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 |
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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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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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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/µL 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 anti-retroviral 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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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint of this study is to demonstrate that prophylactic treatment with WILATE lowers the patients’ total annualized bleeding rate (TABR) observed during on-demand treatment by more than 50%. |
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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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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:GPIbm) 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 |
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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 |
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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
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 2 |
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 |
Lebanon |
Russian Federation |
Ukraine |
United States |
Bulgaria |
Croatia |
Hungary |
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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 | 2 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |