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The purpose of this study is to prospectively obtain reliable data on the bleeding and treatment pattern of patients with VWD undergoing on-demand treatment with a VWF-containing product over a period of 6 months. The data obtained will be used as a basis for historical comparisons with the bleeding and treatment pattern obtained from a clinical study on the efficacy of prophylactic treatment with a VWF/FVIII concentrate.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Patients undergoing treatment with a VWF-containing product | 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 |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Von Willebrand Factor-Containing Product | Drug | Active substances: VWF concentrates, VWF/FVIII concentrates, Cryoprecipitate VWF-containing products licensed in each participating country |
| Measure | Description | Time Frame |
|---|---|---|
| Total Annualized Bleeding Rate (TABR) | 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. | Screening through study completion (6 months) |
| Measure | Description | Time Frame |
|---|---|---|
| Spontaneous Annualized Bleeding Rate (SABR) | Spontaneous annualized bleeding rate (SABR), calculated in analogy with TABR. This includes all bleeding episodes that occurred spontaneously. | Screening through study completion (6 months) |
| Consumption of the VWF-containing Product |
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Inclusion Criteria:
Patients who meet all of the following criteria are eligible for the study:
Exclusion Criteria:
Patients who meet any of the following criteria are not eligible for the study:
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Overall, 55 previously treated patients aged ≥5.5 years at the time of enrolment, with type 3, type 2 (except 2N), or severe type 1 VWD will be included into this study. Of these 55 patients, at least 6 should have type 3 VWD and at least 6 should be ≥5.5 to <16 years of age.
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| Name | Affiliation | Role |
|---|---|---|
| Cristina Solomon, MD | Octapharma | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Children's Healthcare of Atlanta | Atlanta | Georgia | 30329 | United States | ||
| Republican Research Center for Radiation Medicine and Human Ecology |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 8052974 | Background | Sadler JE. A revised classification of von Willebrand disease. For the Subcommittee on von Willebrand Factor of the Scientific and Standardization Committee of the International Society on Thrombosis and Haemostasis. Thromb Haemost. 1994 Apr;71(4):520-5. | |
| 19474451 | Background | Rodeghiero F, Castaman G, Tosetto A. How I treat von Willebrand disease. Blood. 2009 Aug 6;114(6):1158-65. doi: 10.1182/blood-2009-01-153296. Epub 2009 May 27. |
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| ID | Title | Description |
|---|---|---|
| FG000 | 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. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Full Analysis Set |
| |||||||||||||
| Per Protocol Set |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Patients Undergoing On-demand Treatment With a VWF-containing Product | 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 |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Customized | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Total Annualized Bleeding Rate (TABR) | 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. | Posted | Mean | Standard Deviation | Bleeding events per year | Screening through study completion (6 months) |
|
6 Months
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Patients Undergoing Treatment With a VWF-containing Product | 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 |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Sigurd Knaub, Senior VP CR&D Haematology | Octapharma | 01554512141 | Sigurd.Knaub@octapharma.com |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Aug 5, 2020 | Oct 6, 2021 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Jun 25, 2021 | Oct 6, 2021 | SAP_001.pdf |
| ID | Term |
|---|---|
| D014842 | von Willebrand Diseases |
| ID | Term |
|---|---|
| D025861 | Blood Coagulation Disorders, Inherited |
| D001778 | Blood Coagulation Disorders |
| D006402 | Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
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| ID | Term |
|---|---|
| D014841 | von Willebrand Factor |
