Von Willebrand Diseases
Conditions
Brief summary
This is a prospective, non-controlled, international, multi-center phase 3 study investigating the efficacy and safety of Wilate in previously treated adult patients with VWD, to obtain additional data on the safety and efficacy of Wilate in previously treated patients with VWD undergoing regular prophylaxis.
Interventions
DRUGWilate
Produced from the plasma of human donors, Wilate is presented as a powder or solvent for intravenous injection containing normally 500 IU or 1000 IU human VWF and human FVIII per vial. The ratio between VWF ristocetin co-factor activity (VWF:RCo) and FVIII:C is 1:1. The product contains approximately 100 IU/ml human VWF when reconstituted with 5ml/10mL water for injection with 0.1% polysorbate 80. The specific activity of Wilate is ≥67 IU VWF:RCo/mg protein. The injection or infusion rate should not exceed 2-3mL per minute.
Sponsors
Octapharma
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
6 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Patients who meet all of the following criteria are eligible for the study: * Aged ≥6 years at the time of screening * VWD type 1 (baseline von Willebrand factor activity \[VWF:Ristocetin Co-factor (RCo)\] \<30 IU/dL, 2A, 2B, 2M, or 3 according to medical history requiring substitution therapy with a VWF-containing product to control bleeding * Currently receiving on-demand treatment with a VWF-containing product with at least 1, and an average of ≥2, documented spontaneous BEs per month in the last 6 months, with at least 2 of these BEs requiring treatment with a VWF-containing product * Availability of records to reliably evaluate type, frequency, and treatment of BEs for at least 6 months of on-demand treatment before screening * Female patients of child-bearing potential must have a negative urine pregnancy test at screening and agree to use adequate birth control measures; in case hormonal contra-ception is used, the medication class should remain unchanged for the duration of the study * All patients to provide voluntarily given, fully informed written and signed consent obtained before any study-related procedures are conducted
Exclusion criteria
Patients who meet any of the following criteria are not eligible for the study: * Having received on-demand or prophylactic treatment with a VWF-containing product but having no records available to reliably evaluate the type, frequency, and treatment of BEs over a period of at least 6 months of on-demand treatment * History, or current suspicion, of VWF or FVIII inhibitors * Medical history of a thromboembolic event within 1 year before enrolment * Severe liver or kidney diseases (alanine aminotransferase \[ALAT\] and aspartate trans-aminase \[ASAT\] levels \>5 times of upper limit of normal, creatinine \>120 µmol/L) * Platelet count \<100,000/µL at screening (except for VWD type 2B) * Body weight \<20 kg at screening * Patients receiving, or scheduled to receive, immunosuppressant drugs (other than an-tiretroviral chemotherapy), such as prednisone (equivalent to \>10 mg/day), or similar drugs * Pregnant or breast-feeding at the time of enrolment * Cervical or uterine conditions causing abnormal uterine bleeding (including infection, dysplasia) * Treatment with any IMP in another interventional clinical study currently or within 4 weeks before enrolment * Other coagulation disorders or bleeding disorders due to anatomical reasons * Known hypersensitivity to any of the components of the study drug
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Total Annualized Bleeding Rate (TABR) | 12 months | The TABR was calculated as the total number of spontaneous bleeds, traumatic bleeds, and other bleeds (except menstrual bleeds) occurring in the time period between first dose of the investigational medicinal product (IMP) and the Study Completion Visit, divided by the duration (in years) between first dose of IMP and the Study Completion Visit. |
| Comparison of Total Annualized Bleeding Rates (TABR) During Prophylaxis Treatment in Study WIL-31 to On-demand Treatment in the Same Patient Population in the Preceding Study WIL-29 | 12 Months | Estimated TABR number calculated using a negative binomial counting regression model. Comparison between this number calculated for studies WIL-29 (NCT04053699) and WIL-31. For the comparison of results from WIL-31 to WIL-29 an estimated total annualized bleeding rate was calculated for each cohort, and compared with a negative binomial counting model. As these were estimated rates, there is only one value for each cohort with no measure of spread |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Comparison of Spontaneous Annualized Bleeding Rates (SABR) During Prophylaxis Treatment in Study WIL-31 to On-demand Treatment in the Same Patient Population in the Preceding Study WIL-29. | 12 Months | Estimated SABR number calculated using a negative binomial counting regression model. Comparison between this number calculated for studies WIL-29 (NCT04053699) and WIL-31. For the comparison of results from WIL-31 to WIL-29 an estimated total annualized bleeding rate was calculated for each cohort, and compared with a negative binomial counting model. As these were estimated rates, there is only one value for each cohort with no measure of spread |
