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

Von Willebrand Disease Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02472665
• Other study ID #: IG1005
• Status: Recruiting
• Phase: Phase 4
• Start date: December 2013
• Est. completion date: December 2024

Study information

• Verified date: March 2024
• Source: Grifols Therapeutics LLC
• Contact: Núria Ribó
• Email: nuria.ribo[@]grifols.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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 information / eligibility

• Status: Recruiting
• Enrollment: 8
• Est. completion date: December 2024
• Est. primary completion date: April 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 2 Months to 6 Years

Eligibility

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.

Related Conditions & MeSH terms

• Von Willebrand Disease
• Von Willebrand Diseases

Intervention

Drug:
• plasma-derived FVIII/VWF concentrate
1 single dose of 80 IU/kg VWF:RCo of Fanhdi will be administered

Locations

Country	Name	City	State
Spain	Hospital Sant Joan de Déu Barcelona	Esplugues De Llobregat	Barcelona
Spain	Hospital Universitario La Paz	Madrid
Spain	Hospital Universitario Virgen del Rocío	Sevilla
Spain	Hospital Universitario Miguel Servet	Zaragoza

Sponsors (2)

Lead Sponsor	Collaborator
Grifols Therapeutics LLC	Instituto Grifols, S.A.

Country where clinical trial is conducted

Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	in vivo recovery of FVIII:C		Prior to the first infusion up to 72 hours postinfusion
Primary	in vivo recovery of VWF:RCo		Prior to the first infusion up to 72 hours postinfusion
Primary	in vivo recovery of VWF:Ag		Prior to the first infusion up to 72 hours postinfusion
Primary	in vivo recovery of VWF:CB		Prior to the first infusion up to 72 hours postinfusion
Primary	Half-life of FVIII:C	Terminal elimination half-life	Prior to the first infusion up to 72 hours postinfusion
Primary	Half-life of VWF:RCo	Terminal elimination half-life	Prior to the first infusion up to 72 hours postinfusion
Primary	Half-life of VWF:Ag	Terminal elimination half-life	Prior to the first infusion up to 72 hours postinfusion
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	Elimination rate constant of FVIII:C		Prior to the first infusion up to 72 hours postinfusion
Primary	Elimination rate constant of VWF:RCo		Prior to the first infusion up to 72 hours postinfusion
Primary	Elimination rate constant of VWF:Ag		Prior to the first infusion up to 72 hours postinfusion
Primary	Elimination rate constant of VWF:CB		Prior to the first infusion up to 72 hours postinfusion
Primary	Volume of distribution of FVIII:C		Prior to the first infusion up to 72 hours postinfusion
Primary	Volume of distribution of VWF:RCo		Prior to the first infusion up to 72 hours postinfusion
Primary	Volume of distribution of VWF:Ag		Prior to the first infusion up to 72 hours postinfusion
Primary	Volume of distribution of VWF:CB		Prior to the first infusion up to 72 hours postinfusion
Primary	VWF multimeric pattern	For type 3 VWD subjects	Prior to the first infusion up to 12 hours postinfusion