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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Bayer
ClinicalTrials.gov Identifier:
NCT01029340
First received: December 8, 2009
Last updated: September 12, 2013
Last verified: September 2013
  Purpose

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)


Condition Intervention Phase
Blood Coagulation Disorders
Hemophilia A
Biological: Recombinant Factor VIII (BAY81-8973)
Biological: Recombinant Factor VIII (Kogenate FS, BAY14-2222)
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Crossover Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Bayer:

Primary Outcome 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. ] [ Designated as safety issue: No ]
    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. ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    The annualized number of bleeds experienced by participants


Secondary Outcome Measures:
  • Part B - The in Vivo Recovery Values of Human Factor VIII (FVIII) [ Time Frame: 15-30 minutes after the injection ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: Yes ]
    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: 12 months ] [ Designated as safety issue: Yes ]
    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 ] [ Designated as safety issue: Yes ]
    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 4 weeks after drug administration ] [ Designated as safety issue: Yes ]
    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: 12 months ] [ Designated as safety issue: Yes ]
    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 ] [ Designated as safety issue: Yes ]
    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 ] [ Designated as safety issue: Yes ]
    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: 12 months ] [ Designated as safety issue: Yes ]
    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 ] [ Designated as safety issue: Yes ]
    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 ] [ Designated as safety issue: Yes ]
    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 ] [ Designated as safety issue: Yes ]
    An assessment made by surgeons of how effective BAY81-8973 was in stopping bleeding during major operations


Enrollment: 74
Study Start Date: December 2009
Study Completion Date: March 2013
Primary Completion Date: June 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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
Biological: Recombinant Factor VIII (BAY81-8973)
Single dose of BAY81-8973 crossed over to single dose of Kogenate FS
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
Biological: Recombinant Factor VIII (Kogenate FS, BAY14-2222)
Single dose of Kogenate FS crossed over to Single dose of BAY81-8973
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
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.
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
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.
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
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

  Eligibility

Ages Eligible for Study:   12 Years to 65 Years
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01029340

  Show 61 Study Locations
Sponsors and Collaborators
Bayer
Investigators
Study Director: Bayer Study Director Bayer
  More Information

Additional Information:
No publications provided

Responsible Party: Bayer
ClinicalTrials.gov Identifier: NCT01029340     History of Changes
Other Study ID Numbers: 12954, 2009-012149-43
Study First Received: December 8, 2009
Results First Received: May 27, 2013
Last Updated: September 12, 2013
Health Authority: Austria: Agency for Health and Food Safety
China: Food and Drug Administration
Finland: Finnish Medicines Agency
Germany: Paul-Ehrlich-Institut
Hong Kong: Department of Health
Indonesia: National Agency of Drug and Food Control
Israel: Ministry of Health
Italy: The Italian Medicines Agency
Norway: Norwegian Medicines Agency
Spain: Spanish Agency of Medicines
Sweden: Medical Products Agency
United Kingdom: Medicines and Healthcare Products Regulatory Agency
Taiwan: Department of Health
Denmark: Danish Medicines Agency
Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
United States: Food and Drug Administration

Keywords provided by Bayer:
Hemophilia A
Factor VIII
Prophylaxis

Additional relevant MeSH terms:
Blood Coagulation Disorders
Hemostatic Disorders
Hematologic Diseases
Vascular Diseases
Cardiovascular Diseases
Hemorrhagic Disorders
Blood Coagulation Disorders, Inherited
Coagulation Protein Disorders
Genetic Diseases, Inborn
Hemophilia A
Factor VIII
Coagulants
Hematologic Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on April 22, 2014