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
  Purpose

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.


Condition Intervention Phase
Hemophilia A
Biological: rFVIII (BAY81-8973) on demand
Biological: rFVIII (BAY81-8973) prophylaxis low-dose
Biological: rFVIII (BAY81-8973) prophylaxis high-dose
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Crossover Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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)

Resource links provided by NLM:


Further study details as provided by Bayer:

Primary Outcome Measures:
  • 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) ] [ Designated as safety issue: No ]
    The annualized number of bleeds experienced by participants


Secondary Outcome Measures:
  • Annualized Number of All Bleeds During CS/EP Period [ Time Frame: Up to 6 months (6 months on CS/EP potency assignment) ] [ Designated as safety issue: No ]
    The annualized number of bleeds experienced by participants while they were taking rFVIII (BAY81-8973) assayed by CS/EP

  • Annualized Number of All Bleeds During CS/ADJ Period [ Time Frame: Up to 6 months (6 months on CS/ADJ potency assignment) ] [ Designated as safety issue: No ]
    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) [ Time Frame: Up to 12 months (6 months per mode of potency assignment according to the randomized cross-over design) ] [ Designated as safety issue: No ]
    The percentage of bleeds per participant on on-demand treatment that stopped after two or fewer injections


Other Outcome Measures:
  • Number of Bleeds During Treatment [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    The number of bleeds experienced by each participant

  • Number of Participants With Inhibitory Antibody Formation [ Time Frame: 3, 6, 9 and 12 months after baseline ] [ Designated as safety issue: Yes ]
    A test to ensure that participants have not developed antibodies that will interfere with the action of rFVIII (BAY81-8973)


Enrollment: 80
Study Start Date: January 2011
Study Completion Date: December 2012
Primary Completion Date: December 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm 1: rFVIII on demand first CS/EP then CS/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.
Biological: 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
Experimental: Arm 2: rFVIII on demand first CS/ADJ then CS/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.
Biological: 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
Experimental: Arm 3: rFVIII prophylaxis low-dose first CS/EP then CS/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.
Biological: 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.
Experimental: Arm 4: rFVIII prophylaxis low-dose first CS/ADJ then CS/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.
Biological: 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.
Experimental: Arm 5: rFVIII prophylaxis high-dose first CS/EP then CS/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.
Biological: 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.
Experimental: Arm 6: rFVIII prophylaxis high-dose first CS/ADJ then CS/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.
Biological: 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.

  Eligibility

Ages Eligible for Study:   12 Years to 65 Years
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01233258

  Show 47 Study Locations
Sponsors and Collaborators
Bayer
Investigators
Study Director: Bayer Study Director Bayer
  More Information

Additional Information:
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

Keywords provided by Bayer:
Haemophilia treatment
rFVIII

Additional relevant MeSH terms:
Hemophilia A
Blood Coagulation Disorders, Inherited
Blood Coagulation Disorders
Hematologic Diseases
Coagulation Protein Disorders
Hemorrhagic Disorders
Genetic Diseases, Inborn
Factor VIII
Coagulants
Hematologic Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on July 22, 2014