AzTrials
AzTrials

Blood Coagulation DisordersPhase 3Leopold INCT01029340

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

A Phase 3 study testing Recombinant Factor VIII (BAY81-8973) and Recombinant Factor VIII (Kogenate FS, BAY14-2222) in people with Blood Coagulation Disorders and Hemophilia A, run by Bayer at 60 sites in 22 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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). Read more about this study

Who is it for?
Ages 12 to 65 years, men only
Conditions the study is for
Blood Coagulation Disorders, Hemophilia A
What is being tested?
Recombinant Factor VIII (BAY81-8973) and Recombinant Factor VIII (Kogenate FS, BAY14-2222)
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
74 participants
Where
60 sitesin 22 countries
Study dates
Dec 2009to Mar 2013
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 12 to 65 years
  • Men only
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • 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

Who cannot join

  • 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

Trial locations and contacts

60 sites in 22 countries.

60 sites in 22 countries

United States7 sites

  • Study site

    Boston, Massachusetts, 02115

  • Study site

    Cleveland, Ohio, 44106-2602

  • Study site

    East Lansing, Michigan, 48823

  • Study site

    Kansas City, Missouri, 64108-9898

  • Study site

    Orange, California, 92868

  • Study site

    Sacramento, California, 95817

  • Study site

    Tampa, Florida, 33607

Other trials in United States

Italy6 sites

  • Study site

    Catanzaro, Calabria, 88100

  • Study site

    Milan, Lombardy, 20122

  • Study site

    Naples, Campania, 80131

  • Study site

    Naples, Campania, 80144

  • Study site

    Rome, Lazio, 00168

  • Study site

    Vicenza, Veneto, 36100

Other trials in Italy

Spain6 sites

  • Study site

    A Coruña, A Coruña, 15006

  • Study site

    Barcelona, Barcelona, 08035

  • Study site

    Jaén, Jaén, 23007

  • Study site

    Oviedo, Principality of Asturias, 33006

  • Study site

    Santander, Cantabria, 39008

  • Study site

    Valencia, Valencia, 46026

Other trials in Spain

Germany5 sites

  • Study site

    Bonn, North Rhine-Westphalia, 53127

  • Study site

    Frankfurt am Main, Hesse, 60596

  • Study site

    Homburg, Saarland, 66421

  • Study site

    Magdeburg, Saxony-Anhalt, 39112

  • Study site

    Mainz, Rhineland-Palatinate, 55131

Other trials in Germany

United Kingdom4 sites

  • Study site

    Dundee, Dundee City, DD1 9SY

  • Study site

    London, SE1 7EH

  • Study site

    Oxford, Oxfordshire, OX3 7LJ

  • Study site

    Sheffield, South Yorkshire, S10 2JF

Other trials in United Kingdom

India3 sites

  • Study site

    Bangalore, 34

  • Study site

    Mumbai, 400012

  • Study site

    Pune, 411005

Other trials in India

Serbia3 sites

  • Study site

    Belgrade, 11000

  • Study site

    Niš, 18000

  • Study site

    Novi Sad, 21000

Other trials in Serbia

Sweden3 sites

  • Study site

    Gothenburg, 413 45

  • Study site

    Malmö, 205 02

  • Karolinska Universitetssjukhuset i Solna

    Stockholm, 171 76

Other trials in Sweden

Taiwan3 sites

  • Study site

    Changhua, 500

  • Study site

    Taipei, Taipei, 10016

  • Study site

    Taipei, 11217

Other trials in Taiwan

Turkey (Türkiye)3 sites

  • Study site

    Adana, 01330

  • Study site

    Antalya, 07059

  • Study site

    Izmir, 35-100

Other trials in Turkey (Türkiye)