| Spontaneous Annualized Bleeding Rate (SABR) | 12 months | Spontaneous annualized bleeding rate (SABR) calculated in analogy with TABR |
| Wilate Consumption for Prophylaxis (mFAS Population) | 12 months | Data on the consumption of Wilate (VWF/FVIII IU/kg per month and per week per patient) for prophylactic treatment |
| Incremental In Vivo Recovery (IVR) of Von Willebrand Factor Activity (VWF:RCo) | From baseline and 12-month visit | Incremental VWF:RCo IVR of Wilate over time (at baseline and at 1, 2, 3, 6, 9, and 12 months of treatment) |
| Incremental In Vivo Recovery (IVR) of FVIII | Baseline and 12-month visit | FVIII:C of Wilate in pediatric patients (at baseline PK visit) measured by chromogenic assay |
| Efficacy of Wilate in the Treatment of Breakthrough Bleeding Events (BEs) | 12 months | Treatment efficacy will be assessed at the end of a BE by the patient using predefined criteria of 'Excellent', 'Good', 'Moderate' or 'None'. All effectiveness ratings assessed as either excellent or good will be considered successfully treated. |
| Wilate Exposure for Prophylaxis (mFAS Population) | 12 months | Data on the exposure days of Wilate prophylactic treatment |
Other
| Measure | Time frame | Description |
|---|---|---|
| Quality of Life (QoL) Assessed Using a 10-Item Short Form Health Survey (SF-10) | 12 months | QoL assessment based on the results from a SF-10 parent-completed questionnaire for patients ≥6 and \<16 years of age, in order to score physical and psychosocial health. Norm-based scoring is used for the SF-36, setting the general population mean to 50 and the SD to 10 for all scales. Scores typically range from 20 to 60, with higher scores indicating better health. |
| Joint Health Status Assessed Using Hemophilia Joint Health Score (HJHS) | Baseline and 12 months | 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. The maximum score for an individual index joint is 20. Higher scores indicate worse joint health. |
| Menstrual Bleeding Assessed Using Pictorial Blood Loss Assessment Chart (PBAC) Score | 12 months | 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 electronic case report form (eCRF). The PBAC score is from 0 onwards, with no theoretical maximum. A score of \>100 defines abnormal coagulation and heavy menstrual bleeding (\>80ml of blood loss per menstrual cycle). |
| Quality of Life (QoL) Assessed Using a 36-Item Short Form Health Survey, Version 2 (SF-36v2) | 12 months | QoL assessment based on the results from the SF-36v2 (Short Form Health Survey) 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). Norm-based scoring is used for the SF-36, setting the general population mean to 50 and the SD to 10 for all scales. Scores typically range from 20 to 60, with higher scores indicating better health. |
| Efficacy Rating for Wilate in Surgical Prophylaxis | 12 months | Efficacy will be assessed by the surgeon at the end of surgery and by the hematologist at the end of the postoperative period using predefined criteria of 'Excellent', 'Good', 'Moderate' or 'None'. In addition, an overall assessment using the 'Excellent', 'Good', 'Moderate' or 'None' scale taking both the intra- and postoperative assessments into account will be made at the end of the postoperative period by the investigator based on an algorithm. |
| Quality of Life (QoL) Assessed Using the Patient-Reported Outcomes Measurement Information System (PROMIS-29) | 12 months | QoL assessment based on the results from the PROMIS-29 (Patient-Reported Outcomes Measurement Information System) survey, which monitors and evaluates the physical, mental, and social health in all patients. 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, each domain using a scale of a minimum score of 0 and a maximum score of 10. Derived T-score values are presented with higher scores equalling higher levels of the outcome being measured (e.g. more fatigue, more physical function). T-scores were calculated using the scoring service from the HealthMeasures Assessment Center. For this T-score metric 50 is the mean of a relevant reference population and 10 is the standard deviation (SD) of that population. |
Countries
Belarus, Bulgaria, Croatia, Hungary, Lebanon, Russia, Ukraine, United States
Participant flow
Recruitment details
Overall, 43 patients were enrolled and treated at 14 study sites worldwide. Twenty-two patients had Type 3 VWD, 10 patients were aged 6-11 years, and 8 patients were aged 12-16 years. Thirty-three patients were evaluable for the primary endpoint. The sample sizes were therefore met.
