Recombinant Factor VIIa BI (rFVIIa BI) Treatment of Acute Bleeding Episodes Per an On-demand Regimen

Hemophilia A Clinical Trial

Official title:

A PHASE 3, PROSPECTIVE, OPEN-LABEL, RANDOMIZED STUDY TO EVALUATE SAFETY AND EFFICACY OF RECOMBINANT ACTIVATED FVII BI (rFVIIa BI) IN THE TREATMENT OF ACUTE BLEEDING EPISODES PER AN ON-DEMAND REGIMEN IN PATIENTS WITH HEMOPHILIA A OR B WITH INHIBITORS

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01757405
• Other study ID #: 021101
• Secondary ID: 2011-006294-26
• Status: Completed
• Phase: Phase 3
• Start date: February 20, 2013
• Est. completion date: November 11, 2014

Study information

• Verified date: April 2021
• Source: Takeda
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of the study is to determine the efficacy and safety of rFVIIa BI as part of a six-month on-demand treatment regimen in hemophilia A or B subjects with inhibitors.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 40
• Est. completion date: November 11, 2014
• Est. primary completion date: November 11, 2014
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 12 Years to 65 Years

Eligibility

Main Inclusion Criteria:

• Participant is male with hemophilia A or B with inhibitors, with a high titer (=5 Bethesda unit (BU)) or a historical high anamnestic response.
• Participant is 12 to 65 years old at the time of screening.
• Participant is currently using or has used bypassing agents for treatment of bleeding episodes.
• Participant has an annualized bleed rate of 5 or more bleeding episodes per year on average over the 2 years prior to the Screening visit.
• Participant has a Karnofsky Performance Score =60.
• Participant is hepatitis C virus negative (HCV-) either by antibody testing or polymerase chain reaction (PCR); or hepatitis C virus positive (HCV+) with stable hepatic disease.
• Participant is human immunodeficiency virus negative (HIV-) or HIV+ with stable disease, CD4+ count =200 cells/mm^3 at screening.
• Participant is willing and able to comply with the requirements of the protocol.

Main Exclusion Criteria:

• Participant is not willing to go on an on-demand treatment scheme.
• Participant is positive for a FVII inhibitor at screening.
• Participant has clinically symptomatic liver disease.
• Participant has a platelet count <100,000/µL.
• The use of a-interferon with or without ribavirin is planned for an HCV-infected participant or the use of a protease inhibitor is planned for an HIV-infected participant.
• Participants currently taking any of these medications for =30 days are eligible.
• Participant has a known hypersensitivity to rFVIIa, hamster or murine proteins, or Tween 80.
• Participant has a known history of being non-responsive to rFVIIa treatment of bleeding episodes.
• Participant has a prior history of thromboembolic event or diagnosis of other diseases that may increase the participant's risk of thromboembolic complications.
• Participant has participated in another clinical study involving an investigational product (IP) or investigational device within 30 days prior to enrollment or is scheduled to participate in another clinical study involving an IP or investigational device during the course of this study.
• Participant is a family member or employee of the investigator.
• Participant is scheduled for surgery during the study period.

Related Conditions & MeSH terms

• Hemophilia A
• Hemophilia B

Intervention

Biological:
• Recombinant Factor VIIa BI (rFVIIa BI)
Administered approximately every 3 hours as an intravenous bolus injection on-demand
• Recombinant Factor VIIa BI (rFVIIa BI)
Administered as a single intravenous bolus injection on-demand

