A Phase III Study on the Safety, Pharmacokinetics and Efficacy of Coagulation Factor VIIa (Recombinant) in Congenital Hemophilia A or B Patients With Inhibitors to Factor VIII or IX

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Laboratoire français de Fractionnement et de Biotechnologies
Information provided by (Responsible Party):
rEVO Biologics
ClinicalTrials.gov Identifier:
NCT02020369
First received: December 18, 2013
Last updated: May 4, 2015
Last verified: November 2014
  Purpose

The purpose of the study is to assess the safety, efficacy and pharmacokinetics of 2 separate dose regimens (75µg/kg and 225 µg/kg) of Coagulation Factor VIIa (Recombinant) for the treatment of bleeding episodes in hemophilia A or B patients with inhibitors to Factor VIII/IX


Condition Intervention Phase
Hemophilia A With Inhibitors
Hemophilia B With Inhibitors
Biological: Coagulation Factor VIIa (Recombinant)
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Crossover Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase III Study on the Safety, Pharmacokinetics and Efficacy of Coagulation Factor VIIa (Recombinant) in Congenital Hemophilia A or B Patients With Inhibitors to Factor VIII or IX

Resource links provided by NLM:


Further study details as provided by rEVO Biologics:

Primary Outcome Measures:
  • Bleeding episode treatment success [ Time Frame: 12 hours after first administration of study drug ] [ Designated as safety issue: No ]
    No additional hemostatic product required after12 hours of first dose.


Secondary Outcome Measures:
  • Time to bleeding success [ Time Frame: at 12 hours ] [ Designated as safety issue: No ]
    Patients shall rate the treatment of each bleeding episode. If treatment occurs under direct supervision of treating physician, then physician shall rate the response. Ratings based on a four point scale:Excellent, Good, Moderate, None


Other Outcome Measures:
  • Immunogenicity assessment [ Time Frame: Pre-dose, 6 week, 12 weeks, 24 weeks then every 12 weeks and end of study visit ] [ Designated as safety issue: Yes ]
    Based on Coagulation Factor VIIa (Recombinant), binding antibody levels

  • Pharmacokinetic assessment [ Time Frame: 7 timepoints from pre-dosing on Day 1 up to 8 hours ] [ Designated as safety issue: No ]
    Based on plasma concentrations of Coagulation Factor VIIa (Recombinant)


Estimated Enrollment: 25
Study Start Date: April 2014
Estimated Study Completion Date: May 2015
Estimated Primary Completion Date: May 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Coagulation Factor VIIa (Recombinant): 75 µg/kg
Coagulation Factor VIIa (Recombinant): 75 µg/kg for 3 months
Biological: Coagulation Factor VIIa (Recombinant)
A cross over design to assess the efficacy of 2 separate dose regimens (75µg/kg and 225 µg/kg) of Coagulation Factor VIIa (Recombinant) for the treatment of bleeding episodes in hemophilia A or B patients with inhibitors to Factor VIII/IX
Active Comparator: Coagulation Factor VIIa (Recombinant): 225 µg/kg
Coagulation Factor VIIa (Recombinant) : 225 µg/kg for 3 months
Biological: Coagulation Factor VIIa (Recombinant)
A cross over design to assess the efficacy of 2 separate dose regimens (75µg/kg and 225 µg/kg) of Coagulation Factor VIIa (Recombinant) for the treatment of bleeding episodes in hemophilia A or B patients with inhibitors to Factor VIII/IX

  Eligibility

Ages Eligible for Study:   12 Years to 75 Years
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • be male with a diagnosis of congenital hemophilia A and/or B of any severity
  • have one of the following:
  • a positive inhibitor test Bethesda Unit (BU) ≥ 5 (as confirmed at screening by the institutional lab), OR
  • a BU<5 but expected to have a high anamnestic response to FVIII or FIX, as demonstrated from the subject's medical history, precluding the use of Factor VIII or IX products to treat bleedings, OR
  • a BU<5 but expected to be refractory to increased dosing of FVIII or FIX, as demonstrated from the subject's medical history, precluding the use of Factor VIII or IX products to treat bleedings
  • be 12 years or older, up to and including 75 years of age (NOTE: different age restrictions may apply per local regulation and/or ethical considerations)
  • have at least 3 bleeding episodes of any severity in the past 6 months be capable of understanding and willing to comply with the conditions of the protocol
  • have read, understood and provided written informed consent (patient and/or parent(s)/legal guardian(s) if <18 years of age)

