Trial to Evaluate the Efficacy and Safety of a New Full Length Recombinant Human FVIII for Hemophilia A (Leopold I)

Bayer

Status and phase: Completed; Phase 3

Conditions: Hemophilia A; Blood Coagulation Disorders

Treatments: Biological: Recombinant Factor VIII (BAY81-8973); Biological: Recombinant Factor VIII (Kogenate FS, BAY14-2222)

Study type: Interventional

Funder types: Industry

Identifiers

NCT01029340

2009-012149-43 (EudraCT Number)

12954

Details and patient eligibility

About

The study will assess the pharmacokinetics (part A) safety, tolerability, and efficacy of prophylaxis treatment (2 to 3 times a week) (part B) with BAY81-8973 over a one year period (split into two six month treatment periods). The study will compare 2 different methods (assays) for measuring the amount of study drug, the chromogenic substrate assay per European Pharmacopeia (CS/EP) with the classical assay (Chromogenic Substrate Adjusted, CS/ADJ). During one six month period patients will receive the study drug where the dose has been measured using the" (CS/EP) and during the other six months period the dose will be measured based on the Chromogenic Substrate Adjusted assay CS/ADJ)

Enrollment: 74 patients

Sex: Male

Ages: 12 to 65 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Male, aged 12 to 65 years
• Severe hemophilia A defined as < 1% FVIII:C
• >/= 150 days of previous treatment with FVIII in lifetime
• Currently receiving on-demand or any type of prophylaxis treatment regimen with any FVIII product
• No history of or current FVIII inhibitors

Exclusion criteria

• Presence of another bleeding disease that is different from hemophilia A (e.g., von Willebrand disease, hemophilia B)
• Low platelet count, abnormal kidney function, or liver disease
• Received treatment with immune suppressing drugs within the last 3 months prior or requires treatment during the study. (Some drugs for hepatitis C, Human immunodeficiency virus (HIV), and steroids are allowed)
• Receiving or has received other experimental drugs within 3 months prior to study entry
• Allergy to Factor VIII or hamsters or mouse protein

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: None (Open label)

---

74 participants in 5 patient groups

Arm 1: Recombinant Factor VIII (BAY81-8973) then Kogenate FS

Experimental group

Description:

Part A - Arm 1: Participants first received one single intravenous (IV) injection of BAY81-8973 50 IU/kg, then 1 single IV injection of Kogenate FS (BAY14-2222) 50 IU/kg with a wash-out period of at least 2-3 days in between

Treatment:

Biological: Recombinant Factor VIII (BAY81-8973)

Biological: Recombinant Factor VIII (BAY81-8973)

Biological: Recombinant Factor VIII (BAY81-8973)

Arm 2: Kogenate FS then Recombinant Factor VIII (BAY81-8973)

Experimental group

Description:

Part A - Arm 2: Participants first received one single intravenous (IV) injection of Kogenate FS (BAY14-2222) 50 IU/kg, then 1 single IV injection of BAY81-8973 50 IU/kg with a wash-out period of at least 2-3 days in between

Treatment:

Biological: Recombinant Factor VIII (Kogenate FS, BAY14-2222)

Arm 3: Recombinant Factor VIII by CS/EP then by CS/ADJ

Experimental group

Description:

Part B - Arm 3: Participants received IV injection of BAY81-8973 at 20-50 IU/kg 2-3 times per week with BAY81-8973 measured by Chromogenic Substrate Assay Potency Per European Pharmacopeia for 6 months and then crossed over to study drug measured by Chromogenic Substrate Assay/Adjusted to Label Potency for 6 months

Treatment:

Biological: Recombinant Factor VIII (BAY81-8973)

Biological: Recombinant Factor VIII (BAY81-8973)

Biological: Recombinant Factor VIII (BAY81-8973)

Arm 4: Recombinant Factor VIII by CS/ADJ then by CS/EP

Experimental group

Description:

Part B - Arm 4:. Participants received IV injection of BAY81-8973 at 20-50 IU/kg 2-3 times per week with BAY81-8973 measured by Chromogenic Substrate Assay/Adjusted to Label Potency for 6 months and then crossed over to study drug measured by Chromogenic Substrate Assay Per European Pharmacopeia for 6 months

Treatment:

Biological: Recombinant Factor VIII (BAY81-8973)

Biological: Recombinant Factor VIII (BAY81-8973)

Biological: Recombinant Factor VIII (BAY81-8973)

Arm 5: Recombinant Factor VIII by CS/EP

Experimental group

Description:

Part C - Arm 5: Participants received a loading dose of approximately 50 IU/kg of BAY 81-8973 before the first surgical incision followed by further treatment with BAY 81-8973 according to surgical requirements for up to 3 weeks

Treatment:

Biological: Recombinant Factor VIII (BAY81-8973)

Biological: Recombinant Factor VIII (BAY81-8973)

Biological: Recombinant Factor VIII (BAY81-8973)