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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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ClinicalTrials.gov Identifier: NCT02267226
Recruitment Status : Completed
First Posted : October 17, 2014
Last Update Posted : June 7, 2018
Sponsor:
Information provided by (Responsible Party):
Octapharma

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.

Condition or disease Intervention/treatment Phase
Congenital Fibrinogen Deficiency Drug: Octafibrin Phase 3

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 25 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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 Start Date : September 2014
Actual Primary Completion Date : January 23, 2018
Actual Study Completion Date : January 23, 2018


Arm Intervention/treatment
Experimental: Octafibrin Drug: Octafibrin



Primary Outcome Measures :
  1. 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 ]

    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 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). The number of subjects per outcome category will be assessed in the final analysis.



Secondary Outcome Measures :
  1. Maximum clot firmness (MCF) assessment of each documented bleeding episode [ Time Frame: Before first infusion and 1 hour after end of first and last infusion of each documented bleeding episode ]
    MCF will be determined using thromboelastography (TEG) and will be used as a surrogate marker for haemostatic efficacy. TEG 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.

  2. Assessment of fibrinogen plasma level [ Time Frame: Before and 1 hour 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) ]
    Fibrinogen plasma level will be assessed using the Clauss fibrinogen assay.

  3. Response as indicated by incremental in vivo recovery (IVR), calculated as the maximum increase in plasma fibrinogen between pre- and post-infusion [ Time Frame: Pre-infusion and 1 and 3 hours post-infusion ]

    IVR will be determined using the following approaches:

    • 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.
    • Classical IVR: 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 total dose of Octafibrin per expected plasma volume.

  4. Efficacy of Octafibrin in all bleeding episodes collected in the study [ Time Frame: 24 hours after last infusion for each bleeding episode ]
    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).

  5. 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 ]
    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.

  6. Analysis of safety: Adverse events [ Time Frame: 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 ]
    Adverse events, including thromboembolic complications and early signs of allergic or hypersensitivity reactions.

  7. Analysis of safety: Immunogenicity testing for anti-fibrinogen antibodies [ Time Frame: 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 ]
    Immunogenicity testing for the presence of anti-fibrinogen antibodies at Day 14 and Day 30 after the administration of Octafibrin for bleeding.



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Ages Eligible for Study:   12 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02267226


Locations
United States, Florida
Miami Children's Hospital
Miami, Florida, United States, 33155
Bulgaria
Dept of Clinical Hematology for Hemorrhagic Diatheses and Anaemia, SHAT "Joan Pavel"
Sofia, Bulgaria
India
St. John's Medical College Hospital
Bangalore, India
Dept of Hematology, Christian Medical College
Vellore, India
Iran, Islamic Republic of
Seyed Al Shohada Hospital
Isfahan, Iran, Islamic Republic of
Dastgheib Hospital
Shīrāz, Iran, Islamic Republic of
Lebanon
Hotel-Dieu de France
Beirut, Lebanon
Russian Federation
Haematological Scientific Center of Ministry of Healthcare of the Russian Federation
Moscow, Russian Federation
Saudi Arabia
Centre of Excellence in Thrombosis & Hemostasis, King Saud University
Riyadh, Saudi Arabia
Turkey
Dept of Haematology, Ege University Children's Hospital
Izmir, Turkey
United Kingdom
Centre for Haemostasis & Thrombosis, St Thomas' Hospital
London, United Kingdom
Sponsors and Collaborators
Octapharma
Investigators
Study Director: Cristina Solomon, MD Octapharma

Responsible Party: Octapharma
ClinicalTrials.gov Identifier: NCT02267226     History of Changes
Other Study ID Numbers: FORMA-02
First Posted: October 17, 2014    Key Record Dates
Last Update Posted: June 7, 2018
Last Verified: June 2018

Additional relevant MeSH terms:
Hemorrhage
Afibrinogenemia
Pathologic Processes
Blood Coagulation Disorders, Inherited
Blood Coagulation Disorders
Hematologic Diseases
Coagulation Protein Disorders
Hemorrhagic Disorders
Genetic Diseases, Inborn