Back to resultsEfficacy and Safety of Fanhdi®, a High-purity Von Willebrand Containing FVIII Concentrate, in Pediatric Patients With Von Willebrand Disease
Primary Purpose
Von Willebrand Disease
Status
Recruiting
Phase
Phase 4
Locations
Spain
Study Type
Interventional
Intervention
plasma-derived FVIII/VWF concentrate
Sponsored by
About this trial
This is an interventional treatment trial for Von Willebrand Disease focused on measuring pediatric, plasma-derived FVIII concentrate
Eligibility Criteria
Inclusion Criteria:
- Subjects diagnosed with severe (type 2 or 3) hereditary VWD (VWF:RCo<15-20 IU/dL), or VWF:Act<15-20 IU/dL.
- Subjects under 6 years of age.
- Signed informed consent form (ICF) provided by an authorized representative on behalf of the subject in accordance with local law and institutional policy.
Exclusion Criteria:
- Subjects diagnosed with acquired VWD.
- Subjects with active bleeding at the time of the first infusion or within 10 days prior to the infusion.
- Subjects who have been treated with DDAVP or another FVIII containing VWF concentrate during the 5 days prior to the infusion of the Fanhdi. This treatment-free period may be reduced to 3 days for subjects with type 3 VWD.
- Subject who are positive for anti-VWF or anti-FVIII antibodies (≥0.5 Bethesda Units) or has been positive in the history of their disease.
- Subjects with a known allergies/intolerance to any substance contained in Fanhdi.
- Subjects with a known history of anaphylactic reaction(s) to blood or blood components.
- Subjects presenting severe platelet activity dysfunction due to the use of drugs (aspirin, other nonsteroidal anti-inflammatory drugs [NSAIDs], etc.) or a congenital or acquired platelet function disorder or other concomitant processes that may interfere with coagulation.
- Subjects have a known previous infection with hepatitis A virus (HAV), hepatitis B virus (HBV), hepatitis C virus (HCV), or human immunodeficiency virus (HIV), or have clinical signs and symptoms consistent with current HAV, HBV, HCV or HIV infection.
- Subjects presenting anemia (hemoglobin <11 g/dL).
- Subjects diagnosed with metabolic diseases that are not clinically controlled, such as diabetes mellitus, which could potentially interfere with the interpretations of the study.
- Participated in another clinical trial within 30 days prior to the screening visit or has received any investigational product (IP) within 3 months prior to the screening visit.
- If it is anticipated that the subject will be treated with other products containing FVIII or VWF different from Fanhdi throughout the subject's participation.
- Subjects who, in the opinion of the investigator, may have compliance problems with the protocol.
Sites / Locations
- Hospital Sant Joan de Déu BarcelonaRecruiting
- Hospital Universitario La PazRecruiting
- Hospital Universitario Virgen del RocíoRecruiting
- Hospital Universitario Miguel ServetRecruiting
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
plasma-derived FVIII/VWF concentrate
Arm Description
Pharmacokinetic single dose study with Fanhdi (high-purity Von Willebrand containing FVIII concentrate)
Outcomes
Primary Outcome Measures
AUC^0-inf of coagulation factor VIII activity (FVIII:C)
Cumulative area under the concentration time curve extrapolated to infinity of FVIII:C
AUC^0-inf of von Willebrand factor: Ristocetin cofactor activity (VWF:RCo)
Cumulative area under the concentration time curve extrapolated to infinity of VWF:RCo
AUC^0-inf of von Willebrand factor antigen (VWF:Ag)
Cumulative area under the concentration time curve extrapolated to infinity of VWF:Ag
AUC^0-inf of von Willebrand factor: Collagen binding activity (VWF:CB)
Cumulative area under the concentration time curve extrapolated to infinity of VWF:CB
