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

Hemophilia A With Inhibitors Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02020369
• Other study ID #: RB-FVIIa-006-13
• Status: Completed
• Phase: Phase 3
• First received: December 18, 2013
• Last updated: September 3, 2015
• Start date: April 2014
• Est. completion date: August 2015

Study information

• Verified date: September 2015
• Source: rEVO Biologics
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 27
• Est. completion date: August 2015
• Est. primary completion date: July 2015
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 12 Years to 75 Years

Eligibility

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).

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Crossover Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Hemophilia A
• Hemophilia A With Inhibitors
• Hemophilia B
• Hemophilia B With Inhibitors

Intervention

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

Locations

Country	Name	City	State
Belarus	Republican Research Center for Radiation Medicine and Human Ecology	Gomel
Bulgaria	Specialized Hospital for Active Treatment of Hematological Diseases	Sofia
Georgia	LTD HEMA	Tbilisi
Israel	Chaim Sheba Medical Center, Tel-hashomer hospital	Ramat Gan
Poland	Institute of Hematology and Transfusion Medicine	Warsaw
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
Ukraine	Kyiv City Clinical Hospital #9	Kyiv
Ukraine	Institute of Blood Pathology and Transfusion Medicine of Academy of Medical Sciences of Ukraine	Lviv
United Kingdom	Basingstoke and North Hampshire Hospital, Hemophilia, Hemostasis and Thrombosis Center	Basingstoke, Hampshire, RG24 9NA,
United States	University of Colorado Hemophilia and Thrombosis Center	Aurora	Colorado
United States	Rush University Medical Center	Chicago	Illinois
United States	Orthopaedic Hemophilia Treatment Center	Los Angeles	California
United States	University of Minnesota Medical Center Fairview	Minneapolis	Minnesota
United States	University of California Davis Comprehensive Cancer Center	Sacramento	California

Sponsors (2)

Lead Sponsor	Collaborator
rEVO Biologics	Laboratoire français de Fractionnement et de Biotechnologies

Countries where clinical trial is conducted

United States,  Belarus,  Bulgaria,  Georgia,  Israel,  Poland,  Russian Federation,  Ukraine,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Immunogenicity assessment	Based on Coagulation Factor VIIa (Recombinant), binding antibody levels	Pre-dose, 6 week, 12 weeks, 24 weeks then every 12 weeks and end of study visit	Yes
Other	Pharmacokinetic assessment	Based on plasma concentrations of Coagulation Factor VIIa (Recombinant)	7 timepoints from pre-dosing on Day 1 up to 8 hours	No
Primary	Bleeding episode treatment success	No additional hemostatic product required after12 hours of first dose.	12 hours after first administration of study drug	No
Secondary	Time to bleeding success	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	at 12 hours	No