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

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

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.

Study Overview

• Status: Completed
• Conditions: Hemophilia A; Hemophilia B
• Intervention / Treatment: Biological: Recombinant Factor VIIa BI (rFVIIa BI); Biological: Recombinant Factor VIIa BI (rFVIIa BI)

• Study Type: Interventional
• Enrollment (Actual): 40
• Phase: Phase 3

Contacts and Locations

Study Locations

• Japan
  • Nara, Japan, 6348522
    • Nara Medical University Hospital
  • Tokyo, Japan, 1600023
    • Tokyo Medical University Hospital
• Poland
  • Krakow, Poland, 31-501
    • Kracow Medical Center, LLC
  • Warszawa, Poland, 02-776
    • Institute of Haematology and Transfusion Medicine, Clinic of Haemostatic Disorders and Internal Diseases
• Romania
  • Timisoara, Romania, 300011
    • Louis Turcanu Emergency Clinical Children´s Hospital
• Russian Federation
  • Kirov, Russian Federation, 610027
    • Kirov Hematology and Blood Transfusion Research Institute under the Federal Medical and Biological Agency of Russia
  • Moscow, Russian Federation, 125167
    • Hematology Research Center under RAMS (State Institution), Department of Reconstructive Orthopedic Surgery for Hemophilia Patients
  • St. Petersburg, Russian Federation, 195213
    • St. Petersburg City Healthcare Institution Municipal Policlinic # 37
• Serbia
  • Belgrade, Serbia, 11000
    • Clinic for Hematology of the Clinical Center of Serbia
• Spain
  • A Coruña, Spain, 15006
    • Hospital Teresa Herrera Materno Infantil del C.H.U.Carretera del Pasajes/nlaboratorio de hematología
  • Sevilla, Spain, 41013
    • University Hospital Virgen del Rocio
• Taiwan
  • Taipei City, Taiwan, 11490
    • Tri-Service General Hospital (TSGH)
• Ukraine
  • Donetsk, Ukraine, 83045
    • V.K. Gusak Institute of Urgent and Reconstructive Surgery within the Ukrainian National Academy of Medical Sciences, Hematology Department
  • Kiev, Ukraine, 79044
    • Kyiv City Clinical Hospital #9, City Scientific-Practical Center for Diagnostics and Treatment of Patients with Hemostatic Pathlogies
  • Lviv, Ukraine
    • State Institution "Institute of Blood Pathology and Transfusion Medicine within the Ukrainian National Academy of Medical Sciences", Hematology Department
• United States
  • Florida
    • Tampa, Florida, United States, 33607
      • Health Point Medical Group "St Joseph's Children's Hospital"

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years to 65 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

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 α-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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ≤ 3 doses of 90 µg/kg rFVIIa BI	Biological: Recombinant Factor VIIa BI (rFVIIa BI); Administered approximately every 3 hours as an intravenous bolus injection on-demand; Biological: Recombinant Factor VIIa BI (rFVIIa BI); Administered as a single intravenous bolus injection on-demand
Experimental: One dose of 270 µg/kg rFVIIa BI	Biological: Recombinant Factor VIIa BI (rFVIIa BI); Administered approximately every 3 hours as an intravenous bolus injection on-demand; Biological: Recombinant Factor VIIa BI (rFVIIa BI); Administered as a single intravenous bolus injection on-demand

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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)
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)
Percentage of Participants With Inhibitor Development to FVII	Development of rFVII inhibitors or FVIIa binding antibodies during the study.	6 months (throughout study period)

Collaborators and Investigators

• Sponsor: Baxalta now part of Shire

Study record dates

Study Major Dates

• Study Start (Actual): February 20, 2013
• Primary Completion (Actual): November 11, 2014
• Study Completion (Actual): November 11, 2014

Study Registration Dates

• First Submitted: December 21, 2012
• First Submitted That Met QC Criteria: December 21, 2012
• First Posted (Estimate): December 28, 2012

Study Record Updates

• Last Update Posted (Actual): May 11, 2021
• Last Update Submitted That Met QC Criteria: April 14, 2021
• Last Verified: April 1, 2021

More Information

Terms related to this study

• Keywords: with Factor VIII (FVIII) or Factor IX (FIX) inhibitors
• Additional Relevant MeSH Terms: Hematologic Diseases; Blood Coagulation Disorders, Inherited; Coagulation Protein Disorders; Hemorrhagic Disorders; Genetic Diseases, Inborn; Genetic Diseases, X-Linked; Blood Coagulation Disorders; Hemophilia A; Hemophilia B
• Other Study ID Numbers: 021101; 2011-006294-26 (EudraCT Number)