A fibrinogen concentrate study in paediatric patients with inherited fibrinogen deficiency

• Register: EUCTR
• Last refreshed on: 7 April 2014
• Main ID: EUCTR2013-000261-36-Outside-EU/EEA
• Date of registration: 04/04/2014
• Prospective Registration: Yes
• Primary sponsor: LFB Biotechnologies
• Public title: A fibrinogen concentrate study in paediatric patients with inherited fibrinogen deficiency
• Scientific title: Clinical pharmacology, efficacy and safety study of FGTW in paediatric patients with severe congenital fibrinogen deficiency
• Target sample size: 12
• Recruitment status: NA
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2013-000261-36
• 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

Lebanon, Morocco, Turkey

Contacts

• Name: Clinical trial information desk
• Affiliation: LFB Biotechnologies

• Name: Clinical trial information desk
• Affiliation: LFB Biotechnologies

Key inclusion & exclusion criteria

Inclusion criteria:
1. Signed and dated informed consent form by parents or a legal representative
2. Age 12 years old
3. Patients with inherited afibrinogenaemia (fibrinogen antigen levels 0.2 g/L and unclottable PT, aPTT and TT) or severe hypofibrinogenaemia defined as fibrinogen antigen levels 0.5 g/L and activity to antigen ratio ˜ 1
4. Negative results on HCG-based pregnancy test at the selection visit, before PK/PD part and before each event to be treated for females of childbearing potential (presence of menstruation)
5. Covered by healthcare insurance in accordance with local requirements

Are the trial subjects under 18? yes
Number of subjects for this age range: 12
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. Dysfibrinogenaemia
2. Acquired fibrinogen deficiency
3. Suspected present or past anticoagulation inhibitor
4. Personal history of venous or arterial thrombosis or thromboembolic event
5. Co-morbidity with other/unrelated coagulopathies
6. Administration of any fibrinogen concentrate or fibrinogen containing blood product during the last 15 days (applicable only if fibrinogen levels to be measured at inclusion)
7. Platelet count less than 100 x 109/L
8. Serum creatinine > 2 times the upper limit of normal
9. AST and / or ALT > 5 times the upper limit of normal
10. Known history of hypersensitivity or other severe reaction to any component of the investigational medicinal product
11. Any other condition which, in the opinion of the investigator, could interfere with the study results or would not be in the best interest of the patient.
12. Participation in another drug clinical trial at the same time or within the previous 30 days
13. Anticipated poor compliance with study procedures
14. Legal incapacity or limited capacity
15. Permanent treatment with antithrombotic or anti-platelet agents such as heparins, anti-IIa or anti-Xa agents, aspirin, clopidogrel and NSAIDs.
Additional exclusion criteria specific to PK/PD Part
1. Patients with hypofibrinogenaemia defined as fibrinogen antigen levels 0.5 g/L and activity to antigen ratio ˜ 1
2. Significant bleeding(s) within 7 days prior to the start of the PK/PD part that could have an impact on the patient's plasma volume
3. Administration of any fibrinogen concentrate or fibrinogen containing blood product during the last 15 days prior to the start of the PK/PD part
4. Treatment with antithrombotic or anti-platelet agents such as heparins, anti-IIa or anti-Xa agents, aspirin, clopidogrel and NSAIDs within 10 days prior to the start of the PK/PD part.
5. Elective surgery within 14 days after administration of FGTW for PK/PD part



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

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Blood and lymphatic diseases [C15]

Afibrinogenaemia or severe hypofibrinogenaemia
MedDRA version: 16.1 Level: LLT Classification code 10052651 Term: Afibrinogenaemia System Organ Class: 100000004850
MedDRA version: 16.1 Level: PT Classification code 10051125 Term: Hypofibrinogenaemia System Organ Class: 10005329 - Blood and lymphatic system disorders

Intervention(s)

Trade Name: CLOTTAFACT 1.5 g/100ml, powder and solvent for infusion
Product Name: Clottafact
Product Code: FGTW
Pharmaceutical Form: Powder and solvent for solution for infusion

