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)

• Register: EUCTR
• Last refreshed on: 5 August 2013
• Main ID: EUCTR2009-012150-20-CZ
• Date of registration: 13/10/2010
• Prospective Registration: Yes
• Primary sponsor: Bayer HealthCare AG
• Public 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)
• Scientific 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)
• Date of first enrolment: 02/02/2011
• Target sample size: 80
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2009-012150-20
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: yes Single blind: no Double blind: no Parallel group: no Cross over: yes Other: If controlled, specify comparator, Other Medicinial Product: no Placebo: no Other: yes Other specify the comparator: Comparing different doses of the same study drug: BAY 81-8973 (~18% difference between 2 doses)

Countries of recruitment

Argentina, China, Colombia, Czech Republic, Japan, Mexico, Romania, Russian Federation, Serbia, South Africa, Taiwan, Turkey, Ukraine, United States

Contacts

• Name: CTP Team / Ref: "EU CTR" / S102 - R
• Affiliation: Bayer HealthCare AG

• Name: CTP Team / Ref: "EU CTR" / S102 - R
• Affiliation: Bayer HealthCare AG

Key inclusion & exclusion criteria

Inclusion criteria:
• Male, aged 12 to 65 years
• Severe hemophilia A, defined as < 1% FVIII:C as determined by one-stage clotting assay at the time of screening. If screening result turns out to be equal to or higher than 1%, then severe hemophilia A may be confirmed by one of the following (as of Amd 3):
Documented historical evidence from a recognized (certified) clinical laboratory (acceptable to GCL) demonstrating < 1% FVIII:C as determined by one-stage clotting assay
Assay results from a previous Bayer hemophilia clinical trial
• =150 exposure days (ED) in total with any recombinant FVIII or plasma-derived FVIII only. Cryoprecipitate and fresh frozen plasma treatments are not considered in this total. (as of Amd 1)
• Currently receiving episodic treatment with FVIII; and no regular prophylaxis for > 6 consecutive months in the previous 5 years
• No current evidence of inhibitor antibody as measured by the Nijmegen-modified Bethesda assay [<0.3 Bethesda units (BU/mL)] (as of Amd 1) in 2 consecutive samples and absence of clinical signs or symptoms of decreased response to FVIII administration. (First negative sample can be historical if obtained within 3 months prior to screening with a result of ? 0.6 BU/mL by a classical Bethesda assay. The testing for a second negative, confirmatory sample must, in all cases, be performed by a central laboratory using the Nijmegen test. If a first recent sample is not available, then testing for 2 negative samples must be performed by the central laboratory at least 1 week apart). Subjects may not receive FVIII within 72 hours (as of Amd 1) prior tothe collection of samples for inhibitor testing. The time period since the last FVIII injection should not be longer than 4 weeks.
• No history of FVIII inhibitor formation defined as inhibitor antibody <0.6 BU/mL by the Nijmegen-modified or classical Bethesday assay. However subjects with a maximum historical titer of 1.0 BU with the Classical Bethesda assay on no more than 1 occasion but with at least 3 subsequent (as of Amd 1) successive negative results (<0.6 BU) thereafter are also eligible.
• Willingness and ability to complete training in the use of the study electronic patient diary (EPD) by the subject or a surrogate (a caregiver or family member over 18 years of age). (as of Amd 1).
• Written informed consent by subject and parent/legal representative, if under age of consent per local regulation.

Are the trial subjects under 18? yes
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
• Presence of another bleeding disease that is different from hemophilia A (e.g., von Willebrand disease, hemophilia B)
• Thrombocytopenia (platelet count < 100 000/mm3)
• Abnormal renal function (serum creatinine > 2.0 mg/dL)
• Presence of active liver disease verified by medical history or persistent and increased alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 5x the upper limit of normal (ULN) or severe liver disease as evidenced by an INR >4, hypoalbuminemia, and portal vein hypertension.
• Received treatment with immunomodulatory agents within the last 3 months prior to study entry or requires treatment during the study. [The following drugs are allowed: interferon-a treatment for hepatitis C virus (HCV), highly active antiretroviral therapy (HAART) for human immunodeficiency virus (HIV), and or a total of 2 courses of pulse treatment with steroids for a maximum of 7 days at 1 mg/kg or less].
• Absolute CD4 lymphocyte cell count < 250 cells/?L (as of Amd 1).
• Receiving or has received other experimental drugs within 3 months prior to study entry, with the exception of Bayer Kogenate (Bayer factor VIII study drugs) received in studies within 2 weeks prior to study entry. (as of Amd 1)
• Requires any pre-medication to tolerate FVIII injections (e.g., antihistamines)
• Unwilling to comply with study visits or other protocol requirements or is not suitable for participation in this study for any reason, according to the Investigator
• Known hypersensitivity to hamster and/or mouse protein.
• Any subject who cannot forego at least 2-3 days without receiving FVIII for washout purposes. (as of Amd 3)