Argentina2 sites

  • Study site

    Bahía Blanca, Buenos Aires, B8001HXM

  • Study site

    Rosario, Santa Fe Province, S2000CKF

Other trials in Argentina

Austria2 sites

  • Study site

    Graz, 8036

  • Study site

    Vienna, State of Vienna, 1090

Other trials in Austria

Poland2 sites

  • Study site

    Krakow, 31-501

  • Study site

    Warsaw, 02-776

Other trials in Poland

South Africa2 sites

  • Study site

    Parktown, 2132

  • Study site

    Pretoria, Gauteng, 0001

Other trials in South Africa

Thailand2 sites

  • Study site

    Bangkok, 10330

  • Study site

    Bangkok, 10400

Other trials in Thailand

Croatia1 site

  • Study site

    Zagreb, 10000

Other trials in Croatia

Denmark1 site

  • Study site

    DK-Aarhus N, 8200

Other trials in Denmark

Hong Kong1 site

  • Study site

    Hong Kong

Other trials in Hong Kong

Indonesia1 site

  • Study site

    Jakarta, 10430

Other trials in Indonesia

Israel1 site

  • Study site

    Ramat Gan, 5262000

Other trials in Israel

Norway1 site

  • Study site

    Oslo, 0027

Other trials in Norway

Pakistan1 site

  • Study site

    Karachi, 75300

Other trials in Pakistan

About this study

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

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)

Being tested
Recombinant Factor VIII (BAY81-8973), Recombinant Factor VIII (Kogenate FS, BAY14-2222)
Keywords
Hemophilia A, Factor VIII, Prophylaxis
Medical subject headings
Blood Coagulation Disorders, Hemophilia A

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Recombinant Factor VIII (BAY81-8973)Biological

    Single dose of BAY81-8973 crossed over to single dose of Kogenate FS

  • Recombinant Factor VIII (Kogenate FS, BAY14-2222)Biological

    Single dose of Kogenate FS crossed over to Single dose of BAY81-8973

  • Recombinant Factor VIII (BAY81-8973)Biological

    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.

  • Recombinant Factor VIII (BAY81-8973)Biological

    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

Study groups in NCT01029340
Study groupRoleWhat they receive
Arm 1: Recombinant Factor VIII (BAY81-8973) then Kogenate FSExperimentalPart 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
Receives: Biological: Recombinant Factor VIII (BAY81-8973)
Arm 2: Kogenate FS then Recombinant Factor VIII (BAY81-8973)ExperimentalPart 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
Receives: Biological: Recombinant Factor VIII (Kogenate FS, BAY14-2222)
Arm 3: Recombinant Factor VIII by CS/EP then by CS/ADJExperimentalPart 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
Receives: Biological: Recombinant Factor VIII (BAY81-8973)
Arm 4: Recombinant Factor VIII by CS/ADJ then by CS/EPExperimentalPart 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
Receives: Biological: Recombinant Factor VIII (BAY81-8973)
Arm 5: Recombinant Factor VIII by CS/EPExperimentalPart 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
Receives: Biological: Recombinant Factor VIII (BAY81-8973)

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Part A - Area Under the Drug Concentration-time Curve (AUC)

    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.

    Measured: 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.

  2. Part A - Half-life (t 1/2)

    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.

    Measured: Samples taken at pre-injection, and at 0.25, 0.5, 1, 3, 6, 8, 24, 30 and 48 hours post injection.

  3. Part B - Annualized Number of Total Bleeds

    The annualized number of bleeds experienced by participants

    Measured: 12 months after randomization

Secondary outcomes (16)

  1. Part B - The in Vivo Recovery Values of Human Factor VIII (FVIII)

    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.

    Measured: 15-30 minutes after the injection

  2. Part B - Annualized Number of Bleeds in Each 6-month Potency Assignment Period

    The annualized number of bleeds experienced by participants in each of the two treatment periods

    Measured: 6 months on each potency

  3. Part B - Control of Bleeding as Measured by the Number of Injections Required to Treat a Bleed

    The number of injections needed by participants to stop a bleed

    Measured: 6 months on each potency

  4. Part B - Changes From Baseline at 12 Months in Quality of Life (QoL) as Measured by Transformed Total Score of Haemo-QoL Questionnaire

    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.

