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| ID | Type | Description | Link |
|---|---|---|---|
| 2009-012150-20 | EudraCT Number |
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The objective of the trial is to demonstrate that 2-3 times per week prophylaxis therapy with BAY81-8973 is superior to on-demand therapy with BAY81-8973 in patients with severe Hemophilia A. The hypothesis is that prophylaxis will result in fewer bleeds than on-demand treatment.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Arm 1: rFVIII on demand first CS/EP then CS/ADJ | Experimental | Participants received on-demand treatment with recombinant factor VIII (rFVIII, BAY81-8973) assayed by CS/EP (Chromogenic Substrate Assay per European Pharmacopoeia) for 6 months, followed by cross-over to study drug assayed by CS/ADJ (Chromogenic Substrate Assay/label adjusted to one-stage assay) for 6 months. |
|
| Arm 2: rFVIII on demand first CS/ADJ then CS/EP | Experimental | Participants received on-demand treatment with rFVIII (BAY81-8973) assayed by CS/ADJ for 6 months, followed by cross-over to study drug assayed by CS/EP for 6 months. |
|
| Arm 3: rFVIII prophylaxis low-dose first CS/EP then CS/ADJ | Experimental | Participants received low dose prophylaxis treatment at 20, 25 or 30 IU/kg twice per week with rFVIII(BAY81-8973) measured by CS/ EP for 6 months then crossed over to study drug measured by CS/ADJ for 6 months. |
|
| Arm 4: rFVIII prophylaxis low-dose first CS/ADJ then CS/EP | Experimental | Participants received low dose prophylaxis treatment at 20, 25 or 30 IU/kg twice per week with rFVIII (BAY81-8973) measured by CS/ADJ for 6 months then crossed over to study drug measured by CS/ EP for 6 months. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| rFVIII (BAY81-8973) on demand | Biological | Participants received on-demand treatment with rFVIII (BAY81-8973) assayed by CS/EP (Chromogenic Substrate Assay per European Pharmacopoeia) for 6 months and by CS/ADJ (Chromogenic Substrate Assay/label adjusted to one-stage assay) for 6 months, sequence according to randomization |
| Measure | Description | Time Frame |
|---|---|---|
| Annualized Number of All Bleeds | The annualized number of bleeds experienced by participants | Up to 12 months (6 months per mode of potency assignment according to the randomized cross-over design) |
| Measure | Description | Time Frame |
|---|---|---|
| Annualized Number of All Bleeds During CS/EP Period | The annualized number of bleeds experienced by participants while they were taking rFVIII (BAY81-8973) assayed by CS/EP | Up to 6 months (6 months on CS/EP potency assignment) |
| Annualized Number of All Bleeds During CS/ADJ Period |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Bleeds During Treatment | The number of bleeds experienced by each participant | 12 months |
| Number of Participants With Inhibitory Antibody Formation | A test to ensure that participants have not developed antibodies that will interfere with the action of rFVIII (BAY81-8973) |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Bayer Study Director | Bayer | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Dayton | Ohio | 45404 | United States | |||
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 27002680 | Result | Kitchen S, Katterle Y, Beckmann H, Maas Enriquez M. Chromogenic assay for BAY 81-8973 potency assignment has no impact on clinical outcome or monitoring in patient samples. J Thromb Haemost. 2016 Jun;14(6):1192-9. doi: 10.1111/jth.13322. Epub 2016 May 3. | |
| 26931631 | Result | Oldenburg J, Windyga J, Hampton K, Lalezari S, Tseneklidou-Stoeter D, Beckmann H, Maas Enriquez M. Safety and efficacy of BAY 81-8973 for surgery in previously treated patients with haemophilia A: results of the LEOPOLD clinical trial programme. Haemophilia. 2016 May;22(3):349-53. doi: 10.1111/hae.12839. Epub 2016 Mar 1. |
| Label | URL |
|---|---|
| Click here to find information about studies related to Bayer Healthcare products conducted in Europe | View source |
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83 participants were randomized, but 3 of these terminated the study before their first injection of study drug.