AUC^0-T of FVIII:C
Cumulative area under the concentration time curve calculated from 0 to time of last observed quantifiable concentration of FVIII:C
AUC^0-T of VWF:RCo
Cumulative area under the concentration time curve calculated from 0 to time of last observed quantifiable concentration of VWF:RCo
AUC^0-T of VWF:Ag
Cumulative area under the concentration time curve calculated from 0 to time of last observed quantifiable concentration of VWF:Ag
AUC^0-T of VWF:CB
Cumulative area under the concentration time curve calculated from 0 to time of last observed quantifiable concentration of VWF:CB
in vivo recovery of FVIII:C
in vivo recovery of VWF:RCo
in vivo recovery of VWF:Ag
in vivo recovery of VWF:CB
Half-life of FVIII:C
Terminal elimination half-life
Half-life of VWF:RCo
Terminal elimination half-life
Half-life of VWF:Ag
Terminal elimination half-life
C^max of FVIII:C
Maximum observed plasma and/or serum concentration of FVIII:C
C^max of VWF:RCo
Maximum observed plasma and/or serum concentration of VWF:RCo
C^max of VWF:Ag
Maximum observed plasma and/or serum concentration of VWF:Ag
C^max of VWF:CB
Maximum observed plasma and/or serum concentration of VWF:CB
T^max of FVIII:C
Time of maximum observed plasma and/or serum concentration of FVIII:C
T^max of VWF:RCo
Time of maximum observed plasma and/or serum concentration of VWF:RCo
T^max of VWF:Ag
Time of maximum observed plasma and/or serum concentration of VWF:Ag
T^max of VWF:CB
Time of maximum observed plasma and/or serum concentration of VWF:CB
Mean residence time of FVIII:C
Average amount of time that a single molecule of drug stays in the body.
Mean residence time of VWF:RCo
Average amount of time that a single molecule of drug stays in the body of VWF:RCo
Mean residence time of VWF:Ag
Average amount of time that a single molecule of drug stays in the body of VWF:Ag
Mean residence time of VWF:CB
Average amount of time that a single molecule of drug stays in the body of VWF:CB
Clearance of FVIII:C
Total plasma and/or serum clearance
Clearance of VWF:RCo
Total plasma and/or serum clearance
Clearance of VWF:Ag
Total plasma and/or serum clearance
Clearance of VWF:CB
Total plasma and/or serum clearance
Elimination rate constant of FVIII:C
Elimination rate constant of VWF:RCo
Elimination rate constant of VWF:Ag
Elimination rate constant of VWF:CB
Volume of distribution of FVIII:C
Volume of distribution of VWF:RCo
Volume of distribution of VWF:Ag
Volume of distribution of VWF:CB
VWF multimeric pattern
For type 3 VWD subjects
Secondary Outcome Measures
Full Information
NCT ID
NCT02472665
First Posted
June 10, 2015
Last Updated
March 6, 2023
Sponsor
Grifols Therapeutics LLC
Collaborators
Instituto Grifols, S.A.
1. Study Identification
Unique Protocol Identification Number
NCT02472665
Brief Title
Efficacy and Safety of Fanhdi®, a High-purity Von Willebrand Containing FVIII Concentrate, in Pediatric Patients With Von Willebrand Disease
Official Title
Evaluation of the Pharmacokinetic Profile, Clinical Efficacy and Safety of the Von Willebrand Factor Contained in FANHDI® (Double-inactivated Human Anti-hemophilic Factor) in Pediatric Subjects With Severe Von Willebrand Disease
Study Type
Interventional
2. Study Status
Record Verification Date
March 2023
Overall Recruitment Status
Recruiting
Study Start Date
December 2013 (undefined)
Primary Completion Date
April 2024 (Anticipated)
Study Completion Date
December 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Grifols Therapeutics LLC
Collaborators
Instituto Grifols, S.A.
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
Multicenter, prospective, non-controlled study in a pediatric cohort (<6 years-old) with severe (type 2 or 3) hereditary Von Willebrand Disease (VWD).
