a scale
Standard Deviation 9.428
|
SECONDARY outcome
Timeframe: At screeningPopulation: 37 patients from 42 patients in the PP set completed HJHS
Joint health status will be assessed using the Hemophilia Joint Health Score (HJHS), which has been specifically validated for the assessment of the clinical outcome in VWD. HJHS evaluates six index joints to produce a score between 0-124. Higher scores indicate worse joint health.
Outcome measures
| Measure |
Patients Undergoing On-demand Treatment With a VWF-containing Product
n=37 Participants
Patients with type 3, type 2 (except 2N), or severe type 1 VWF activity undergoing routine on-demand treatment with a VWF-containing product over a period of 6 months
VWF-containing products: Active substances: VWF concentrates, VWF/FVIII concentrates, Cryoprecipitate VWF-containing products licensed in each participating country
|
|---|---|
|
Joint Health Status Assessed Using Hemophilia Joint Health Score (HJHS)
|
6.76 Units on a scale
Standard Deviation 14.611
|
SECONDARY outcome
Timeframe: Screening through study completion (6 months)Population: All subjects of child bearing potential who experienced menstrual cycle
Bleeding information from each menstrual period while in this study will be collected using the Pictorial Blood Loss Assessment Chart (PBAC). The PBAC will be provided to all female patients of child-bearing potential. The data documented in the PBAC and the investigator-calculated final score will be recorded in the eCRF. The PBAC records pad and tampon use (as either light \[1 point\], medium \[5 points\], or heavy \[10 points\] flow), clots (small \[1 point\] or large \[5 points\]), and flooding episodes (1 point each) which can be recorded as many times as necessary any day of the month. The PBAC is scored from 0 (no bleeding) onwards, with a score of \>100 defining abnormal coagulation and heavy menstrual bleeding (corresponds to \>80ml of blood loss per menstrual cycle).
Outcome measures
| Measure |
Patients Undergoing On-demand Treatment With a VWF-containing Product
n=15 Participants
Patients with type 3, type 2 (except 2N), or severe type 1 VWF activity undergoing routine on-demand treatment with a VWF-containing product over a period of 6 months
VWF-containing products: Active substances: VWF concentrates, VWF/FVIII concentrates, Cryoprecipitate VWF-containing products licensed in each participating country
|
|---|---|
|
Menstrual Bleeding Assessed Using Pictorial Blood Loss Assessment Chart (PBAC) Score
MC01
|
521.7 Units on a scale
Standard Deviation 790.96
|
|
Menstrual Bleeding Assessed Using Pictorial Blood Loss Assessment Chart (PBAC) Score
MC02
|
279.2 Units on a scale
Standard Deviation 219.69
|
|
Menstrual Bleeding Assessed Using Pictorial Blood Loss Assessment Chart (PBAC) Score
MC03
|
311.0 Units on a scale
Standard Deviation 261.98
|
|
Menstrual Bleeding Assessed Using Pictorial Blood Loss Assessment Chart (PBAC) Score
MC04
|
408.8 Units on a scale
Standard Deviation 471.92
|
|
Menstrual Bleeding Assessed Using Pictorial Blood Loss Assessment Chart (PBAC) Score
MC05
|
289.9 Units on a scale
Standard Deviation 267.53
|
|
Menstrual Bleeding Assessed Using Pictorial Blood Loss Assessment Chart (PBAC) Score
MC06
|
330.4 Units on a scale
Standard Deviation 327.02
|
|
Menstrual Bleeding Assessed Using Pictorial Blood Loss Assessment Chart (PBAC) Score
MC07
|
411.6 Units on a scale
Standard Deviation 314.99
|
|
Menstrual Bleeding Assessed Using Pictorial Blood Loss Assessment Chart (PBAC) Score
MC08
|
348.5 Units on a scale
Standard Deviation 102.53
|
|
Menstrual Bleeding Assessed Using Pictorial Blood Loss Assessment Chart (PBAC) Score
MC09
|
361.5 Units on a scale
Standard Deviation 400.93
|
SECONDARY outcome
Timeframe: Screening through study completion (6 months)Population: All participants that were treated with at least one dose of a VWF-containing product
Noxious and unintended reactions arising from the use of Wilate will be monitored throughout the study.
Outcome measures
| Measure |
Patients Undergoing On-demand Treatment With a VWF-containing Product
n=52 Participants
Patients with type 3, type 2 (except 2N), or severe type 1 VWF activity undergoing routine on-demand treatment with a VWF-containing product over a period of 6 months
VWF-containing products: Active substances: VWF concentrates, VWF/FVIII concentrates, Cryoprecipitate VWF-containing products licensed in each participating country
|
|---|---|
|
Number of Participants With Adverse Drug Reactions (ADRs) Associated With Use of Wilate
|
0 Participants
|
Adverse Events
Patients Undergoing Treatment With a VWF-containing Product
Serious adverse events
Adverse event data not reported
Other adverse events
Adverse event data not reported
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place