A Phase 2/ 3 Trial to Evaluate the Efficacy and Safety of BAY86-6150

Study Overview
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Brief Summary
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Haemophilia is a disorder, usually genetic, affecting mostly male individuals, in which one of the proteins needed to form blood clots (FVIII) is missing or not present in sufficient levels. In a person with haemophilia, the clotting process is much slower and the person experiences bleeding episodes that can result in serious problems and potential disability. The current haemophilia standard of care is to maintain FVIII activity level above 1%. Sometimes, patients can develop antibodies (so called inhibitors) against FVIII and it is no longer effective at controlling bleeds. Bleeds in these patients are currently treated using other proteins involved in the clotting process. The purpose of this study is to investigate how effectively BAY86-6150 may stop acute bleeds in inhibitor patients. This study consists of two parts, A and B. The purpose of part A is to find the most effective yet tolerable out of four doses of BAY86-6150 with regard to efficacy and safety (dose-finding part). Part A is expected to last 9 - 29 months. The purpose of part B is to confirm efficacy and safety of the dose found in part A in all participating patients (confirmatory part). Part B is expected to last 12-32 months. Approximately 60 male subjects 12 to 62 years-of-age with moderate or severe haemophilia A or B, with inhibitors to FVIII or FIX, who have had 4 or more bleeding episodes in the last 6 months, will participate in this study. Patient's bleeds will be treated with BAY86-6150 and with a rescue medication if no response is made to BAY86-6150. Patients will attend the treatment centre at regular intervals and be required to keep an electronic diary.

Official Title
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A Phase 2/3, Multicenter, Open-label Clinical Study to Assess the Safety and Efficacy of BAY86-6150 in Subjects With Hemophilia A or B With Inhibitors, Composed of 2 Parts (A & B). Part A: Sequential Cohorts of Four Dose Levels of the Modified rFVIIa BAY86-6150 Assessed in a Non-controlled Dose Response Design in Acutely Bleeding Subjects and for PK/ PD in an Intra-individual Crossover Design Compared With One Fixed Dose of Eptacog Alfa in Non-bleeding Subjects. Part B: Confirmatory Study to Further Investigate the Efficacy and Safety of BAY86-6150

Conditions
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Hemophilia A, Hemophilia B

Intervention / Treatment
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* Drug: BAY86-6150
* Drug: eptacog alfa [activated]
* Drug: BAY86-6150


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male subjects 12 to 62 years-of-age History of moderate or severe congenital hemophilia A or B with inhibitors to FVIII or FIX 4 or more bleeding episodes in the last 6 months before enrollment. Exclusion Criteria: Clinically relevant coagulation disorder other than congenital hemophilia A or B with inhibitors History of coronary and/or peripheral atherosclerotic disease Disseminated intravascular coagulopathy, or stage 2 hypertension Angina pectoris Myocardial infarction Transient ischemic attack Stroke Congestive heart failure Thromboembolic event

Ages Eligible for Study
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Minimum Age: 12 Years
Maximum Age: 62 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm 1<br> | Drug: BAY86-6150<br>* Four dose levels (6.5 µg/kg, 20 µg/kg, 50 µg/kg and 90 µg/kg) of BAY86-6150 will be studied.<br>|
| Active Comparator: Arm 2<br> | Drug: eptacog alfa [activated]<br>* comparative PK/PD (pharmacokinetics/pharmacodynamics) evaluation<br>|
| Experimental: Arm 3<br> | Drug: BAY86-6150<br>* Confirmation of recommended dose of BAY86-6150 to be evaluated further as determined in Part A.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Successful treatments of bleeding episodes. | A bleed was defined as successfully treated, if no administration of rescue medication was required. | 10 hours after each bleed | 
| Proportion of successful treatments of bleeding episodes on subject level. | Proportion of successful treatments of bleeding episodes was calculated as number of bleeding episodes treated successfully - without rescue medication - divided by the total number of bleeding episodes on a dose level. | 10 hours after each bleed | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to stop the bleed |  | 10 hours after each bleed | 
| Number of injections needed to stop the bleeding episode. |  | 10 hours after each bleed | 
| Effectiveness of treatment as rated by the subject's assessment (very effective, effective, partially effective, not effective). |  | 10 hours after each bleed | 
| Participant's reported outcome as assessed by Euro QoL (EQ-5D). |  | 14 days after last exposure to BAY86-6150 | 
| Participant's reported outcome as assessed by Brief Pain Inventory. |  | 7 days after last exposure to BAY86-6150 | 
| Participant's reported outcome as assessed by Work Productivity and Activity Impairment Questionaire. |  | 14 days after last exposure to BAY86-6150 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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hemophilia, haemophilia, inhibitor, FVIIa, Factor VII activated, bypassing