Detailed Description
This is a multicenter, prospective, open-label, and single-arm study. The study population is planned to include 8 pediatric subjects (<6 years of age) with severe (type 2 or 3) hereditary VWD without inhibitors and with no active bleeding at the time of inclusion. Eligible subjects will receive a single dose of Fanhdi for a PK evaluation and will be followed for 12 months for which the efficacy and safety of Fanhdi will be assessed. In addition, the type 3 VWD subjects, after 6 months of follow-up of the first infusion, will receive the second dose as in the 1st PK evaluation and undergo a 2nd PK evaluation.
The study will consist of 2 phases:
PK profile evaluation in which all eligible subjects will receive a single dose of 80 IU/kg von Willebrand factor: Ristocetin cofactor activity (VWF:RCo) of Fanhdi. In addition, after 6 months of follow-up of the first infusion, type 3 VWD subjects will receive the second dose of Fanhdi and undergo a 2nd PK evaluation with a reduced sampling schedule.
A 12-month Follow-up period during which the safety and efficacy of Fanhdi will be assessed in the prevention and management of bleeding episodes and/or management of perioperative hemostasis during surgery and/or invasive procedures.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Von Willebrand Disease
Keywords
pediatric, plasma-derived FVIII concentrate
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
8 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
plasma-derived FVIII/VWF concentrate
Arm Type
Experimental
Arm Description
Pharmacokinetic single dose study with Fanhdi (high-purity Von Willebrand containing FVIII concentrate)
Intervention Type
Drug
Intervention Name(s)
plasma-derived FVIII/VWF concentrate
Other Intervention Name(s)
Fanhdi
Intervention Description
1 single dose of 80 IU/kg VWF:RCo of Fanhdi will be administered
Primary Outcome Measure Information:
Title
AUC^0-inf of coagulation factor VIII activity (FVIII:C)
Description
Cumulative area under the concentration time curve extrapolated to infinity of FVIII:C
Time Frame
Prior to the first infusion up to 72 hours postinfusion
Title
AUC^0-inf of von Willebrand factor: Ristocetin cofactor activity (VWF:RCo)
Description
Cumulative area under the concentration time curve extrapolated to infinity of VWF:RCo
Time Frame
Prior to the first infusion up to 72 hours postinfusion
Title
AUC^0-inf of von Willebrand factor antigen (VWF:Ag)
Description
Cumulative area under the concentration time curve extrapolated to infinity of VWF:Ag
Time Frame
Prior to the first infusion up to 72 hours postinfusion
Title
AUC^0-inf of von Willebrand factor: Collagen binding activity (VWF:CB)
Description
Cumulative area under the concentration time curve extrapolated to infinity of VWF:CB
Time Frame
Prior to the first infusion up to 72 hours postinfusion
Title
AUC^0-T of FVIII:C
Description
Cumulative area under the concentration time curve calculated from 0 to time of last observed quantifiable concentration of FVIII:C
Time Frame
Prior to the first infusion up to 72 hours postinfusion
Title
AUC^0-T of VWF:RCo
Description
Cumulative area under the concentration time curve calculated from 0 to time of last observed quantifiable concentration of VWF:RCo
Time Frame
Prior to the first infusion up to 72 hours postinfusion
Title
AUC^0-T of VWF:Ag
Description
Cumulative area under the concentration time curve calculated from 0 to time of last observed quantifiable concentration of VWF:Ag
Time Frame
Prior to the first infusion up to 72 hours postinfusion
Title
AUC^0-T of VWF:CB
Description
Cumulative area under the concentration time curve calculated from 0 to time of last observed quantifiable concentration of VWF:CB
Time Frame
Prior to the first infusion up to 72 hours postinfusion
Title
in vivo recovery of FVIII:C
Time Frame
Prior to the first infusion up to 72 hours postinfusion
Title
in vivo recovery of VWF:RCo
Time Frame
Prior to the first infusion up to 72 hours postinfusion
Title
in vivo recovery of VWF:Ag
Time Frame
Prior to the first infusion up to 72 hours postinfusion
Title
in vivo recovery of VWF:CB
Time Frame
Prior to the first infusion up to 72 hours postinfusion
Title
Half-life of FVIII:C
Description
Terminal elimination half-life
Time Frame
Prior to the first infusion up to 72 hours postinfusion
Title
Half-life of VWF:RCo
Description
