Efficacy and Safety Study of Octafibrin for On-demand Treatment of Acute Bleeding and to Prevent Bleeding During and After Surgery

Inclusion Criteria:

- Aged ≥12 years (only 18 and above in Russia)

- Documented diagnosis of congenital fibrinogen deficiency, expected to require
on-demand treatment for bleeding or surgical prophylaxis:

- Fibrinogen deficiency manifested as afibrinogenaemia or severe hypofibrinogenaemia.

- 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 or legal guardian.

Exclusion Criteria:

- Life expectancy <6 months.

- Bleeding disorder other than congenital fibrinogen deficiency, including
dysfibrinogenaemia.

- Prophylactic treatment with a fibrinogen concentrate.

Treatment with:

- Any fibrinogen concentrate or other fibrinogen-containing blood product within 2 weeks
prior to start of treatment for the bleeding episode or surgery.

- Any coagulation-active drug (i.e., non-steroidal anti-inflammatory drugs, warfarin,
coumarin derivatives, platelet aggregation inhibitors) within 1 week prior to start of
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.

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).

Pregnant women within the first 20 weeks of gestation.

Currently breast-feeding.

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

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

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

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, prednisone (equivalent to >10 mg/day), or similar drugs at
study start.

- Subjects having evidence or a history (within the previous 12 months) of abuse of any
licit or illicit drug substance.

Participation in another interventional clinical study currently or during the past 4
weeks.