Working…
Help guide our efforts to modernize ClinicalTrials.gov.
Send us your comments by March 14, 2020.
ClinicalTrials.gov
ClinicalTrials.gov Menu

Pharmacokinetics, Efficacy, and Safety of Human Plasma-Derived Fibrinogen (FIB Grifols) in Patients With Congenital Afibrinogenemia (IG0902)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02281500
Recruitment Status : Recruiting
First Posted : November 2, 2014
Last Update Posted : July 5, 2019
Sponsor:
Collaborator:
Instituto Grifols, S.A.
Information provided by (Responsible Party):
Grifols Therapeutics LLC

Brief Summary:
Multicenter, Prospective, Open-Label, Single-Arm Trial to Evaluate the Pharmacokinetics, Efficacy, and Safety of Human Plasma-Derived Fibrinogen (FIB Grifols) in Patients with Congenital Afibrinogenemia

Condition or disease Intervention/treatment Phase
Congenital Afibrinogenemia Biological: Human Plasma-Derived Fibrinogen Concentrate Phase 1 Phase 2

Detailed Description:

This study is a phase I-II, multi-center, prospective, open-label, single-arm, clinical trial to evaluate PK, efficacy, and safety of human plasma-derived fibrinogen concentrate (FIB Grifols) in adult and pediatric subjects with congenital afibrinogenemia.

Approximately 10 adult subjects (≥18 years) with congenital afibrinogenemia will be administered a single dose of FIB Grifols at 70 mg/kg body weight and will be followed for PK, efficacy, and safety assessments.

After the safety of fibrinogen concentrate FIB Grifols is assessed in at least 10 adult subjects and no safety issues are raised by the sponsor, the study will start to enroll approximately 10 pediatric subjects (<18 years) who will be dosed with study drug and followed for PK, efficacy, and safety assessments.

All enrolled subjects (both adult and pediatric) will have documented congenital fibrinogen deficiency manifested as afibrinogenemia but will not have received any fibrinogen-containing product therapy within the preceding 21 days before the infusion of study drug.

All subjects (both adult and pediatrics) will be infused with the investigational product at 70 mg/kg body weight. PK parameters that will be calculated from plasma fibrinogen levels measured at different time points include: incremental in vivo recovery [IVR], area under the curve (AUC) calculated as AUC from zero to 14 days (AUC^0-14days) and AUC from zero to infinity (AUC^0-∞), maximum plasma concentration (C^max), time to the observed maximum plasma concentration (t^max), half-life (t^1/2), mean residence time (MRT), volume of distribution (Vd), and clearance (Cl).

Hemostatic efficacy of the investigational product will be assessed by means of rotational thromboelastometry (ROTEM) measure of maximum clot firmness (MCF) at baseline and 1 hour post-infusion. Other thromboelastographic measures as well as standard coagulation tests will be also determined pre- and post-infusion.

Clinical safety, viral safety, and immunogenicity will be assessed in this clinical trial. Safety variables include adverse events (AEs), vital signs, physical assessments, laboratory tests, viral markers, and antibodies against human fibrinogen.

A monitoring plan will be implemented by the sponsor to carefully monitor and evaluate allergic/hypersensitivity reactions and thrombotic events during the study.

Stopping criteria have been established for immunogenic and thrombogenic events. If a single case of any these events is reported after a subject has been dosed with study drug, any further enrollment and dosing of subjects in the study will be suspended until the event can be adequately assessed by the sponsor. The enrollment and dosing will only resume if the sponsor deems it is safe to do so.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 22 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Multicenter, Prospective, Open-Label, Single-Arm Trial to Evaluate the Pharmacokinetics, Efficacy, and Safety of Human Plasma-Derived Fibrinogen (FIB Grifols) in Patients With Congenital Afibrinogenemia
Actual Study Start Date : May 2016
Estimated Primary Completion Date : November 2019
Estimated Study Completion Date : December 2019

