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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)

Primary Purpose

Hemophilia A

Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
rFVIII (BAY81-8973) on demand
rFVIII (BAY81-8973) prophylaxis low-dose
rFVIII (BAY81-8973) prophylaxis high-dose
Sponsored by
Bayer
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Hemophilia A focused on measuring Haemophilia treatment, rFVIII

Eligibility Criteria

12 Years - 65 Years (Child, Adult, Older Adult)MaleDoes not accept healthy volunteers

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

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm Type

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Arm Label

Arm 1: rFVIII on demand first CS/EP then CS/ADJ

Arm 2: rFVIII on demand first CS/ADJ then CS/EP

Arm 3: rFVIII prophylaxis low-dose first CS/EP then CS/ADJ

Arm 4: rFVIII prophylaxis low-dose first CS/ADJ then CS/EP

Arm 5: rFVIII prophylaxis high-dose first CS/EP then CS/ADJ

Arm 6: rFVIII prophylaxis high-dose first CS/ADJ then CS/EP

Arm Description

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.

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.

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.

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.

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.

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.

Outcomes

Primary Outcome Measures

Annualized Number of All Bleeds
The annualized number of bleeds experienced by participants

Secondary Outcome Measures

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
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
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

Full Information

First Posted
November 2, 2010
Last Updated
October 14, 2016
Sponsor
Bayer
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1. Study Identification

Unique Protocol Identification Number
NCT01233258
Brief Title
A Trial to Compare Prophylaxis Therapy to On-demand Therapy With a New Full Length Recombinant FVIII in Patients With Severe Hemophilia A
Acronym
Leopold II
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)
Study Type
Interventional

2. Study Status

Record Verification Date
October 2016
Overall Recruitment Status
Completed
Study Start Date
January 2011 (undefined)
Primary Completion Date
December 2012 (Actual)
Study Completion Date
December 2012 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Bayer

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hemophilia A
Keywords
Haemophilia treatment, rFVIII

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Crossover Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
80 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Arm 1: rFVIII on demand first CS/EP then CS/ADJ
Arm Type
Experimental
Arm Description
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 Title
Arm 2: rFVIII on demand first CS/ADJ then CS/EP
Arm Type
Experimental
Arm Description
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 Title
Arm 3: rFVIII prophylaxis low-dose first CS/EP then CS/ADJ
Arm Type
Experimental
Arm Description
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 Title
Arm 4: rFVIII prophylaxis low-dose first CS/ADJ then CS/EP
Arm Type
Experimental
Arm Description
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 Title
Arm 5: rFVIII prophylaxis high-dose first CS/EP then CS/ADJ
Arm Type
Experimental
Arm Description
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.
Arm Title
Arm 6: rFVIII prophylaxis high-dose first CS/ADJ then CS/EP
Arm Type
Experimental
Arm Description
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.
Intervention Type
Biological
Intervention Name(s)
rFVIII (BAY81-8973) on demand
Intervention Description
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
Intervention Type
Biological
Intervention Name(s)
rFVIII (BAY81-8973) prophylaxis low-dose
Intervention Description
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.
Intervention Type
Biological
Intervention Name(s)
rFVIII (BAY81-8973) prophylaxis high-dose
Intervention Description
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.
Primary Outcome Measure Information:
Title
Annualized Number of All Bleeds
Description
The annualized number of bleeds experienced by participants
Time Frame
Up to 12 months (6 months per mode of potency assignment according to the randomized cross-over design)
Secondary Outcome Measure Information:
Title
Annualized Number of All Bleeds During CS/EP Period
Description
The annualized number of bleeds experienced by participants while they were taking rFVIII (BAY81-8973) assayed by CS/EP
Time Frame
Up to 6 months (6 months on CS/EP potency assignment)
Title
Annualized Number of All Bleeds During CS/ADJ Period
Description
The annualized number of bleeds experienced by participants while they were taking rFVIII (BAY81-8973) assayed by CS/ADJ
Time Frame
Up to 6 months (6 months on CS/ADJ potency assignment)
Title
Percentage of Bleeds Per Participant Controlled With ≤ 2 Injections in Participants Treated on Demand With rFVIII (BAY81-8973)
Description
The percentage of bleeds per participant on on-demand treatment that stopped after two or fewer injections
Time Frame
Up to 12 months (6 months per mode of potency assignment according to the randomized cross-over design)
Other Pre-specified Outcome Measures:
Title
Number of Bleeds During Treatment
Description
The number of bleeds experienced by each participant
Time Frame
12 months
Title
Number of Participants With Inhibitory Antibody Formation
Description
A test to ensure that participants have not developed antibodies that will interfere with the action of rFVIII (BAY81-8973)
Time Frame
3, 6, 9 and 12 months after baseline