Participants by arm
| Arm | Count |
|---|---|
| Wilate Routine Prophylaxis in Patients With VWD Prophylactic treatment with Wilate of previously treated patients (PTPs) with Type 3, Type 2 (except 2N), or severe Type 1 VWD. | 43 |
| Total | 43 |
Baseline characteristics
| Characteristic | Wilate Routine Prophylaxis in Patients With VWD |
|---|---|
| Age, Continuous | 22.4 years STANDARD_DEVIATION 14.59 |
| Blood Group Blood Group A | 22 Participants |
| Blood Group Blood Group AB | 1 Participants |
| Blood Group Blood Group B | 6 Participants |
| Blood Group Blood Group O | 14 Participants |
| Body Mass Index (BMI) | 22.9 kg/m2 STANDARD_DEVIATION 6.21 |
| Family History of VWD No | 21 Participants |
| Family History of VWD Yes | 22 Participants |
| Height | 161.3 centimetres STANDARD_DEVIATION 18.22 |
| No Factor VIII Inhibitor History | 43 Participants |
| No Von Willebrand Factor inhibitor history | 43 Participants |
| Race/Ethnicity, Customized Black or African American | 1 Participants |
| Race/Ethnicity, Customized White | 42 Participants |
| Sex: Female, Male Sex Female | 17 Participants |
| Sex: Female, Male Sex Male | 26 Participants |
| VWD Type Severe Type 1 VWD | 6 Participants |
| VWD Type Type 2 VWD | 5 Participants |
| VWD Type Type 3 VWD | 22 Participants |
| VWD Type Unconfirmed disease status | 10 Participants |
| Weight | 62.4 kilograms STANDARD_DEVIATION 24.96 |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 43 |
| other Total, other adverse events | 26 / 43 |
| serious Total, serious adverse events | 4 / 43 |
Outcome results
Primary
Comparison of Total Annualized Bleeding Rates (TABR) During Prophylaxis Treatment in Study WIL-31 to On-demand Treatment in the Same Patient Population in the Preceding Study WIL-29
Estimated TABR number calculated using a negative binomial counting regression model. Comparison between this number calculated for studies WIL-29 (NCT04053699) and WIL-31. For the comparison of results from WIL-31 to WIL-29 an estimated total annualized bleeding rate was calculated for each cohort, and compared with a negative binomial counting model. As these were estimated rates, there is only one value for each cohort with no measure of spread
Time frame: 12 Months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 6-<12 Yrs | Comparison of Total Annualized Bleeding Rates (TABR) During Prophylaxis Treatment in Study WIL-31 to On-demand Treatment in the Same Patient Population in the Preceding Study WIL-29 | 33.3751 bleeding events per year |
| 12-<17 Yrs | Comparison of Total Annualized Bleeding Rates (TABR) During Prophylaxis Treatment in Study WIL-31 to On-demand Treatment in the Same Patient Population in the Preceding Study WIL-29 | 5.4914 bleeding events per year |
p-value: <0.000195% CI: [0.10194, 0.26558]Regression, Linear
Primary
Total Annualized Bleeding Rate (TABR)
The TABR was calculated as the total number of spontaneous bleeds, traumatic bleeds, and other bleeds (except menstrual bleeds) occurring in the time period between first dose of the investigational medicinal product (IMP) and the Study Completion Visit, divided by the duration (in years) between first dose of IMP and the Study Completion Visit.
Time frame: 12 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 6-<12 Yrs | Total Annualized Bleeding Rate (TABR) | 3.73 bleeding events per year | Standard Deviation 4.838 |
| 12-<17 Yrs | Total Annualized Bleeding Rate (TABR) | 4.28 bleeding events per year | Standard Deviation 4.647 |
| ≥17 Yrs | Total Annualized Bleeding Rate (TABR) | 6.31 bleeding events per year | Standard Deviation 9.634 |
| Total | Total Annualized Bleeding Rate (TABR) | 5.24 bleeding events per year | Standard Deviation 7.745 |
Secondary
Comparison of Spontaneous Annualized Bleeding Rates (SABR) During Prophylaxis Treatment in Study WIL-31 to On-demand Treatment in the Same Patient Population in the Preceding Study WIL-29.