Age minimum:
Age maximum:
Gender:
Female: no
Male: yes

Health Condition(s) or Problem(s) studied

Severe Hemophilia-A (< 1% FVIII:C)
MedDRA version: 13.1 Level: LLT Classification code 10060613 Term: Hemophilia A (Factor VIII) System Organ Class: 10010331 - Congenital, familial and genetic disorders
MedDRA version: 13.1 Level: LLT Classification code 10053753 Term: Hemophilia A without inhibitors System Organ Class: 10010331 - Congenital, familial and genetic disorders
MedDRA version: 13.1 Level: LLT Classification code 10060612 Term: Hemophilia A System Organ Class: 10010331 - Congenital, familial and genetic disorders

Intervention(s)

Product Name: BAY 81-8973 (250 IU/vial)
Product Code: BAY 81-8973
Pharmaceutical Form: Powder and solvent for solution for injection
INN or Proposed INN: Octocog alfa
Current Sponsor code: BAY 81-8973
Other descriptive name: rFVIII
Concentration unit: IU international unit(s)
Concentration type: equal
Concentration number: 250-

Product Name: BAY 81-8973 (500 IU/vial)
Product Code: BAY 81-8973
Pharmaceutical Form: Powder and solvent for solution for injection
INN or Proposed INN: Octocog alfa
Current Sponsor code: BAY 81-8973
Other descriptive name: rFVIII
Concentration unit: IU international unit(s)
Concentration type: equal
Concentration number: 500-

Product Name: BAY 81-8973 (1000 IU/vial)
Product Code: BAY 81-8973
Pharmaceutical Form: Powder and solvent for solution for injection
INN or Proposed INN: Octocog alfa
Current Sponsor code: BAY 81-8973
Other descriptive name: rFVIII
Concentration unit: IU international unit(s)
Concentration type: equal
Concentration number: 1000-

Product Name: BAY 81-8973 (2000 IU/vial)
Product Code: BAY 81-8973
Pharmaceutical Form: Powder and solvent for solution for injection
INN or Proposed INN: Octocog alfa
Current Sponsor code: BAY 81-8973
Other descriptive name: rFVIII
Concentration unit: IU international unit(s)
Concentration type: equal
Concentration number: 2000-

Primary Outcome(s)

Main Objective: To demonstrate the superiority of prophylaxis over on demand therapy by a clinically significant decrease in bleeding rate following 12 months of treatment with BAY 81-8973.

Primary end point(s): To demonstrate the superiority of prophylaxis over on demand therapy by a clinically significant decrease in bleeding rate following 12 months of treatment with BAY 81-8973.

Secondary Objective: - To demonstrate superiority of prophylaxis versus on-demand treatment with BAY 81-8973 (dose determined by CS/EP) as measured by bleeding rate.
- To demonstrate superiority of prophylaxis versus on-demand treatment with BAY 81-8973 (dose determined by CS/ADJ) as measured by bleeding rate.
- To demonstrate the non-inferiority of prophylactic treatment with BAY 81 8973 (dose determined by CS/EP versus dose determined by CS/ADJ) as measured by bleeding rate (after combining results of this study with results from Protocol 12954).
- To demonstrate the non-inferiority of BAY 81-8973 dose determined by CS/EP versus BAY 81-8973 dose determined by CS/ADJ as measured by the proportion of bleeds controlled by 1 or 2 infusions (among all bleeds) in on-demand patients. (as of Amd 1)
- To demonstrate the non-inferiority of prophylactic treatment with BAY 81 8973 (dose determined by CS/EP versus dose determined by CS/ADJ) as measured by in vivo recovery (IVR).

Secondary ID(s)

BAY81-8973/14319

Source(s) of Monetary Support

Bayer HealthCare AG