Study to Assess the Efficacy, Safety and Pharmacokinetic of Octafibrin in Paediatric Subjects With Fibrinogen Deficiency

Prospective, Open-label, Uncontrolled, Phase III Study to Assess the Efficacy, Safety and Pharmacokinetic of Octafibrin for On-demand Treatment of Acute Bleeding and to Prevent Bleeding During and After Surgery in Paediatric Subjects With Congenital Fibrinogen Deficiency

This study will assess the efficacy of Octafibrin, a fibrinogen concentrate in in the on-demand treatment of spontaneous or traumatic bleeding episodes in paediatric patients less than 12 years of age.The planned study duration is up to 5 years. The study will be considered completed when a minimum of 6 subjects (i.e., at least 3 subjects aged between 0 and <6 years and 3 subjects aged between 6 and <12 years) have at least one documented bleeding episode and when in total a minimum of 2 surgical procedures have been performed.

All patients will undergo a pharmacokinetic (PK) study after screening. This will have a duration of 14 days, after which a patient can be treated for a bleeding episode or planned surgical procedure when they occur.

Inclusion Criteria:

• Aged <12 years (at the start of treatment).
• Documented diagnosis of congenital fibrinogen deficiency, expected to require on-demand treatment for bleeding or surgical prophylaxis:
• Fibrinogen deficiency manifested as afibrinogenaemia or severe hypofibrino-genaemia.
• Historical plasma fibrinogen activity of <50 mg/dL or levels below the limit of detection of the local assay method.
• Expected to have an acute bleeding episode (spontaneous or after trauma) or planning to undergo elective surgery.
• Informed consent signed by the subject's legal guardian.

Exclusion Criteria:

1. Life expectancy <6 months.

2. Bleeding disorder other than congenital fibrinogen deficiency, including dysfi-brinogenaemia.

3. Prophylactic treatment with a fibrinogen concentrate.

4. Treatment with:

   • Any fibrinogen concentrate or other fibrinogen-containing blood product within 2 weeks prior to start of treatment for the PK phase, a bleeding episode, or surgery.
   • Any coagulation-active drug (i.e., non-steroidal anti-inflammatory drugs, war-farin, coumarin derivatives, platelet aggregation inhibitors) within 1 week prior to start of the PK phase or treatment for the bleeding episode or surgery, or as a planned or expected medication during the time period from Day 1 until 24 hours (i.e., 1 day) after the last Octafibrin infusion.

5. Presence or history of:

   • Hypersensitivity to study medication.
   • Deep vein thrombosis or pulmonary embolism within 1 year prior to start of treatment for the bleeding episode or surgery.
   • Arterial thrombosis within 1 year prior to start of treatment for the bleeding episode or surgery
   • Hypersensitivity to human plasma proteins.
   • Oesophageal varicose bleeding.
   • End-stage liver disease (i.e., Child-Pugh score B or C).

6. Known positive HIV infection with a viral load >200 particles/μL or >400,000 copies/mL.

7. Polytrauma 1 year prior to start of treatment for the bleeding episode or surgery.

8. Diagnosis or suspicion of a neutralizing anti-fibrinogen inhibitor currently or any time in the past.

9. Acute or chronic medical condition which may, in the opinion of investigator, affect the conduct of the study, including subjects receiving immune-modulating drugs (other than anti-retroviral chemotherapy), such as alpha-interferon, predni-sone (equivalent to >10 mg/day), or similar drugs, at study start.

10. Treatment with IMP in another interventional clinical study currently or during the past 4 weeks.