10. Eligibility

Sex
Male
Minimum Age & Unit of Time
12 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Bayer Study Director
Organizational Affiliation
Bayer
Official's Role
Study Director
Facility Information:
City
Dayton
State/Province
Ohio
ZIP/Postal Code
45404
Country
United States
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
City
Buenos Aires
State/Province
Ciudad Auton. de Buenos Aires
ZIP/Postal Code
C1221ADC
Country
Argentina
City
Rosario
State/Province
Santa Fe
ZIP/Postal Code
S2000CKF
Country
Argentina
City
Corrientes
ZIP/Postal Code
W3410AVV
Country
Argentina
City
Guangzhou
State/Province
Guangdong
ZIP/Postal Code
510515
Country
China
City
Suzhou
State/Province
Jiangsu
ZIP/Postal Code
215006
Country
China
City
Beijing
ZIP/Postal Code
100730
Country
China
City
Shanghai
ZIP/Postal Code
200025
Country
China
City
Tianjin
ZIP/Postal Code
300020
Country
China
City
Bogotá
State/Province
Distrito Capital de Bogotá
Country
Colombia
City
Bucaramanga
State/Province
Santander
Country
Colombia
City
Olomouc
ZIP/Postal Code
77520
Country
Czech Republic
City
Hyderabad
ZIP/Postal Code
500034
Country
India
City
Jakarta
ZIP/Postal Code
10430
Country
Indonesia
City
Nishinomiya
State/Province
Hyogo
ZIP/Postal Code
663-8501
Country
Japan
City
Kashihara
State/Province
Nara
ZIP/Postal Code
634-8522
Country
Japan
City
Shinjuku-ku
State/Province
Tokyo
ZIP/Postal Code
160-0023
Country
Japan
City
Suginami
State/Province
Tokyo
ZIP/Postal Code
167-0035
Country
Japan
City
Hiroshima
ZIP/Postal Code
734-8551
Country
Japan
City
Guadalajara
State/Province
Jalisco
ZIP/Postal Code
44280
Country
Mexico
City
San Luis Potosí
ZIP/Postal Code
78200
Country
Mexico
City
Timisoara
State/Province
Timis
ZIP/Postal Code
300011
Country
Romania
City
Baia Mare
ZIP/Postal Code
430031
Country
Romania
City
Bucharest
ZIP/Postal Code
011026
Country
Romania
City
Bucharest
ZIP/Postal Code
022328
Country
Romania
City
Barnaul
ZIP/Postal Code
656050
Country
Russian Federation
City
Khabarovsk
ZIP/Postal Code
680009
Country
Russian Federation
City
St. Petersburg
ZIP/Postal Code
191186
Country
Russian Federation
City
Yekaterinburg
ZIP/Postal Code
620149
Country
Russian Federation
City
Beograd
ZIP/Postal Code
11000
Country
Serbia
City
Kragujevac
ZIP/Postal Code
34000
Country
Serbia
City
Nis
ZIP/Postal Code
18000
Country
Serbia
City
Novi Sad
ZIP/Postal Code
21000
Country
Serbia
City
Bratislava
ZIP/Postal Code
851 07
Country
Slovakia
City
Johannesburg
State/Province
Gauteng
ZIP/Postal Code
2193
Country
South Africa
City
Pretoria
State/Province
Gauteng
ZIP/Postal Code
0001
Country
South Africa
City
Taichung
ZIP/Postal Code
40447
Country
Taiwan
City
Taipei
ZIP/Postal Code
11217
Country
Taiwan
City
Bangkok
ZIP/Postal Code
10400
Country
Thailand
City
Bangkok
ZIP/Postal Code
10700
Country
Thailand
City
Adana
ZIP/Postal Code
01330
Country
Turkey
City
Antalya
ZIP/Postal Code
07059
Country
Turkey
City
Izmir
ZIP/Postal Code
35-100
Country
Turkey
City
Kiev
Country
Ukraine
City
Lviv
ZIP/Postal Code
79044
Country
Ukraine
City
Simferopol
ZIP/Postal Code
95023
Country
Ukraine

12. IPD Sharing Statement

Citations:
PubMed Identifier
27002680
Citation
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.
Results Reference
result
PubMed Identifier
26931631
Citation
Oldenburg 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.
Results Reference
result
PubMed Identifier
25546368
Citation
Kavakli 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.
Results Reference
derived
Links:
URL
http://www.clinicaltrialsregister.eu/
Description
Click here to find information about studies related to Bayer Healthcare products conducted in Europe

Learn more about this trial

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

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