Clinical Study to Investigate the Efficacy and Safety of Wilate During Prophylaxis in Previously Treated Patients With VWD
- Registration Number
- NCT04052698
- Lead Sponsor
- Octapharma
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 43
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
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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description All patients Wilate Patients with type 3, type 2 (except 2N), or severe type 1 VWD aged ≥6 years at screening receiving Wilate for prophylactic treatment.
- Primary Outcome Measures
Name Time Method 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 Outcome Measures
Name Time Method 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
Wilate Exposure for Prophylaxis (mFAS Population) 12 months Data on the exposure days of Wilate prophylactic treatment
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
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".
Trial Locations
- Locations (14)
Republican Research Center for Radiation Medicine and Human Ecology
🇧🇾Gomel, Belarus
State Institution "National Children's Specialized Hospital "OKHMATDYT" of the Ministry of Health of Ukraine," Center of Hemostasis Pathology
🇺🇦Kyiv, Ukraine
"Specialized Hospital for Active Treatment of Haematological Diseases" EAD, Sofia
🇧🇬Sofia, Bulgaria
Debreceni Egyetem Klinikai Központ, Regionális Haemophilia és Thrombophilia Központ
🇭🇺Debrecen, Hungary
University Hospital Centre Zagreb
🇭🇷Zagreb, Croatia
Hotel Dieu de France Hospital
🇱🇧Beirut, Lebanon
American University of Beirut Medical Center
🇱🇧Beirut, Lebanon
Federal State Budgetary Scientific Institution Kirov Scientific-Research Institute of Hematology and Blood Transfusion of Federal
🇷🇺Kirov, Russian Federation
Morosovskaya Children Clinical Hospital, Moscow Health Department, Department of General Hematology with the Pathology of Hemostasis
🇷🇺Moscow, Russian Federation
Communal Nonprofit Enterprise "Western Ukrainian Specialized Children's Medical Center"of Lviv Regional Council
🇺🇦Lviv, Ukraine
Children's Healthcare of Atlanta
🇺🇸Atlanta, Georgia, United States
Medical Centre Hungarian Defence Forces
🇭🇺Budapest, Hungary
Pediatric Clinic of Haematology and Oncology
🇧🇬Varna, Bulgaria
Nini Hospital
🇱🇧Tripoli, Lebanon