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

Primary Purpose

Hemophilia A, Hemophilia B

Status

Completed

Phase

Phase 3

Locations

International

Study Type

Interventional

Intervention

Recombinant Factor VIIa BI (rFVIIa BI)

About this trial

This is an interventional treatment trial for Hemophilia A focused on measuring with Factor VIII (FVIII) or Factor IX (FIX) inhibitors

Eligibility Criteria

12 Years - 65 Years (Child, Adult, Older Adult)MaleDoes not accept healthy volunteers

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.

Sites / Locations

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

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Arm Label

≤ 3 doses of 90 µg/kg rFVIIa BI

One dose of 270 µg/kg rFVIIa BI

Arm Description

Outcomes

Primary Outcome Measures

Percentage of Bleeding Episode With "Treatment Success"

No additional hemostatic product required within 12 hours of first dose other than the prescribed dosing regimen.

Secondary Outcome Measures

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.

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).

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).

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]).

Percentage of Participants With Inhibitor Development to FVII

Development of rFVII inhibitors or FVIIa binding antibodies during the study.

Full Information

NCT ID

NCT01757405

First Posted

December 21, 2012

Last Updated

April 14, 2021

Sponsor

Baxalta now part of Shire

1. Study Identification

Unique Protocol Identification Number

NCT01757405

Brief Title

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

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

Study Type

Interventional

2. Study Status

Record Verification Date

April 2021

Overall Recruitment Status

Completed

Study Start Date

February 20, 2013 (Actual)

Primary Completion Date

November 11, 2014 (Actual)

Study Completion Date

November 11, 2014 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Baxalta now part of Shire

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

Brief 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Hemophilia A, Hemophilia B

Keywords

with Factor VIII (FVIII) or Factor IX (FIX) inhibitors

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 3

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

40 (Actual)

8. Arms, Groups, and Interventions

Arm Title

≤ 3 doses of 90 µg/kg rFVIIa BI

Arm Type

Experimental

Arm Title

One dose of 270 µg/kg rFVIIa BI

Arm Type

Experimental

Intervention Type

Biological

Intervention Name(s)

Recombinant Factor VIIa BI (rFVIIa BI)

Intervention Description

Administered approximately every 3 hours as an intravenous bolus injection on-demand

Intervention Type

Biological

Intervention Name(s)

Recombinant Factor VIIa BI (rFVIIa BI)

Intervention Description

Administered as a single intravenous bolus injection on-demand

Primary Outcome Measure Information:

Title

Percentage of Bleeding Episode With "Treatment Success"

Description

No additional hemostatic product required within 12 hours of first dose other than the prescribed dosing regimen.

Time Frame

within 12 hours of first dose

Secondary Outcome Measure Information:

Title

Treatment Response for Each Bleeding Episode

Description

Time Frame

within 24 hours of infusion

Title

Percentage of Clinical Responders (Sustained Bleeding Control) for All Acute Bleeding Episodes

Description

Time Frame

24 hours post infusion

Title

Safety and Tolerability of Treatment Regimens by Clinical Assessment of Percentage of Participants With Adverse Events (AEs)

Description

Time Frame

6 months (throughout study period)

Title

Safety and Tolerability of Treatment Regimens by Clinical Assessment of Adverse Events (AEs)

Description

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]).

Time Frame

6 months (throughout study period)

Title

Percentage of Participants With Inhibitor Development to FVII

Description

Development of rFVII inhibitors or FVIIa binding antibodies during the study.

Time Frame

6 months (throughout study period)

10. Eligibility

Sex

Male

Minimum Age & Unit of Time

12 Years

Maximum Age & Unit of Time

65 Years

Accepts Healthy Volunteers

Eligibility Criteria

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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Study Director

Organizational Affiliation

Shire

Official's Role

Study Director

Facility Information:

Facility Name

Health Point Medical Group "St Joseph's Children's Hospital"

City

Tampa

State/Province

Florida

ZIP/Postal Code

33607

Country

United States

Facility Name

Nara Medical University Hospital

City

Nara

ZIP/Postal Code

6348522

Country

Japan

Facility Name

Tokyo Medical University Hospital

City

Tokyo

ZIP/Postal Code

1600023

Country

Japan

Facility Name

Kracow Medical Center, LLC

City

Krakow

ZIP/Postal Code

31-501

Country

Poland

Facility Name

Institute of Haematology and Transfusion Medicine, Clinic of Haemostatic Disorders and Internal Diseases

City

Warszawa

ZIP/Postal Code

02-776

Country

Poland

Facility Name

Louis Turcanu Emergency Clinical Children´s Hospital

City

Timisoara

ZIP/Postal Code

300011

Country

Romania

Facility Name

Kirov Hematology and Blood Transfusion Research Institute under the Federal Medical and Biological Agency of Russia

City

Kirov

ZIP/Postal Code

610027

Country

Russian Federation

Facility Name

Hematology Research Center under RAMS (State Institution), Department of Reconstructive Orthopedic Surgery for Hemophilia Patients

City

Moscow

ZIP/Postal Code

125167

Country

Russian Federation

Facility Name

St. Petersburg City Healthcare Institution Municipal Policlinic # 37

City

St. Petersburg

ZIP/Postal Code

195213

Country

Russian Federation

Facility Name

Clinic for Hematology of the Clinical Center of Serbia

City

Belgrade

ZIP/Postal Code

11000

Country

Serbia

Facility Name

Hospital Teresa Herrera Materno Infantil del C.H.U.Carretera del Pasajes/nlaboratorio de hematología

City

A Coruña

ZIP/Postal Code

15006

Country

Spain

Facility Name

University Hospital Virgen del Rocio

City

Sevilla

ZIP/Postal Code

41013

Country

Spain

Facility Name

Tri-Service General Hospital (TSGH)

City

Taipei City

ZIP/Postal Code

11490

Country

Taiwan

Facility Name

V.K. Gusak Institute of Urgent and Reconstructive Surgery within the Ukrainian National Academy of Medical Sciences, Hematology Department

City

Donetsk

ZIP/Postal Code

83045

Country

Ukraine

Facility Name

Kyiv City Clinical Hospital #9, City Scientific-Practical Center for Diagnostics and Treatment of Patients with Hemostatic Pathlogies

City

Kiev

ZIP/Postal Code

79044

Country

Ukraine

Facility Name

State Institution "Institute of Blood Pathology and Transfusion Medicine within the Ukrainian National Academy of Medical Sciences", Hematology Department

City

Lviv

Country

Ukraine

12. IPD Sharing Statement

Learn more about this trial

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

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