Participants were recruited from specialized hemophilia treatment centers.
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| ID | Title | Description |
|---|---|---|
| FG000 | On Demand, BAY 81-8973 Potency First EP Then ADJ | Participants received on-demand treatment with recombinant factor VIII (rFVIII, BAY81-8973) assayed by CS/EP (Chromogenic Substrate Assay per European Pharmacopoeia) for 6 months, followed by cross-over to study drug assayed by CS/ADJ (Chromogenic Substrate Assay/label adjusted to one-stage assay) for 6 months. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| First Intervention (6 Months) |
|
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| Arm 5: rFVIII prophylaxis high-dose first CS/EP then CS/ADJ | Experimental | Participants received high dose prophylaxis treatment at 30, 35 or 40 IU/kg 3 times per week with rFVIII (BAY81-8973) measured by CS/ EP for 6 months then crossed over to study drug measured by CS/ADJ for 6 months. |
|
| Arm 6: rFVIII prophylaxis high-dose first CS/ADJ then CS/EP | Experimental | Participants received high dose prophylaxis treatment at 30, 35 or 40 IU/kg 3 times per week with rFVIII(BAY81-8973) measured by CS/ADJ for 6 months then crossed over to study drug measured by CS/ EP for 6 months. |
|
|
| rFVIII (BAY81-8973) prophylaxis low-dose | Biological | Participants received low dose prophylaxis treatment at 20, 25 or 30 IU/kg twice per week with rFVIII (BAY81-8973) assayed by CS/EP for 6 months and by CS/ADJ for 6 months, sequence according to randomization. |
|
| rFVIII (BAY81-8973) prophylaxis high-dose | Biological | Participants received high dose prophylaxis treatment at 30, 35 or 40 IU/kg 3 times per week with rFVIII (BAY81-8973) assayed by CS/EP for 6 months and by CS/ADJ for 6 months, sequence according to randomization. |
|
The annualized number of bleeds experienced by participants while they were taking rFVIII (BAY81-8973) assayed by CS/ADJ |
| Up to 6 months (6 months on CS/ADJ potency assignment) |
| Percentage of Bleeds Per Participant Controlled With ≤ 2 Injections in Participants Treated on Demand With rFVIII (BAY81-8973) | The percentage of bleeds per participant on on-demand treatment that stopped after two or fewer injections | Up to 12 months (6 months per mode of potency assignment according to the randomized cross-over design) |
| 3, 6, 9 and 12 months after baseline |
| Houston |
| Texas |
| 77030 |
| United States |
| Buenos Aires | Ciudad Auton. de Buenos Aires | C1221ADC | Argentina |
| Corrientes | Corrientes Province | W3410AVV | Argentina |
| Rosario | Santa Fe Province | S2000CKF | Argentina |
| Guangzhou | Guangdong | 510515 | China |
| Suzhou | Jiangsu | 215006 | China |
| Beijing | 100730 | China |
| Shanghai | 200025 | China |
| Tianjin | 300020 | China |
| Bogotá | Bogota D.C. | Colombia |
| Bucaramanga | Santander Department | Colombia |
| Olomouc | 77520 | Czechia |
| Hyderabad | 500034 | India |
| Jakarta | 10430 | Indonesia |
| Hiroshima | Hiroshima | 734-8551 | Japan |
| Nishinomiya | Hyōgo | 663-8501 | Japan |
| Kashihara | Nara | 634-8522 | Japan |
| Shinjuku-ku | Tokyo | 160-0023 | Japan |
| Suginami | Tokyo | 167-0035 | Japan |
| Guadalajara | Jalisco | 44280 | Mexico |
| San Luis Potosí City | San Luis Potosí | 78200 | Mexico |
| Timișoara | Timiș County | 300011 | Romania |
| Baia Mare | 430031 | Romania |
| Bucharest | 011026 | Romania |
| Bucharest | 022328 | Romania |
| Barnaul | 656050 | Russia |
| Khabarovsk | 680009 | Russia |
| Saint Petersburg | 191186 | Russia |
| Yekaterinburg | 620149 | Russia |
| Belgrade | 11000 | Serbia |
| Kragujevac | 34000 | Serbia |
| Niš | 18000 | Serbia |
| Novi Sad | 21000 | Serbia |
| Bratislava | 851 07 | Slovakia |
| Johannesburg | Gauteng | 2193 | South Africa |
| Pretoria | Gauteng | 0001 | South Africa |
| Taichung | 40447 | Taiwan |
| Taipei | 11217 | Taiwan |
| Bangkok | Thailand | 10400 | Thailand |