| ID | Term |
|---|---|
| D001779 | Blood Coagulation Factors |
| D001798 | Blood Proteins |
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
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Data on the consumption of the VWF-containing product (VWF/FVIII IU/kg per month per patient) used for routine on-demand treatment |
| Screening through study completion (6 months) |
| Number of Bleeding Episodes (BEs) Based on a 4-point Efficacy Scale | 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. | Screening through study completion (6 months) |
| Number of Surgery With Successful/Unsuccessful Efficacy Assessment | 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'. | From start of surgery until end of post-operative period (within 8 days after surgery) |
| 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 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 | At screening visit |
| 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 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. | At screening visit |
| 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 ≥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. | At screening |
| 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. Higher scores indicate worse joint health. | At screening |
| 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 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). | Screening through study completion (6 months) |
| Number of Participants With Adverse Drug Reactions (ADRs) Associated With Use of Wilate | Noxious and unintended reactions arising from the use of Wilate will be monitored throughout the study. | Screening through study completion (6 months) |
| Homyel |
| Belarus |
| Specialized Hospital for Active Treatment of Haematological Diseases" EAD, Sofia | Sofia | Bulgaria |
| "UMHAT Sveta Marina" EAD. | Varna | 9010 | Bulgaria |
| University Hospital Centre Zagreb | Zagreb | 10000 | Croatia |
| Medical Centre Hungarian Defence Forces | Budapest | 1134 | Hungary |
| Debreceni Egyetem Klinikai Központ, Regionális Haemophilia és Thrombophilia Központ | Debrecen | 4032 | Hungary |
| University Clinical Center, Department of Internal Medicine, Hematology | Pécs | 7624 | Hungary |
| Hotel Dieu de France Hospital | Beirut | BP166830 | Lebanon |
| American University of Beirut Medical Center | Beirut | Lebanon |
| Nini Hospital | Tripoli | Lebanon |
| Federal State Budgetary Scientific Institution Kirov Scientific-Research Institute of Hematology and Blood Transfusion of Federal | Kirov | 610027 | Russia |
| Morosovskaya Children Clinical Hospital, Moscow Health Department, Department of General Hematology with the Pathology of Hemostasis | Moscow | 119049 | Russia |
| State Institution "National Children's Specialized Hospital "OKHMATDYT" of the Ministry of Health of Ukraine," Center of Hemostasis Pathology | Kyiv | 01135 | Ukraine |
| Community Institution of Lviv Oblast Council "West-Ukrainian Specialized Children's Medical Center | Lviv | 79035 | Ukraine |
| 23633542 | Background | Castaman G, Goodeve A, Eikenboom J; European Group on von Willebrand Disease. Principles of care for the diagnosis and treatment of von Willebrand disease. Haematologica. 2013 May;98(5):667-74. doi: 10.3324/haematol.2012.077263. |
| 19226411 | Background | Mondorf W, Siegmund B, Mahnel R, Richter H, Westfeld M, Galler A, Pollmann H. Haemoassist--a hand-held electronic patient diary for haemophilia home care. Haemophilia. 2009 Mar;15(2):464-72. doi: 10.1111/j.1365-2516.2008.01941.x. Epub 2009 Feb 16. |
| 22681182 | Background | Broderick CR, Herbert RD, Latimer J, Mathieu E, van Doorn N, Curtin JA. Feasibility of short message service to document bleeding episodes in children with haemophilia. Haemophilia. 2012 Nov;18(6):906-10. doi: 10.1111/j.1365-2516.2012.02869.x. Epub 2012 Jun 11. |
| 23672744 | Background | Sholapur NS, Barty R, Wang G, Almonte T, Heddle NM. A survey of patients with haemophilia to understand how they track product used at home. Haemophilia. 2013 Sep;19(5):e289-95. doi: 10.1111/hae.12170. Epub 2013 May 15. |
| Background | Maruish M. User's manual for the SF-36v2 Health Survey (3rd edition). Optum Incorporated; 2011. |
| Background | Saris-Baglama, R,DeRosa, M, Raczek, A, Bjorner, J,Turner-Bowker, D, Ware, J. The SF-10™ Health Survey for Children: A User's Guide. QualityMetric Incorporated; 2007. |
| 29569016 | Background | Hays RD, Spritzer KL, Schalet BD, Cella D. PROMIS(R)-29 v2.0 profile physical and mental health summary scores. Qual Life Res. 2018 Jul;27(7):1885-1891. doi: 10.1007/s11136-018-1842-3. Epub 2018 Mar 22. |
