Efficacy and Safety of Fanhdi®, a High-purity Von Willebrand Containing FVIII Concentrate, in Pediatric Patients With Von Willebrand Disease

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

Multicenter, prospective, non-controlled study in a pediatric cohort (<6 years-old) with severe (type 2 or 3) hereditary Von Willebrand Disease (VWD).

Study Overview

• Status: Recruiting
• Conditions: Von Willebrand Disease
• Intervention / Treatment: Drug: plasma-derived FVIII/VWF concentrate

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.

• Study Type: Interventional
• Enrollment (Estimated): 8
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Núria Ribó; Email: nuria.ribo@grifols.com

Study Locations

• Spain
  • Madrid, Spain
    • Recruiting
    • Hospital Universitario La Paz
    • Contact: Jiménez-Yuste, MD
  • Sevilla, Spain, 41013
    • Recruiting
    • Hospital Universitario Virgen Del Rocio
    • Principal Investigator: Ramiro Núñez, MD
  • Zaragoza, Spain
    • Recruiting
    • Hospital Universitario Miguel Servet
    • Contact: Fernández Monteserín, MD
  • Barcelona
    • Esplugues De Llobregat, Barcelona, Spain, 08950
      • Recruiting
      • Hospital Sant Joan de Déu Barcelona
      • Contact: Berrueco Moreno, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 months to 6 years (Child)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: plasma-derived FVIII/VWF concentrate; Pharmacokinetic single dose study with Fanhdi (high-purity Von Willebrand containing FVIII concentrate)	Drug: plasma-derived FVIII/VWF concentrate; 1 single dose of 80 IU/kg VWF:RCo of Fanhdi will be administered; Other Names: Fanhdi

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
AUC^0-inf of coagulation factor VIII activity (FVIII:C)	Cumulative area under the concentration time curve extrapolated to infinity of FVIII:C	Prior to the first infusion up to 72 hours postinfusion
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	Prior to the first infusion up to 72 hours postinfusion
AUC^0-inf of von Willebrand factor antigen (VWF:Ag)	Cumulative area under the concentration time curve extrapolated to infinity of VWF:Ag	Prior to the first infusion up to 72 hours postinfusion
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	Prior to the first infusion up to 72 hours postinfusion
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	Prior to the first infusion up to 72 hours postinfusion
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	Prior to the first infusion up to 72 hours postinfusion
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	Prior to the first infusion up to 72 hours postinfusion
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	Prior to the first infusion up to 72 hours postinfusion
in vivo recovery of FVIII:C		Prior to the first infusion up to 72 hours postinfusion
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
in vivo recovery of VWF:CB		Prior to the first infusion up to 72 hours postinfusion
Half-life of FVIII:C	Terminal elimination half-life	Prior to the first infusion up to 72 hours postinfusion
Half-life of VWF:RCo	Terminal elimination half-life	Prior to the first infusion up to 72 hours postinfusion
Half-life of VWF:Ag	Terminal elimination half-life	Prior to the first infusion up to 72 hours postinfusion
C^max of FVIII:C	Maximum observed plasma and/or serum concentration of FVIII:C	Prior to the first infusion up to 72 hours postinfusion
C^max of VWF:RCo	Maximum observed plasma and/or serum concentration of VWF:RCo	Prior to the first infusion up to 72 hours postinfusion
C^max of VWF:Ag	Maximum observed plasma and/or serum concentration of VWF:Ag	Prior to the first infusion up to 72 hours postinfusion
C^max of VWF:CB	Maximum observed plasma and/or serum concentration of VWF:CB	Prior to the first infusion up to 72 hours postinfusion
T^max of FVIII:C	Time of maximum observed plasma and/or serum concentration of FVIII:C	Prior to the first infusion up to 72 hours postinfusion
T^max of VWF:RCo	Time of maximum observed plasma and/or serum concentration of VWF:RCo	Prior to the first infusion up to 72 hours postinfusion
T^max of VWF:Ag	Time of maximum observed plasma and/or serum concentration of VWF:Ag	Prior to the first infusion up to 72 hours postinfusion
T^max of VWF:CB	Time of maximum observed plasma and/or serum concentration of VWF:CB	Prior to the first infusion up to 72 hours postinfusion
Mean residence time of FVIII:C	Average amount of time that a single molecule of drug stays in the body.	Prior to the first infusion up to 72 hours postinfusion
Mean residence time of VWF:RCo	Average amount of time that a single molecule of drug stays in the body of VWF:RCo	Prior to the first infusion up to 72 hours postinfusion
Mean residence time of VWF:Ag	Average amount of time that a single molecule of drug stays in the body of VWF:Ag	Prior to the first infusion up to 72 hours postinfusion
Mean residence time of VWF:CB	Average amount of time that a single molecule of drug stays in the body of VWF:CB	Prior to the first infusion up to 72 hours postinfusion
Clearance of FVIII:C	Total plasma and/or serum clearance	Prior to the first infusion, 30 minutes postinfusion, 10 hours postinfusion, and at 24, 48, and 72 hours postinfusion
Clearance of VWF:RCo	Total plasma and/or serum clearance	Prior to the first infusion, 30 minutes postinfusion, 10 hours postinfusion, and at 24, 48, and 72 hours postinfusion
Clearance of VWF:Ag	Total plasma and/or serum clearance	Prior to the first infusion, 30 minutes postinfusion, 10 hours postinfusion, and at 24, 48, and 72 hours postinfusion
Clearance of VWF:CB	Total plasma and/or serum clearance	Prior to the first infusion, 30 minutes postinfusion, 10 hours postinfusion, and at 24, 48, and 72 hours postinfusion
Elimination rate constant of FVIII:C		Prior to the first infusion up to 72 hours postinfusion
Elimination rate constant of VWF:RCo		Prior to the first infusion up to 72 hours postinfusion
Elimination rate constant of VWF:Ag		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
Volume of distribution of FVIII:C		Prior to the first infusion up to 72 hours postinfusion
Volume of distribution of VWF:RCo		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
Volume of distribution of VWF:CB		Prior to the first infusion up to 72 hours postinfusion
VWF multimeric pattern	For type 3 VWD subjects	Prior to the first infusion up to 12 hours postinfusion

Collaborators and Investigators

• Sponsor: Grifols Therapeutics LLC
• Collaborators: Instituto Grifols, S.A.

Study record dates

Study Major Dates

• Study Start: December 1, 2013
• Primary Completion (Estimated): April 1, 2024
• Study Completion (Estimated): December 1, 2024

Study Registration Dates

• First Submitted: June 10, 2015
• First Submitted That Met QC Criteria: June 15, 2015
• First Posted (Estimated): June 16, 2015

Study Record Updates

• Last Update Posted (Actual): March 13, 2024
• Last Update Submitted That Met QC Criteria: March 11, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: pediatric; plasma-derived FVIII concentrate
• Additional Relevant MeSH Terms: Hematologic Diseases; Blood Coagulation Disorders, Inherited; Coagulation Protein Disorders; Hemorrhagic Disorders; Genetic Diseases, Inborn; Blood Coagulation Disorders; Blood Platelet Disorders; Von Willebrand Diseases
• Other Study ID Numbers: IG1005

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No