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

December 21, 2020 updated by: Octapharma

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

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.

Study Overview

Status

Completed

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

25

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

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

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

12 years and older (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

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

This section provides details of the study plan, including how the study is designed and what the study is measuring.

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
Experimental: Octafibrin

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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 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

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
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.
Before first infusion and 1 hour after end of first and last infusion of each documented bleeding episode
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)
Fibrinogen plasma level was assessed using the Clauss fibrinogen assay
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)
Response as Indicated by Incremental in Vivo Recovery (IVR)
Time Frame: Pre-infusion and 1 and 3 hours post-infusion
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.
Pre-infusion and 1 and 3 hours post-infusion
Efficacy of Octafibrin for 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)
24 hours after last infusion for each bleeding episode
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
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
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)
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.
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)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

September 1, 2014

Primary Completion (Actual)

February 14, 2018

Study Completion (Actual)

February 14, 2018

Study Registration Dates

First Submitted

August 7, 2014

First Submitted That Met QC Criteria

October 14, 2014

First Posted (Estimate)

October 17, 2014

Study Record Updates

Last Update Posted (Actual)

January 15, 2021

Last Update Submitted That Met QC Criteria

December 21, 2020

Last Verified

December 1, 2020

More Information

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.

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