    Measured: Baseline and 12 months

  5. Part B - Changes From Baseline at 12 Months in Utility Index as Measured by EQ-5D Questionaire

    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.

    Measured: Baseline and 12 months

  6. Part A - Number of Participants With Inhibitory Antibody Formation

    A test to ensure that participants have not developed antibodies that will interfere with the action of BAY81-8973

    Measured: Up to 6 weeks after first injection of study drug

  7. Part B - Number of Participants With Incidence of Inhibitory Antibody Formation

    A test to ensure that participants have not developed antibodies that will interfere with the action of BAY81-8973

    Measured: Up to 12 months after drug administration

  8. Part C - Number of Participants With Incidence of Inhibitory Antibody Formation

    A test to ensure that participants have not developed antibodies that will interfere with the action of BAY81-8973

    Measured: before and 3 weeks after surgery

  9. Part A - Number of Participants With Incidence of Antibody Formation to Heat-shock Protein (HSP-70)

    A test to analyze the formation of antibodies to HSP-70

    Measured: Up to 6 weeks after drug administration

  10. Part B - Number of Participants With Incidence of Antibody Formation to Heat-shock Protein (HSP-70)

    A test to analyze the formation of antibodies to HSP-70

    Measured: Up to 12 months after drug administration

  11. Part C - Number of Participants With Incidence of Antibody Formation to Heat-shock Protein (HSP-70)

    A test to analyze the formation of antibodies to HSP-70

    Measured: before and 3 weeks after surgery

  12. Part A - Number of Participants With Incidence of Antibody Formation to Host Cell Proteins (HCP)

    A test to ensure that participants have not developed antibodies to HCP during the study

    Measured: Up to 4 weeks after drug administration

  13. Part B - Number of Participants With Incidence of Antibody Formation to Host Cell Proteins (HCP)

    A test to ensure that participants have not developed antibodies to HCP during the study

    Measured: Up to 12 months after drug administration

  14. Part C - Number of Participants With Incidence of Antibody Formation to Host Cell Proteins (HCP)

    A test to ensure that participants have not developed antibodies to HCP during the study

    Measured: before and 3 weeks after surgery

  15. Part B - Number of Participants With Assessment of the Hemostasis During Major Surgery

    An assessment made by surgeons of how effective BAY81-8973 was in stopping bleeding during major operations

    Measured: An average of 1 month after start of treatment

  16. Part C - Number of Participants With Assessment of the Hemostasis During Major Surgery

    An assessment made by surgeons of how effective BAY81-8973 was in stopping bleeding during major operations

    Measured: at the time of surgery

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted9 Dec 2009 (estimated)
  2. Study startDec 2009
  3. Primary completionJun 2012
  4. Study completionMar 2013

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Crossover
Masking
None (open label)
Enrolment
74 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01029340
Sponsor's protocol ID
12954
Other IDs
2009-012149-43, 2009
Acronym
Leopold I
Status last verified
Oct 2016
First submitted
8 Dec 2009
Last updated
28 Nov 2016
Data monitoring committee
Yes

Publications

  • 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.

    PubMed 27002680

  • 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.

    PubMed 26931631

  • Saxena K, Lalezari S, Oldenburg J, Tseneklidou-Stoeter D, Beckmann H, Yoon M, Maas Enriquez M. Efficacy and safety of BAY 81-8973, a full-length recombinant factor VIII: results from the LEOPOLD I trial. Haemophilia. 2016 Sep;22(5):706-12. doi: 10.1111/hae.12952. Epub 2016 Jun 24.

    PubMed 27339736

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Recombinant Factor VIII (BAY81-8973) and Recombinant Factor VIII (Kogenate FS, BAY14-2222) in people with Blood Coagulation Disorders and Hemophilia A, run by Bayer at 60 sites in 22 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 28 Nov 2016. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 60 sites in United States, Italy, Spain, Germany, United Kingdom and 17 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 18 Nov 2013). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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.). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01029340, which also lists 3 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Nov 2016.

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