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
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)
2 other identifiers
interventional
80
18 countries
47
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at below P25 for phase_3
Started Jan 2011
47 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
November 2, 2010
CompletedFirst Posted
Study publicly available on registry
November 3, 2010
CompletedStudy Start
First participant enrolled
January 1, 2011
CompletedPrimary Completion
Last participant's last visit for primary outcome
December 1, 2012
CompletedStudy Completion
Last participant's last visit for all outcomes
December 1, 2012
CompletedResults Posted
Study results publicly available
February 11, 2014
CompletedNovember 28, 2016
October 1, 2016
1.9 years
November 2, 2010
October 30, 2013
October 14, 2016
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
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 Outcomes (3)
Annualized Number of All Bleeds During CS/EP Period
Up to 6 months (6 months on CS/EP potency assignment)
Annualized Number of All Bleeds During CS/ADJ Period
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)
Up to 12 months (6 months per mode of potency assignment according to the randomized cross-over design)
Other Outcomes (2)
Number of Bleeds During Treatment
12 months
Number of Participants With Inhibitory Antibody Formation
3, 6, 9 and 12 months after baseline
Study Arms (6)
Arm 1: rFVIII on demand first CS/EP then CS/ADJ
EXPERIMENTALParticipants 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 2: rFVIII on demand first CS/ADJ then CS/EP
EXPERIMENTALParticipants 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 3: rFVIII prophylaxis low-dose first CS/EP then CS/ADJ
EXPERIMENTALParticipants 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 4: rFVIII prophylaxis low-dose first CS/ADJ then CS/EP
EXPERIMENTALParticipants 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 5: rFVIII prophylaxis high-dose first CS/EP then CS/ADJ
EXPERIMENTALParticipants 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.
Arm 6: rFVIII prophylaxis high-dose first CS/ADJ then CS/EP
EXPERIMENTALParticipants 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.
Interventions
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
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.
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 Criteria
You may qualify if:
- 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
You may not qualify if:
- Presence of another bleeding disease that is different from hemophilia A
- Thrombocytopenia
- Abnormal renal function
- Presence of active liver disease
- Known hypersensitivity to FVIII
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Bayerlead
Study Sites (47)
Unknown Facility
Dayton, Ohio, 45404, United States
Unknown Facility
Houston, Texas, 77030, United States
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Buenos Aires, Ciudad Auton. de Buenos Aires, C1221ADC, Argentina
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Corrientes, Corrientes Province, W3410AVV, Argentina
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Rosario, Santa Fe Province, S2000CKF, Argentina
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Guangzhou, Guangdong, 510515, China
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Suzhou, Jiangsu, 215006, China
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Beijing, 100730, China
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Shanghai, 200025, China
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Tianjin, 300020, China
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Bogotá, Bogota D.C., Colombia
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Bucaramanga, Santander Department, Colombia
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Olomouc, 77520, Czechia
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Hyderabad, 500034, India
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Jakarta, 10430, Indonesia
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Hiroshima, Hiroshima, 734-8551, Japan
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Nishinomiya, Hyōgo, 663-8501, Japan
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Kashihara, Nara, 634-8522, Japan
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Shinjuku-ku, Tokyo, 160-0023, Japan
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Suginami, Tokyo, 167-0035, Japan
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Guadalajara, Jalisco, 44280, Mexico
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San Luis Potosí City, San Luis Potosí, 78200, Mexico
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Timișoara, Timiș County, 300011, Romania
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Baia Mare, 430031, Romania
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Bucharest, 011026, Romania
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Bucharest, 022328, Romania
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Barnaul, 656050, Russia
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Khabarovsk, 680009, Russia
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Saint Petersburg, 191186, Russia
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Yekaterinburg, 620149, Russia
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Belgrade, 11000, Serbia
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Kragujevac, 34000, Serbia
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Niš, 18000, Serbia
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Novi Sad, 21000, Serbia
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Bratislava, 851 07, Slovakia
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Johannesburg, Gauteng, 2193, South Africa
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Pretoria, Gauteng, 0001, South Africa
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Taichung, 40447, Taiwan
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Taipei, 11217, Taiwan
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Bangkok, Thailand, 10400, Thailand
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Bangkok, Thailand, 10700, Thailand
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Adana, 01330, Turkey (Türkiye)
Unknown Facility
Antalya, 07059, Turkey (Türkiye)
Unknown Facility
Izmir, 35-100, Turkey (Türkiye)
Unknown Facility
Kiev, Ukraine
Unknown Facility
Lviv, 79044, Ukraine
Unknown Facility
Simferopol, 95023, Ukraine
Related Publications (3)
Kitchen S, Katterle Y, Beckmann H, Maas Enriquez M. Chromogenic assay for BAY 81-8973 potency assignment has no impact on clinical outcome or monitoring in patient samples. J Thromb Haemost. 2016 Jun;14(6):1192-9. doi: 10.1111/jth.13322. Epub 2016 May 3.
PMID: 27002680RESULTOldenburg J, Windyga J, Hampton K, Lalezari S, Tseneklidou-Stoeter D, Beckmann H, Maas Enriquez M. Safety and efficacy of BAY 81-8973 for surgery in previously treated patients with haemophilia A: results of the LEOPOLD clinical trial programme. Haemophilia. 2016 May;22(3):349-53. doi: 10.1111/hae.12839. Epub 2016 Mar 1.
PMID: 26931631RESULTKavakli K, Yang R, Rusen L, Beckmann H, Tseneklidou-Stoeter D, Maas Enriquez M; LEOPOLD II Study Investigators. Prophylaxis vs. on-demand treatment with BAY 81-8973, a full-length plasma protein-free recombinant factor VIII product: results from a randomized trial (LEOPOLD II). J Thromb Haemost. 2015 Mar;13(3):360-9. doi: 10.1111/jth.12828.
PMID: 25546368DERIVED
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Therapeutic Area Head
- Organization
- BAYER
Study Officials
- STUDY DIRECTOR
Bayer Study Director
Bayer
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- GT60
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- CROSSOVER
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
November 2, 2010
First Posted
November 3, 2010
Study Start
January 1, 2011
Primary Completion
December 1, 2012
Study Completion
December 1, 2012
Last Updated
November 28, 2016
Results First Posted
February 11, 2014
Record last verified: 2016-10