Estimated SABR number calculated using a negative binomial counting regression model. Comparison between this number calculated for studies WIL-29 (NCT04053699) and WIL-31. For the comparison of results from WIL-31 to WIL-29 an estimated total annualized bleeding rate was calculated for each cohort, and compared with a negative binomial counting model. As these were estimated rates, there is only one value for each cohort with no measure of spread
Time frame: 12 Months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 6-<12 Yrs | Comparison of Spontaneous Annualized Bleeding Rates (SABR) During Prophylaxis Treatment in Study WIL-31 to On-demand Treatment in the Same Patient Population in the Preceding Study WIL-29. | 24.4168 bleeding events per year |
| 12-<17 Yrs | Comparison of Spontaneous Annualized Bleeding Rates (SABR) During Prophylaxis Treatment in Study WIL-31 to On-demand Treatment in the Same Patient Population in the Preceding Study WIL-29. | 3.3925 bleeding events per year |
p-value: <0.000195% CI: [0.07664, 0.25187]Regression, Linear
Secondary
Efficacy of Wilate in the Treatment of Breakthrough Bleeding Events (BEs)
Treatment efficacy will be assessed at the end of a BE by the patient using predefined criteria of 'Excellent', 'Good', 'Moderate' or 'None'. All effectiveness ratings assessed as either excellent or good will be considered successfully treated.
Time frame: 12 months
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| 6-<12 Yrs | Efficacy of Wilate in the Treatment of Breakthrough Bleeding Events (BEs) | Good | 11 bleeding episodes treated |
| 6-<12 Yrs | Efficacy of Wilate in the Treatment of Breakthrough Bleeding Events (BEs) | Excellent | 109 bleeding episodes treated |
| 6-<12 Yrs | Efficacy of Wilate in the Treatment of Breakthrough Bleeding Events (BEs) | Moderate | 1 bleeding episodes treated |
| 6-<12 Yrs | Efficacy of Wilate in the Treatment of Breakthrough Bleeding Events (BEs) | None | 0 bleeding episodes treated |
Secondary
Incremental In Vivo Recovery (IVR) of FVIII
FVIII:C of Wilate in pediatric patients (at baseline PK visit) measured by chromogenic assay
Time frame: Baseline and 12-month visit
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| 6-<12 Yrs | Incremental In Vivo Recovery (IVR) of FVIII | Baseline | 1.697 kg/dL |
| 6-<12 Yrs | Incremental In Vivo Recovery (IVR) of FVIII | 12-month visit | 2.140 kg/dL |
Secondary
Incremental In Vivo Recovery (IVR) of Von Willebrand Factor Activity (VWF:RCo)
Incremental VWF:RCo IVR of Wilate over time (at baseline and at 1, 2, 3, 6, 9, and 12 months of treatment)
Time frame: From baseline and 12-month visit
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 6-<12 Yrs | Incremental In Vivo Recovery (IVR) of Von Willebrand Factor Activity (VWF:RCo) | Baseline | 1.439 kg/dL | Standard Deviation 0.5259 |
| 6-<12 Yrs | Incremental In Vivo Recovery (IVR) of Von Willebrand Factor Activity (VWF:RCo) | 12-Month Visit | 1.273 kg/dL | Standard Deviation 0.604 |
Secondary
Spontaneous Annualized Bleeding Rate (SABR)
Spontaneous annualized bleeding rate (SABR) calculated in analogy with TABR
Time frame: 12 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 6-<12 Yrs | Spontaneous Annualized Bleeding Rate (SABR) | 2.53 bleeding events per year | Standard Deviation 4.145 |
| 12-<17 Yrs | Spontaneous Annualized Bleeding Rate (SABR) | 6 bleeding events per year | Standard Deviation 1.49 |
| ≥17 Yrs | Spontaneous Annualized Bleeding Rate (SABR) | 4.16 bleeding events per year | Standard Deviation 7.382 |
