Clinical Trial Results:
Prospective, Open-Label, Multi-Center, Phase III Clinical Study To Investigate The Efficacy And Safety Of Human Factor VWF/VIII Concentrate (Wilate) In Subjects With Inherited Type 3 Von Willebrand Disease (VWD) Who Undergo Major Surgical Procedures.
|
Summary
|
|
EudraCT number |
2010-021162-30 |
Trial protocol |
BG IT |
Global end of trial date |
12 Mar 2014
|
|
Results information
|
|
Results version number |
v1(current) |
This version publication date |
28 Jul 2016
|
First version publication date |
28 Jul 2016
|
Other versions |
|
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
|
|||
|
Trial identification
|
|||
Sponsor protocol code |
WIL-24
|
||
|
Additional study identifiers
|
|||
ISRCTN number |
- | ||
US NCT number |
NCT01365546 | ||
WHO universal trial number (UTN) |
- | ||
|
Sponsors
|
|||
Sponsor organisation name |
Octapharma AG
|
||
Sponsor organisation address |
Seidenstrasse 2, Lachen, Switzerland, CH-8853
|
||
Public contact |
Clinical Research and Development, Octapharma Pharmazeutika Produktionsges.m.b.H, Oberlaaer Strasse 235, A-1100 Vienna, Austria, 0043 1610320, clinical.department@octapharma.com
|
||
Scientific contact |
Clinical Research and Development, Octapharma Pharmazeutika Produktionsges.m.b.H, Oberlaaer Strasse 235, A-1100 Vienna, Austria, 0043 1610320, clinical.department@octapharma.com
|
||
|
Paediatric regulatory details
|
|||
Is trial part of an agreed paediatric investigation plan (PIP) |
No
|
||
Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
|
||
Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
|
||
|
Results analysis stage
|
|||
Analysis stage |
Final
|
||
Date of interim/final analysis |
25 Jul 2014
|
||
Is this the analysis of the primary completion data? |
No
|
||
Global end of trial reached? |
Yes
|
||
Global end of trial date |
12 Mar 2014
|
||
Was the trial ended prematurely? |
No
|
||
|
General information about the trial
|
|||
Main objective of the trial |
The primary objective of the study is to evaluate the overall hemostatic efficacy of Wilate in preventing excessive intra- and post-operative bleeding in pediatric and adult subjects with Type 3 VWD who require a Von Willebrand Factor (VWF) product and undergo a major surgical procedure.
|
||
Protection of trial subjects |
This trial was conducted in accordance with the ethical principles of the Declaration of Helsinki, and ICH-GCP (Note for Guidance CPMP/ICH/135/95), and national regulatory requirements ensuring that the rights, safety and well-being of patients are protected and in consistency with the the Declaration of Helsinki. Inclusion and exclusion criteria were carefully defined in order to protect subjects from contraindications, interactions with other medication and risk factors associated with the investigational medicinal product.
Throughout the study safety was assessed, such as occurrence of AEs, safety labs, vital signs and physical examinations.
