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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Bayer
ClinicalTrials.gov Identifier:
NCT01233258
First received: November 2, 2010
Last updated: January 13, 2014
Last verified: January 2014
Results First Received: October 30, 2013  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Crossover Assignment;   Masking: Open Label;   Primary Purpose: Treatment
Condition: Hemophilia A
Interventions: Biological: rFVIII (BAY81-8973) on demand
Biological: rFVIII (BAY81-8973) prophylaxis low-dose
Biological: rFVIII (BAY81-8973) prophylaxis high-dose

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
Participants were recruited from specialized hemophilia treatment centers.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
83 participants were randomized, but 3 of these terminated the study before their first injection of study drug.

Reporting Groups
  Description
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.
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.
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.
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.
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.
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.

Participant Flow for 3 periods

Period 1:   First Intervention (6 Months)
    On Demand, BAY 81-8973 Potency First EP Then ADJ     On Demand, BAY 81-8973 Potency First ADJ Then EP     Low Dose Prophylaxis, BAY 81-8973 Potency First EP Then ADJ     Low Dose Prophylaxis, BAY 81-8973 Potency First ADJ Then EP     High Dose Prophylaxis, BAY 81-8973 Potency First EP Then ADJ     High Dose Prophylaxis, BAY 81-8973 Potency First ADJ Then EP  
STARTED     11     10     14     16     16     16  
Participants Received Treatment     11     10     13     15     16     15  
COMPLETED     10     10     13     15     16     15  
NOT COMPLETED     1     0     1     1     0     1  
Withdrawal by Subject                 0                 0                 0                 1                 0                 1  
Protocol Violation                 0                 0                 1                 0                 0                 0  
Non-compliance with study medication                 1                 0                 0                 0                 0                 0  

Period 2:   Washout (2-3 Days)
    On Demand, BAY 81-8973 Potency First EP Then ADJ     On Demand, BAY 81-8973 Potency First ADJ Then EP     Low Dose Prophylaxis, BAY 81-8973 Potency First EP Then ADJ     Low Dose Prophylaxis, BAY 81-8973 Potency First ADJ Then EP     High Dose Prophylaxis, BAY 81-8973 Potency First EP Then ADJ     High Dose Prophylaxis, BAY 81-8973 Potency First ADJ Then EP  
STARTED     10     10     13     15     16     15  
COMPLETED     10     10     13     15     16     15  
NOT COMPLETED     0     0     0     0     0     0  

Period 3:   Second Intervention (6 Months)
    On Demand, BAY 81-8973 Potency First EP Then ADJ     On Demand, BAY 81-8973 Potency First ADJ Then EP     Low Dose Prophylaxis, BAY 81-8973 Potency First EP Then ADJ     Low Dose Prophylaxis, BAY 81-8973 Potency First ADJ Then EP     High Dose Prophylaxis, BAY 81-8973 Potency First EP Then ADJ     High Dose Prophylaxis, BAY 81-8973 Potency First ADJ Then EP  
STARTED     10     10     13     15     16     15  
COMPLETED     10     10     13     15     16     15  
NOT COMPLETED     0     0     0     0     0     0  



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
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.
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.
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.
Total Total of all reporting groups

Baseline Measures
    rFVIII (BAY81-8973) on Demand     rFVIII (BAY81-8973) Prophylaxis Low-dose     rFVIII (BAY81-8973) Prophylaxis High-dose     Total  
Number of Participants  
[units: participants]
  21     28     31     80  
Age  
[units: years]
Mean ± Standard Deviation
  31.4  ± 10.9     28.8  ± 10.9     29.1  ± 11.5     29.6  ± 11.0  
Gender  
[units: Participants]
       
Female     0     0     0     0  
Male     21     28     31     80  



  Outcome Measures
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1.  Primary:   Annualized Number of All Bleeds   [ Time Frame: Up to 12 months (6 months per mode of potency assignment according to the randomized cross-over design) ]

2.  Secondary:   Annualized Number of All Bleeds During CS/EP Period   [ Time Frame: Up to 6 months (6 months on CS/EP potency assignment) ]

3.  Secondary:   Annualized Number of All Bleeds During CS/ADJ Period   [ Time Frame: Up to 6 months (6 months on CS/ADJ potency assignment) ]

4.  Secondary:   Percentage of Bleeds Per Participant Controlled With ≤ 2 Injections in Participants Treated on Demand With rFVIII (BAY81-8973)   [ Time Frame: Up to 12 months (6 months per mode of potency assignment according to the randomized cross-over design) ]

5.  Other Pre-specified:   Number of Bleeds During Treatment   [ Time Frame: 12 months ]

6.  Other Pre-specified:   Number of Participants With Inhibitory Antibody Formation   [ Time Frame: 3, 6, 9 and 12 months after baseline ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
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  More Information
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Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed.


Results Point of Contact:  
Name/Title: Therapeutic Area Head
Organization: BAYER
e-mail: clinical-trials-contact@bayerhealthcare.com


No publications provided


Responsible Party: Bayer
ClinicalTrials.gov Identifier: NCT01233258     History of Changes
Other Study ID Numbers: 14319, 2009-012150-20
Study First Received: November 2, 2010
Results First Received: October 30, 2013
Last Updated: January 13, 2014
Health Authority: Argentina: Administracion Nacional de Medicamentos, Alimentos y Tecnologia Medica
China: Food and Drug Administration
Colombia: INVIMA Instituto Nacional de Vigilancia de Medicamentos y Alimentos
Czech Republic: State Institute for Drug Control
Japan: Pharmaceuticals and Medical Devices Agency
Mexico: Federal Commission for Protection Against Health Risks
Romania: National Medicines Agency
Russia: Ministry of Health of the Russian Federation
Serbia and Montenegro: Agency for Drugs and Medicinal Devices
Slovakia: State Institute for Drug Control
South Africa: Medicines Control Council
Taiwan : Food and Drug Administration
Turkey: Ministry of Health
Ukraine: State Pharmacological Center - Ministry of Health
United States: Food and Drug Administration