Fibrinogen Concentrate (Human) − Efficacy and Safety Study - Full Text View

Purpose

This is a multinational, multicenter, prospective, open-label historically controlled Phase IIIb non-inferiority clinical trial on the efficacy and safety of Fibrinogen Concentrate (Human).

It is estimated that 150-300 patients in the U.S. suffer from afibrinogenemia. Substitution with cryoprecipitate or alternative treatments have limited safety and efficacy.

The primary purpose of the study is to demonstrate the hemostatic efficacy of Fibrinogen Concentrate (Human) by adequately controlling acute bleeding (spontaneous or after trauma) in patients with congenital fibrinogen deficiency (afibrinogenemia and hypofibrinogenemia). Cryoprecipitate hemostatic efficacy data from a retrospective physician survey will be used as a historical control.

Condition	Intervention	Phase
Afibrinogenemia Hypofibrinogenemia Fibrinogen Deficiency	Biological: Fibrinogen Concentrate, Human (FCH) Biological: Cryoprecipitate	Phase 3

Study Type:	Interventional
Study Design:	Allocation: Non-Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	Efficacy and Safety of Fibrinogen Concentrate (Human) (FCH) for On-demand Treatment of Acute Bleeding in Subjects With Congenital Fibrinogen Deficiency

Resource links provided by NLM:

Genetics Home Reference related topics: congenital afibrinogenemia

Drug Information available for: Fibrinogen

U.S. FDA Resources

Further study details as provided by CSL Behring:

Primary Outcome Measures:

Clinical assessment of hemostatic efficacy [ Time Frame: 24 hours after last infusion or at Day 14 (whichever occurs first) ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Maximum clot firmness (MCF) [ Time Frame: Prior to and 60 minutes after the end of each infusion ] [ Designated as safety issue: No ]
Fibrinogen plasma level [ Time Frame: 60 minutes, 3 hours, 6 hours, and 12 hours after the end of the first infusion; before and 60 minutes after each subsequent infusion ] [ Designated as safety issue: No ]
In vivo recovery of fibrinogen [ Time Frame: 60 minutes, 3 hours, 6 hours and 12 hours after the end of the first infusion; before and 60 minutes after the end of each subsequent infusion and at the time of the overall clinical assessment of hemostatic efficacy ] [ Designated as safety issue: No ]
Virus safety markers [ Time Frame: Day 1 to Day 45 ] [ Designated as safety issue: Yes ]

Estimated Enrollment:	23
Study Start Date:	October 2009
Estimated Study Completion Date:	September 2014
Estimated Primary Completion Date:	March 2014 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Prospective Arm	Biological: Fibrinogen Concentrate, Human (FCH) Intravenous (IV) infusion to reach the peak target levels of 100 mg/dL with an accepted lower limit of 80 mg/dL on at least 3 subsequent days for minor bleeding episodes and 150 mg/dL with an accepted lower limit of 130 mg/dL on at least 7 subsequent days for major bleeding episodes. If a subject's fibrinogen level is not known on Day 1, at the time treatment is initiated for the acute bleed (e.g., because they did not have a screening visit), the starting dose is to be 70 mg/kg b.w. Otherwise, the dose will be calculated individually. Other Names: Haemocomplettan P RIASTAP
Historical Control	Biological: Cryoprecipitate Patients that received on-demand treatment with Cryoprecipitate for a classified bleeding event (minor or major) with a documented hemostatic efficacy assessment.

Arms

Assigned Interventions

Experimental: Prospective Arm

Biological: Fibrinogen Concentrate, Human (FCH)

Intravenous (IV) infusion to reach the peak target levels of 100 mg/dL with an accepted lower limit of 80 mg/dL on at least 3 subsequent days for minor bleeding episodes and 150 mg/dL with an accepted lower limit of 130 mg/dL on at least 7 subsequent days for major bleeding episodes.

If a subject's fibrinogen level is not known on Day 1, at the time treatment is initiated for the acute bleed (e.g., because they did not have a screening visit), the starting dose is to be 70 mg/kg b.w. Otherwise, the dose will be calculated individually.

Other Names:

Haemocomplettan P
RIASTAP

Historical Control

Biological: Cryoprecipitate

Patients that received on-demand treatment with Cryoprecipitate for a classified bleeding event (minor or major) with a documented hemostatic efficacy assessment.

Eligibility

Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Documented congenital fibrinogen deficiency (afibrinogenemia and hypofibrinogenemia), expected to require treatment for bleeding
Presenting with an episode of acute bleeding (either spontaneous or after trauma) not requiring surgery
Provide informed consent

Exclusion Criteria:

Life expectancy < 6 months
Bleeding disorder other than congenital fibrinogen deficiency, but including dysfibrinogenemia
Treatment with any investigational medicinal product (IMP) in the 30 days prior to enrollment
Treatment with any fibrinogen concentrate or other fibrinogen containing blood product in the 2 weeks prior to enrollment
Treatment with any coagulation active drug (i.e., non-steroidal-antirheumatics, warfarin, cumarin derivates, platelet aggregation inhibitors) in 1 week prior to enrollment or as a planned or expected medication during the time period from Day 1 until 24 hours after the last FCH infusion
Presence or history of hypersensitivity to FCH
Presence or history of deep vein thrombosis or pulmonary embolism within 1 year prior to enrollment
Presence or history of arterial thrombosis within 1 year prior to enrollment
Presence or history of hypersensitivity to human plasma proteins
Presence or history of esophageal varicose bleeding
End stage liver disease (i.e., Child Pugh score B or C)
Planned or expected surgery (i.e., for bleedings from aneurysm or splenic rupture)
Pregnancy, or an intention to become pregnant during the study
Currently breast-feeding, or with the intention of breast-feeding during the study
Human immunodeficiency virus (HIV) positive
Polytrauma, present or within 6 months prior to enrollment
Suspicion of an anti-fibrinogen inhibitor as indicated by previous in-vivo recovery (IVR), if available (< 0.5 (mg/dL)/(mg/kg))
Previous inclusion and treatment in the prospective part of the study
Participation in any clinical study in the 30 days prior to enrollment

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00916656

Contacts

Contact: Central Contact: Clinical Trial Registration Coordinator

clinicaltrials@cslbehring.com

Locations

Italy
Study Site	Active, not recruiting
Milano, Italy, 20122
Study Site	Recruiting
Sassari, Italy, 07100
Contact: Use Central Contact
Study Site	Recruiting
Vincenza, Italy, 36100

Sponsors and Collaborators

CSL Behring

Investigators

Study Director:

Program Director, Clinical R&D

CSL Behring

More Information

Additional Information:

Click here to request more information about this study This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	CSL Behring
ClinicalTrials.gov Identifier:	NCT00916656 History of Changes
Other Study ID Numbers:	BI3023_3001, 1475, 2007-004088-22
Study First Received:	June 8, 2009
Last Updated:	May 2, 2013
Health Authority:	United States: Food and Drug Administration

Keywords provided by CSL Behring:

Congenital fibrinogen deficiency

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 May 19, 2013