Evaluation of the dynamic behavior, efficacy and safety of Fanhdi®, a high-purity von Willebrand containing FVIII concentrate, in pediatric patients with von Willebrand disease.

• Register: EUCTR
• Last refreshed on: 23 December 2013
• Main ID: EUCTR2012-003450-92-ES
• Date of registration: 29/11/2012
• Prospective Registration: Yes
• Primary sponsor: Instituto Grifols S.A.
• Public title: Evaluation of the dynamic behavior, efficacy and safety of Fanhdi®, a high-purity von Willebrand containing FVIII concentrate, in pediatric patients with von Willebrand disease.
• Scientific 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 PATIENTS WITH VON WILLEBRAND DISEASE - Study of Fanhdi® in pediatric patients with VWD
• Date of first enrolment: 23/11/2013
• Target sample size: 8
• Recruitment status: Authorised-recruitment may be ongoing or finished
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2012-003450-92
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no Randomised: no Open: yes Single blind: no Double blind: no Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: no Other: no

Countries of recruitment

Spain

Contacts

• Name: Fanhdi pediatric study VWD
• Affiliation: Instituto Grifols S.A.

• Name: Fanhdi pediatric study VWD
• Affiliation: Instituto Grifols S.A.

Key inclusion & exclusion criteria

Inclusion criteria:
1. Patients diagnosed with severe hereditary von Willebrand's disease (VWF:RCof<20 IU/dl) type 1, 2 or 3, independent of prior treatment
2. Patients less than 6 years of age
3. Patients that do not adequately respond to treatment with desmopressin
4. Positive anti-HBs and anti-HAV antibodies due to prior exposure or vaccination. If negative, vaccination to hepatitis A and B with be initiated before the first infusion of Fanhdi®
5. Signed informed consent by the patient's legal representative (mother, father o tutor)
Are the trial subjects under 18? yes
Number of subjects for this age range: 8
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
1. The subject has been diagnosed of acquired VWD2. Patients bleeding at the time of the first infusion or the 10 days prior to the infusion
3. Subjects treated with desmopressin or another VWF containing FVIII concentrate during the 5 days prior to the infusion of the investigational product
4. The subject is known or suspected to have present or past inhibitor activity (antibodies) directed against FVIII or VWF
5. The subject is known to have history of intolerance to any Fanhdi® containing substance
6. The subject is known to have history of anaphylactic reaction(s) to blood or blood components
7. Subjects presenting severe platelet dysfunctions due to drugs (aspirin, other NSAIDs, etc.) or other pathologies (uremic thrombopathy, hematological diseases)
8. Immunocompromised subjects or HIV positive that have less than 400 CD4+/?l, a viral load >400 copies/ml, platelet count lower than 100x10·9/l, present any additional factor that elevates the risk of bleeding or that have a life expectancy less than 1 year
9. Subjects presenting 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. The subject is participating in another clinical study involving an investigational treatment, or participated within the past month
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
14. Any subject that does not dispose of a frozen plasma sample prior to the first infusion of Fanhdi®


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Severe von Willebrand disease including types I, II, and III with VWF:RCof <15-20%
MedDRA version: 14.1 Level: PT Classification code 10068986 Term: Von Willebrand's factor activity decreased System Organ Class: 10022891 - Investigations
MedDRA version: 14.1 Level: PT Classification code 10047715 Term: Von Willebrand's disease System Organ Class: 10010331 - Congenital, familial and genetic disorders
MedDRA version: 14.1 Level: LLT Classification code 10055168 Term: Von Willebrand's factor deficiency System Organ Class: 10010331 - Congenital, familial and genetic disorders

Therapeutic area: Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16]

Intervention(s)

Trade Name: Fanhdi
Pharmaceutical Form: Concentrate and solvent for solution for injection

Primary Outcome(s)

Primary end point(s): 1. Determine the half-life and in vivo recovery of VWF:RCof and VWF:Ag, the half-life and the apparent in vivo recovery of FVIII:C, and other pharmacokinetic parameters after a single dose of Fanhdi® in pediatric patients with severe VWD.
2. Determine the clinical efficacy of Fanhdi® as replacement therapy in preventing excessive bleeding during spontaneous or traumatic induced bleeding episodes through the study of the duration and severity of the bleed, achievement of hemostasis, total number of infusions and doses administered for each bleeding episode.
3. Determine the clinical efficacy of Fanhdi® as replacement therapy in preventing excessive bleeding in patients who undergo surgical procedures or invasive procedures through the study of the duration and seriousness of bleeding episodes and the achievement of hemostasis.

Main Objective: 1. Evaluate the in vivo recovery and the pharmacokinetic profile of Fanhdi® in a pediatric population (<6 years of age) with severe von Willebrand disease
2. Evaluate the efficacy of the product as a treatment for bleeds.
3. Evaluate the efficacy of the product as prophylaxis for surgeries.

Secondary Objective: 1. Determine the long term clinical efficacy of prophylactic and/or on-demand treatment.
2. Evaluate the clinical safety, as well as the immunogenicity and thrombogenicity of the product.
3. Evaluate the tolerance to the product administration

Timepoint(s) of evaluation of this end point: 1. Pharmacokinetic parameters will be assessed within a maximum of 15 days after the recruitment visit. Subjects with type III VWD will undergo a second pharmacokinetic study 6 months after the first PK analysis.
2. Whenever a bleeding treated in the hospital occurs throughout the 12 month follow-up period.
3. Whenever a surgery or invasive procedure occurs throughout the 12 month follow-up period.

Secondary Outcome(s)

Secondary end point(s): 1. Evaluate long term clinical efficacy of profilaxis and/or long term demand studying concentrates requirements and the number of haemorragic epsiodes treated.
2. Evaluate product's clinical security, inmunogenicity and trombogenicity detecting presence of FVIII and FVW inhibitors and evaluating clinical trombosis in patients undergoing quirurgic or invasive procedures.
3. Evaluate the product's administration tolerance detecting adverese reactions, including clinically significant changes in vital signs or lab paramenters.

Timepoint(s) of evaluation of this end point: 1. The clinical safety and tolerance to Fanhdi will be assessed since recruitment and throughout the 12 month follow-up period.
2. Immunogenicity will be measured before the first infusion of the investigational product, every three months throughout the follow-up period and when there exists a clinical suspicion of the formation of inhibitors.
3. Thrombogenicity will be measured in all subjects undergoing surgery or an invasive procedure.

Secondary ID(s)

IG1005

Source(s) of Monetary Support

Instituto Grifols S.A.