E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Von Willebrand disease, type 3, type 2 (except 2N), or severe type 1 |
von Willebrandova bolest, tip 3, tip 2 (osim 2N) ili teški tip 1 |
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E.1.1.1 | Medical condition in easily understood language |
Von Willebrand disease (VWD) is an inherited condition that can sometimes cause heavy bleeding.
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von Willebrandova bolest je naslijeđeno stanje koje ponekad može uzrokovati obilno krvarenje |
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E.1.1.2 | Therapeutic area | Diseases [C] - Blood and lymphatic diseases [C15] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10055168 |
E.1.2 | Term | Von Willebrand's factor deficiency |
E.1.2 | System Organ Class | 100000004850 |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The primary objective of this study is to determine the efficacy of Wilate in the prophylactic treatment of previously treated patients with type 3, type 2 (except 2N), or severe type 1 VWD |
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E.2.2 | Secondary objectives of the trial |
The secondary objectives of this study are to: - Assess the incremental IVR of Wilate for VWF:Ac and FVIII:C over time - Determine the pharmacokinetics (PK) of WIlate for VWF:Ac and FVIII:C in paediatric patients aged 6 to 16 years - Assess the safety and tolerability of Wilate - Determine Wilate consumption data
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Patients aged ≥6 years at the time of screening 2. VWD type 1 (baseline von Willebrand factor activity [VWF:RCo] <30 IU/dL), 2A, 2B, 2M, or 3 according to medical history requiring substitution therapy with a VWF-containing product to control bleeding 3. Currently receiving on-demand treatment with a VWF-containing product AND having experienced at least 6 BEs (excluding menstrual bleeds) over a period of 6 months, with at least 2 of these BEs treated with a VWF containing product AND having records available to reliably evaluate the type, frequency, and treatment of BEs in this 6-month period OR Having switched to prophylactic treatment with a VWF-containing product within the past 2 years AND having records available to reliably evaluate the type, frequency, and treatment of BEs over a period of 6 months of on-demand treatment 4. 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 contraception is used, the medication class should remain unchanged for the duration of the study 5. Voluntarily given, fully informed written and signed consent obtained before any study-related procedures are conducted
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1. Bolesnici u dobi ≥6 godina u vrijeme probira 2. VWB tip 1 (početna razina aktivnosti von Willebrandovog faktora [VWF:AcRCo], <30 IU/dL), 2A, 2B, 2M ili 3 prema povijesti bolesti koja zahtijeva nadomjesno liječenje lijekom koji sadrži VWF radi kontrole krvarenja 3. Bolesnici koji se trenutno liječe po potrebi lijekom koji sadrži VWF I koji su iskusili najmanje 6 spontanih epizoda krvarenja (isključujući menstrualno krvarenja) u periodu od 6 mjeseci, s najmanje dvije od tih epizoda kojima je bilo potrebno liječenje lijekom koji sadrži VWF I s dostupnim podatacima za pouzdanu procjenu tipa, učestalosti i liječenja epizoda krvarenja u 6 mjeseci ILI Bolesnici koji su prešli na profilaktičko liječenje lijekom koji sadrži VWF u zadnje dvije godine I s dostupnim podacima za pouzdanu procjenu tipa, učestalosti i liječenja epizoda krvarenja u 6 mjeseci tijekom redovnog liječenja 4. Žene reproduktivne dobi moraju imati negativan test na trudnoću iz urina na probiru i pristati na korištenje primjerene kontracepcije; u slučaju korištenja hormonske kontracepcije, vrsta kontraceptiva mora ostati nepromijenjena do završetka ispitivanja 5. Dobrovoljno dat, potpisani informirani pristanak dobiven prije početka bilo kakvih postupaka vezanih uz ispitivanje
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E.4 | Principal exclusion criteria |