| 38237075 | Derived | Sidonio RF Jr, Boban A, Dubey L, Inati A, Kiss C, Boda Z, Lissitchkov T, Nemes L, Novik D, Peteva E, Taher AT, Timofeeva MA, Vilchevska KV, Vdovin V, Werner S, Knaub S, Djambas Khayat C. von Willebrand factor/factor VIII concentrate (Wilate) prophylaxis in children and adults with von Willebrand disease. Blood Adv. 2024 Mar 26;8(6):1405-1414. doi: 10.1182/bloodadvances.2023011742. |
| Participants |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
|
|
| Secondary | Spontaneous Annualized Bleeding Rate (SABR) | Spontaneous annualized bleeding rate (SABR), calculated in analogy with TABR. This includes all bleeding episodes that occurred spontaneously. | Posted | Mean | Standard Deviation | Bleeding events per year | Screening through study completion (6 months) |
|
|
|
| Secondary | Consumption of the VWF-containing Product | Data on the consumption of the VWF-containing product (VWF/FVIII IU/kg per month per patient) used for routine on-demand treatment | Four subjects were not treated with VCP, for two subjects the dose administered is unknown for all infusions | Posted | Mean | Standard Deviation | IUs per kg per month per patient | Screening through study completion (6 months) |
|
|
|
| Secondary | Number of Bleeding Episodes (BEs) Based on a 4-point Efficacy Scale | 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. | 39 patients who received VWF-containing product in the treatment of BEs | Posted | Number | Number of Bleeding Episodes | Screening through study completion (6 months) | Number of Bleeding Episodes | Number of Bleeding Episodes |
|
|
|
| Secondary | Number of Surgery With Successful/Unsuccessful Efficacy Assessment | 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'. | 6 patients had 7 surgeries that were treated with VWF | Posted | Number | Surgeries | From start of surgery until end of post-operative period (within 8 days after surgery) | Number of Surgeries | Number of Surgeries |
|
|
|
| Secondary | 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 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 | Posted | Mean | Standard Deviation | T-Scores | At screening visit |
|
|
|
| Secondary | 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 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. | 31 patients complete SF-36 questionnaire | Posted | Mean | Standard Deviation | Units on a scale | At screening visit |
|
|
|
| Secondary | 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 ≥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. | 25 subjects completed SF-10 questionnaire | Posted | Mean | Standard Deviation | Units on a scale | At screening |
|
|
|
| Secondary | 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. Higher scores indicate worse joint health. | 37 patients from 42 patients in the PP set completed HJHS | Posted | Mean | Standard Deviation | Units on a scale | At screening |
|
|
|
| Secondary | 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 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). | All subjects of child bearing potential who experienced menstrual cycle | Posted | Mean | Standard Deviation | Units on a scale | Screening through study completion (6 months) |
|
|
|
| Secondary | Number of Participants With Adverse Drug Reactions (ADRs) Associated With Use of Wilate | Noxious and unintended reactions arising from the use of Wilate will be monitored throughout the study. | All participants that were treated with at least one dose of a VWF-containing product | Posted | Count of Participants | Participants | Screening through study completion (6 months) |
|
|
|
| 0 |
| 51 |
| 0 |
| 51 |
| 0 |
| 51 |
Not provided
Not provided
| D020147 | Coagulation Protein Disorders |
| D001791 | Blood Platelet Disorders |
| D006474 | Hemorrhagic Disorders |
| D030342 | Genetic Diseases, Inborn |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D001685 |
| Biological Factors |
| Title | Measurements |
|---|
|
| None |
|
| Title | Measurements |
|---|
|
| Poor |
|
| Title | Measurements |
|---|---|
|
| Fatigue |
|
| Sleep Disturbance |
|
| Ability to Participate in Social Roles/Activities |
|
| Pain Interference |
|
| Title | Measurements |
|---|---|
|
| Physical Functioning |
|
| Role Emotional |
|
| Role Physical |
|
| Social Functioning |
|
| Vitality |
|
|
| MC03 |
|
|
| MC04 |
|
|
| MC05 |
|
|
| MC06 |
|
|
| MC07 |
|
|
| MC08 |
|
|
| MC09 |
|
|