| Bangkok | Thailand | 10700 | Thailand |
| Adana | 01330 | Turkey (Türkiye) |
| Antalya | 07059 | Turkey (Türkiye) |
| Izmir | 35-100 | Turkey (Türkiye) |
| Kiev | Ukraine |
| Lviv | 79044 | Ukraine |
| Simferopol | 95023 | Ukraine |
| 25546368 | Derived | Kavakli K, Yang R, Rusen L, Beckmann H, Tseneklidou-Stoeter D, Maas Enriquez M; LEOPOLD II Study Investigators. Prophylaxis vs. on-demand treatment with BAY 81-8973, a full-length plasma protein-free recombinant factor VIII product: results from a randomized trial (LEOPOLD II). J Thromb Haemost. 2015 Mar;13(3):360-9. doi: 10.1111/jth.12828. |
| FG001 |
| On Demand, BAY 81-8973 Potency First ADJ Then EP |
Participants received on-demand treatment with rFVIII (BAY81-8973) assayed by CS/ADJ for 6 months, followed by cross-over to study drug assayed by CS/EP for 6 months. |
| FG002 | Low Dose Prophylaxis, BAY 81-8973 Potency First EP Then ADJ | Participants received low dose prophylaxis treatment at 20, 25 or 30 IU/kg twice per week with rFVIII(BAY81-8973) measured by CS/ EP for 6 months then crossed over to study drug measured by CS/ADJ for 6 months. |
| FG003 | Low Dose Prophylaxis, BAY 81-8973 Potency First ADJ Then EP | Participants received low dose prophylaxis treatment at 20, 25 or 30 IU/kg twice per week with rFVIII (BAY81-8973) measured by CS/ADJ for 6 months then crossed over to study drug measured by CS/ EP for 6 months. |
| FG004 | High Dose Prophylaxis, BAY 81-8973 Potency First EP Then ADJ | Participants received high dose prophylaxis treatment at 30, 35 or 40 IU/kg 3 times per week with rFVIII (BAY81-8973) measured by CS/ EP for 6 months then crossed over to study drug measured by CS/ADJ for 6 months. |
| FG005 | High Dose Prophylaxis, BAY 81-8973 Potency First ADJ Then EP | Participants received high dose prophylaxis treatment at 30, 35 or 40 IU/kg 3 times per week with rFVIII(BAY81-8973) measured by CS/ADJ for 6 months then crossed over to study drug measured by CS/ EP for 6 months. |
| Participants Received Treatment |
|
| COMPLETED |
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| NOT COMPLETED |
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| Washout (2-3 Days) |
|
| Second Intervention (6 Months) |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | rFVIII (BAY81-8973) on Demand | Participants received on-demand treatment with rFVIII (BAY81-8973) assayed by CS/EP (Chromogenic Substrate Assay per European Pharmacopoeia) for 6 months and by CS/ADJ (Chromogenic Substrate Assay/label adjusted to one-stage assay) for 6 months, sequence according to randomization. |
| BG001 | rFVIII (BAY81-8973) Prophylaxis Low-dose | Participants received low dose prophylaxis treatment at 20, 25 or 30 IU/kg twice per week with rFVIII (BAY81-8973) assayed by CS/EP for 6 months and by CS/ADJ for 6 months, sequence according to randomization. |
| BG002 | rFVIII (BAY81-8973) Prophylaxis High-dose | Participants received high dose prophylaxis treatment at 30, 35 or 40 IU/kg 3 times per week with rFVIII (BAY81-8973) assayed by CS/EP for 6 months and by CS/ADJ for 6 months, sequence according to randomization. |
| BG003 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | years |
| |||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
|
| 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 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Primary | Annualized Number of All Bleeds | The annualized number of bleeds experienced by participants | ITT (Intent to Treat). Low and high dose prophylaxis arms and both potencies combined as planned for the statistical analysis to achieve intended sample size. | Posted | Mean | Standard Deviation | Bleeds per year per participant | Up to 12 months (6 months per mode of potency assignment according to the randomized cross-over design) |
