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

NCT02472665 | Recruiting Phase 4

• 1 other identifier: IG1005
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 4

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).

Conditions

Von Willebrand Disease

Keywords

pediatric; plasma-derived FVIII concentrate

Outcome Measures

Primary Outcomes (40)

• 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

Study Arms (1)

plasma-derived FVIII/VWF concentrate

EXPERIMENTAL

Pharmacokinetic single dose study with Fanhdi (high-purity Von Willebrand containing FVIII concentrate)

Drug: plasma-derived FVIII/VWF concentrate

Interventions

plasma-derived FVIII/VWF concentrate DRUG

1 single dose of 80 IU/kg VWF:RCo of Fanhdi will be administered

Also known as: Fanhdi

plasma-derived FVIII/VWF concentrate

Eligibility Criteria

• Age: 2 Months - 6 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Grifols Therapeutics LLC: lead
• Instituto Grifols, S.A.: collaborator

Study Sites (4)

Hospital Sant Joan de Déu Barcelona

Esplugues de Llobregat, Barcelona, 08950, Spain

RECRUITING

Hospital Universitario La Paz

Madrid, Spain

RECRUITING

Hospital Universitario Virgen del Rocío

Seville, 41013, Spain

RECRUITING

Hospital Universitario Miguel Servet

Zaragoza, Spain

RECRUITING

MeSH Terms

Conditions

von Willebrand Diseases

Condition Hierarchy (Ancestors)

Blood Coagulation Disorders, Inherited; Blood Coagulation Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Coagulation Protein Disorders; Blood Platelet Disorders; Hemorrhagic Disorders; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Central Study Contacts

Núria Ribó

CONTACT

nuria.ribo@grifols.com

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 10, 2015
• First Posted: June 16, 2015
• Study Start: December 1, 2013
• Primary Completion: April 1, 2025
• Study Completion (Estimated): December 1, 2026
• Last Updated: July 8, 2024

Record last verified: 2024-07

Locations

ES (4)