Exclusion Criteria:

  • have any coagulation disorder other than hemophilia A or B
  • be immuno-suppressed (i.e., the patient should not be receiving systemic immunosuppressive medication, cluster of differentiation 4 (CD4) counts at screening should be >200/µl)
  • have a known allergy or hypersensitivity to rabbits
  • have platelet count <100,000/mL
  • have had within one month prior to first administration of the study drug in this study a major surgical procedure (e.g. orthopedic, abdominal)
  • have received an investigational drug within 30 days of the first study drug administration, or is expected to receive such drug during participation in this study
  • have a clinically relevant hepatic (AST and/or alanine aminotransferase (ALT) >3 times the upper limit of normal) and/or renal impairment (creatinine >2 times the upper limit of normal)
  • have a history of arterial and/or venous thromboembolic events (such as myocardial infarction, ischemic strokes, transient ischemic attacks, deep venous thrombosis or pulmonary embolism) within 2 years prior to first dose of study drug, or current New York Heart Association (NYHA) functional classification score of stage II -IV
  • have an active malignancy (those with non-melanoma skin cancer are allowed)
  • have any life-threatening disease or other disease or condition which, according to the investigator's judgment, could imply a potential hazard to the patient, interfere with the trial participation or trial outcome (e.g., a history of non-responsiveness to bypassing products).
  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: NCT02020369

Locations
United States, California
Orthopaedic Hemophilia Treatment Center
Los Angeles, California, United States, 90007
University of California Davis Comprehensive Cancer Center
Sacramento, California, United States, 95817
United States, Colorado
University of Colorado Hemophilia and Thrombosis Center
Aurora, Colorado, United States, 80045
United States, Illinois
Rush University Medical Center
Chicago, Illinois, United States, 60612
United States, Minnesota
University of Minnesota Medical Center Fairview
Minneapolis, Minnesota, United States, 55455
Belarus
Republican Research Center for Radiation Medicine and Human Ecology
Gomel, Belarus
Bulgaria
Specialized Hospital for Active Treatment of Hematological Diseases
Sofia, Bulgaria
Georgia
LTD HEMA
Tbilisi, Georgia
Israel
Chaim Sheba Medical Center, Tel-hashomer hospital
Ramat Gan, Israel, 5261
Poland
Institute of Hematology and Transfusion Medicine
Warsaw, Poland
Russian Federation
Kirov Research Institute of Hematology and Blood Transfusion
Kirov, Russian Federation
Hematology Research Center
Moscow, Russian Federation
City Outpatient Clinic #37
Saint-Petersburg, Russian Federation
Ukraine
Kyiv City Clinical Hospital #9
Kyiv, Ukraine
Institute of Blood Pathology and Transfusion Medicine of Academy of Medical Sciences of Ukraine
Lviv, Ukraine
United Kingdom
Basingstoke and North Hampshire Hospital, Hemophilia, Hemostasis and Thrombosis Center
Basingstoke, Hampshire, RG24 9NA,, United Kingdom
Sponsors and Collaborators
rEVO Biologics
Laboratoire français de Fractionnement et de Biotechnologies
Investigators
Principal Investigator: Jean Francois Schved, MD Saint Eloi Hospital
  More Information

No publications provided

Responsible Party: rEVO Biologics
ClinicalTrials.gov Identifier: NCT02020369     History of Changes
Other Study ID Numbers: RB-FVIIa-006-13
Study First Received: December 18, 2013
Last Updated: May 4, 2015
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Hemophilia A
Hemophilia B
Blood Coagulation Disorders
Blood Coagulation Disorders, Inherited
Coagulation Protein Disorders
Genetic Diseases, Inborn
Genetic Diseases, X-Linked
Hematologic Diseases
Hemorrhagic Disorders
Factor VIII
Coagulants
Hematologic Agents
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on May 29, 2015