Clinical trial NCT02267226: Efficacy and Safety Study of Octafibrin for On-demand Treatment of Acute Bleeding and to Prevent Bleeding During and After Surgery
Official title: Prospective, Open-label, Uncontrolled, Phase III Study to Assess the Efficacy and Safety of Octafibrin for On-demand Treatment of Acute Bleeding and to Prevent Bleeding During and After Surgery in Subjects With Congenital Fibrinogen Deficiency
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Congenital Fibrinogen Deficiency
Lead sponsor: Octapharma
Sponsor class: INDUSTRY
First posted: 2014-10-17
Enrollment: 25
Sex: ALL
Minimum age (years): 12
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of the study is to assess the efficacy and safety of Octafibrin for on-demand treatment of acute bleeding in subjects with congenital fibrinogen deficiency.


Eligibility criteria: 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.

Primary outcomes:
measure: Overall Clinical Assessment of the Haemostatic Efficacy of Octafibrin in Treating the First Documented Bleeding Episode of Each Patient.
timeFrame: 24 hours after last infusion for each bleeding episode
Secondary outcomes:
measure: Maximum Clot Firmness (MCF) After Fibrinogen Infusion in Each Documented Bleeding Episode (BE), Measured in Frozen Plasma in a Central Laboratory.
timeFrame: Before first infusion and 1 hour after end of first and last infusion of each documented bleeding episode
measure: Fibrinogen Plasma Level
timeFrame: Before (pre-infusion), 1 hour and 3 hours after the end of each subsequent infusion as well as at the time of the overall clinical assessment of haemostatic efficacy (i.e., 24 hours after the last infusion of each documented bleeding episode)
measure: Response as Indicated by Incremental in Vivo Recovery (IVR)
timeFrame: Pre-infusion and 1 and 3 hours post-infusion
measure: Efficacy of Octafibrin for All Bleeding Episodes Collected in the Study
timeFrame: 24 hours after last infusion for each bleeding episode
measure: Efficacy of Octafibrin in Preventing Bleeding During and After Surgery
timeFrame: First dose of Octafibrin administered prior to elective surgery to at least 3 post-operative days for minor and 7 post-operative days for major surgeries or last post-operative infusion, whichever comes last
Other outcomes:
measure: Analysis of Safety: Immunogenicity Testing for Anti-fibrinogen Antibodies
timeFrame: Up to 30 days (start of the first Octafibrin infusion until the end of each 30-day observation and follow-up period for on-demand treatment or until the Last Post-Operative Day in surgeries)
Locations:
city: Miami
country: United States
facility: Miami Children's Hospital
state: Florida
city: Sofia
country: Bulgaria
facility: Dept of Clinical Hematology for Hemorrhagic Diatheses and Anaemia, SHAT "Joan Pavel"
city: Bangalore
country: India
facility: St. John's Medical College Hospital
city: Pune
country: India
facility: Sahyadri Specialty Hospital
city: Vellore
country: India
facility: Dept of Hematology, Christian Medical College
city: Isfahan
country: Iran, Islamic Republic of
facility: Seyed Al Shohada Hospital
city: Shīrāz
country: Iran, Islamic Republic of
facility: Dastgheib Hospital
city: Beirut
country: Lebanon
facility: Hotel-Dieu de France
city: Moscow
country: Russian Federation
facility: Haematological Scientific Center of Ministry of Healthcare of the Russian Federation
city: Riyadh
country: Saudi Arabia
facility: Centre of Excellence in Thrombosis & Hemostasis, King Saud University
city: Izmir
country: Turkey
facility: Dept of Haematology, Ege University Children's Hospital
city: London
country: United Kingdom
facility: Centre for Haemostasis & Thrombosis, St Thomas' Hospital
Study officials:
affiliation: Octapharma
name: Cristina Solomon, MD
role: STUDY_DIRECTOR
References: