E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Severe von Willebrand disease patients undergoing elective major surgery |
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E.1.1.1 | Medical condition in easily understood language |
Severe von Willebrand disease patients undergoing elective major surgery |
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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 | 13.1 |
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 | 10010331 - Congenital, familial and genetic disorders |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The primary objective is to evaluate the efficacy of continuous infusion of WILFACTIN for the prevention of perioperative bleeding in patients with severe von Willebrand Disease undergoing elective major surgery. |
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E.2.2 | Secondary objectives of the trial |
The secondary objectives are to evaluate the:
• biological efficacy of continuous infusion of WILFACTIN for achievement of target VWF:RCo levels and maintenance of the pharmacodynamic effect documented by haemostatic FVIII:C levels.
• safety of continuous infusion of WILFACTIN.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Written informed consent
2. At least 18 years of age
3. Severe inherited VWF deficiency with baseline VWF:RCo levels <0.15-0.20 IU/ml (15-20%)
4. Clinical and laboratory diagnosis of VWD that can be expected to show no haemostatic response to desmopressin
5. Elective major surgery
In the study, major surgery in severe VWD patients (at least 6 type 3 patients will be included) is defined as surgery requiring at least 6 days of replacement therapy from among the following:
o orthopaedic surgery
o abdominal surgery
o gynaecological surgery
o urological surgery
o neurological surgery
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E.4 | Principal exclusion criteria |
1. Present or past inhibitor activity against FVIII and/or VWF:RCo
2. Laboratory evidence of abnormal haemostasis other than VWD
3. Platelet count < 100 x 109/l (except for type 2B VWD)
4. Chronic liver disease or AST and ALT > 2.5 times the upper limit of the normal range
5. Creatinine clearance calculated according to Cockroft -Gault formula <60 ml/min
6. Personal history of thromboembolic events
7. History of severe reaction to any component of the IMP
8. Participation in another clinical study involving an investigational drug within the past 30 days or on going participation in another clinical study (except if the patient is participating in another WILFACTIN study)
9. Any other condition that the Investigator believes could interfere with the intent of the study or would not be in the best interest of the patient
10. Pregnant or lactating woman or woman of childbearing age not using a medically acceptable method of birth control during the study
11. Problematic venous access
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy endpoint will be the haematologist’s overall assessment on D7 of haemostasis during and following surgery for at least 6 days (144 hours).
Haemostasis will be rated using the following 4-point scale:
•. 'excellent': bleeding similar to that expected in a normal subject,
•. 'good': mild excessive bleeding,
•. 'moderate': moderate but controlled excessive bleeding,
•. 'none': severe, uncontrolled bleeding.
The physician’s rating will be based on the following parameters:
• blood loss (comparison of predicted and actual volumes),
• haemoglobin levels and transfusion requirements,
• assessment of haemostatic efficacy on D0 by the surgeon using the same
4-point scale,
• daily medical examination of the surgical site.
A successful procedure is defined as a procedure for which the haemostasis assessment is rated 'excellent' or 'good'.
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
The secondary efficacy endpoint will be the achievement of VWF:RCo and FVIII:C levels during the CI. The correlation between VWF:RCo levels and WILFACTIN consumption, i.e. clearance, will be analysed daily.
Safety will be evaluated based on adverse events and immunogenicity.
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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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 | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
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 | Information not present in EudraCT |
E.8.1.2 | Open | Information not present in EudraCT |
E.8.1.3 | Single blind | Information not present in EudraCT |
E.8.1.4 | Double blind | Information not present in EudraCT |
E.8.1.5 | Parallel group | Information not present in EudraCT |
E.8.1.6 | Cross over | Information not present in EudraCT |
E.8.1.7 | Other | Information not present in EudraCT |
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 | 16 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
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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LAST VISIT OF THE LAST PATIENT |
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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 | |
E.8.9.1 | In the Member State concerned months | 36 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial months | 55 |