Terminal elimination half-life
Time Frame
Prior to the first infusion up to 72 hours postinfusion
Title
Half-life of VWF:Ag
Description
Terminal elimination half-life
Time Frame
Prior to the first infusion up to 72 hours postinfusion
Title
C^max of FVIII:C
Description
Maximum observed plasma and/or serum concentration of FVIII:C
Time Frame
Prior to the first infusion up to 72 hours postinfusion
Title
C^max of VWF:RCo
Description
Maximum observed plasma and/or serum concentration of VWF:RCo
Time Frame
Prior to the first infusion up to 72 hours postinfusion
Title
C^max of VWF:Ag
Description
Maximum observed plasma and/or serum concentration of VWF:Ag
Time Frame
Prior to the first infusion up to 72 hours postinfusion
Title
C^max of VWF:CB
Description
Maximum observed plasma and/or serum concentration of VWF:CB
Time Frame
Prior to the first infusion up to 72 hours postinfusion
Title
T^max of FVIII:C
Description
Time of maximum observed plasma and/or serum concentration of FVIII:C
Time Frame
Prior to the first infusion up to 72 hours postinfusion
Title
T^max of VWF:RCo
Description
Time of maximum observed plasma and/or serum concentration of VWF:RCo
Time Frame
Prior to the first infusion up to 72 hours postinfusion
Title
T^max of VWF:Ag
Description
Time of maximum observed plasma and/or serum concentration of VWF:Ag
Time Frame
Prior to the first infusion up to 72 hours postinfusion
Title
T^max of VWF:CB
Description
Time of maximum observed plasma and/or serum concentration of VWF:CB
Time Frame
Prior to the first infusion up to 72 hours postinfusion
Title
Mean residence time of FVIII:C
Description
Average amount of time that a single molecule of drug stays in the body.
Time Frame
Prior to the first infusion up to 72 hours postinfusion
Title
Mean residence time of VWF:RCo
Description
Average amount of time that a single molecule of drug stays in the body of VWF:RCo
Time Frame
Prior to the first infusion up to 72 hours postinfusion
Title
Mean residence time of VWF:Ag
Description
Average amount of time that a single molecule of drug stays in the body of VWF:Ag
Time Frame
Prior to the first infusion up to 72 hours postinfusion
Title
Mean residence time of VWF:CB
Description
Average amount of time that a single molecule of drug stays in the body of VWF:CB
Time Frame
Prior to the first infusion up to 72 hours postinfusion
Title
Clearance of FVIII:C
Description
Total plasma and/or serum clearance
Time Frame
Prior to the first infusion, 30 minutes postinfusion, 10 hours postinfusion, and at 24, 48, and 72 hours postinfusion
Title
Clearance of VWF:RCo
Description
Total plasma and/or serum clearance
Time Frame
Prior to the first infusion, 30 minutes postinfusion, 10 hours postinfusion, and at 24, 48, and 72 hours postinfusion
Title
Clearance of VWF:Ag
Description
Total plasma and/or serum clearance
Time Frame
Prior to the first infusion, 30 minutes postinfusion, 10 hours postinfusion, and at 24, 48, and 72 hours postinfusion
Title
Clearance of VWF:CB
Description
Total plasma and/or serum clearance
Time Frame
Prior to the first infusion, 30 minutes postinfusion, 10 hours postinfusion, and at 24, 48, and 72 hours postinfusion
Title
Elimination rate constant of FVIII:C
Time Frame
Prior to the first infusion up to 72 hours postinfusion
Title
Elimination rate constant of VWF:RCo
Time Frame
Prior to the first infusion up to 72 hours postinfusion
Title
Elimination rate constant of VWF:Ag
Time Frame
Prior to the first infusion up to 72 hours postinfusion
Title
Elimination rate constant of VWF:CB
Time Frame
Prior to the first infusion up to 72 hours postinfusion
Title
Volume of distribution of FVIII:C
Time Frame
Prior to the first infusion up to 72 hours postinfusion
Title
Volume of distribution of VWF:RCo
Time Frame
Prior to the first infusion up to 72 hours postinfusion
Title
Volume of distribution of VWF:Ag
Time Frame
Prior to the first infusion up to 72 hours postinfusion
Title
Volume of distribution of VWF:CB
Time Frame
Prior to the first infusion up to 72 hours postinfusion
Title
VWF multimeric pattern
Description
For type 3 VWD subjects
Time Frame
Prior to the first infusion up to 12 hours postinfusion
10. Eligibility
Sex
All
Minimum Age & Unit of Time
2 Months
Maximum Age & Unit of Time
6 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Subjects diagnosed with severe (type 2 or 3) hereditary VWD (VWF:RCo<15-20 IU/dL), or VWF:Act<15-20 IU/dL.
