Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02472665
Recruitment Status : Recruiting
First Posted : June 16, 2015
Last Update Posted : July 10, 2019
Sponsor:
Collaborator:
Instituto Grifols, S.A.
Information provided by (Responsible Party):
Grifols Therapeutics LLC

Brief Summary:
Multicenter, prospective, non-controlled study in a pediatric cohort (<6 years-old) with severe Von Willebrand Disease (VWD).

Condition or disease Intervention/treatment Phase
Von Willebrand Disease Drug: plasma-derived FVIII/VWF concentrate Phase 4

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 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.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 8 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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 Start Date : December 2013
Estimated Primary Completion Date : April 2020
Estimated Study Completion Date : April 2020

Resource links provided by the National Library of Medicine


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 Name: Fanhdi




Primary Outcome Measures :
  1. AUC^0-inf of coagulation factor VIII activity (FVIII:C) [ Time Frame: Prior to the first infusion up to 72 hours postinfusion ]
    Cumulative area under the concentration time curve extrapolated to infinity of FVIII:C

  2. AUC^0-inf of von Willebrand factor: Ristocetin cofactor activity (VWF:RCo) [ Time Frame: Prior to the first infusion up to 72 hours postinfusion ]
    Cumulative area under the concentration time curve extrapolated to infinity of VWF:RCo

  3. AUC^0-inf of von Willebrand factor antigen (VWF:Ag) [ Time Frame: Prior to the first infusion up to 72 hours postinfusion ]
    Cumulative area under the concentration time curve extrapolated to infinity of VWF:Ag

  4. AUC^0-inf of von Willebrand factor: Collagen binding activity (VWF:CB) [ Time Frame: Prior to the first infusion up to 72 hours postinfusion ]
    Cumulative area under the concentration time curve extrapolated to infinity of VWF:CB

  5. AUC^0-T of FVIII:C [ Time Frame: 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

  6. AUC^0-T of VWF:RCo [ Time Frame: 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

  7. AUC^0-T of VWF:Ag [ Time Frame: 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

  8. AUC^0-T of VWF:CB [ Time Frame: 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

  9. in vivo recovery of FVIII:C [ Time Frame: Prior to the first infusion up to 72 hours postinfusion ]
  10. in vivo recovery of VWF:RCo [ Time Frame: Prior to the first infusion up to 72 hours postinfusion ]
  11. in vivo recovery of VWF:Ag [ Time Frame: Prior to the first infusion up to 72 hours postinfusion ]
  12. in vivo recovery of VWF:CB [ Time Frame: Prior to the first infusion up to 72 hours postinfusion ]
  13. Half-life of FVIII:C [ Time Frame: Prior to the first infusion up to 72 hours postinfusion ]
    Terminal elimination half-life

  14. Half-life of VWF:RCo [ Time Frame: Prior to the first infusion up to 72 hours postinfusion ]
    Terminal elimination half-life

  15. Half-life of VWF:Ag [ Time Frame: Prior to the first infusion up to 72 hours postinfusion ]
    Terminal elimination half-life

  16. C^max of FVIII:C [ Time Frame: Prior to the first infusion up to 72 hours postinfusion ]
    Maximum observed plasma and/or serum concentration of FVIII:C

  17. C^max of VWF:RCo [ Time Frame: Prior to the first infusion up to 72 hours postinfusion ]
    Maximum observed plasma and/or serum concentration of VWF:RCo

  18. C^max of VWF:Ag [ Time Frame: Prior to the first infusion up to 72 hours postinfusion ]
    Maximum observed plasma and/or serum concentration of VWF:Ag

  19. C^max of VWF:CB [ Time Frame: Prior to the first infusion up to 72 hours postinfusion ]
    Maximum observed plasma and/or serum concentration of VWF:CB

  20. T^max of FVIII:C [ Time Frame: Prior to the first infusion up to 72 hours postinfusion ]
    Time of maximum observed plasma and/or serum concentration of FVIII:C

  21. T^max of VWF:RCo [ Time Frame: Prior to the first infusion up to 72 hours postinfusion ]
    Time of maximum observed plasma and/or serum concentration of VWF:RCo

  22. T^max of VWF:Ag [ Time Frame: Prior to the first infusion up to 72 hours postinfusion ]
    Time of maximum observed plasma and/or serum concentration of VWF:Ag

  23. T^max of VWF:CB [ Time Frame: Prior to the first infusion up to 72 hours postinfusion ]
    Time of maximum observed plasma and/or serum concentration of VWF:CB

  24. Mean residence time of FVIII:C [ Time Frame: Prior to the first infusion up to 72 hours postinfusion ]
    Average amount of time that a single molecule of drug stays in the body.

