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)

• ClinicalTrials.gov Identifier: NCT01233258
• Recruitment Status: Completed
• First Posted: November 3, 2010
• Results First Posted: February 11, 2014
• Last Update Posted: November 28, 2016
• Sponsor: Bayer
• Information provided by (Responsible Party): Bayer

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.

Condition or disease	Intervention/treatment	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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 80 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: None (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)
• Study Start Date: January 2011
• Actual Primary Completion Date: December 2012
• Actual Study Completion Date: December 2012

Arms and Interventions

Arm	Intervention/treatment
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.

Outcome Measures

Primary Outcome Measures :

1. 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) ]
   The annualized number of bleeds experienced by participants

Secondary Outcome Measures :

1. Annualized Number of All Bleeds During CS/EP Period [ Time Frame: 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
2. Annualized Number of All Bleeds During CS/ADJ Period [ Time Frame: 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
3. 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) ]
   The percentage of bleeds per participant on on-demand treatment that stopped after two or fewer injections

Other Outcome Measures:

1. Number of Bleeds During Treatment [ Time Frame: 12 months ]
   The number of bleeds experienced by each participant
2. Number of Participants With Inhibitory Antibody Formation [ Time Frame: 3, 6, 9 and 12 months after baseline ]
   A test to ensure that participants have not developed antibodies that will interfere with the action of rFVIII (BAY81-8973)

Eligibility Criteria

• Ages Eligible for Study: 12 Years to 65 Years (Child, Adult, Older Adult)
• Sexes 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

Locations

United States, Ohio

Dayton, Ohio, United States, 45404

United States, Texas

Houston, Texas, United States, 77030

Argentina

Buenos Aires, Ciudad Auton. de Buenos Aires, Argentina, C1221ADC

Rosario, Santa Fe, Argentina, S2000CKF

Corrientes, Argentina, W3410AVV

China, Guangdong

Guangzhou, Guangdong, China, 510515

China, Jiangsu

Suzhou, Jiangsu, China, 215006

China

Beijing, China, 100730

Shanghai, China, 200025

Tianjin, China, 300020

Colombia

Bogotá, Distrito Capital de Bogotá, Colombia

Bucaramanga, Santander, Colombia

Czech Republic

Olomouc, Czech Republic, 77520

India

Hyderabad, India, 500034

Indonesia

Jakarta, Indonesia, 10430

Japan

Nishinomiya, Hyogo, Japan, 663-8501

Kashihara, Nara, Japan, 634-8522

Shinjuku-ku, Tokyo, Japan, 160-0023

Suginami, Tokyo, Japan, 167-0035

Hiroshima, Japan, 734-8551

Mexico

Guadalajara, Jalisco, Mexico, 44280

San Luis Potosí, Mexico, 78200

Romania

Timisoara, Timis, Romania, 300011

Baia Mare, Romania, 430031

Bucharest, Romania, 011026

Bucharest, Romania, 022328

Russian Federation

Barnaul, Russian Federation, 656050

Khabarovsk, Russian Federation, 680009

St. Petersburg, Russian Federation, 191186

Yekaterinburg, Russian Federation, 620149

Serbia

Beograd, Serbia, 11000

Kragujevac, Serbia, 34000

Nis, Serbia, 18000

Novi Sad, Serbia, 21000

Slovakia

Bratislava, Slovakia, 851 07

South Africa

Johannesburg, Gauteng, South Africa, 2193

Pretoria, Gauteng, South Africa, 0001

Taiwan

Taichung, Taiwan, 40447

Taipei, Taiwan, 11217

Thailand

Bangkok, Thailand, 10400

Bangkok, Thailand, 10700

Turkey

Adana, Turkey, 01330

Antalya, Turkey, 07059

Izmir, Turkey, 35-100

Ukraine

Kiev, Ukraine

Lviv, Ukraine, 79044

Simferopol, Ukraine, 95023

Sponsors and Collaborators

Bayer

Investigators

• Study Director: Bayer Study Director; Bayer

More Information

Additional Information:

Click here to find information about studies related to Bayer Healthcare products conducted in Europe 

Publications of Results:

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.

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.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: Bayer
• ClinicalTrials.gov Identifier: NCT01233258
• Other Study ID Numbers: 14319; 2009-012150-20 ( EudraCT Number )
• First Posted: November 3, 2010
• Results First Posted: February 11, 2014
• Last Update Posted: November 28, 2016
• Last Verified: October 2016

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