Subjects under 6 years of age.
Signed informed consent form (ICF) provided by an authorized representative on behalf of the subject in accordance with local law and institutional policy.
Exclusion Criteria:
Subjects diagnosed with acquired VWD.
Subjects with active bleeding at the time of the first infusion or within 10 days prior to the infusion.
Subjects who have been treated with DDAVP or another FVIII containing VWF concentrate during the 5 days prior to the infusion of the Fanhdi. This treatment-free period may be reduced to 3 days for subjects with type 3 VWD.
Subject who are positive for anti-VWF or anti-FVIII antibodies (≥0.5 Bethesda Units) or has been positive in the history of their disease.
Subjects with a known allergies/intolerance to any substance contained in Fanhdi.
Subjects with a known history of anaphylactic reaction(s) to blood or blood components.
Subjects presenting severe platelet activity dysfunction due to the use of drugs (aspirin, other nonsteroidal anti-inflammatory drugs [NSAIDs], etc.) or a congenital or acquired platelet function disorder or other concomitant processes that may interfere with coagulation.
Subjects have a known previous infection with hepatitis A virus (HAV), hepatitis B virus (HBV), hepatitis C virus (HCV), or human immunodeficiency virus (HIV), or have clinical signs and symptoms consistent with current HAV, HBV, HCV or HIV infection.
Subjects presenting anemia (hemoglobin <11 g/dL).
Subjects diagnosed with metabolic diseases that are not clinically controlled, such as diabetes mellitus, which could potentially interfere with the interpretations of the study.
Participated in another clinical trial within 30 days prior to the screening visit or has received any investigational product (IP) within 3 months prior to the screening visit.
If it is anticipated that the subject will be treated with other products containing FVIII or VWF different from Fanhdi throughout the subject's participation.
Subjects who, in the opinion of the investigator, may have compliance problems with the protocol.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Núria Ribó
Email
nuria.ribo@grifols.com
Facility Information:
Facility Name
Hospital Sant Joan de Déu Barcelona
City
Esplugues De Llobregat
State/Province
Barcelona
ZIP/Postal Code
08950
Country
Spain
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Berrueco Moreno, MD
Facility Name
Hospital Universitario La Paz
City
Madrid
Country
Spain
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jiménez-Yuste, MD
Facility Name
Hospital Universitario Virgen del Rocío
City
Sevilla
ZIP/Postal Code
41013
Country
Spain
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Ramiro Núñez, MD
Facility Name
Hospital Universitario Miguel Servet
City
Zaragoza
Country
Spain
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Fernández Monteserín, MD
12. IPD Sharing Statement
Plan to Share IPD
Undecided
Learn more about this trial
Efficacy and Safety of Fanhdi®, a High-purity Von Willebrand Containing FVIII Concentrate, in Pediatric Patients With Von Willebrand Disease
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