Resource links provided by the National Library of Medicine

Drug Information available for: Fibrinogen

Arm Intervention/treatment
Experimental: Single
Human Plasma-Derived Fibrinogen Concentrate Grifols (FIB Grifols)
Biological: Human Plasma-Derived Fibrinogen Concentrate
A sterile freeze-dried fibrinogen concentrate filled in vials containing 1 g of FIB Grifols. FIB Grifols contains 20 mg/ml of active substance fibrinogen when reconstituted.
Other Name: FIB Grifols




Primary Outcome Measures :
  1. Change in MCF measured by ROTEM [ Time Frame: Baseline to one hour post-infusion ]
    MCF, as a functional parameter of blood's ability to coagulate, provides an indirect measure of hemostatic efficacy of replacement treatment with fibrinogen concentrates in patients with fibrinogen deficiency.


Secondary Outcome Measures :
  1. Difference (improvement) in Clotting time (CT) [ Time Frame: Baseline to one hour post-infusion ]
  2. Difference (improvement) in Clot Formation Time (CFT) [ Time Frame: Baseline to one hour post-infusion ]
  3. Difference (improvement) in Alpha angle (α) [ Time Frame: Baseline to one hour post-infusion ]
  4. Difference (improvement) in Prothrombin tme (PT) [ Time Frame: Baseline to one hour post-infusion ]
  5. Difference (improvement) in Thrombin tme (TT) [ Time Frame: Baseline to one hour post-infusion ]
  6. Difference (improvement) in Activated Partial Thromboplastin Time (aPTT) [ Time Frame: Baseline to one hour post-infusion ]


Information from the National Library of Medicine

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, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   up to 70 Years   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Male or female subjects less than 70 years old.
  2. Sign the written Informed Consent Form (ICF), or the subject's parent or legal guardian signs the ICF where applicable, and the Subject Authorization Form where applicable. Pediatric subjects, as defined by local regulations, will be asked to sign an age appropriate assent form
  3. Subjects diagnosed with congenital fibrinogen deficiency manifested as afibrinogenemia
  4. Subjects with a fibrinogen level undetectable or equal or less than 30 mg/dL determined by both Clauss and antigen methods at baseline (sample drawn within 24 hours prior to infusion on Day 0 Visit) or at Screening Visit (sample drawn at least 14 days prior to infusion on Day 0 Visit)
  5. Female subjects of child-bearing potential must have a negative test for pregnancy blood or urine human chorionic gonadotropin (HCG-based assay) at baseline (sample drawn within 24 hours prior to infusion on Day 0 Visit)
  6. Female subjects of child-bearing potential and their partners have agreed to practice contraception using a method of proven reliability (i.e., hormonal methods; barrier methods; intrauterine devices methods) to prevent a pregnancy during the course of the clinical trial
  7. Subjects must be willing to comply with all aspects of the clinical trial protocol, including blood sampling, for the whole duration of the study

Exclusion Criteria:

