E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Routine prophylaxis in children under the age of 6 years with severe VWD |
|
E.1.1.1 | Medical condition in easily understood language |
Von Willebrand disease (VWD) is an inherited condition that can cause heavy bleeding. |
|
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 |
|
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 up to 12 paediatric patients (eight evaluable) with severe VWD (defined as screening von Willebrand factor ristocetin cofactor activity [VWF:RCo] <20%) under the age of 6 years, for a period of 12 months. |
|
E.2.2 | Secondary objectives of the trial |
- Determine the pharmacokinetics (PK) of wilate for VWF:Ac (VWF:VWF:RCo) and FVIII:C (one-stage, OS)
- Determine incremental in-vivo recovery (IVR) of wilate over time
- Evaluate the rate of traumatic and spontaneous breakthrough bleeds under prophylactic treatment, including the corresponding treatment efficacy
- Assess the treatment response in minor and major bleeds and surgeries
- Determine wilate consumption data for prophylactic treatment, on-demand treatment, and surgeries
- Investigate the immunogenic potential of wilate by screening for VWF and FVIII inhibitors
- Investigate the thrombogenic potential of wilate
- Assess the patients' joint status with the Haemophilia Joint Health Score (HJHS)
- Assess the safety and tolerability of wilate |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Inclusion Criteria:
1. Patients aged <6 years at the time of screening
2. Type 3 (at least four patients), severe type 2 (except 2N) or severe type 1 VWD (any of which with VWF:RCo <20%) according to medical history, requiring substitution therapy with a VWF-containing product
3. Minimum body weight 11.0 kg at the time of screening
4. Voluntarily given, fully informed written and signed consent obtained before any study-related procedures are conducted (obtained from the patient’s parent(s)/ legal guardian(s)) |
|
E.4 | Principal exclusion criteria |
Exclusion Criteria:
1. History, or current suspicion of VWF or FVIII inhibitors
2. Injection of DDAVP or VWF-containing product within 72 hours prior to inclusion
3. Medical history of a thromboembolic event
4. Platelet count <100,000/µL at screening (except for VWD type 2B)
5. Patients receiving, or scheduled to receive, immunosuppressant drugs (other than antiretroviral chemotherapy), such as prednisone (equivalent to >10 mg/day), or similar drugs
6. Treatment with any investigational medicinal product (IMP) in another interventional clinical study currently or within four weeks before enrolment
7. Other coagulation disorders or bleeding disorders
8. Known hypersensitivity to any of the components of the study drug |
|
E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint of this study is to determine the total annualised bleeding rate (tABR) during prophylactic treatment with wilate |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
E.5.2 | Secondary end point(s) |
The secondary endpoints of this study are to determine:
a. PK profile characteristics of VWF:Ac (VWF:RCo) and FVIII:C (OS) based on blood samples taken pre-dose (baseline), 15 minutes, 3, 9, 24, 48 and 72 hours after dosing of 80 IU/kg BW wilate
b. Incremental in-vivo recovery (IVR) of wilate for VWF:Ac (VWF:RCo) and FVIII:C (OS) over time (at baseline and at 1, 2, 3, 6, 9, and 12 months of treatment
c. Efficacy of wilate in the prevention and treatment of spontaneous and traumatic breakthrough BEs based on their rate and the proportion of spontaneous and traumatic BEs successfully treated with wilate as assessed by the use of a 4-point ordinal haemostatic efficacy scale (excellent – good – moderate – none), respectively
d. The overall efficacy of wilate in perioperative prophylaxis against excessive bleeding as assessed at the end of the postoperative period by the responsible treating investigator. A 4-point ordinal haemostatic efficacy scale (excellent – good – moderate – none) will be used
- Wilate consumption data for prophylactic treatment, for on-demand treatment and during surgical prophylaxis
- Incidence of VWF and FVIII inhibitors
- Incidence of thromboembolic events
- Joint Health Status determination by the use of the HJHS, given the patient’s age and constitutional development allow this assessment
- Safety and tolerability of wilate by monitoring adverse events (AEs) throughout the study |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
a. at the beginning of the study
b. at baseline and at 1, 2, 3, 6, 9*, and 12 months of treatment throughout the study.
*FVIII:C (OS) sample at 9 hours to be omitted in patients with <12.5 kg body weight
c. by the use of a 4-point ordinal haemostatic efficacy scale (excellent – good – moderate – none) throughout the study.
d. at the end of the postoperative period by the responsible treating investigator throughout the study.
|
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | Yes |
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 | Yes |
E.6.13.1 | Other scope of the trial description |
Immunogenicity and Tolerability |
|
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) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 1 |
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 | 3 |
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 |
North Macedonia |
Moldova, Republic of |
Ukraine |
Albania |
Belarus |
Canada |
Russian Federation |
United States |
Belgium |
Czechia |
France |
Germany |
Netherlands |
|
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
|
|
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 | 1 |
E.8.9.1 | In the Member State concerned days | 17 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 3 |
E.8.9.2 | In all countries concerned by the trial days | 9 |