| Total | Spontaneous Annualized Bleeding Rate (SABR) | 3.23 bleeding events per year | Standard Deviation 5.915 |
Secondary
Wilate Consumption for Prophylaxis (mFAS Population)
Data on the consumption of Wilate (VWF/FVIII IU/kg per month and per week per patient) for prophylactic treatment
Time frame: 12 months
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 6-<12 Yrs | Wilate Consumption for Prophylaxis (mFAS Population) | Dose per exposure day | 31.06 IU/kilogram | Standard Deviation 6.589 |
| 6-<12 Yrs | Wilate Consumption for Prophylaxis (mFAS Population) | Dose per injection | 31.04 IU/kilogram | Standard Deviation 6.559 |
| 6-<12 Yrs | Wilate Consumption for Prophylaxis (mFAS Population) | Dose per Week in Study | 66.06 IU/kilogram | Standard Deviation 23.359 |
| 6-<12 Yrs | Wilate Consumption for Prophylaxis (mFAS Population) | Dose per Month in Study | 287.26 IU/kilogram | Standard Deviation 101.569 |
Secondary
Wilate Exposure for Prophylaxis (mFAS Population)
Data on the exposure days of Wilate prophylactic treatment
Time frame: 12 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 6-<12 Yrs | Wilate Exposure for Prophylaxis (mFAS Population) | 105.55 days | Standard Deviation 32.782 |
Other Pre-specified
Efficacy Rating for Wilate in Surgical Prophylaxis
Efficacy will be assessed by the surgeon at the end of surgery and by the hematologist at the end of the postoperative period using predefined criteria of 'Excellent', 'Good', 'Moderate' or 'None'. In addition, an overall assessment using the 'Excellent', 'Good', 'Moderate' or 'None' scale taking both the intra- and postoperative assessments into account will be made at the end of the postoperative period by the investigator based on an algorithm.
Time frame: 12 months
Population: A total of 3 patients had 13 surgeries that were included in the SURG population.10 of these surgeries were minor and 3 were major.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| 6-<12 Yrs | Efficacy Rating for Wilate in Surgical Prophylaxis | Efficacy Assessment Rated 'Excellent' | 13 surgeries |
| 6-<12 Yrs | Efficacy Rating for Wilate in Surgical Prophylaxis | Efficacy Assessment Rated 'Good' | 0 surgeries |
| 6-<12 Yrs | Efficacy Rating for Wilate in Surgical Prophylaxis | Efficacy Assessment Rated 'Moderate' | 0 surgeries |
| 6-<12 Yrs | Efficacy Rating for Wilate in Surgical Prophylaxis | Efficacy Assessment Rated 'None' | 0 surgeries |
Other Pre-specified
Joint Health Status Assessed Using Hemophilia Joint Health Score (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. The maximum score for an individual index joint is 20. Higher scores indicate worse joint health.
Time frame: Baseline and 12 months
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 6-<12 Yrs | Joint Health Status Assessed Using Hemophilia Joint Health Score (HJHS) | Total Score (Baseline) | 0.44 HJHS score | Standard Deviation 0.882 |
| 6-<12 Yrs | Joint Health Status Assessed Using Hemophilia Joint Health Score (HJHS) | Total Score (Change from Baseline) | 0.22 HJHS score | Standard Deviation 1.563 |
| 6-<12 Yrs | Joint Health Status Assessed Using Hemophilia Joint Health Score (HJHS) | Total Score (12-month) | 0.67 HJHS score | Standard Deviation 2 |
| 12-<17 Yrs | Joint Health Status Assessed Using Hemophilia Joint Health Score (HJHS) | Total Score (Baseline) | 2.83 HJHS score | Standard Deviation 5.231 |
| 12-<17 Yrs | Joint Health Status Assessed Using Hemophilia Joint Health Score (HJHS) | Total Score (Change from Baseline) | -0.17 HJHS score | Standard Deviation 0.983 |
| 12-<17 Yrs | Joint Health Status Assessed Using Hemophilia Joint Health Score (HJHS) | Total Score (12-month) | 2.67 HJHS score | Standard Deviation 4.546 |
| ≥17 Yrs | Joint Health Status Assessed Using Hemophilia Joint Health Score (HJHS) | Total Score (Baseline) | 11.47 HJHS score | Standard Deviation 19.622 |
| ≥17 Yrs | Joint Health Status Assessed Using Hemophilia Joint Health Score (HJHS) | Total Score (12-month) | 8.33 HJHS score | Standard Deviation 20.78 |
| ≥17 Yrs | Joint Health Status Assessed Using Hemophilia Joint Health Score (HJHS) | Total Score (Change from Baseline) | -4.33 HJHS score | Standard Deviation 7.247 |
| Total | Joint Health Status Assessed Using Hemophilia Joint Health Score (HJHS) | Total Score (Baseline) | 6.75 HJHS score | Standard Deviation 15.168 |
| Total | Joint Health Status Assessed Using Hemophilia Joint Health Score (HJHS) | Total Score (Change from Baseline) | -2.13 HJHS score | Standard Deviation 5.588 |
| Total | Joint Health Status Assessed Using Hemophilia Joint Health Score (HJHS) | Total Score (12-month) | 4.90 HJHS score | Standard Deviation 15.027 |
Other Pre-specified
Menstrual Bleeding Assessed Using Pictorial Blood Loss Assessment Chart (PBAC) Score
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 electronic case report form (eCRF). The PBAC score is from 0 onwards, with no theoretical maximum. A score of \>100 defines abnormal coagulation and heavy menstrual bleeding (\>80ml of blood loss per menstrual cycle).
Time frame: 12 months
| Arm | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| 6-<12 Yrs | Menstrual Bleeding Assessed Using Pictorial Blood Loss Assessment Chart (PBAC) Score | 219.0 PBAC score | Standard Deviation 91.71 |
| 12-<17 Yrs | Menstrual Bleeding Assessed Using Pictorial Blood Loss Assessment Chart (PBAC) Score | 143.5 PBAC score | Standard Deviation 59.91 |
Other Pre-specified
Quality of Life (QoL) Assessed Using a 10-Item Short Form Health Survey (SF-10)
QoL assessment based on the results from a SF-10 parent-completed questionnaire for patients ≥6 and \<16 years of age, in order to score physical and psychosocial health. Norm-based scoring is used for the SF-36, setting the general population mean to 50 and the SD to 10 for all scales. Scores typically range from 20 to 60, with higher scores indicating better health.
Time frame: 12 months
Population: Analysis based on number of completed SF-10 questionnaires completed for 6-15 year old children.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 6-<12 Yrs | Quality of Life (QoL) Assessed Using a 10-Item Short Form Health Survey (SF-10) | Physical Summary Score | 40.59 derived scores | Standard Deviation 10.907 |
| 6-<12 Yrs | Quality of Life (QoL) Assessed Using a 10-Item Short Form Health Survey (SF-10) | Psychosocial Summary Score | 50.15 derived scores | Standard Deviation 7.161 |
| 12-<17 Yrs | Quality of Life (QoL) Assessed Using a 10-Item Short Form Health Survey (SF-10) | Physical Summary Score | 6.06 derived scores | Standard Deviation 13.141 |
| 12-<17 Yrs | Quality of Life (QoL) Assessed Using a 10-Item Short Form Health Survey (SF-10) | Psychosocial Summary Score | -0.48 derived scores | Standard Deviation 10.735 |
Other Pre-specified
Quality of Life (QoL) Assessed Using a 36-Item Short Form Health Survey, Version 2 (SF-36v2)
QoL assessment based on the results from the SF-36v2 (Short Form Health Survey) 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). Norm-based scoring is used for the SF-36, setting the general population mean to 50 and the SD to 10 for all scales. Scores typically range from 20 to 60, with higher scores indicating better health.
