Trial to Evaluate the Efficacy and Safety of a New Full Length Recombinant Human FVIII for Hemophilia A (Leopold I)
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| ClinicalTrials.gov Identifier: NCT01029340 |
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Recruitment Status :
Completed
First Posted : December 9, 2009
Results First Posted : November 18, 2013
Last Update Posted : November 28, 2016
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Sponsor:
Bayer
Information provided by (Responsible Party):
Bayer
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Brief 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). 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 or disease | Intervention/treatment | 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 (Clinical Trial) |
| Actual Enrollment : | 74 participants |
| Allocation: | Randomized |
| Intervention Model: | Crossover Assignment |
| Masking: | None (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 |
| Study Start Date : | December 2009 |
| Actual Primary Completion Date : | June 2012 |
| Actual Study Completion Date : | March 2013 |
Resource links provided by the National Library of Medicine
MedlinePlus Genetics related topics:
Hemophilia
MedlinePlus related topics:
Hemophilia
| Arm | Intervention/treatment |
|---|---|
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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
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Biological: Recombinant Factor VIII (BAY81-8973)
Single dose of BAY81-8973 crossed over to single dose of Kogenate FS |
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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
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Biological: Recombinant Factor VIII (Kogenate FS, BAY14-2222)
Single dose of Kogenate FS crossed over to Single dose of BAY81-8973 |
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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
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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. |
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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
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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. |
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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
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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 |
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. ]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 Outcome 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
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| Ages Eligible for Study: | 12 Years to 65 Years (Child, Adult, Older Adult) |
| Sexes 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
Information from the National Library of Medicine
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01029340
Locations
Show 61 study locations
Sponsors and Collaborators
Bayer
Investigators
| Study Director: | Bayer Study Director | Bayer |
Additional Information:
Publications of Results:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Publications of Results:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
| Responsible Party: | Bayer |
| ClinicalTrials.gov Identifier: | NCT01029340 |
| Other Study ID Numbers: |
12954 2009-012149-43 ( EudraCT Number ) |
| First Posted: | December 9, 2009 Key Record Dates |
| Results First Posted: | November 18, 2013 |
| Last Update Posted: | November 28, 2016 |
| Last Verified: | October 2016 |
Keywords provided by Bayer:
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Hemophilia A Factor VIII Prophylaxis |
Additional relevant MeSH terms:
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Hemostatic Disorders Hemophilia A Blood Coagulation Disorders Blood Coagulation Disorders, Inherited Hematologic Diseases Coagulation Protein Disorders |
Hemorrhagic Disorders Genetic Diseases, Inborn Vascular Diseases Cardiovascular Diseases Factor VIII Coagulants |