  1. Subjects who received any fibrinogen-containing product within 21 days prior to Day 0 Visit - infusion day
  2. Subjects who present with active bleeding within 10 days prior to infusion on Day 0 Visit
  3. Subjects with acquired (secondary) fibrinogen deficiency
  4. Subjects diagnosed with dysfibrinogenemia
  5. Subjects with documented history of deep vein thrombosis, pulmonary embolism, or arterial thrombosis within 1 year prior to enrollment in this clinical trial
  6. Subjects with known antibodies against fibrinogen
  7. Subjects with a history of anaphylactic reactions or severe reactions to any blood-derived product
  8. Subjects with a history of intolerance to any component of the investigational products
  9. Subjects with a documented history of IgA deficiency and antibodies against IgA
  10. Females who are pregnant or are breastfeeding
  11. Subjects with renal impairment (i.e., serum creatinine exceeds more than 2.0 times the upper limit of normal [ULN] at baseline [sample drawn within 24 hours prior to infusion on Day 0 Visit])
  12. Subjects with aspartate aminotransferase or alanine aminotransferase levels exceeding more than 2.5 times the ULN at baseline (sample drawn within 24 hours prior to infusion on Day 0 Visit)
  13. Subjects with a history of chronic alcoholism or illicit drug addiction in the preceding 12 months prior to enrollment in this clinical trial
  14. Subjects with any medical condition which is likely to interfere with the evaluation of the study drugs and/or the satisfactory conduct of the clinical trial according to the investigator's judgment (e.g., congenital or acquired bleeding disorders other than congenital fibrinogen deficiency, planned surgery needing blood transfusion)
  15. Subjects received aspirin-containing products and nonsteroidal anti-inflammatory drugs within 7 days prior to Day 0 Visit
  16. Subjects currently receiving, or having received within 3 months prior to enrollment into this clinical trial, any investigational drug or device
  17. Subjects who were previously administered the investigational product FIB Grifols during this clinical trial (i.e., every subject can only participate in the study once).
  18. Subjects who are unlikely to adhere the protocol requirements, or are likely to be uncooperative, or unable to provide a storage serum sample prior to investigational drug infusion

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): NCT02281500


Contacts
Layout table for location contacts
Contact: Jordi Navarro jordi.navarro@grifols.com
Contact: Karen Rucker karen.rucker@grifols.com

Locations
Layout table for location information
United States, New York
Northshore Long Island Jewish Medical Center Recruiting
New Hyde Park, New York, United States, 11040
Contact: Joe Stanco    718-470-4434    jstanco@northwell.edu   
Principal Investigator: Suchitra S. Acharya, MD         
India
S.S. Institute of Medical Sciences and Research Centre Recruiting
Davangere, Karnataka, India
Contact: Umesh V Kumar, SN    +91-9739427409    umeshk836@gmail.com   
Principal Investigator: N. K. Kalappanavar, MD         
St. Johns Medical College and Hospital Recruiting
Bangalore, India
Contact: Alekya Vemula, CRC    91 8897752905    hemtrials.stjohns@sjri.res.in   
Contact: Arpita Taran, CRC    91-9620719377    ataran@jssresearch.com   
Principal Investigator: Cecil Rueben Ross, MD         
Sahyadri Specialty Hospital Recruiting
Pune, India
Contact: Manali Sapre, CRC    +91-7756858299    cru.manali@sahyadrihospitals.com   
Principal Investigator: Kannan Subramanian, MD         
Italy
Agenzia per l'Emofilia Centro di Riferimento Regionale per le Coaugulopatie Congenite A.O. di Carreggi Not yet recruiting
Firenze, Italy, 50134
Contact: Giancarlo Castamann, MD         
Principal Investigator: Giancarlo Castamann, MD         
Lebanon
Hôtel-Dieu de France Hospital Recruiting
Beirut, Lebanon
Contact: Claudia Khayat, MD    9611613027    claudiakhayat@yahoo.fr   
Principal Investigator: Claudia Khayat, MD         
Sponsors and Collaborators
Grifols Therapeutics LLC
Instituto Grifols, S.A.
Investigators
Layout table for investigator information
Study Chair: Flora Peyvandi, MD Centro Emofilia & Trombosi Angelo Bianchi Bonomi

Layout table for additonal information
Responsible Party: Grifols Therapeutics LLC
ClinicalTrials.gov Identifier: NCT02281500    
Other Study ID Numbers: IG0902
First Posted: November 2, 2014    Key Record Dates
Last Update Posted: July 5, 2019
Last Verified: July 2019
Additional relevant MeSH terms:
Layout table for MeSH terms
Afibrinogenemia
Blood Coagulation Disorders, Inherited
Blood Coagulation Disorders
Hematologic Diseases
Coagulation Protein Disorders
Hemorrhagic Disorders
Genetic Diseases, Inborn