Efficacy and Safety of Fanhdi®, a High-purity Von Willebrand Containing FVIII Concentrate, in Pediatric Patients With Von Willebrand Disease
- Conditions
- Von Willebrand Disease
- Interventions
- Registration Number
- NCT02472665
- Lead Sponsor
- Grifols Therapeutics LLC
- 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.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 8
- 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.
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description plasma-derived FVIII/VWF concentrate plasma-derived FVIII/VWF concentrate Pharmacokinetic single dose study with Fanhdi (high-purity Von Willebrand containing FVIII concentrate)
- Primary Outcome Measures
Name Time Method in vivo recovery of VWF:CB Prior to the first infusion up to 72 hours postinfusion Volume of distribution of VWF:Ag Prior to the first infusion up to 72 hours postinfusion AUC^0-inf of coagulation factor VIII activity (FVIII:C) Prior to the first infusion up to 72 hours postinfusion Cumulative area under the concentration time curve extrapolated to infinity of FVIII:C
in vivo recovery of FVIII:C Prior to the first infusion up to 72 hours postinfusion Clearance of FVIII:C Prior to the first infusion, 30 minutes postinfusion, 10 hours postinfusion, and at 24, 48, and 72 hours postinfusion Total plasma and/or serum clearance
AUC^0-inf of von Willebrand factor antigen (VWF:Ag) Prior to the first infusion up to 72 hours postinfusion Cumulative area under the concentration time curve extrapolated to infinity of VWF:Ag
AUC^0-T of VWF:Ag Prior to the first infusion up to 72 hours postinfusion 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 Prior to the first infusion up to 72 hours postinfusion Cumulative area under the concentration time curve calculated from 0 to time of last observed quantifiable concentration of VWF:CB
in vivo recovery of VWF:RCo Prior to the first infusion up to 72 hours postinfusion in vivo recovery of VWF:Ag Prior to the first infusion up to 72 hours postinfusion C^max of VWF:Ag Prior to the first infusion up to 72 hours postinfusion Maximum observed plasma and/or serum concentration of VWF:Ag
C^max of VWF:RCo Prior to the first infusion up to 72 hours postinfusion Maximum observed plasma and/or serum concentration of VWF:RCo
Elimination rate constant of FVIII:C Prior to the first infusion up to 72 hours postinfusion C^max of VWF:CB Prior to the first infusion up to 72 hours postinfusion Maximum observed plasma and/or serum concentration of VWF:CB
T^max of VWF:RCo Prior to the first infusion up to 72 hours postinfusion Time of maximum observed plasma and/or serum concentration of VWF:RCo
Clearance of VWF:Ag Prior to the first infusion, 30 minutes postinfusion, 10 hours postinfusion, and at 24, 48, and 72 hours postinfusion Total plasma and/or serum clearance
Clearance of VWF:RCo Prior to the first infusion, 30 minutes postinfusion, 10 hours postinfusion, and at 24, 48, and 72 hours postinfusion Total plasma and/or serum clearance
Elimination rate constant of VWF:RCo Prior to the first infusion up to 72 hours postinfusion Elimination rate constant of VWF:CB Prior to the first infusion up to 72 hours postinfusion AUC^0-inf of von Willebrand factor: Ristocetin cofactor activity (VWF:RCo) Prior to the first infusion up to 72 hours postinfusion Cumulative area under the concentration time curve extrapolated to infinity of VWF:RCo
AUC^0-inf of von Willebrand factor: Collagen binding activity (VWF:CB) Prior to the first infusion up to 72 hours postinfusion Cumulative area under the concentration time curve extrapolated to infinity of VWF:CB
AUC^0-T of FVIII:C Prior to the first infusion up to 72 hours postinfusion Cumulative area under the concentration time curve calculated from 0 to time of last observed quantifiable concentration of FVIII:C
Half-life of VWF:Ag Prior to the first infusion up to 72 hours postinfusion Terminal elimination half-life
AUC^0-T of VWF:RCo Prior to the first infusion up to 72 hours postinfusion Cumulative area under the concentration time curve calculated from 0 to time of last observed quantifiable concentration of VWF:RCo
Half-life of FVIII:C Prior to the first infusion up to 72 hours postinfusion Terminal elimination half-life
Half-life of VWF:RCo Prior to the first infusion up to 72 hours postinfusion Terminal elimination half-life
C^max of FVIII:C Prior to the first infusion up to 72 hours postinfusion Maximum observed plasma and/or serum concentration of FVIII:C
Mean residence time of FVIII:C Prior to the first infusion up to 72 hours postinfusion Average amount of time that a single molecule of drug stays in the body.
Volume of distribution of VWF:RCo Prior to the first infusion up to 72 hours postinfusion T^max of FVIII:C Prior to the first infusion up to 72 hours postinfusion Time of maximum observed plasma and/or serum concentration of FVIII:C
T^max of VWF:Ag Prior to the first infusion up to 72 hours postinfusion Time of maximum observed plasma and/or serum concentration of VWF:Ag
T^max of VWF:CB Prior to the first infusion up to 72 hours postinfusion Time of maximum observed plasma and/or serum concentration of VWF:CB
Mean residence time of VWF:RCo Prior to the first infusion up to 72 hours postinfusion Average amount of time that a single molecule of drug stays in the body of VWF:RCo
Mean residence time of VWF:Ag Prior to the first infusion up to 72 hours postinfusion Average amount of time that a single molecule of drug stays in the body of VWF:Ag
Mean residence time of VWF:CB Prior to the first infusion up to 72 hours postinfusion Average amount of time that a single molecule of drug stays in the body of VWF:CB
Clearance of VWF:CB Prior to the first infusion, 30 minutes postinfusion, 10 hours postinfusion, and at 24, 48, and 72 hours postinfusion Total plasma and/or serum clearance
Elimination rate constant of VWF:Ag Prior to the first infusion up to 72 hours postinfusion Volume of distribution of FVIII:C Prior to the first infusion up to 72 hours postinfusion Volume of distribution of VWF:CB Prior to the first infusion up to 72 hours postinfusion VWF multimeric pattern Prior to the first infusion up to 12 hours postinfusion For type 3 VWD subjects
- Secondary Outcome Measures
Name Time Method
Trial Locations
- Locations (4)
Hospital Universitario Virgen del Rocío
🇪🇸Sevilla, Spain
Hospital Universitario Miguel Servet
🇪🇸Zaragoza, Spain
Hospital Sant Joan de Déu Barcelona
🇪🇸Esplugues De Llobregat, Barcelona, Spain
Hospital Universitario La Paz
🇪🇸Madrid, Spain