E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Von Willebrand’s disease (VWD) is a common hereditary bleeding disorder. The impaired formation and adhesion of the initial platelet plug is reflected in the prolonged skin bleeding time. In addition, reduced levels of von Willebrand factor:ristocetin cofactor activity, von Willebrand factor antigen, factor VIII coagulation activity, factor VIII antigen, and abnormalities of the multimeric structure of VWF are variably found among the several types and subtypes of VWD. |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 7.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10047715 |
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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 |
To demonstrate the efficacy and safety of Humate P® in preventing excessive bleeding in pediatric and adult surgical subjects with VWD using individualized dosing based on VWF:RCo and FVIII:C monitoring. |
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E.2.2 | Secondary objectives of the trial |
To document the pharmacokinetics of Humate-P® in pediatric and adult subjects with various types of VWD. To document the intra- and inter-subject variability in IVR per 1 IU VWF:RCo/kg b.w. over the range of doses (IU/kg) administered. To document the capability of Humate-P® to normalize the coagulation defect in VWD as demonstrated by an increment of the plasma activity of VWF:RCo and FVIII:C.
To analyze the actual dosage and duration of treatment in surgical procedures.
To analyze the actual dosage and duration of treatment in VWD Type I, II and III subjects.
To explore the correlation among VWF:RCo levels, closure time (PFA), FVIII:C levels, CBA and clinical efficacy.
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E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
Subjects of any age Clinical and laboratory diagnosis of VWD (VWF:RCo level of <35 IU/dL or VWF:RCo level of <50 IU/dL and a family and/or personal history consistent with VWD) that can be expected to respond to exogenously administered von Willebrand factor, or Type IIN VWD Can not be expected to show a hemostatic response to desmopressin acetate (DDAVP) sufficient to control bleeding throughout surgery, as judged by the investigator Require substitution with VWF/FVIII complex due to a surgery Expectation of at least 2 consecutive days of post-operative treatment with Humate-P® Informed written consent has been obtained (for pediatric subjects - signed by his/her legal guardian, representative with subject assent as appropriate) |
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E.4 | Principal exclusion criteria |
Known significant hemostatic disorder other than VWD Acquired VWD Known antibodies to FVIII or VWF Known platelet type VWD Emergency surgery or any surgery with a degree of urgency not permitting completion of a pharmacokinetic assessment required by the study protocol History of allergic reaction to Humate-P® Treatment with any other investigational drug in the last four weeks before the entry into the study (with exception of trials concerning anti-HIV agents) Progressive fatal disease/life expectancy of less than 6 months Treatment with DDAVP, cryoprecipitate, whole blood, plasma and plasma derivatives containing substantial quantities of FVIII and/or VWF within 5 days of the pre-surgical pharmacokinetic assessment Subject/family judged unable to comply with study protocol and requirements Currently taking concomitant therapies listed in Section 5.3 of the study protocol Pediatric subjects of insufficient body weight to permit PK sampling Woman in the first 20 weeks of pregnancy Subjects who were previously enrolled and completed this study may not be re-enrolled |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy endpoint is the investigator’s overall hemostatic efficacy assessment based on a four point ordinal scale (excellent, good, moderate/poor, none), to be assessed 24 hours after the last Humate-P® infusion or on Day 14 (whichever is earlier). The primary efficacy analysis will be based on the full analysis dataset. For subjects who withdraw from the study due to lack of efficacy (after pre-surgery loading dose) the efficacy assessment will be assigned as ‘none.’ Subjects receiving desmopressin, cryoprecipitate, or concentrates containing FVIII or VWF other than Humate-P® after the pre-surgical loading dose and before efficacy assessment are considered treatment failures, and an unfavorable response (none) will be assigned unless it is clearly documented that these products were administered for reasons unrelated to efficacy (e.g., pharmacy error). If the assessment at 24 hours after the last infusion is missing, the Day 14 assessment will be used in the analysis instead. If the Day 14 assessment is missing as well, the assessment made immediately after surgery will be used.
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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 | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
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) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
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.8.5 | The trial involves multiple Member States | Yes |
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 | Information not present in EudraCT |
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 |
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E.8.7 | Trial has a data monitoring committee | Information not present in EudraCT |
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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End of the trial is the last visit of the last subject. |
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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 | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 4 |
E.8.9.2 | In all countries concerned by the trial months | 6 |