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

Phase 3

Completed

• Conditions: Blood Coagulation Disorders; Hemophilia A
• Interventions: Biological: Recombinant Factor VIII (Kogenate FS, BAY14-2222); Biological: Recombinant Factor VIII (BAY81-8973)

• Registration Number: NCT01029340
• Lead Sponsor: Bayer

Brief Summary

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)

Detailed Description

Not available

Study Timeline

• Study Start: 2009-12
• Study First Submitted: 2009-12-08
• Study First Submitted QC: 2009-12-08
• Study First Posted: 2009-12-09
• Primary Completion: 2012-06
• Study Completion: 2013-03
• Results First Submitted: 2013-05-27
• Results First Submitted QC: 2013-09-12
• Results First Posted: 2013-11-18
• Status Verified: 2016-10
• Last Update Submitted: 2016-10-14
• Last Update Posted: 2016-11-28

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Male
• Target Recruitment: 74

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Arm 2: Kogenate FS then Recombinant Factor VIII (BAY81-8973)	Recombinant Factor VIII (Kogenate FS, BAY14-2222)	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
Arm 4: Recombinant Factor VIII by CS/ADJ then by CS/EP	Recombinant Factor VIII (BAY81-8973)	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
Arm 1: Recombinant Factor VIII (BAY81-8973) then Kogenate FS	Recombinant Factor VIII (BAY81-8973)	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
Arm 3: Recombinant Factor VIII by CS/EP then by CS/ADJ	Recombinant Factor VIII (BAY81-8973)	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
Arm 5: Recombinant Factor VIII by CS/EP	Recombinant Factor VIII (BAY81-8973)	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

Primary Outcome Measures

Name	Time	Method
Part A - Area Under the Drug Concentration-time Curve (AUC)	Samples taken at pre-injection, and at 0.25, 0.5, 1, 3, 6, 8, 24, 30 and 48 hours post injection. AUC calculated from time of injection to infinity.	To examine the Pharmacokinetic (PK) characteristics of BAY 81-8973 and ensure that the new drug is similar to Kogenate FS. All results are based on the chromogenic assay.
Part A - Half-life (t 1/2)	Samples taken at pre-injection, and at 0.25, 0.5, 1, 3, 6, 8, 24, 30 and 48 hours post injection.	To examine the PK characteristics of BAY81-8973 and ensure that the new drug is similar to Kogenate FS. All results are based on the chromogenic assay.
Part B - Annualized Number of Total Bleeds	12 months after randomization	The annualized number of bleeds experienced by participants

Secondary Outcome Measures

Name	Time	Method
Part B - The in Vivo Recovery Values of Human Factor VIII (FVIII)	15-30 minutes after the injection	The amount of Factor VIII found in blood samples taken after the injection of the study drug at the beginning of the CS/EP treatment period.
Part B - Annualized Number of Bleeds in Each 6-month Potency Assignment Period	6 months on each potency	The annualized number of bleeds experienced by participants in each of the two treatment periods
Part B - Control of Bleeding as Measured by the Number of Injections Required to Treat a Bleed	6 months on each potency	The number of injections needed by participants to stop a bleed
Part B - Changes From Baseline at 12 Months in Quality of Life (QoL) as Measured by Transformed Total Score of Haemo-QoL Questionnaire	Baseline and 12 months	A measure of how treatment with BAY81-8973 affected the daily life of participants. the scoring system has 100 points. 0 is the worst possible score. 100 is the best possible score. Positive changes from baseline indicate an improvement in quality of life and negative changes indicate a deterioration.
Part B - Changes From Baseline at 12 Months in Utility Index as Measured by EQ-5D Questionaire	Baseline and 12 months	A measure of how treatment with BAY81-8973 affected the daily life of participants. 1.0 = Best possible score, -0.594 = Worst possible score. Positive changes from baseline indicate an improvement and negative changes indicate a deterioration.
Part C - Number of Participants With Incidence of Inhibitory Antibody Formation	before and 3 weeks after surgery	A test to ensure that participants have not developed antibodies that will interfere with the action of BAY81-8973
Part A - Number of Participants With Incidence of Antibody Formation to Heat-shock Protein (HSP-70)	Up to 6 weeks after drug administration	A test to analyze the formation of antibodies to HSP-70
Part B - Number of Participants With Incidence of Antibody Formation to Heat-shock Protein (HSP-70)	Up to 12 months after drug administration	A test to analyze the formation of antibodies to HSP-70
Part A - Number of Participants With Inhibitory Antibody Formation	Up to 6 weeks after first injection of study drug	A test to ensure that participants have not developed antibodies that will interfere with the action of BAY81-8973
Part B - Number of Participants With Incidence of Inhibitory Antibody Formation	Up to 12 months after drug administration	A test to ensure that participants have not developed antibodies that will interfere with the action of BAY81-8973
Part C - Number of Participants With Incidence of Antibody Formation to Heat-shock Protein (HSP-70)	before and 3 weeks after surgery	A test to analyze the formation of antibodies to HSP-70
Part B - Number of Participants With Incidence of Antibody Formation to Host Cell Proteins (HCP)	Up to 12 months after drug administration	A test to ensure that participants have not developed antibodies to HCP during the study
Part A - Number of Participants With Incidence of Antibody Formation to Host Cell Proteins (HCP)	Up to 4 weeks after drug administration	A test to ensure that participants have not developed antibodies to HCP during the study
Part B - Number of Participants With Assessment of the Hemostasis During Major Surgery	An average of 1 month after start of treatment	An assessment made by surgeons of how effective BAY81-8973 was in stopping bleeding during major operations
Part C - Number of Participants With Incidence of Antibody Formation to Host Cell Proteins (HCP)	before and 3 weeks after surgery	A test to ensure that participants have not developed antibodies to HCP during the study
Part C - Number of Participants With Assessment of the Hemostasis During Major Surgery	at the time of surgery	An assessment made by surgeons of how effective BAY81-8973 was in stopping bleeding during major operations

Trial Locations

Locations (1)

Karolinska Universitetssjukhuset i Solna; 🇸🇪 Stockholm, Sweden