Back to resultsEfficacy and Safety Study of Octafibrin for On-demand Treatment of Acute Bleeding and to Prevent Bleeding During and After Surgery
Primary Purpose
Congenital Fibrinogen Deficiency
Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Octafibrin
Sponsored by
About this trial
This is an interventional treatment trial for 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.
Sites / Locations
- Miami Children's Hospital
- Dept of Clinical Hematology for Hemorrhagic Diatheses and Anaemia, SHAT "Joan Pavel"
- St. John's Medical College Hospital
- Sahyadri Specialty Hospital
- Dept of Hematology, Christian Medical College
- Seyed Al Shohada Hospital
- Dastgheib Hospital
- Hotel-Dieu de France
- Haematological Scientific Center of Ministry of Healthcare of the Russian Federation
- Centre of Excellence in Thrombosis & Hemostasis, King Saud University
- Dept of Haematology, Ege University Children's Hospital
- Centre for Haemostasis & Thrombosis, St Thomas' Hospital
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Octafibrin
Arm Description
Outcomes
Primary Outcome Measures
Overall Clinical Assessment of the Haemostatic Efficacy of Octafibrin in Treating the First Documented Bleeding Episode of Each Patient.
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).
Secondary Outcome Measures
Maximum Clot Firmness (MCF) After Fibrinogen Infusion in Each Documented Bleeding Episode (BE), Measured in Frozen Plasma in a Central Laboratory.
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.
Fibrinogen Plasma Level
Fibrinogen plasma level was assessed using the Clauss fibrinogen assay
Response as Indicated by Incremental in Vivo Recovery (IVR)
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.
Efficacy of Octafibrin for All Bleeding Episodes Collected in the Study
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)
Efficacy of Octafibrin in Preventing Bleeding During and After Surgery
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
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02267226
Brief Title
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
2. Study Status
Record Verification Date
December 2020
Overall Recruitment Status
Completed
Study Start Date
September 2014 (undefined)
Primary Completion Date
February 14, 2018 (Actual)
Study Completion Date
February 14, 2018 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Octapharma
4. Oversight
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Congenital Fibrinogen Deficiency
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
25 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Octafibrin
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
Octafibrin
Primary Outcome Measure Information:
Title
Overall Clinical Assessment of the Haemostatic Efficacy of Octafibrin in Treating the First Documented Bleeding Episode of Each Patient.
Description
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).
Time Frame
24 hours after last infusion for each bleeding episode
Secondary Outcome Measure Information:
Title
Maximum Clot Firmness (MCF) After Fibrinogen Infusion in Each Documented Bleeding Episode (BE), Measured in Frozen Plasma in a Central Laboratory.
Description
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.
Time Frame
Before first infusion and 1 hour after end of first and last infusion of each documented bleeding episode
Title
Fibrinogen Plasma Level
Description
Fibrinogen plasma level was assessed using the Clauss fibrinogen assay
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)
Title
Response as Indicated by Incremental in Vivo Recovery (IVR)
Description
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.
Time Frame
Pre-infusion and 1 and 3 hours post-infusion
Title
Efficacy of Octafibrin for All Bleeding Episodes Collected in the Study
Description
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)
Time Frame
24 hours after last infusion for each bleeding episode
Title
Efficacy of Octafibrin in Preventing Bleeding During and After Surgery
Description
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
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
Other Pre-specified Outcome Measures:
Title
Analysis of Safety: Immunogenicity Testing for Anti-fibrinogen Antibodies
Description
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.
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)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
12 Years
Accepts Healthy Volunteers
No
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Cristina Solomon, MD
Organizational Affiliation
Octapharma
Official's Role
Study Director
Facility Information:
Facility Name
Miami Children's Hospital
City
Miami
State/Province
Florida
ZIP/Postal Code
33155
Country
United States
Facility Name
Dept of Clinical Hematology for Hemorrhagic Diatheses and Anaemia, SHAT "Joan Pavel"
City
Sofia
Country
Bulgaria
Facility Name
St. John's Medical College Hospital
City
Bangalore
Country
India
Facility Name
Sahyadri Specialty Hospital
City
Pune
Country
India
Facility Name
Dept of Hematology, Christian Medical College
City
Vellore
Country
India
Facility Name
Seyed Al Shohada Hospital
City
Isfahan
Country
Iran, Islamic Republic of
Facility Name
Dastgheib Hospital
City
Shīrāz
Country
Iran, Islamic Republic of
Facility Name
Hotel-Dieu de France
City
Beirut
Country
Lebanon
Facility Name
Haematological Scientific Center of Ministry of Healthcare of the Russian Federation
City
Moscow
Country
Russian Federation
Facility Name
Centre of Excellence in Thrombosis & Hemostasis, King Saud University
City
Riyadh
Country
Saudi Arabia
Facility Name
Dept of Haematology, Ege University Children's Hospital
City
Izmir
Country
Turkey
Facility Name
Centre for Haemostasis & Thrombosis, St Thomas' Hospital
City
London
Country
United Kingdom
12. IPD Sharing Statement
Learn more about this trial
Efficacy and Safety Study of Octafibrin for On-demand Treatment of Acute Bleeding and to Prevent Bleeding During and After Surgery
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