- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02267226
Efficacy and Safety Study of Octafibrin for On-demand Treatment of Acute Bleeding and to Prevent Bleeding During and After Surgery
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 Overview
Status
Conditions
Intervention / Treatment
Study Type
Enrollment (Actual)
Phase
- Phase 3
Contacts and Locations
Study Locations
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Sofia, Bulgaria
- Dept of Clinical Hematology for Hemorrhagic Diatheses and Anaemia, SHAT "Joan Pavel"
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Bangalore, India
- St. John's Medical College Hospital
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Pune, India
- Sahyadri Specialty Hospital
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Vellore, India
- Dept of Hematology, Christian Medical College
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Isfahan, Iran, Islamic Republic of
- Seyed Al Shohada Hospital
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Shīrāz, Iran, Islamic Republic of
- Dastgheib Hospital
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Beirut, Lebanon
- Hotel-Dieu de France
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Moscow, Russian Federation
- Haematological Scientific Center of Ministry of Healthcare of the Russian Federation
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Riyadh, Saudi Arabia
- Centre of Excellence in Thrombosis & Hemostasis, King Saud University
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Izmir, Turkey
- Dept of Haematology, Ege University Children's Hospital
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London, United Kingdom
- Centre for Haemostasis & Thrombosis, St Thomas' Hospital
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Florida
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Miami, Florida, United States, 33155
- Miami Children's Hospital
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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Experimental: Octafibrin
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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Overall Clinical Assessment of the Haemostatic Efficacy of Octafibrin in Treating the First Documented Bleeding Episode of Each Patient.
Time Frame: 24 hours after last infusion for each bleeding episode
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The first bleeding episode covers the time period from the first Octafibrin infusion until 24 hours (i.e., 1 day) after the last infusion. The investigator's overall clinical assessment of haemostatic efficacy for bleeding was based on a 4 point haemostatic efficacy scale. The final efficacy assessment of each patient was adjudicated by the Independent Data Monitoring & Endpoint Adjudication Committee (IDMEAC). |
24 hours after last infusion for each bleeding episode
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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Maximum Clot Firmness (MCF) After Fibrinogen Infusion in Each Documented Bleeding Episode (BE), Measured in Frozen Plasma in a Central Laboratory.
Time Frame: Before first infusion and 1 hour after end of first and last infusion of each documented bleeding episode
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MCF (mm) was determined using ROTEM and was used as a surrogate marker for haemostatic efficacy.
ROTEM is a method for the continuous measurement of clot formation and clot firmness.
It utilises a mechanical detection system which is based on the ability of the blood or plasma clot to form a mechanical coupling over a distance of 1 mm.
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Before first infusion and 1 hour after end of first and last infusion of each documented bleeding episode
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Fibrinogen Plasma Level
Time Frame: 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)
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Fibrinogen plasma level was assessed using the Clauss fibrinogen assay
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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)
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Response as Indicated by Incremental in Vivo Recovery (IVR)
Time Frame: Pre-infusion and 1 and 3 hours post-infusion
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Incremental IVR (response): calculated as the maximum increase in plasma fibrinogen (i.e., Clauss data) between pre-infusion and 1 and 3 hours post-infusion, divided by the exact dose of Octafibrin.
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Pre-infusion and 1 and 3 hours post-infusion
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Efficacy of Octafibrin for All Bleeding Episodes Collected in the Study
Time Frame: 24 hours after last infusion for each bleeding episode
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The investigator's overall clinical assessment of haemostatic efficacy for bleeding will be based on a 4-point haemostatic efficacy scale.
The final efficacy assessment of each patient will be adjudicated by the Independent Data Monitoring & Endpoint Adjudication Committee (IDMEAC)
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24 hours after last infusion for each bleeding episode
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Efficacy of Octafibrin in Preventing Bleeding During and After Surgery
Time Frame: 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
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The efficacy of Octafibrin will be assessed at the end of surgery by the surgeon and post-operatively by the haematologist using two 4-point haemostatic efficacy scales.
An overall efficacy assessment taking both the intra- and post-operative assessment into account will be adjudicated by the IDMEAC
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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
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Other Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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Analysis of Safety: Immunogenicity Testing for Anti-fibrinogen Antibodies
Time Frame: 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)
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Immunogenicity testing for the presence of anti-fibrinogen antibodies at Day 14 and Day 30 after the administration of Octafibrin for bleeding.
An experimental non-standard ELISA was developed for this study for evaluating anti-fibrinogen antibodies.
No specific test was performed to discern for neutralizing antibodies.
The clinical implications of the assay results are not known.
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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)
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Collaborators and Investigators
Sponsor
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- FORMA-02
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Congenital Fibrinogen Deficiency
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OctapharmaCompletedCongenital Fibrinogen DeficiencyIndia, Iran, Islamic Republic of, Lebanon
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OctapharmaRecruitingCongenital Fibrinogen DeficiencyGermany
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OctapharmaCompletedCongenital Fibrinogen Deficiency | AfibrinogenemiaIran, Islamic Republic of, United States, Bulgaria, India, Switzerland, United Kingdom
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CSL BehringCompletedCongenital Fibrinogen DeficiencyUnited States, Canada
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Hospital Clinic of BarcelonaUniversity of BarcelonaCompletedFibrinogen; Deficiency, Acquired | PHARMACOKINETICSSpain
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University Health Network, TorontoCompleted
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Laboratoire français de Fractionnement et de BiotechnologiesCompletedHypofibrinogenemia, Congenital | Afibrinogenemia, CongenitalFrance, Lebanon, Morocco, Turkey
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BiotestAccovion GmbH; ICON plc; SYNLAB Analytics and Services Germany GmbH; Phoenix Clinical... and other collaboratorsCompletedCongenital Afibrinogenemia | Congenital HypofibrinogenemiaBulgaria, Egypt, Germany, Lebanon, Tunisia
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IsalaCSL BehringCompletedFibrinogen Deficiency in Complex Cardiac SurgeryNetherlands
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Royal College of Surgeons, IrelandEnterprise Ireland; Dublin City UniversityUnknown
Clinical Trials on Octafibrin
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University Health Network, TorontoCompleted
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OctapharmaCompletedCongenital Fibrinogen DeficiencyIndia, Iran, Islamic Republic of, Lebanon
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OctapharmaCompletedCongenital Fibrinogen Deficiency | AfibrinogenemiaIran, Islamic Republic of, United States, Bulgaria, India, Switzerland, United Kingdom