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| Secondary | Annualized Number of All Bleeds During CS/EP Period | The annualized number of bleeds experienced by participants while they were taking rFVIII (BAY81-8973) assayed by CS/EP | ITT. Low and high dose prophylaxis arms combined as planned for the statistical analysis to achieve sufficient sample size. | Posted | Mean | Standard Deviation | Bleeds per year per participant | Up to 6 months (6 months on CS/EP potency assignment) |
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| Secondary | Annualized Number of All Bleeds During CS/ADJ Period | The annualized number of bleeds experienced by participants while they were taking rFVIII (BAY81-8973) assayed by CS/ADJ | ITT. Low and high dose prophylaxis arms combined as planned for the statistical analysis to achieve sufficient sample size. | Posted | Mean | Standard Deviation | Bleeds per year per participant | Up to 6 months (6 months on CS/ADJ potency assignment) |
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| Secondary | Percentage of Bleeds Per Participant Controlled With ≤ 2 Injections in Participants Treated on Demand With rFVIII (BAY81-8973) | The percentage of bleeds per participant on on-demand treatment that stopped after two or fewer injections | ITT | Posted | Median | Full Range | Percentage of bleeds | Up to 12 months (6 months per mode of potency assignment according to the randomized cross-over design) |
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| Other Pre-specified | Number of Bleeds During Treatment | The number of bleeds experienced by each participant | ITT | Posted | Median | Inter-Quartile Range | Bleeds | 12 months |
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| Other Pre-specified | Number of Participants With Inhibitory Antibody Formation | A test to ensure that participants have not developed antibodies that will interfere with the action of rFVIII (BAY81-8973) | Safety population | Posted | Number | Participants | 3, 6, 9 and 12 months after baseline |
|
Treatment-emergent adverse event data reported here were collected from start of first treatment up to 12.5 months (end of observation period).
Abbreviations used in the Adverse Events section: Medical Dictionary for Regulatory Activities (MedDRA)
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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 | rFVIII (BAY81-8973) Treatment | Participants received on-demand or prophylaxis treatment with recombinant factor VIII (rFVIII, BAY81-8973) assayed by CS/EP for 6 months and by CS/ADJ for 6 months, sequence according to randomization | 2 | 80 | 23 | 80 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Head injury | Injury, poisoning and procedural complications | MedDRA (15.1) | Non-systematic Assessment |
| |
| Asthma | Respiratory, thoracic and mediastinal disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Influenza | Infections and infestations | MedDRA (15.1) | Non-systematic Assessment |
| |
| Nasopharyngitis | Infections and infestations | MedDRA (15.1) | Non-systematic Assessment |
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| Upper respiratory tract infection | Infections and infestations | MedDRA (15.1) | Non-systematic Assessment |
| |
| Headache | Nervous system disorders | MedDRA (15.1) | Non-systematic Assessment |
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| Insomnia | Psychiatric disorders | MedDRA (15.1) | Non-systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Therapeutic Area Head | BAYER | clinical-trials-contact@bayerhealthcare.com |
| ID | Term |
|---|---|
| D006467 | Hemophilia A |
| 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 |
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| ID | Term |
|---|---|
| D005169 | Factor VIII |
| ID | Term |
|---|---|
| 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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| Male |
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