Clinical trial NCT02472665: 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
Overall status: RECRUITING
Phase: PHASE4
Conditions: Von Willebrand Disease
Keywords: pediatric
plasma-derived FVIII concentrate
Lead sponsor: Grifols Therapeutics LLC
Sponsor class: INDUSTRY
Collaborators: name: Instituto Grifols, S.A.
First posted: 2015-06-16
Enrollment: 8
Sex: ALL
Minimum age (years): 2
Maximum age (years): 6
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: Inclusion Criteria:

1. Subjects diagnosed with severe (type 2 or 3) hereditary VWD (VWF:RCo\<15-20 IU/dL), or VWF:Act\<15-20 IU/dL.
2. Subjects under 6 years of age.
3. 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:

1. Subjects diagnosed with acquired VWD.
2. Subjects with active bleeding at the time of the first infusion or within 10 days prior to the infusion.
3. 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.
4. 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.
5. Subjects with a known allergies/intolerance to any substance contained in Fanhdi.
6. Subjects with a known history of anaphylactic reaction(s) to blood or blood components.
7. 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.
8. 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.
9. Subjects presenting anemia (hemoglobin \<11 g/dL).
10. Subjects diagnosed with metabolic diseases that are not clinically controlled, such as diabetes mellitus, which could potentially interfere with the interpretations of the study.
11. 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.
12. 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.
13. Subjects who, in the opinion of the investigator, may have compliance problems with the protocol.

Primary outcomes:
measure: AUC^0-inf of coagulation factor VIII activity (FVIII:C)
timeFrame: Prior to the first infusion up to 72 hours postinfusion
measure: AUC^0-inf of von Willebrand factor: Ristocetin cofactor activity (VWF:RCo)
timeFrame: Prior to the first infusion up to 72 hours postinfusion
measure: AUC^0-inf of von Willebrand factor antigen (VWF:Ag)
timeFrame: Prior to the first infusion up to 72 hours postinfusion
measure: AUC^0-inf of von Willebrand factor: Collagen binding activity (VWF:CB)
timeFrame: Prior to the first infusion up to 72 hours postinfusion
measure: AUC^0-T of FVIII:C
timeFrame: Prior to the first infusion up to 72 hours postinfusion
measure: AUC^0-T of VWF:RCo
timeFrame: Prior to the first infusion up to 72 hours postinfusion
measure: AUC^0-T of VWF:Ag
timeFrame: Prior to the first infusion up to 72 hours postinfusion
measure: AUC^0-T of VWF:CB
timeFrame: Prior to the first infusion up to 72 hours postinfusion
measure: in vivo recovery of FVIII:C
timeFrame: Prior to the first infusion up to 72 hours postinfusion
measure: in vivo recovery of VWF:RCo
timeFrame: Prior to the first infusion up to 72 hours postinfusion
measure: in vivo recovery of VWF:Ag
timeFrame: Prior to the first infusion up to 72 hours postinfusion
measure: in vivo recovery of VWF:CB
timeFrame: Prior to the first infusion up to 72 hours postinfusion
measure: Half-life of FVIII:C
timeFrame: Prior to the first infusion up to 72 hours postinfusion
measure: Half-life of VWF:RCo
timeFrame: Prior to the first infusion up to 72 hours postinfusion
measure: Half-life of VWF:Ag
timeFrame: Prior to the first infusion up to 72 hours postinfusion
measure: C^max of FVIII:C
timeFrame: Prior to the first infusion up to 72 hours postinfusion
measure: C^max of VWF:RCo
timeFrame: Prior to the first infusion up to 72 hours postinfusion
measure: C^max of VWF:Ag
timeFrame: Prior to the first infusion up to 72 hours postinfusion
measure: C^max of VWF:CB
timeFrame: Prior to the first infusion up to 72 hours postinfusion
measure: T^max of FVIII:C
timeFrame: Prior to the first infusion up to 72 hours postinfusion
measure: T^max of VWF:RCo
timeFrame: Prior to the first infusion up to 72 hours postinfusion
measure: T^max of VWF:Ag
timeFrame: Prior to the first infusion up to 72 hours postinfusion
measure: T^max of VWF:CB
timeFrame: Prior to the first infusion up to 72 hours postinfusion
measure: Mean residence time of FVIII:C
timeFrame: Prior to the first infusion up to 72 hours postinfusion
measure: Mean residence time of VWF:RCo
timeFrame: Prior to the first infusion up to 72 hours postinfusion
measure: Mean residence time of VWF:Ag
timeFrame: Prior to the first infusion up to 72 hours postinfusion
measure: Mean residence time of VWF:CB
timeFrame: Prior to the first infusion up to 72 hours postinfusion
measure: Clearance of FVIII:C
timeFrame: Prior to the first infusion, 30 minutes postinfusion, 10 hours postinfusion, and at 24, 48, and 72 hours postinfusion
measure: Clearance of VWF:RCo
timeFrame: Prior to the first infusion, 30 minutes postinfusion, 10 hours postinfusion, and at 24, 48, and 72 hours postinfusion
measure: Clearance of VWF:Ag
timeFrame: Prior to the first infusion, 30 minutes postinfusion, 10 hours postinfusion, and at 24, 48, and 72 hours postinfusion
measure: Clearance of VWF:CB
timeFrame: Prior to the first infusion, 30 minutes postinfusion, 10 hours postinfusion, and at 24, 48, and 72 hours postinfusion
measure: Elimination rate constant of FVIII:C
timeFrame: Prior to the first infusion up to 72 hours postinfusion
measure: Elimination rate constant of VWF:RCo
timeFrame: Prior to the first infusion up to 72 hours postinfusion
measure: Elimination rate constant of VWF:Ag
timeFrame: Prior to the first infusion up to 72 hours postinfusion
measure: Elimination rate constant of VWF:CB
timeFrame: Prior to the first infusion up to 72 hours postinfusion
measure: Volume of distribution of FVIII:C
timeFrame: Prior to the first infusion up to 72 hours postinfusion
measure: Volume of distribution of VWF:RCo
timeFrame: Prior to the first infusion up to 72 hours postinfusion
measure: Volume of distribution of VWF:Ag
timeFrame: Prior to the first infusion up to 72 hours postinfusion
measure: Volume of distribution of VWF:CB
timeFrame: Prior to the first infusion up to 72 hours postinfusion
measure: VWF multimeric pattern
timeFrame: Prior to the first infusion up to 12 hours postinfusion
Secondary outcomes:
Other outcomes:
Locations:
city: Esplugues De Llobregat
country: Spain
facility: Hospital Sant Joan de Déu Barcelona
state: Barcelona
city: Madrid
country: Spain
facility: Hospital Universitario La Paz
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen del Rocío
city: Zaragoza
country: Spain
facility: Hospital Universitario Miguel Servet
Study officials:
References: