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Pharmacokinetic, Efficacy, and Safety Study of Octafibrin Compared to Haemocomplettan/Riastap

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Octapharma
ClinicalTrials.gov Identifier:
NCT01575756
First received: April 9, 2012
Last updated: October 5, 2016
Last verified: October 2016
  Purpose
The purpose of this study is to investigate pharmacokinetic properties, surrogate efficacy and safety of Octafibrin compared to Haemocomplettan® P/RiaSTAPTM in patients with congenital fibrinogen deficiency

Condition Intervention Phase
Congenital Fibrinogen Deficiency
Afibrinogenemia
Biological: Octafibrin
Biological: Haemocomplettan® P or RiaSTAPTM
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Crossover Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Prospective, Controlled, Randomised, Crossover Study Investigating the Pharmacokinetic Properties, Surrogate Efficacy and Safety of Octafibrin Compared to Haemocomplettan® P/RiaSTAPTM in Patients With Congenital Fibrinogen Deficiency

Resource links provided by NLM:


Further study details as provided by Octapharma:

Primary Outcome Measures:
  • Fibrinogen Activity Normalized Area Under the Curve Standardized [ Time Frame: Baseline to 0.5, 1, 2, 4, 8, 24, 48, 96, 144, 216, and 312 hours post-treatment ] [ Designated as safety issue: No ]
    Fibrinogen activity was determined via a validated Clauss assay (fibrinogen activity) and fibrinogen-specific enzyme-linked immunosorbent assay (ie, fibrinogen antigen) using paired antibodies for fibrinogen antigen. All determinations were performed on frozen plasma samples in a central laboratory. The Clauss assay was modified and validated to achieve a limit of quantification of 0.2 g/L. The pharmacokinetic analysis was assessed individually using a non-compartmental model. Plasma levels were measured at Baseline, 0.5, 1, 2, 4, 8, 24, 48, 96, 144, 216, and 312 hours post-treatment. The normalized area under the curve was standardized to a dose of 70 mg/kg.

  • Comparison of Maximum Clot Firmness Between Octafibrin and Haemocomplettan P/RiaSTAP at 1 hr Post Infusion [ Time Frame: Baseline to 1 hour post-treatment ] [ Designated as safety issue: No ]
    Thromboelastography (TEG) using rotational thromboelastometry (ROTEM®) was used to measure maximum clot firmness. Rotational thromboelastometry is a method for the continuous measurement of clot formation. Maximum clot firmness is a functional parameter that depends on the activation of coagulation, the platelet and fibrinogen content of the blood sample, and the polymerisation and cross-linking of the fibrin network. In order to obtain comparable results from all study centres, maximum clot firmness data were assessed from frozen citrated plasma samples in a central laboratory. As these samples did not contain platelets that would be found in the whole blood assay, only the fibrinogen content defined the maximum clot firmness.


Secondary Outcome Measures:
  • Fibrinogen Activity Normalized Area Under the Curve Unstandardized [ Time Frame: Baseline to 0.5, 1, 2, 4, 8, 24, 48, 96, 144, 216, and 312 hours post-treatment ] [ Designated as safety issue: No ]
    fibrinogen-specific enzyme-linked immunosorbent assay (ie, fibrinogen antigen) using paired antibodies for fibrinogen antigen. All determinations were performed on frozen plasma samples in a central laboratory. The Clauss assay was modified and validated to achieve a limit of quantification of 0.2 g/L. The pharmacokinetic analysis was assessed individually using a non-compartmental model. Plasma levels were measured at Baseline, 0.5, 1, 2, 4, 8, 24, 48, 96, 144, 216, and 312 hours post-treatment.

  • Incremental in Vivo Recovery [ Time Frame: Baseline to 0.5, 1, 2, 4, 8, 24, 48, 96, 144, 216, and 312 hours post-treatment ] [ Designated as safety issue: No ]
    Incremental in vivo recovery was calculated as the maximum increase in plasma fibrinogen (fibrinogen activity assay data) within 4 hours post-treatment as compared with pre-treatment (expressed as an absolute mg/dL concentration in plasma), divided by the exact dose of Octafibrin or Haemocomplettan® P or RiaSTAPTM (expressed as mg/kg dosed).

  • Terminal Half-life (t½) [ Time Frame: Baseline to 0.5, 1, 2, 4, 8, 24, 48, 96, 144, 216, and 312 hours post-treatment ] [ Designated as safety issue: No ]
    Fibrinogen activity was determined via a validated Clauss assay (fibrinogen activity) and fibrinogen-specific enzyme-linked immunosorbent assay (ie, fibrinogen antigen) using paired antibodies for fibrinogen antigen. All determinations were performed on frozen plasma samples in a central laboratory. The Clauss assay was modified and validated to achieve a limit of quantification of 0.2 g/L. The pharmacokinetic analysis was assessed individually using a non-compartmental model. Plasma levels were measured at Baseline, 0.5, 1, 2, 4, 8, 24, 48, 96, 144, 216, and 312 hours post-treatment.

  • Clearance [ Time Frame: Baseline to 0.5, 1, 2, 4, 8, 24, 48, 96, 144, 216, and 312 hours post-treatment ] [ Designated as safety issue: No ]
    Fibrinogen activity was determined via a validated Clauss assay (fibrinogen activity) and fibrinogen-specific enzyme-linked immunosorbent assay (ie, fibrinogen antigen) using paired antibodies for fibrinogen antigen. All determinations were performed on frozen plasma samples in a central laboratory. The Clauss assay was modified and validated to achieve a limit of quantification of 0.2 g/L. The pharmacokinetic analysis was assessed individually using a non-compartmental model. Plasma levels were measured at Baseline, 0.5, 1, 2, 4, 8, 24, 48, 96, 144, 216, and 312 hours post-treatment.


Enrollment: 22
Study Start Date: June 2013
Study Completion Date: January 2015
Primary Completion Date: January 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Octafibrin followed by Haemocomplettan® P or RiaSTAPTM
Participants received Octafibrin 70 mg/kg intravenously once followed by Haemocomplettan® P or RiaSTAPTM 70 mg/kg intravenously once 45 days later.
Biological: Octafibrin
Octafibrin was supplied as a powder for reconstitution with water for injection.
Other Name: Plasma derived fibrinogen concentrate
Biological: Haemocomplettan® P or RiaSTAPTM
Commercially available Haemocomplettan® P or RiaSTAPTM (same product with different names in different markets) were supplied as powders for reconstitution with water for injection.
Other Name: Plasma derived fibrinogen concentrate
Experimental: Haemocomplettan® P or RiaSTAPTM followed by Octafibrin
Participants received Haemocomplettan® P or RiaSTAPTM 70 mg/kg intravenously once followed by Octafibrin 70 mg/kg intravenously once 45 days later.
Biological: Octafibrin
Octafibrin was supplied as a powder for reconstitution with water for injection.
Other Name: Plasma derived fibrinogen concentrate
Biological: Haemocomplettan® P or RiaSTAPTM
Commercially available Haemocomplettan® P or RiaSTAPTM (same product with different names in different markets) were supplied as powders for reconstitution with water for injection.
Other Name: Plasma derived fibrinogen concentrate

  Eligibility

Ages Eligible for Study:   12 Years and older   (Child, Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Age ≥ 12 years.
  • Documented congenital fibrinogen deficiency (afibrinogenemia).

Exclusion Criteria:

  • Life expectancy > 6 month.
  • Bleeding disorder other than congenital fibrinogen deficiency.
  • Presence or history of hypersensitivity to study medication.
  • Presence or history of deep vein thrombosis or pulmonary embolism within 1 year prior to enrollment.
  • Presence or history of arterial thrombosis with 1 year prior to enrollment.
  • Hypersensitivity to human plasma products.
  • Acute bleeding.
  • Pregnant or currently breast-feeding women.
  • Suspicion of an anti-fibrinogen inhibitor as indicated by previous in vivo recovery (if available).
  • Blood or plasma donation in the 3 months prior to enrollment.
  • Human immunodeficiency virus (HIV) positive with a viral load > 200 particles/µl or > 400000 copies/mL.
  • End-stage liver disease.
  • History of oesophageal varicose bleeding.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01575756

Locations
United States, Colorado
University of Colorado Hemophilia & Thrombosis Center
Aurora, Colorado, United States, 80045
United States, New York
Cohen Children's Medical Center of New York
New Hyde Park, New York, United States, 11040
Bulgaria
Specialized Hospital for Active Treatment "Joan Pavel"
Sofia, Bulgaria
India
Department of Hematology St. John's Medical College Hospital
Bangalore, India
Sahyadri Speciality Hospital
Prune, India
Department of Hematology Christian Medical College
Vellore, India
Iran, Islamic Republic of
Nemazee Hospital Shiraz University of Medical Sciences
Shiraz, Iran, Islamic Republic of
Tehran University of Medical Sciences
Tehran, Iran, Islamic Republic of
Switzerland
Department of Hematology University Hospital
Zurich, Switzerland
United Kingdom
The Centre for Haemostatis and Thrombosis
London, United Kingdom
Sponsors and Collaborators
Octapharma
Investigators
Study Director: Sigurd Knaub, PhD Octapharma
  More Information

Responsible Party: Octapharma
ClinicalTrials.gov Identifier: NCT01575756     History of Changes
Other Study ID Numbers: FORMA-01 
Study First Received: April 9, 2012
Results First Received: October 5, 2016
Last Updated: October 5, 2016
Health Authority: United States: Food and Drug Administration
United Kingdom: Medicines and Healthcare Products Regulatory Agency
Germany: Paul-Ehrlich-Institut
Bulgaria: Bulgarian Drug Agency
Switzerland: Swissmedic
India: Drugs Controller General of India
Italy: Instituto Superiore di Sanita
Iran: Ministry of Health/Food & Drug Department (MOH), Drug and Narcotics surveillance department

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

ClinicalTrials.gov processed this record on December 07, 2016