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| ID | Type | Description | Link |
|---|---|---|---|
| 2011-006294-26 | EudraCT Number |
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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| ≤ 3 doses of 90 µg/kg rFVIIa BI | Experimental |
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| One dose of 270 µg/kg rFVIIa BI | Experimental |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Recombinant Factor VIIa BI (rFVIIa BI) | Biological | Administered approximately every 3 hours as an intravenous bolus injection on-demand |
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| 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 |
| 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. |
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Main Inclusion Criteria:
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.
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.
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| Name | Affiliation | Role |
|---|---|---|
| Study Director | Shire | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Health Point Medical Group "St Joseph's Children's Hospital" | Tampa | Florida | 33607 | United States | ||
40 participants provided informed consent and were screened for study participation, of which there was 1 screen failure. 39 participants (in pre-assignment period) were randomized where 1 participant withdrew after randomization but prior to treatment, therefore 38 participants were treated with recombinant activated factor VII BI (rFVIIa).
Enrollment was conduced at 16 clinical sites from the following countries: Japan, Taiwan, Poland, Romania, Russian Federation, Serbia, Spain, Ukraine and the United States.
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| ID | Title | Description |
|---|---|---|
| FG000 | Arm 1: up to 3 x 90 Micrograms/kg rFVIIa BI | Bleeding episodes treated with up to 3 doses of 90 micrograms/kg of recombinant activated factor VII BI (rFVIIaBI) every 3 hours as on-demand intravenous bolus infusions. |
| FG001 | Arm 2: 1 x 270 Micrograms/kg rFVIIa BI |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
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| Recombinant Factor VIIa BI (rFVIIa BI) | Biological | Administered as a single intravenous bolus injection on-demand |
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| 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) |
| Nara Medical University Hospital |
| Nara |
| 6348522 |
| Japan |
| Tokyo Medical University Hospital | Tokyo | 1600023 | Japan |
| Kracow Medical Center, LLC | Krakow | 31-501 | Poland |
| Institute of Haematology and Transfusion Medicine, Clinic of Haemostatic Disorders and Internal Diseases | Warsaw | 02-776 | Poland |
| Louis Turcanu Emergency Clinical Children´s Hospital | Timișoara | 300011 | Romania |
| Kirov Hematology and Blood Transfusion Research Institute under the Federal Medical and Biological Agency of Russia | Kirov | 610027 | Russia |
| Hematology Research Center under RAMS (State Institution), Department of Reconstructive Orthopedic Surgery for Hemophilia Patients | Moscow | 125167 | Russia |
| St. Petersburg City Healthcare Institution Municipal Policlinic # 37 | Saint Petersburg | 195213 | Russia |
| Clinic for Hematology of the Clinical Center of Serbia | Belgrade | 11000 | Serbia |
| Hospital Teresa Herrera Materno Infantil del C.H.U.Carretera del Pasajes/nlaboratorio de hematologÃa | A Coruña | 15006 | Spain |
| University Hospital Virgen del Rocio | Seville | 41013 | Spain |
| Tri-Service General Hospital (TSGH) | Taipei | 11490 | Taiwan |
| V.K. Gusak Institute of Urgent and Reconstructive Surgery within the Ukrainian National Academy of Medical Sciences, Hematology Department | Donetsk | 83045 | Ukraine |
| Kyiv City Clinical Hospital #9, City Scientific-Practical Center for Diagnostics and Treatment of Patients with Hemostatic Pathlogies | Kiev | 79044 | Ukraine |
| State Institution "Institute of Blood Pathology and Transfusion Medicine within the Ukrainian National Academy of Medical Sciences", Hematology Department | Lviv | Ukraine |
Bleeding episodes treated with 1 dose of 270 micrograms/kg of recombinant activated factor VII BI (rFVIIa BI) as on-demand intravenous bolus infusion. |
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| NOT COMPLETED |
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| ID | Title | Description |
|---|---|---|
| BG000 | Arm 1: up to 3 x 90 Micrograms/kg rFVIIa BI | Bleeding episodes treated with up to 3 doses of 90 micrograms/kg of recombinant activated factor VII BI (rFVIIaBI) every 3 hours as on-demand intravenous bolus infusions. |
| BG001 | Arm 2: 1 x 270 Micrograms/kg rFVIIa BI | Bleeding episodes treated with 1 dose of 270 micrograms/kg of recombinant activated factor VII BI (rFVIIa BI) as on-demand intravenous bolus infusion. |
| BG002 | Total | Total of all reporting groups |
| Units | Counts |
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| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Median | Full Range | Years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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. | Full Analysis Dataset | Posted | Number | 95% Confidence Interval | percent of bleeding episodes | within 12 hours of first dose | Bleeding Episodes | Bleeding Episodes |
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| 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. | Full Analysis Dataset | Posted | Number | 95% Confidence Interval | percent of bleeding episodes | within 24 hours of infusion | Bleeding Episodes | Bleeding Episodes |
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| 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). | Full Analysis Dataset | Posted | Number | 95% Confidence Interval | percent of bleeding episodes | 24 hours post infusion | Bleeding Episodes | Bleeding Episodes |
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| 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). | Safety Analysis Dataset | Posted | Number | percent of participants with AEs | 6 months (throughout study period) |
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| 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]). | Safety Analysis Dataset | Posted | Number | percent of AEs | 6 months (throughout study period) | adverse events | adverse events |
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| Secondary | Percentage of Participants With Inhibitor Development to FVII | Development of rFVII inhibitors or FVIIa binding antibodies during the study. | Safety Analysis Dataset | Posted | Number | percent of participants | 6 months (throughout study period) |
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6 months (throughout study period)
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Arm 1: up to 3 x 90 Micrograms/kg rFVIIa BI | Bleeding episodes treated with up to 3 doses of 90 micrograms/kg of recombinant activated factor VII BI (rFVIIa BI) every 3 hours as on-demand intravenous bolus infusions. | 2 | 18 | 4 | 18 | ||
| EG001 | Arm 2: 1 x 270 Micrograms/kg rFVIIa BI | Bleeding episodes treated with 1 dose of 270 micrograms/kg of recombinant activated factor VII BI (rFVIIa BI) as on-demand intravenous bolus infusion. | 2 | 20 | 2 | 20 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Craniocerebral injury | Injury, poisoning and procedural complications | MedDRA 17.1 | Non-systematic Assessment |
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| Joint injury | Injury, poisoning and procedural complications | MedDRA 17.1 | Non-systematic Assessment |
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| Head Injury | Injury, poisoning and procedural complications | MedDRA 17.1 | Non-systematic Assessment |
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| Limb Injury | Injury, poisoning and procedural complications | MedDRA 17.1 | Non-systematic Assessment |
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| Drug Ineffective | General disorders | MedDRA 17.1 | Non-systematic Assessment |
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| Muscle Haemorrhage | Musculoskeletal and connective tissue disorders | MedDRA 17.1 | Non-systematic Assessment |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Laceration | Injury, poisoning and procedural complications | MedDRA 17.1 | Non-systematic Assessment |
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| Hepatic Enzyme Increased | Investigations | MedDRA 17.1 | Systematic Assessment |
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| Nasal Congestion | Respiratory, thoracic and mediastinal disorders | MedDRA 17.1 | Non-systematic Assessment |
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| Oropharyngeal Pain | Respiratory, thoracic and mediastinal disorders | MedDRA 17.1 | Non-systematic Assessment |
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| Drug Hypersensitivity | Immune system disorders | MedDRA 17.1 | Non-systematic Assessment |
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| Headache | Nervous system disorders | MedDRA 17.1 | Non-systematic Assessment |
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| Sinus Headache | Nervous system disorders | MedDRA 17.1 | Non-systematic Assessment |
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| Pyrexia | General disorders | MedDRA 17.1 | Non-systematic Assessment |
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| Influenza | Infections and infestations | MedDRA 17.1 | Non-systematic Assessment |
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| Nasopharyngitis | Infections and infestations | MedDRA 17.1 | Non-systematic Assessment |
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| Tinea Versicolour | Infections and infestations | MedDRA 17.1 | Non-systematic Assessment |
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Baxalta's agreements with PIs may vary per requirements of individual PI, but contain common elements. For this study, results may not be published without prior written approval of Sponsor.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Study Director | Shire | +1 866 842 5335 | ClinicalTransparency@shire.com |
| ID | Term |
|---|---|
| D006467 | Hemophilia A |
| D002836 | Hemophilia B |
| ID | Term |
|---|---|
| D025861 | Blood Coagulation Disorders, Inherited |
| D001778 | Blood Coagulation Disorders |
| D006402 | Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D020147 | Coagulation Protein Disorders |
| D006474 | Hemorrhagic Disorders |
| D030342 | Genetic Diseases, Inborn |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D040181 | Genetic Diseases, X-Linked |
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| ID | Term |
|---|---|
| C103587 | recombinant FVIIa |
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| Male |
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Equivalence of treatment success proportions in all bleeding episodes for the two treatment groups was determined by comparing the 90% two-sided CI of the ratio of success proportions to the equivalence region defined as [0.83, 1.20].
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