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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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 July 23, 2014