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

October 14, 2016 updated by: Bayer

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

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)

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
74

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Argentina
    • Buenos Aires
      • Bahia Blanca, Buenos Aires, Argentina, B8001HXM
    • Santa Fe
      • Rosario, Santa Fe, Argentina, S2000CKF
  • Austria
      • Graz, Austria, 8036
      • Wien, Austria, 1090
  • Croatia
      • Zagreb, Croatia, 10000
  • Denmark
      • DK-Aarhus N, Denmark, 8200
  • Germany
    • Hessen
      • Frankfurt, Hessen, Germany, 60596
    • Nordrhein-Westfalen
      • Bonn, Nordrhein-Westfalen, Germany, 53127
    • Rheinland-Pfalz
      • Mainz, Rheinland-Pfalz, Germany, 55131
    • Saarland
      • Homburg, Saarland, Germany, 66421
    • Sachsen-Anhalt
      • Magdeburg, Sachsen-Anhalt, Germany, 39112
  • Hong Kong
      • Hongkong, Hong Kong
  • India
      • Bangalore, India, 34
      • Mumbai, India, 400012
      • Pune, India, 411005
  • Indonesia
      • Jakarta, Indonesia, 10430
  • Israel
      • Ramat Gan, Israel, 5262000
  • Italy
    • Calabria
      • Catanzaro, Calabria, Italy, 88100
    • Campania
      • Napoli, Campania, Italy, 80131
      • Napoli, Campania, Italy, 80144
    • Lazio
      • Roma, Lazio, Italy, 00168
    • Lombardia
      • Milano, Lombardia, Italy, 20122
    • Veneto
      • Vicenza, Veneto, Italy, 36100
  • Norway
      • Oslo, Norway, 0027
  • Pakistan
      • Karachi, Pakistan, 75300
  • Poland
      • Krakow, Poland, 31-501
      • Warszawa, Poland, 02-776
  • Serbia
      • Belgrade, Serbia, 11000
      • Beograd, Serbia, 11000
      • Nis, Serbia, 18000
      • Novi Sad, Serbia, 21000
  • South Africa
      • Parktown, South Africa, 2132
    • Gauteng
      • Pretoria, Gauteng, South Africa, 0001
  • Spain
      • A Coruña, Spain, 15006
      • Barcelona, Spain, 08035
      • Jaén, Spain, 23007
      • Valencia, Spain, 46026
    • Asturias
      • Oviedo, Asturias, Spain, 33006
    • Cantabria
      • Santander, Cantabria, Spain, 39008
  • Sweden
      • Göteborg, Sweden, 413 45
      • Malmö, Sweden, 205 02
      • Stockholm, Sweden, 171 76
        • Karolinska Universitetssjukhuset i Solna
  • Taiwan
      • Changhua, Taiwan, 500
      • Taipei, Taiwan, 11217
      • Taipei, Taiwan, 10016
  • Thailand
      • Bangkok, Thailand, 10400
      • Bangkok, Thailand, 10330
  • Turkey
      • Adana, Turkey, 01330
      • Antalya, Turkey, 07059
      • Izmir, Turkey, 35-100
  • United Kingdom
      • London, United Kingdom, SE1 7EH
    • Dundee City
      • Dundee, Dundee City, United Kingdom, DD1 9SY
    • Oxfordshire
      • Oxford, Oxfordshire, United Kingdom, OX3 7LJ
    • South Yorkshire
      • Sheffield, South Yorkshire, United Kingdom, S10 2JF
  • United States
    • California
      • Orange, California, United States, 92868
      • Sacramento, California, United States, 95817
    • Florida
      • Tampa, Florida, United States, 33607
    • Massachusetts
      • Boston, Massachusetts, United States, 02115
    • Michigan
      • East Lansing, Michigan, United States, 48823
    • Missouri
      • Kansas City, Missouri, United States, 64108-9898
    • Ohio
      • Cleveland, Ohio, United States, 44106-2602

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

12 years to 65 years (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Male

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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
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
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)
Single dose of BAY81-8973 crossed over to single dose of Kogenate FS
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
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)
Single dose of BAY81-8973 crossed over to single dose of Kogenate FS
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
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)
Single dose of BAY81-8973 crossed over to single dose of Kogenate FS
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

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
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.
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.
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.
Samples taken at pre-injection, and at 0.25, 0.5, 1, 3, 6, 8, 24, 30 and 48 hours post injection.
Part B - Annualized Number of Total Bleeds
Time Frame: 12 months after randomization
The annualized number of bleeds experienced by participants
12 months after randomization

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
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.
15-30 minutes after the injection
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
6 months on each potency
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
6 months on each potency
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.
Baseline and 12 months
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.
Baseline and 12 months
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
Up to 6 weeks after first injection of study drug
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
Up to 12 months after drug administration
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
before and 3 weeks after surgery
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
Up to 6 weeks after drug administration
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
Up to 12 months after drug administration
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
before and 3 weeks after surgery
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
Up to 4 weeks after drug administration
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
Up to 12 months after drug administration
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
before and 3 weeks after surgery
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
An average of 1 month after start of treatment
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
at the time of surgery

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Bayer

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
December 1, 2009

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
June 1, 2012

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
March 1, 2013

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
December 8, 2009

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
December 8, 2009

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
December 9, 2009

Study Record Updates

Last Update Posted (Estimate)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
November 28, 2016

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
October 14, 2016

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
October 1, 2016

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 12954
  • 2009-012149-43 (EudraCT Number)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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