Study to Assess the Efficacy, Safety and Pharmacokinetic of Octafibrin in Paediatric Subjects With Fibrinogen Deficiency

NCT02408484 | Completed Phase 3 Results DMC

• 1 other identifier: FORMA-04
• Study Type: interventional
• Target: 15
• Locations: 3 countries
• Sites: 4

Brief Summary

This study will assess the efficacy of Octafibrin, a fibrinogen concentrate in in the on-demand treatment of spontaneous or traumatic bleeding episodes in paediatric patients less than 12 years of age.The planned study duration is up to 5 years. The study will be considered completed when a minimum of 6 subjects (i.e., at least 3 subjects aged between 0 and \<6 years and 3 subjects aged between 6 and \<12 years) have at least one documented bleeding episode and when in total a minimum of 2 surgical procedures have been performed. All patients will undergo a pharmacokinetic (PK) study after screening. This will have a duration of 14 days, after which a patient can be treated for a bleeding episode or planned surgical procedure when they occur.

Conditions

Congenital Fibrinogen Deficiency

Outcome Measures

Primary Outcomes (2)

• Overall Clinical Assessment of the Haemostatic Efficacy of Octafibrin in the On-demand Treatment of the First Documented Bleeding Episode of Each Patient Based on a 4-point Haemostatic Efficacy Scale

  The overall clinical assessment of the haemostatic efficacy of Octafibrin in treating the first documented bleeding episode (BE) of each patient. The first bleeding episode covered the time from the first Octafibrin infusion until 24 hours (i.e. 1 day) after the last infusion or the end of the treatment observation period, which ever came last. The investigator's overall clinical assessment of haemostatic efficacy for bleeding was based on a 4-point haemostatic efficacy scale (excellent, good, moderate or none). Excellent result was defined as immediate cessation of bleeding; 'Good' was eventual complete cessation of bleeding; 'Moderate' was incomplete cessation of bleeding and 'None' was no cessation of bleeding with alternative haemostatic intervention required. The IDMEAC conducted an independent adjudication of all haemostatic efficacy results and evaluated the investigator's assessments of the efficacy in the treatment of each BE.

  First Octafibrin infusion for the treatment of a bleeding episode until 24 hours (i.e., 1 day) after the last infusion or the end of the treatment observation period, whichever comes last

• Overall Clinical Assessment of the Haemostatic Efficacy of Octafibrin in the On-demand Treatment of the First Documented Bleeding Episode of Each Patient Based on a 2-point Haemostatic Efficacy Scale

  The overall clinical assessment of the haemostatic efficacy of Octafibrin in treating the first documented bleeding episode (BE) of each patient. The first bleeding episode covered the time from the first Octafibrin infusion until 24 hours (i.e. 1 day) after the last infusion or the end of the treatment observation period, which ever came last. The investigator's overall clinical assessment of haemostatic efficacy for bleeding was based on a 2-point haemostatic efficacy scale (success and failure). Efficacy rating of excellent or good on the four-point scale (above) indicated success and efficacy rating of moderate or none indicated failure. The IDMEAC conducted an independent adjudication of all haemostatic efficacy results and evaluated the investigator's assessments of the efficacy in the treatment of each BE.

  From the first Octafibrin infusion until 24 hours (i.e. 1 day) after the last infusion or the end of the treatment observation period, which ever came last.

Secondary Outcomes (18)

• Single-dose Pharmacokinetics of Octafibrin: Area Under the Concentration-time Curve Normalised (AUCnorm)

  Before first infusion, 1 hour, 3 hours, 1 day, 2 days, 4 days, 7 days, 10 days and 14 days post-infusion

• Single-dose Pharmacokinetics of Octafibrin: Response - Incremental in Vivo Recovery (IVR)

  Between the pre-infusion and the 3-hour post-infusion

• Single-dose Pharmacokinetics of Octafibrin: Terminal Elimination Half-life (t1/2)

  Before first infusion, 1 hour, 3 hours, 1 day, 2 days, 4 days, 7 days, 10 days and 14 days post-infusion

• Single-dose Pharmacokinetics of Octafibrin: Maximum Plasma Concentration (Cmax)

  Before first infusion, 1 hour, 3 hours, 1 day, 2 days, 4 days, 7 days, 10 days and 14 days post-infusion

• Single-dose Pharmacokinetics of Octafibrin: Time to Reach Maximum Plasma Concentration (Tmax)

  Before first infusion, 1 hour, 3 hours, 1 day, 2 days, 4 days, 7 days, 10 days and 14 days post-infusion

Study Arms (1)

Octafibrin

EXPERIMENTAL

Plasma-derived fibrinogen concentrate

Biological: Octafibrin

Interventions

Octafibrin BIOLOGICAL

Plasma-derived Fibrinogen concentrate

Also known as: Fibrinogen concentrate

Octafibrin

Eligibility Criteria

• Age: Up to 11 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Aged \<12 years (at the start of treatment).
• Documented diagnosis of congenital fibrinogen deficiency, expected to require on-demand treatment for bleeding or surgical prophylaxis:
• Fibrinogen deficiency manifested as afibrinogenaemia or severe hypofibrino-genaemia.
• 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's legal guardian.

You may not qualify if:

• Life expectancy \<6 months.
• Bleeding disorder other than congenital fibrinogen deficiency, including dysfi-brinogenaemia.
• 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 PK phase, a bleeding episode, or surgery.
• Any coagulation-active drug (i.e., non-steroidal anti-inflammatory drugs, war-farin, coumarin derivatives, platelet aggregation inhibitors) within 1 week prior to start of the PK phase or 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).
• 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.

Sponsors & Collaborators

• Octapharma: lead

Study Sites (4)

St. John's Medical College Hospital

Bangalore, 560034, India

Location

S.S Institute of Medical Science and Research Center

Davangere, 577005, India

Location

Nemazee Hospital Shiraz University of Medical Sciences

Shiraz, Iran

Location

Hotel De Dieu de France

Beirut, Lebanon

Location

MeSH Terms

Interventions

Fibrinogen

Intervention Hierarchy (Ancestors)

Acute-Phase Proteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Blood Coagulation Factors; Protein Precursors; Biological Factors

Results Point of Contact

• Title: Sigurd Knaub
• Organization: Octapharma

sigurd.knaub@octapharma.com

55 451 21 41

Study Officials

• Cristina Solomon, MD

  Octapharma

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 25, 2015
• First Posted: April 3, 2015
• Study Start: December 1, 2015
• Primary Completion: June 11, 2019
• Study Completion: June 11, 2019
• Last Updated: January 15, 2021
• Results First Posted: June 11, 2020

Record last verified: 2020-12

Data Sharing

• IPD Sharing: Will not share

Locations

IN (2); IR (1); LE (1)