Clinical Trial Results:
CLINICAL STUDY TO INVESTIGATE THE EFFICACY, SAFETY AND IMMUNOGENICITY OF WILATE IN CHILDREN < 6 YEARS OF AGE WITH INHERITED VON WILLEBRAND DISEASE
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Summary
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EudraCT number |
2005-001426-84 |
Trial protocol |
DE FR CZ |
Global end of trial date |
01 Aug 2009
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Results information
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Results version number |
v1(current) |
This version publication date |
05 Aug 2016
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First version publication date |
05 Aug 2016
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Other versions |
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Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
WIL-14
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Additional study identifiers
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ISRCTN number |
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US NCT number |
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WHO universal trial number (UTN) |
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Sponsors
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Sponsor organisation name |
Octapharma AG
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Sponsor organisation address |
Seidenstraße 2, Lachen, Switzerland, CH-8853
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Public contact |
Clinical Research and Development, Octapharma Pharmazeutika Produktionsgesellschaft mbH, +43 1610320,
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Scientific contact |
Clinical Research and Development, Octapharma Pharmazeutika Produktionsgesellschaft mbH, +43 1610320,
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
Yes
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
21 Dec 2009
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Is this the analysis of the primary completion data? |
No
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Global end of trial reached? |
Yes
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Global end of trial date |
01 Aug 2009
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
The primary objective of the study was to assess the efficacy of Wilate for the prevention and/or treatment of bleeding episodes and in surgical procedures in children <6 years of age.
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Protection of trial subjects |
This trial was conducted in accordance to the principles of GCP, ensuring that the rights, safety and well-being of patients are protected and in consistency with the Declaration of Helsinki.
Inclusion and exclusion criteria were carefully defined in order to protect subjects from contraindications, interactions with other medication and safety factors associated with the investigational medicinal product.
Throughout the study, safety was assessed, such as occurrence of AEs, lab-values, viral safety testing, vital signs and physician´s and parent´s assessment of tolerability were recorded. Inhibitors against VWF and FVIII were determined prior to first treatment and after 3, 6, 9 and 12 months of study participation, as well as in suspicion of inhibitor development. Thrombogenicity markers (F1+2, D-dimers) were determined at baseline and every 3 months and in all patients undergoing surgical procedures. Viral testing was performed before the first Wilate infusion and every 3 months thereafter.
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Background therapy |
NA | ||
Evidence for comparator |
NA | ||
Actual start date of recruitment |
02 Apr 2006
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Czech Republic: 1
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Country: Number of subjects enrolled |
France: 1
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Country: Number of subjects enrolled |
Germany: 10
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Country: Number of subjects enrolled |
Poland: 5
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Worldwide total number of subjects |
17
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EEA total number of subjects |
17
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
7
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Children (2-11 years) |
10
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
0
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From 65 to 84 years |
0
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85 years and over |
0
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Recruitment
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Recruitment details |
- | ||||||||||
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Pre-assignment
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Screening details |
Patients with defined inherited VWD of any type who require or are suspected to require treatment with Wilate and who are well known to the respective centres were eligible for inclusion into the study. Previously treated and previously untreated patients were eligible for the study. | ||||||||||
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Period 1
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Period 1 title |
overall trial (overall period)
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Is this the baseline period? |
Yes | ||||||||||
Allocation method |
Non-randomised - controlled
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Blinding used |
Not blinded | ||||||||||
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Arms
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Arm title
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VWF/FVIII containing human coagulation concentrate | ||||||||||
Arm description |
Subjects were treated according to their individual clinical situation: prophylactically, for bleeding episodes because of a minor or major surgery. | ||||||||||
Arm type |
Experimental | ||||||||||
Investigational medicinal product name |
VWF/FVIII containing human coagulation concentrate
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Investigational medicinal product code |
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Other name |
WILATE, plasma derived VWF:FVIII concentrate
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Pharmaceutical forms |
Concentrate for solution for infusion
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Routes of administration |
Intravenous use
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Dosage and administration details |
The number of administrations and the actual dose for treatment or prevention of spontaneous bleeding episodes or for treatment before, during and after surgical procedures depended on the clinical situation of the patient, e.g. the severity of the disease and the actual bleeding or the type of surgery. Single administrations, multiple doses and treatment as continuous infusion may have been appropriate.
