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

Phase 3

Completed

• Conditions: Hemophilia A
• Interventions: Biological: rFVIII (BAY81-8973) on demand; Biological: rFVIII (BAY81-8973) prophylaxis low-dose; Biological: rFVIII (BAY81-8973) prophylaxis high-dose

• Registration Number: NCT01233258
• Lead Sponsor: Bayer

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2010-11-02
• Study First Submitted QC: 2010-11-02
• Study First Posted: 2010-11-03
• Study Start: 2011-01
• Primary Completion: 2012-12
• Study Completion: 2012-12
• Results First Submitted: 2013-10-30
• Results First Submitted QC: 2014-01-13
• Results First Posted: 2014-02-11
• Status Verified: 2016-10
• Last Update Submitted: 2016-10-14
• Last Update Posted: 2016-11-28

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Male
• Target Recruitment: 80

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Arm 2: rFVIII on demand first CS/ADJ then CS/EP	rFVIII (BAY81-8973) on demand	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 4: rFVIII prophylaxis low-dose first CS/ADJ then CS/EP	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) measured by CS/ADJ for 6 months then crossed over to study drug measured by CS/ EP for 6 months.
Arm 3: rFVIII prophylaxis low-dose first CS/EP then CS/ADJ	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) 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	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) measured by CS/ADJ for 6 months then crossed over to study drug measured by CS/ EP for 6 months.
Arm 1: rFVIII on demand first CS/EP then CS/ADJ	rFVIII (BAY81-8973) on demand	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 5: rFVIII prophylaxis high-dose first CS/EP then CS/ADJ	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) measured by CS/ EP for 6 months then crossed over to study drug measured by CS/ADJ for 6 months.

Primary Outcome Measures

Name	Time	Method
Annualized Number of All Bleeds	Up to 12 months (6 months per mode of potency assignment according to the randomized cross-over design)	The annualized number of bleeds experienced by participants

Secondary Outcome Measures

Name	Time	Method
Annualized Number of All Bleeds During CS/ADJ Period	Up to 6 months (6 months on CS/ADJ potency assignment)	The annualized number of bleeds experienced by participants while they were taking rFVIII (BAY81-8973) assayed by CS/ADJ
Percentage of Bleeds Per Participant Controlled With ≤ 2 Injections in Participants Treated on Demand With rFVIII (BAY81-8973)	Up to 12 months (6 months per mode of potency assignment according to the randomized cross-over design)	The percentage of bleeds per participant on on-demand treatment that stopped after two or fewer injections
Annualized Number of All Bleeds During CS/EP Period	Up to 6 months (6 months on CS/EP potency assignment)	The annualized number of bleeds experienced by participants while they were taking rFVIII (BAY81-8973) assayed by CS/EP