Study of Safety and Efficacy of Antihemophilic Factor / von Willebrand Factor Complex (Humate-P®) Using Individualized Dosing in Pediatric and Adult Surgical Subjects with von Willebrand’s Disease

• Register: EUCTR
• Last refreshed on: 19 March 2012
• Main ID: EUCTR2004-004868-69-SE
• Date of registration: 09/03/2005
• Prospective Registration: Yes
• Primary sponsor: ZLB Behring LLC
• Public title: Study of Safety and Efficacy of Antihemophilic Factor / von Willebrand Factor Complex (Humate-P®) Using Individualized Dosing in Pediatric and Adult Surgical Subjects with von Willebrand’s Disease
• Scientific title: Study of Safety and Efficacy of Antihemophilic Factor / von Willebrand Factor Complex (Humate-P®) Using Individualized Dosing in Pediatric and Adult Surgical Subjects with von Willebrand’s Disease
• Date of first enrolment: 25/04/2005
• Target sample size: 30
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2004-004868-69
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no Randomised: no Open: Single blind: Double blind: Parallel group: Cross over: Other: If controlled, specify comparator, Other Medicinial Product: Placebo: Other:

Countries of recruitment

Sweden

Key inclusion & exclusion criteria

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)
Are the trial subjects under 18? yes
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

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


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

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.
MedDRA version: 7.1 Level: LLT Classification code 10047715

Intervention(s)

Trade Name: Humate-P
Product Name: Humate-P
Pharmaceutical Form: Powder and solvent for solution for infusion
Current Sponsor code: VWF:RCo
Other descriptive name: Von Willebrand Factor Ristocetin Cofactor
Concentration unit: IU/ml international unit(s)/millilitre
Concentration type: range
Concentration number: 60-100
INN or Proposed INN: Factor VIII concentrate
Current Sponsor code: FVIII:C
Other descriptive name: Factor VIII concentrate
Concentration unit: IU/ml international unit(s)/millilitre
Concentration type: range
Concentration number: 27-40
Current Sponsor code: VWF:Ag
Other descriptive name: Von Willebrand Factor Antigen
Concentration unit: IU/ml international unit(s)/millilitre
Concentration type: range
Concentration number: 65-150

Primary Outcome(s)

Secondary Objective: 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.

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.

Main Objective: 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.

Secondary ID(s)

AP7000_1-4002

N/A