  25. Mean residence time of VWF:RCo [ Time Frame: 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

  26. Mean residence time of VWF:Ag [ Time Frame: 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

  27. Mean residence time of VWF:CB [ Time Frame: 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

  28. Clearance of FVIII:C [ Time Frame: 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

  29. Clearance of VWF:RCo [ Time Frame: 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

  30. Clearance of VWF:Ag [ Time Frame: 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

  31. Clearance of VWF:CB [ Time Frame: 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

  32. Elimination rate constant of FVIII:C [ Time Frame: Prior to the first infusion up to 72 hours postinfusion ]
  33. Elimination rate constant of VWF:RCo [ Time Frame: Prior to the first infusion up to 72 hours postinfusion ]
  34. Elimination rate constant of VWF:Ag [ Time Frame: Prior to the first infusion up to 72 hours postinfusion ]
  35. Elimination rate constant of VWF:CB [ Time Frame: Prior to the first infusion up to 72 hours postinfusion ]
  36. Volume of distribution of FVIII:C [ Time Frame: Prior to the first infusion up to 72 hours postinfusion ]
  37. Volume of distribution of VWF:RCo [ Time Frame: Prior to the first infusion up to 72 hours postinfusion ]
  38. Volume of distribution of VWF:Ag [ Time Frame: Prior to the first infusion up to 72 hours postinfusion ]
  39. Volume of distribution of VWF:CB [ Time Frame: Prior to the first infusion up to 72 hours postinfusion ]
  40. VWF multimeric pattern [ Time Frame: Prior to the first infusion up to 12 hours postinfusion ]
    For type 3 VWD subjects



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   2 Months to 6 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Subjects diagnosed with severe hereditary VWD (VWF:RCo<15-20 IU/dL) of any type
  2. Subjects less than 6 years of age
  3. Subjects that do not adequately respond to treatment with desmopressin (DDAVP) or had a previous treatment failure with DDAVP
  4. Signed informed consent form provided by an authorized representative on behalf of the subject in accordance with local law and institutional policy.

Exclusion Criteria:

  1. Subject has been diagnosed of acquired VWD
  2. Subjects bleeding at the time of the first infusion or the 10 days prior to the infusion
  3. Subjects treated with DDAVP or another FVIII containing VWF concentrate during the 5 days prior to the infusion of the Fanhdi. This may be reduced to 3 days for subjects with type 3 VWD.
  4. Subject is known or suspected to have present or past inhibitor activity (antibodies) directed against FVIII or VWF
  5. Subject is known to have history of intolerance to any Fanhdi® containing substance
  6. Subject is known to have history of anaphylactic reaction(s) to blood or blood components
  7. Subjects presenting with severe platelet dysfunctions due to drugs (aspirin, other NSAIDs, etc.) or other pathologies (uremic thrombopathy, hematological diseases)
  8. Subjects with known previous infection with Hepatitis A Virus (HAV), Hepatitis B Virus (HBV), Hepatitic C Virus (HCV), or HIV or clinical signs and symptoms consistent with current HAV, HBV, HCV or HIV infection.
  9. Subjects presenting with anemia (hemoglobulin <11 g/dL)
  10. Subjects diagnosed with metabolic diseases that are not clinically controlled, such as diabetes mellitus, that could potentially interfere with the interpretations of the study
  11. Subjects participating in another clinical study within 30 days prior to screening or has received any investigational treatment within 3 months prior to screening
  12. If it is anticipated that the subject will be treated with other products containing FVIII or VWF different from Fanhdi® during a period of one year
  13. The subject is unlikely to adhere to the protocol requirements of the study

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02472665


Contacts
Layout table for location contacts
Contact: Núria Ribó nuria.ribo@grifols.com

Locations
Layout table for location information
Spain
Hospital Universitario Virgen del Rocío Recruiting
Sevilla, Spain, 41013
Principal Investigator: Ramiro Núñez, MD         
Sponsors and Collaborators
Grifols Therapeutics LLC
Instituto Grifols, S.A.

Layout table for additonal information
Responsible Party: Grifols Therapeutics LLC
ClinicalTrials.gov Identifier: NCT02472665     History of Changes
Other Study ID Numbers: IG1005
First Posted: June 16, 2015    Key Record Dates
Last Update Posted: July 10, 2019
Last Verified: July 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Grifols Therapeutics LLC:
pediatric
plasma-derived FVIII concentrate
Additional relevant MeSH terms:
Layout table for MeSH terms
Von Willebrand Diseases
Blood Coagulation Disorders, Inherited
Blood Coagulation Disorders
Hematologic Diseases
Coagulation Protein Disorders
Blood Platelet Disorders
Hemorrhagic Disorders
Genetic Diseases, Inborn
Factor VIII
Coagulants