Locations

Country	Name	City	State
Japan	Nara Medical University Hospital	Nara
Japan	Tokyo Medical University Hospital	Tokyo
Poland	Kracow Medical Center, LLC	Krakow
Poland	Institute of Haematology and Transfusion Medicine, Clinic of Haemostatic Disorders and Internal Diseases	Warszawa
Romania	Louis Turcanu Emergency Clinical Children´s Hospital	Timisoara
Russian Federation	Kirov Hematology and Blood Transfusion Research Institute under the Federal Medical and Biological Agency of Russia	Kirov
Russian Federation	Hematology Research Center under RAMS (State Institution), Department of Reconstructive Orthopedic Surgery for Hemophilia Patients	Moscow
Russian Federation	St. Petersburg City Healthcare Institution Municipal Policlinic # 37	St. Petersburg
Serbia	Clinic for Hematology of the Clinical Center of Serbia	Belgrade
Spain	Hospital Teresa Herrera Materno Infantil del C.H.U.Carretera del Pasajes/nlaboratorio de hematología	A Coruña
Spain	University Hospital Virgen del Rocio	Sevilla
Taiwan	Tri-Service General Hospital (TSGH)	Taipei City
Ukraine	V.K. Gusak Institute of Urgent and Reconstructive Surgery within the Ukrainian National Academy of Medical Sciences, Hematology Department	Donetsk
Ukraine	Kyiv City Clinical Hospital #9, City Scientific-Practical Center for Diagnostics and Treatment of Patients with Hemostatic Pathlogies	Kiev
Ukraine	State Institution "Institute of Blood Pathology and Transfusion Medicine within the Ukrainian National Academy of Medical Sciences", Hematology Department	Lviv
United States	Health Point Medical Group "St Joseph's Children's Hospital"	Tampa	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Baxalta now part of Shire

Countries where clinical trial is conducted

United States,  Japan,  Poland,  Romania,  Russian Federation,  Serbia,  Spain,  Taiwan,  Ukraine, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Bleeding Episode With "Treatment Success"	No additional hemostatic product required within 12 hours of first dose other than the prescribed dosing regimen.	within 12 hours of first dose
Secondary	Treatment Response for Each Bleeding Episode	Participants rated the treatment of each bleeding episode. If treatment occurred under direct supervision of treating physician, the physician rated the response. Ratings based on a 4 point scale; EXCELLENT - full relief of pain and cessation of objective signs of bleeding (swelling, tenderness, decrease in range of motion [for muscle bleeds]) within 9 hours of treatment initiation. No additional infusion required to control bleeding, other than prescribed dosing regimen. GOOD - Substantial relief of pain and/or cessation of objective signs of bleeding within 9 hours of treatment initiation. No additional infusion required to control bleeding, other than prescribed dosing regimen. MODERATE - slight relief of pain and slight improvement of signs of bleeding within 9 hours of treatment initiation. Requires additional infusion beyond treatment regimen. NONE - No improvement or condition worsens. SUCCESSFUL = EXCELLENT or GOOD.	within 24 hours of infusion
Secondary	Percentage of Clinical Responders (Sustained Bleeding Control) for All Acute Bleeding Episodes	Clinical responders defined as sustained bleeding control, (no additional hemostatic medication including rFVIIa BI required between 12 and 24 hours after first infusion of the successfully treated bleeding episode).	24 hours post infusion
Secondary	Safety and Tolerability of Treatment Regimens by Clinical Assessment of Percentage of Participants With Adverse Events (AEs)	Safety was determined by the number of AEs (both serious AEs [SAEs] and non-serious AEs [nsAE]). Tolerability was determined by the number of AEs related to rFVIIa BI (both SAEs and nsAEs) as determined by causality assessment of the AEs by the investigator. An AE was deemed Related if the investigator judged the AE to be "possibly related" or "probably related" to rFVIIa BI. The percentage of participants with AEs were presented by seriousness (SAE, nsAE), severity (Mild, Moderate or Severe) and causality (Related or Not Related to rFVIIa BI).	6 months (throughout study period)
Secondary	Safety and Tolerability of Treatment Regimens by Clinical Assessment of Adverse Events (AEs)	Safety was determined by the number of AEs (both serious AEs [SAEs] and non-serious AEs [nsAE]). Tolerability was determined by the number of AEs related to rFVIIa BI (both SAEs and nsAEs) as determined by causality assessment of the AEs by the investigator. An AE was deemed Related if the investigator judges the AE to be "possibly related" or "probably related" to rFVIIa BI. The percentage of AEs were presented by seriousness (SAE, nsAE), severity (Mild, Moderate or Severe) and causality (Related or Not Related [to rFVIIa BI]).	6 months (throughout study period)
Secondary	Percentage of Participants With Inhibitor Development to FVII	Development of rFVII inhibitors or FVIIa binding antibodies during the study.	6 months (throughout study period)