1. 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 2. History, or current suspicion, of VWF or FVIII inhibitors 3. Medical history of a thromboembolic event within 1 year before enrolment 4. Severe liver or kidney diseases (alanine aminotransferase [ALAT] and aspartate transaminase [ASAT] levels >5 times of upper limit of normal, creatinine >120 µmol/L) 5. Platelet count <100,000/mL at screening (except for VWD type 2B) 6. Body weight <20 kg at screening 7. Patients receiving, or scheduled to receive, immunosuppressant drugs (other than an-tiretroviral chemotherapy), such as prednisone (equivalent to >10 mg/day), or similar drugs 8. Pregnant or breast-feeding at the time of enrolment 9. Cervical or uterine conditions causing abnormal uterine bleeding (including infection, dysplasia) 10. Treatment with any investigational medicinal product (IMP) in another interventional clinical study currently or within 4 weeks before enrolment 11. Other coagulation disorders or bleeding disorders due to anatomical reasons 12. Known hypersensitivity to any of the components of the study drug
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1. Nakon primitka redovne ili profilaktičke terapije sa lijekom koji sadrži VWF, međutim ne postoje podaci za pouzdanu procjenu tipa, učestalosti i liječenja epizoda krvarenja za period od najmanje 6 mjeseci tijekom redovnog liječenja 2. Sumnja na VWF ili FVIII inhibitore, trenutna ili prethodna 3. Anamneza tromboembolije unutar 1 godine prije uključenja u ispitivanje 4. Teške bolesti jetre ili bubrega (alanin aminotransferaza [ALT] i aspartat transaminaza [AST] razine >5 puta veća od normale, kreatinin >120 µmol/L) 5. Broj trombocita <100 000/mL na probiru (osim za VWB tip 2B) 6. Tjelesna težina <20kg tijekom probira 7. Bolesnici koji primaju ili su im propisani imunomodulatorni lijekovi (osim antiretrovirusne kemoterapije), kao što su prednizon (što odgovara >10 mg/dan) ili slični lijekovi 8. Bolesnice koje su trudne ili doje u doba uključenja u ispitivanje 9. Stanja cerviksa ili maternice koja uzrokuju abnormalno krvarenje iz maternice (uključujući infekciju, displaziju) 10. Liječenje bilo kojim ispitivanim lijekom (IMP) u drugom intervencijskom kliničkom ispitivanju, trenutno ili unutar 4 tjedna prije uključenja 11. Ostali poremećaji zgrušavanja ili poremećaji krvarenja s anatomskim uzrocima 12. Poznata preosjetljivost na bilo koji sastojak ispitivanog lijeka |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint of this study is to demonstrate that the total annualised bleeding rate (TABR) during prophylactic treatment with Wilate lowers the patients’ TABR observed during on-demand treatment by more than 50%. |
Primarni cilj ovog ispitivanja je utvrditi djelotvornost lijeka Wilate u profilaktičkom liječenju prethodno liječenih bolesnika s tipom 3, tipom 2 (osim 2N) ili teškim tipom 1 VWB |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Baseline, 1, 2, 3, 6, 9 and 12 months
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Početni, 3, 6, 9 i 12 mjeseci |
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E.5.2 | Secondary end point(s) |
- Spontaneous annualised bleeding rate (SABR) calculated in analogy with TABR - Incremental IVR of Wilate for VWF:Ac (VWF:RCo and VWF:GP1bM) and FVIII:C (OS and CHR) over time (at baseline and at 1, 2, 3, 6, 9, and 12 months of treatment). - For paediatric patients, baseline PK profile characteristics of VWF:Ac (VWF:RCo), and FVIII:C (OS and CHR) based on blood samples taken pre-dose and 1, 3, 9, 24, 48, and 72 hours after dosing - Safety and tolerability of Wilate by monitoring adverse events (AEs) throughout the study - Wilate consumption data (VWF/FVIII IU/kg per month per patient) for prophylaxis |
• Stopa spontanih krvarenja na godišnjoj razini (engl. spontaneous annualised bleeding rate, SABR), izračunato analogno TABR • Tijekom vremena porast IVP-a za lijek Wilate za VWF:Ac (VWF:Rco i VWF:GP1bM) i FVIII:C (OS i KT) (na početku i u 1., 2., 3., 6., 9. i 12. mjesecu liječenja) • Za pedijatrijske bolesnike, obilježja početnog FK profila za VWF:Ac (VWF:Rco) i FVIII:C (OS i KT) temeljeno na uzorcima krvi uzetih prije doze i 1, 3, 9, 24, 48 i 72 sata nakon doziranja • Sigurnost i podnošljivost lijeka Wilate praćenjem štetnih događaja (engl. adverse events, AEs) tijekom cijelog razdoblja ispitivanja • Podaci o potrošnji lijeka Wilate (VWF/FVIII IU/kg po mjesecu po bolesniku) za profilaksu |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Baseline, 1, 2, 3, 6, 9 and 12 months |
Početni, 3, 6, 9 i 12 mjeseci |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | Yes |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 6 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Belarus |
Bulgaria |
Croatia |
Hungary |
Lebanon |
Russian Federation |
Ukraine |
United States |
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E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 10 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 10 |
E.8.9.2 | In all countries concerned by the trial days | 0 |