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The purpose of this study is to evaluate efficacy and safety of a Prothrombin Complex Concentrate (PCC), BE1116. BE1116 will be used for the rapid reversal of coagulopathy induced by vitamin K antagonists in Japanese subjects who require immediate correction of international normalized ratio (INR) due to a major bleed or emergency surgery.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| BE1116 | Experimental | Single intravenous (I.V.) infusion, dosage depending on baseline INR and body weight |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| BE1116 (Prothrombin Complex Concentrate) | Biological |
|
|
| Measure | Description | Time Frame |
|---|---|---|
| Percentage of Subjects With a Rapid Reversal of VKA Effect | A rapid reversal of (Vitamin K antagonist) VKA effect is a reduction of the INR to ≤ 1.3 at 30 minutes after the end of infusion. | At baseline and at 30 minutes after the end of infusion |
| Measure | Description | Time Frame |
|---|---|---|
| Percentage of Subjects Achieving Hemostatic Efficacy During Surgery | Hemostatic efficacy is the binary endpoint of effective or non-effective hemostasis, where 'effective' is a hemostatic efficacy rating of "very good" or "satisfactory", and 'non-effective' is a hemostatic efficacy rating of "questionable" or "none". | From the start of surgery/procedure until the end of surgery/procedure |
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Inclusion Criteria:
Exclusion Criteria:
Subjects for whom administration of I.V. vitamin K and VKA withdrawal, alone, can adequately correct the subject's coagulopathy before the infusion of BE1116
Subjects in whom lowering the INR to within the normal range is not a treatment goal
Use of anticoagulants other than VKAs (or expected use within 1 day)
Medical history for which PCCs are contraindicated
History of thromboembolic event within 3 months of screening
Congenital or acquired abnormality of hemostasis other than receipt of VKAs
Administration of whole blood, plasma, plasma fractions, or platelets within 2 weeks prior to the start of BE1116 infusion
For subjects with intracranial hemorrhage (ICH):
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| Name | Affiliation | Role |
|---|---|---|
| Program Director, Acquired Bleeding | CSL Behring | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Nippon Medical School Hospital | Sendagi | Bunkyo | 113-8603 | Japan | ||
| Kyushu Medical Center |
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| Percentage of Subjects Achieving Hemostatic Efficacy of Stopping an Ongoing Major Bleed | Hemostatic efficacy is the binary endpoint of effective or non-effective hemostasis, where 'effective' is a hemostatic efficacy rating of "excellent" or "good," and 'non-effective' is a hemostatic efficacy rating of "poor/none". | Baseline CT scan, baseline haematology or the end of infusion, until 24 hours after the end of infusion |
| Increase in Plasma Levels of Factor (F)II, FVII, FIX, and FX, and Protein C and Protein S | The increase in plasma levels is assessed through response and in vivo recovery (IVR) of FII, FVII, FIX, FX, and protein C and protein S. The incremental IVR [(IU/dL)/(IU/kg)] is calculated as follows: (IU/dL activity rise in plasma)/(IU/kg body weight infused) = [maximum increase in component plasma level within 3 hours compared to pre-infusion (IU/dL)]/{[exact dose of component in drug administered (IU)]/[body weight (kg)]}. | Before infusion and up to 3 h after the start of infusion |
| Percentage of Subjects With INR Correction | The time taken from the start of infusion to INR correction (defined as an INR ≤ 1.3) is recorded. The percentage of participants with INR correction is calculated. | From the start of infusion until INR correction, up to 24 hours after the end of infusion |
| Percentage of Subjects With INR Correction at Various Times After the End of Infusion | The time taken from the end of infusion to INR correction (defined as an INR ≤ 1.3) is recorded. The percentage of participants with INR correction at 0.5, 1, 3, 6, 12, and 24 h after the end of infusion is calculated. | From the end of infusion until INR correction; calculated at 0.5, 1, 3, 6, 12, and 24 h after the end of infusion |
| Percentage of Subjects Who Receive Red Blood Cells | Red blood cells are packed red blood cells (PRBCs). | From the start of infusion until 24 h after the start of infusion |
| Percentage of Subjects Who Receive Other Blood Products and Hemostatic Agents | Other blood products and hemostatic agents containing coagulation factors (such as whole blood, plasma, albumin, platelets) not including PRBCs. | From the start of infusion until 24 h after the start of infusion |
| 45-Day All-cause Mortality | Until Day 45 |
| Overall Treatment-emergent Adverse Events (TEAEs) | Number of participants with TEAEs. TEAEs are defined as adverse events that developed or worsened following exposure to investigational medicinal product. Serious TEAEs are treatment-emergent serious adverse events (SAEs). | From the start of infusion up to the allowed time window of the Day 14 visit for non-serious AEs and from the start of infusion up to the allowed time window of the Day 45 visit for SAEs |
| Mean modified Rankin Scale for all subjects with intracranial haemorrhage | Before infusion and at Day 45 |
| Mean Predicted and Actual Blood Loss (mls) for all Surgical/Invasive Procedures | From the start of surgery/procedure until the end of surgery/procedure |
| Mean Volume (mls) of Wound Drainage for all Surgical/Invasive Procedures | From the start of wound drainage until the end of wound drainage, up to the final safety follow-up visit (Day 45) |
| Mean Time (mins) Between Last Suture and Cessation of Wound Drainage for all Surgical/Invasive Procedure | From the time of last suture until the end of wound drainage, up to the final safety follow-up visit (Day 45) |
| Vital signs | Percentage of participants with a clinically significant change in vital signs (including blood pressure, respiratory rate, temperature and pulse rate) | At baseline and until 24 hours after the end of infusion |
| Viral serology | Percentage of participants with negative viral serology (for Human immunodeficiency virus, Hepatitis B, Hepatitis A, Hepatitis C and Parvovirus B19) before infusion who become positive after infusion. | At baseline and until Day 45 |
| Chūōku |
| Fukuoka |
| 810-8563 |
| Japan |
| Nippon Medical School Chiba Hokusoh Hospital | Kamagari | Inzai | 270-1694 | Japan |
| Kurashiki Central Hospital | Miwa | Kurashiki | 710-0052 | Japan |
| Osaka National Hospital | Chuo-ku | Osaka | 540-0006 | Japan |
| Kinki University | Higashiosaka | Osaka | 577-0818 | Japan |
| National Cerebral and Cardiovascular Center | Suita | Osaka | 565-0873 | Japan |
| Tohoku University Hospital | Aoba-ku | Sendai | 980-8574 | Japan |
| National Center for Global Health and Medicine | Toyama | Shinjuku | 162-0052 | Japan |
| Osaka University Hospital | Yamadaoka | Suita | 565-0871 | Japan |
| St. Luke's International Hospital | Chūō | Tokyo | 104-8560 | Japan |
| ID | Term |
|---|---|
| D005164 | Factor IX |
| ID | Term |
|---|---|
| D004792 | Enzyme Precursors |
| D045762 | Enzymes and Coenzymes |
| D001779 | Blood Coagulation Factors |
| D001798 | Blood Proteins |
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
| D011498 | Protein Precursors |
| D001685 | Biological Factors |
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