|
||
Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
31 Aug 2011
|
||
Long term follow-up planned |
No
|
||
Independent data monitoring committee (IDMC) involvement? |
Yes
|
||
|
Population of trial subjects
|
|||
Number of subjects enrolled per country |
|||
Country: Number of subjects enrolled |
Poland: 2
|
||
Country: Number of subjects enrolled |
Bulgaria: 1
|
||
Country: Number of subjects enrolled |
Italy: 5
|
||
Country: Number of subjects enrolled |
United States: 7
|
||
Country: Number of subjects enrolled |
India: 13
|
||
Country: Number of subjects enrolled |
Turkey: 1
|
||
Country: Number of subjects enrolled |
South Africa: 2
|
||
Country: Number of subjects enrolled |
Romania: 8
|
||
Country: Number of subjects enrolled |
Oman: 2
|
||
Worldwide total number of subjects |
41
|
||
EEA total number of subjects |
16
|
||
Number of subjects enrolled per age group |
|||
In utero |
0
|
||
Preterm newborn - gestational age < 37 wk |
0
|
||
Newborns (0-27 days) |
0
|
||
Infants and toddlers (28 days-23 months) |
0
|
||
Children (2-11 years) |
0
|
||
Adolescents (12-17 years) |
3
|
||
Adults (18-64 years) |
33
|
||
From 65 to 84 years |
5
|
||
85 years and over |
0
|
||
|
|||||||||||||||
|
Recruitment
|
|||||||||||||||
Recruitment details |
- | ||||||||||||||
|
Pre-assignment
|
|||||||||||||||
Screening details |
Gene defect, race, family/inhibitor history, viral status, co-morbidity & concomitant medications, medical history, vital signs, body weight and height were documented, physical examination performed.In/Exclusion criteria checked.Pt should not have taken any VWF-containing product for at least 3 days prior to the screening. | ||||||||||||||
|
Period 1
|
|||||||||||||||
Period 1 title |
overall trial (overall period)
|
||||||||||||||
Is this the baseline period? |
Yes | ||||||||||||||
Allocation method |
Not applicable
|
||||||||||||||
Blinding used |
Not blinded | ||||||||||||||
|
Arms
|
|||||||||||||||
|
Arm title
|
Wilate | ||||||||||||||
Arm description |
Wilate was administered before, during and after surgical procedures according to the patient's individual IVR, the guidelines defined in the protocol and the patient’s clinical condition. For baseline IVR investigations, Wilate was administered at a dose of 60 VWF:RCo IU/kg (labeled potency). | ||||||||||||||
Arm type |
Experimental | ||||||||||||||
Investigational medicinal product name |
WILATE, plasma derived VWF:FVIII concentrate
|
||||||||||||||
Investigational medicinal product code |
|||||||||||||||
Other name |
|||||||||||||||
Pharmaceutical forms |
Concentrate for solution for infusion
|
||||||||||||||
Routes of administration |
Intravenous use
|
||||||||||||||
Dosage and administration details |
All pt received 60 IU/kg of wilate® for the in vivo recovery (IVR) investigation at study start to calculate the recommended dosing for surgeries. In addition the following guidelines were given: Major surgery: A loading dose of 40−60 VWF:RCo IU/kg within 3 h of start of procedure to achieve peak plasma VWF:RCo level of 100%. A maintenance dose of 20−40 VWF:RCo IU/kg or half of the loading dose every 12−24 h. Trough levels of VWF:RCo were to be maintained at > 50% for at least 6 days. At least 2 maintenance doses were to be administered within the first 24 h after the start of surgery.Minor surgery: A loading dose of 30−60 VWF:RCo IU/kg within 3 h of start of procedure to achieve peak plasma VWF:RCo level of 50%. A maintenance dose of 20−40 VWF:RCo IU/kg or half of the loading dose every 12−24 h. Trough levels of VWF:RCo were to be maintained at > 30% for at least 2 days. These dosing recommendations were adjusted based on baseline recovery and the individual clinical situation.
|
||||||||||||||
|
|||||||||||||||
|
||||||||||||||||||||||||||||||||||||||||
|
Baseline characteristics reporting groups
|
||||||||||||||||||||||||||||||||||||||||
Reporting group title |
overall trial
|
|||||||||||||||||||||||||||||||||||||||
Reporting group description |
- | |||||||||||||||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||||||||||||||
|
Subject analysis sets
|
||||||||||||||||||||||||||||||||||||||||
Subject analysis set title |
ITT population
|
|||||||||||||||||||||||||||||||||||||||
Subject analysis set type |
Intention-to-treat | |||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
The intention to treat (ITT) data set consists of all surgical procedures in the safety analysis data set that were performed in subjects with the underlying disease (VWD), and for which any data were collected after treatment with Wilate®.
|
|||||||||||||||||||||||||||||||||||||||
Subject analysis set title |
Safety population
|
|||||||||||||||||||||||||||||||||||||||
Subject analysis set type |
Safety analysis | |||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
The safety analysis population consists of all subjects who receive at least part of one dose of Wilate®. The safety analysis data set consists of all surgical procedures and planned surgical procedures for which the subject received at least part of one dose of Wilate®. If a subject is administered Wilate® in anticipation of a planned surgical procedure and the procedure is not performed, the patient is included in the safety analysis data set but is not counted in the sample size of the trial with respect to the primary or hemostatic endpoints.