Time frame: 12 months
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 6-<12 Yrs | Quality of Life (QoL) Assessed Using a 36-Item Short Form Health Survey, Version 2 (SF-36v2) | Physical Component Scores | 46.11 component scores | Standard Deviation 10.572 |
| 6-<12 Yrs | Quality of Life (QoL) Assessed Using a 36-Item Short Form Health Survey, Version 2 (SF-36v2) | Mental Component Scores | 50.08 component scores | Standard Deviation 10.434 |
| 12-<17 Yrs | Quality of Life (QoL) Assessed Using a 36-Item Short Form Health Survey, Version 2 (SF-36v2) | Physical Component Scores | 3.58 component scores | Standard Deviation 6.971 |
| 12-<17 Yrs | Quality of Life (QoL) Assessed Using a 36-Item Short Form Health Survey, Version 2 (SF-36v2) | Mental Component Scores | 3.82 component scores | Standard Deviation 9.887 |
Other Pre-specified
Quality of Life (QoL) Assessed Using the Patient-Reported Outcomes Measurement Information System (PROMIS-29)
QoL assessment based on the results from the PROMIS-29 (Patient-Reported Outcomes Measurement Information System) survey, which monitors and evaluates the physical, mental, and social health in all patients. 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, each domain using a scale of a minimum score of 0 and a maximum score of 10. Derived T-score values are presented with higher scores equalling higher levels of the outcome being measured (e.g. more fatigue, more physical function). T-scores were calculated using the scoring service from the HealthMeasures Assessment Center. For this T-score metric 50 is the mean of a relevant reference population and 10 is the standard deviation (SD) of that population.
Time frame: 12 months
Population: Analysis provided on a total number of 31 completed PROMIS-29 questionnaires.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 6-<12 Yrs | Quality of Life (QoL) Assessed Using the Patient-Reported Outcomes Measurement Information System (PROMIS-29) | Depression/Sadness | 46.97 T-score | Standard Deviation 7.427 |
| 6-<12 Yrs | Quality of Life (QoL) Assessed Using the Patient-Reported Outcomes Measurement Information System (PROMIS-29) | Sleep Disturbances | 45.35 T-score | Standard Deviation 9.884 |
| 6-<12 Yrs | Quality of Life (QoL) Assessed Using the Patient-Reported Outcomes Measurement Information System (PROMIS-29) | Anxiety/Fear | 49.64 T-score | Standard Deviation 7.521 |
| 6-<12 Yrs | Quality of Life (QoL) Assessed Using the Patient-Reported Outcomes Measurement Information System (PROMIS-29) | Ability to Participate in Social Roles/Activites | 54.20 T-score | Standard Deviation 9.31 |
| 6-<12 Yrs | Quality of Life (QoL) Assessed Using the Patient-Reported Outcomes Measurement Information System (PROMIS-29) | Fatigue | 47.32 T-score | Standard Deviation 9.408 |
| 6-<12 Yrs | Quality of Life (QoL) Assessed Using the Patient-Reported Outcomes Measurement Information System (PROMIS-29) | Pain Interference | 51.04 T-score | Standard Deviation 8.99 |
| 6-<12 Yrs | Quality of Life (QoL) Assessed Using the Patient-Reported Outcomes Measurement Information System (PROMIS-29) | Physical Function | 47.63 T-score | Standard Deviation 8.892 |
| 12-<17 Yrs | Quality of Life (QoL) Assessed Using the Patient-Reported Outcomes Measurement Information System (PROMIS-29) | Pain Interference | -3.65 T-score | Standard Deviation 7.182 |
| 12-<17 Yrs | Quality of Life (QoL) Assessed Using the Patient-Reported Outcomes Measurement Information System (PROMIS-29) | Physical Function | 0.59 T-score | Standard Deviation 5.457 |
| 12-<17 Yrs | Quality of Life (QoL) Assessed Using the Patient-Reported Outcomes Measurement Information System (PROMIS-29) | Anxiety/Fear | -1.47 T-score | Standard Deviation 8.386 |
| 12-<17 Yrs | Quality of Life (QoL) Assessed Using the Patient-Reported Outcomes Measurement Information System (PROMIS-29) | Depression/Sadness | -2.15 T-score | Standard Deviation 6.103 |
| 12-<17 Yrs | Quality of Life (QoL) Assessed Using the Patient-Reported Outcomes Measurement Information System (PROMIS-29) | Fatigue | -2.15 T-score | Standard Deviation 8.658 |
| 12-<17 Yrs | Quality of Life (QoL) Assessed Using the Patient-Reported Outcomes Measurement Information System (PROMIS-29) | Sleep Disturbances | -1.21 T-score | Standard Deviation 12.494 |
| 12-<17 Yrs | Quality of Life (QoL) Assessed Using the Patient-Reported Outcomes Measurement Information System (PROMIS-29) | Ability to Participate in Social Roles/Activites | 0.97 T-score | Standard Deviation 8.472 |