Bolus infusion: Wilate should be injected intravenously at a maximum speed of 4 mL per minute, using an aseptic technique. Continuos infusion: preparation of the product was idential to bolus infusion. The solution was then transferred into plastic bags provided by the supplier of the infusion pump.
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Baseline characteristics reporting groups
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Reporting group title |
overall trial
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Reporting group description |
- | ||||||||||||||||||||||||||||||
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Subject analysis sets
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Subject analysis set title |
Intention-to-treat
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Subject analysis set type |
Intention-to-treat | ||||||||||||||||||||||||||||||
Subject analysis set description |
The Intention-to-treat (ITT) data set comprised all patients included in the study who received at least one dose of Wilate, and this population was included in the statistical evaluation. Safety population was identical to the ITT population.
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End points reporting groups
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Reporting group title |
VWF/FVIII containing human coagulation concentrate
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Reporting group description |
Subjects were treated according to their individual clinical situation: prophylactically, for bleeding episodes because of a minor or major surgery. | ||
Subject analysis set title |
Intention-to-treat
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Subject analysis set type |
Intention-to-treat | ||
Subject analysis set description |
The Intention-to-treat (ITT) data set comprised all patients included in the study who received at least one dose of Wilate, and this population was included in the statistical evaluation. Safety population was identical to the ITT population.
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End point title |
Amount of IMP required [1] | ||||||||
End point description |
The average dose for all sites combined was investigated. In general, across all bleeding sites, more severe bleeding episodes required higher mean doses.
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End point type |
Primary
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End point timeframe |
at the end of the study
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| Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: The endpoint was evaluated by descriptive statistics only, including mean and standard deviation. |
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| No statistical analyses for this end point | |||||||||
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End point title |
Overall efficacy assessment of investigators [2] | ||||||||||||||||
End point description |
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End point type |
Primary
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End point timeframe |
at the end of the study
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| Notes [2] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: This endpoint was evaluated by descriptive statistics only (absolute and relative frequencies). |
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| No statistical analyses for this end point | |||||||||||||||||
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End point title |
Overall efficacy assessment of patients [3] | ||||||||||||||||
End point description |
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End point type |
Primary
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End point timeframe |
at the end of the study
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| Notes [3] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: This endpoint was evaluated by descriptive statistics only (absolute and relative frequencies). |
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| No statistical analyses for this end point | |||||||||||||||||
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End point title |
Number of bleeding episodes [4] | ||||||||||||||||||||||
End point description |
Estimate and Pearson-Clopper 95 % confidence interval for the frequeny of major bleeding episodes
Subjects included in ITT analysis, N=15
Incidence: 4
Total: 68
Incidence estimate (%): 5.88
two-sided CI: 1.63 - 14.38
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End point type |
Primary
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End point timeframe |
at the end of the study
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| Notes [4] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Statistical information is entered in the endpoint description. The system does not allow statistical data to be entered in the statisticial analysis section for studies with 1 treatment arm. |
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| No statistical analyses for this end point | |||||||||||||||||||||||
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Adverse events information
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Timeframe for reporting adverse events |
24 hours SAE reporting requirement.
Waiver from 24 hours SAE reporting: hospitalization for the treatment of a (disease-related) BE.
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Adverse event reporting additional description |
All SAEs, whether suspected to be related to study treatment or not, are reported by telephone, fax
or e-mail immediately to the responsible Clinical Project Manager, study monitor, or to the
responsible local CRO.
AEs were evalutaed at each patient visit.
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
9.0
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Reporting groups
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Reporting group title |
all patients exposed to treatment (ITI, safety set)
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Reporting group description |
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| Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
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29 Jun 2006 |
Addition of an optional PK investigation and a follow-up recovery investigation in patients with severe or type 3 VWD
Addition of thrombogenicity marker (F1+2, D-dimers) determination
Addition of 3 new investigators and study centres from France and removal of 4 investigators and study centres from Germany |
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03 Jul 2007 |
Addition of a new investigator and study centre from Germany
Addition of a second central laboratory and reassignment of blood coagulation and viral marker assessments between the two laboratories |
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05 Sep 2007 |
Addition of 2 new investigators and study centres, one from Germany and one from the Czech Republic |
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07 Jan 2008 |
Addition of an appendix listing participating study centres, with new centres indicated in italics
Prolongation of the study duration
Addition of two external CROs, one to monitor centres in France and one in the Czech Republic |
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Interruptions (globally) |
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| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| None reported | |||