|
|||||||||||||||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||||||||||||||
|
|||
|
End points reporting groups
|
|||
Reporting group title |
Wilate
|
||
Reporting group description |
Wilate was administered before, during and after surgical procedures according to the patient's individual IVR, the guidelines defined in the protocol and the patient’s clinical condition. For baseline IVR investigations, Wilate was administered at a dose of 60 VWF:RCo IU/kg (labeled potency). | ||
Subject analysis set title |
ITT population
|
||
Subject analysis set type |
Intention-to-treat | ||
Subject analysis set description |
The intention to treat (ITT) data set consists of all surgical procedures in the safety analysis data set that were performed in subjects with the underlying disease (VWD), and for which any data were collected after treatment with Wilate®.
|
||
Subject analysis set title |
Safety population
|
||
Subject analysis set type |
Safety analysis | ||
Subject analysis set description |
The safety analysis population consists of all subjects who receive at least part of one dose of Wilate®. The safety analysis data set consists of all surgical procedures and planned surgical procedures for which the subject received at least part of one dose of Wilate®. If a subject is administered Wilate® in anticipation of a planned surgical procedure and the procedure is not performed, the patient is included in the safety analysis data set but is not counted in the sample size of the trial with respect to the primary or hemostatic endpoints.
|
||
|
|||||||||
End point title |
overall hemostatic efficacy of Wilate in surgeries. [1] | ||||||||
End point description |
The primary endpoint is the overall hemostatic efficacy of Wilate® in the treatment in VWD subjects who undergo a surgical procedure, based on both the intra-operative assessment of the surgeon and the assessment by the Investigator covering the post-surgical period from the end of the procedure to 24 hours following the last infusion, both of which use a 4-point ordinal hemostatic efficacy scales.
The primary analysis focused on the overall proportion of surgical episodes declared as successful treatment (rated as per the composite assessment algorithm).
An independent data monitoring committee (IDMC) conducted an independent adjudication of all hemostatic efficacy results and adjudicated the Investigator’s and surgeon’s assessments of the intra- and post-operative assessments ("secondary adjudication"). The primary endpoint (success or failure) was derived from the adjudicated intra- and post-operative assessments according to an agreed composite assessment algorithm.
|
||||||||
End point type |
Primary
|
||||||||
End point timeframe |
post surgery, 24 hours after the last infusion
|
||||||||
| 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 proportion of surgeries with successful treatment were calculated and the following null and alternative primary hypotheses tested: H0: p0 <0.6 versus Ha: p0 ≥0.6 where p0 represents the overall proportion of successfully treated surgical episodes. Result is documented in section END POINT of this report. This is a single arm study, so no comparison between groups was done. |
|||||||||
|
|||||||||
| Notes [2] - subjects in this case refers to the number of surgical procedures (30 procedures in 28 patients) |
|||||||||
| No statistical analyses for this end point | |||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Adverse events information
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Timeframe for reporting adverse events |
The condition of the patients was monitored throughout the study . At each (scheduled or unscheduled) study visit, AEs were documented by the investigator
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Dictionary used for adverse event reporting
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
14.0
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Reporting groups
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
All patients exposed to treatment ( Safety Set)
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
- | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||
Substantial protocol amendments (globally) |
|||
| Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
||
24 Sep 2012 |
After discussion with the FDA, a protocol amendment was implemented and the study design was changed to accept all VWD types as well as minor surgeries, with the requirement that at least 10 patients would have VWD Type 3 and at least at least 20 surgeries would be major. This version was sent to FDA for comments only. It was never sent or implemented at any other participating country or site.
|
||
10 Dec 2012 |
Includes all changes of Amendment, dated 24-Sep-2012 and changes as discussed with the FDA on 19-Nov-2012 as questions arose during the course of the study from Regulatory Authorities and study centers regarding the number of subjects to be enrolled. Therefore, the text regarding the number of subjects was re-worded and clarified. |
||
Interruptions (globally) |
|||
| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
|||
| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| None reported | |||