Primary Outcome(s)

Secondary Objective: The secondary objectives are:
- to assess the pharmacokinetic (PK) and pharmacodynamic (PD) properties of FGTW.
- to assess the safety of FGTW

Main Objective: The primary objective of the study is to assess the efficacy of FGTW as a replacement therapy in paediatric patients with afibrinogenaemia or severe hypofibrinogenaemia:
? in preventing excessive bleeding in patients undergoing a surgical procedure,
? in treating bleeding of non-surgical origin

Timepoint(s) of evaluation of this end point: At the end of each treatment episode:
- at 24h-48h after treatment when the patient is not hospitalised,
- at the day of hospital discharge when the patient is hospitalised.

Primary end point(s): The primary endpoint will be the investigator’s overall assessment of the efficacy of FGTW on haemostasis at the end of each treatment episode (at 24h-48h after treatment when the patient is not hospitalised, or at the day of hospital discharge when the patient is hospitalised).
Surgical Event:
The investigator’s overall assessment of the efficacy of FGTW on haemostasis will be rated using the following 4-point scale :
• Excellent: bleeding similar to that expected in a normal subjects,
• Good: mild excessive bleeding,
• Moderate: moderate but controlled excessive bleeding,
• None: severe, uncontrolled bleeding.
and will take into account the following parameters (when applicable):
- Assessment of haemostatic efficacy of FGTW rated by the surgeon or a qualified physician at the end of the surgical procedure and on a daily basis using the same 4-point scale described above,
- Blood loss (comparison of predicted and actual volumes), unless it cannot be measured (e.g. dental surgery),
- Haemoglobin levels and blood product transfusion units used according to standard care,
- Daily medical examination,
- Amounts of administered FGTW.

Bleeding Event Study:
The investigator’s overall assessment of the efficacy of FGTW on haemostasis will be rated using the following 4-point scale :
• Excellent: bleeding stopped immediately,
• Good: bleeding stopped within the expected time period,
• Moderate: bleeding was controlled with difficulty,
• None: uncontrolled bleeding or need of other haemostatic treatments.
and will take into account the following parameters (when applicable):
- Daily assessment of haemostatic efficacy of FGTW rated by a qualified physician using the same 4-point scale described above,
- Haemoglobin levels and blood product transfusion units used according to standard care,
- Daily medical examination,
- Amounts of administered FGTW.

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: The timepoints of evaluation of secondary endpoints are variable (the individual timepoints and periods are described in the synopsis and flow charts of the study protocol).

Secondary end point(s): Efficacy:
- Daily assessment of haemostatic efficacy of FGTW using the 4-point surgical/bleeding scales described above,
- Amounts of administered FGTW,
- Plasma levels of fibrinogen activity after infusion,
- Time to wound healing, if applicable,
- ROTEM® FIBTEM assay parameters in frozen plasma.

Clinical Pharmacology:
- Fibrinogen plasma concentrations determined by the Clauss method and the nephelometric method.
- Pharmacodynamic profile will be assessed by measuring FIBTEM-MCF (ROTEM®) over time in frozen plasma. TT, PT, aPTT will also be measured.
- Based on a prior PK model obtained from another clinical study with afibrinogenaemic adults, individual fibrinogen values will be reconstructed by Bayesian analysis, and primary PK model parameters will be estimated (e.g. CL (L/h), and Vss (L)). Secondary PK parameters will be derived: Cmax, tmax, AUC, and terminal half-life.
-Incremental recovery will also be calculated.

Safety:
Safety will be assessed throughout the study until the last visit of the patient by incidence, nature, severity, seriousness, outcome, relationship to IMP of adverse events and changes in physical examination findings, clinical laboratory tests, and vital sign measurements.

Secondary ID(s)

FGTW-1004

2013-000261-36-FR

Source(s) of Monetary Support

LFB Biotechnologies