A Trial to Compare Prophylaxis Therapy to On-demand Therapy With a New Full Length Recombinant FVIII in Patients With Severe Hemophilia A

Study Overview
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Brief Summary
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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.

Official Title
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A Phase II/III, Randomized, Cross-over, Open-label Trial to Demonstrate Superiority of Prophylaxis Over On-demand Therapy in Previously Treated Subjects With Severe Hemophilia A Treated With Plasma Protein-free Recombinant FVIII Formulated With Sucrose (BAY 81-8973)

Conditions
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Hemophilia A

Intervention / Treatment
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* Biological: rFVIII (BAY81-8973) on demand
* Biological: rFVIII (BAY81-8973) prophylaxis low-dose
* Biological: rFVIII (BAY81-8973) prophylaxis high-dose


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male, aged 12 to 65 years Severe hemophilia A History of more than 150 exposure days (ED) with clotting factor concentrates Currently receiving episodic treatment with FVIII; no regular prophylaxis for more than 6 consecutive months in the past 5 years No current Factor VIII inhibitor or history of inhibitor Willing to use electronic patient diary Exclusion Criteria: Presence of another bleeding disease that is different from hemophilia A Thrombocytopenia Abnormal renal function Presence of active liver disease Known hypersensitivity to FVIII

Ages Eligible for Study
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Minimum Age: 12 Years
Maximum Age: 65 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: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm 1: rFVIII on demand first CS/EP then CS/ADJ<br>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. | Biological: rFVIII (BAY81-8973) on demand<br>* 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<br>|
| Experimental: Arm 2: rFVIII on demand first CS/ADJ then CS/EP<br>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. | Biological: rFVIII (BAY81-8973) on demand<br>* 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<br>|
| Experimental: Arm 3: rFVIII prophylaxis low-dose first CS/EP then CS/ADJ<br>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. | Biological: rFVIII (BAY81-8973) prophylaxis low-dose<br>* 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.<br>|
| Experimental: Arm 4: rFVIII prophylaxis low-dose first CS/ADJ then CS/EP<br>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. | Biological: rFVIII (BAY81-8973) prophylaxis low-dose<br>* 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.<br>|
| Experimental: Arm 5: rFVIII prophylaxis high-dose first CS/EP then CS/ADJ<br>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. | Biological: rFVIII (BAY81-8973) prophylaxis high-dose<br>* 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.<br>|
| Experimental: Arm 6: rFVIII prophylaxis high-dose first CS/ADJ then CS/EP<br>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. | Biological: rFVIII (BAY81-8973) prophylaxis high-dose<br>* 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.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | 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) | 

Secondary Outcome Measures

| Outcome Measure | 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 | 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) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Haemophilia treatment, rFVIII