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

Overview

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)

Full Title of Study: “A Two Part Randomized Cross-Over Trial to Evaluate the Pharmacokinetics, Efficacy, and Safety Profile of Plasma Protein-Free Recombinant FVIII Formulated With Sucrose (BAY81-8973) in Previously Treated Subjects With Severe Hemophilia A Under Prophylaxis Therapy”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Randomized
    • Intervention Model: Crossover Assignment
    • Primary Purpose: Treatment
    • Masking: None (Open Label)
  • Study Primary Completion Date: June 2012

Interventions

  • Biological: Recombinant Factor VIII (BAY81-8973)
    • Single dose of BAY81-8973 crossed over to single dose of Kogenate FS
  • Biological: Recombinant Factor VIII (Kogenate FS, BAY14-2222)
    • Single dose of Kogenate FS crossed over to Single dose of BAY81-8973
  • Biological: Recombinant Factor VIII (BAY81-8973)
    • Participants received IV injections 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 (CS/EP) for 6 months and by Chromogenic Substrate Assay/Adjusted to Label Potency (CS/ADJ) for 6 months, sequence according to randomization.
  • Biological: Recombinant Factor VIII (BAY81-8973)
    • 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

Arms, Groups and Cohorts

  • Experimental: Arm 1: Recombinant Factor VIII (BAY81-8973) then Kogenate FS
    • 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
  • Experimental: Arm 2: Kogenate FS then Recombinant Factor VIII (BAY81-8973)
    • 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
  • Experimental: Arm 3: Recombinant Factor VIII by CS/EP then by CS/ADJ
    • 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
  • Experimental: Arm 4: Recombinant Factor VIII by CS/ADJ then by CS/EP
    • 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
  • Experimental: Arm 5: Recombinant Factor VIII by CS/EP
    • 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

Clinical Trial Outcome Measures

Primary Measures

  • Part A – Area Under the Drug Concentration-time Curve (AUC)
    • Time Frame: 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)
    • Time Frame: 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
    • Time Frame: 12 months after randomization
    • The annualized number of bleeds experienced by participants

Secondary Measures

  • Part B – The in Vivo Recovery Values of Human Factor VIII (FVIII)
    • Time Frame: 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
    • Time Frame: 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
    • Time Frame: 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
    • Time Frame: 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
    • Time Frame: 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 A – Number of Participants With Inhibitory Antibody Formation
    • Time Frame: 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
    • Time Frame: 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 Inhibitory Antibody Formation
    • Time Frame: 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)
    • Time Frame: 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)
    • Time Frame: Up to 12 months after drug administration
    • A test to analyze the formation of antibodies to HSP-70
  • Part C – Number of Participants With Incidence of Antibody Formation to Heat-shock Protein (HSP-70)
    • Time Frame: before and 3 weeks after surgery
    • A test to analyze the formation of antibodies to HSP-70
  • Part A – Number of Participants With Incidence of Antibody Formation to Host Cell Proteins (HCP)
    • Time Frame: 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 Incidence of Antibody Formation to Host Cell Proteins (HCP)
    • Time Frame: Up to 12 months after drug administration
    • A test to ensure that participants have not developed antibodies to HCP during the study
  • Part C – Number of Participants With Incidence of Antibody Formation to Host Cell Proteins (HCP)
    • Time Frame: before and 3 weeks after surgery
    • 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
    • Time Frame: 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 Assessment of the Hemostasis During Major Surgery
    • Time Frame: at the time of surgery
    • An assessment made by surgeons of how effective BAY81-8973 was in stopping bleeding during major operations

Participating in This Clinical Trial

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

Gender Eligibility: Male

Minimum Age: 12 Years

Maximum Age: 65 Years

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • Bayer
  • Provider of Information About this Clinical Study
    • Sponsor
  • Overall Official(s)
    • Bayer Study Director, Study Director, Bayer

Citations Reporting on 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.

Clinical trials entries are delivered from the US National Institutes of Health and are not reviewed separately by this site. Please see the identifier information above for retrieving further details from the government database.

At TrialBulletin.com, we keep tabs on over 200,000 clinical trials in the US and abroad, using medical data supplied directly by the US National Institutes of Health. Please see the About and Contact page for details.