Back to resultsAssess the Safety and Efficacy of Individually Tailored Prophylaxis With Human-cl rhFVIII in Patients With Severe Haemophilia A
Primary Purpose
Severe Haemophilia A
Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Human-cl rhFVIII
Sponsored by
About this trial
This is an interventional prevention trial for Severe Haemophilia A
Eligibility Criteria
Inclusion Criteria:
- Severe haemophilia A (FVIII:C < 1%) according to medical history.
- Male patients ≥ 18 years old.
- Previous treatment with a FVIII concentrate (regular prophylaxis with good compliance or on-demand treatment) for at least 150 exposure days (EDs).
- Good documentation regarding dosing and bleeding frequency in the 6 months preceding study start.
- Immunocompetence (CD4+ count > 200/microliter).
- HIV-negative, if positive, viral load < 200 particles/microliter or < 400,000 copies/mL.
- Freely given written informed consent
Exclusion Criteria:
- Any coagulation disorder other than haemophilia A.
- Present or past FVIII inhibitor activity (> 0.6 Bethesda Unit [BU])
- Severe liver or kidney disease.
Sites / Locations
- Medical University Vienna
- University Multiprofile Hospital for Active Treatment
- Specialized Hospital for Active Treatment
- Multiprofile Hospital for Active Treatment
- Vivantes Hospital in Friedrichshain
- SRH Kurpfalzklinik Heidelberg GMBH
- Hungarian National Healthcare Center
- University of Debrecen, Medical and Health Science Center
- University Teaching Hospital in Bialystok, Teaching Department of Hematology with a Subdepartment of Vascular Diseases
- University Clinical Center, Teaching Department of Hematology and Transplantology
- Nicolaus Copernicus Municipal Specialist Hospital, Department of Hematology
- Institute of Hematology and Transfusion Medicine, Depart. of Hemostatic Disorders and Internal Diseases
- Sanador SRL
- Louis Turcanu Emergency Clinical Children's Hospital
- University Hospital Saint Cyril and Metod
- University Hospital Martin, Department of Hematology and Transfusiology
- Basingstoke and North Hampshire Hospital, Hemophilia, Hemostasis and Thrombosis Center
- Royal London Hospital, Barts and the London Hemophilia Center
- Manchester Royal Infirmary, Department of Clinical Hematology
- Royal Hallamshire Hospital
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Human-cl rhFVIII
Arm Description
Up to 60-80 IU/kg of intravenous Human-cl rhFVIII was administered at an individually determined dose and dose interval.
Outcomes
Primary Outcome Measures
Annualized Number of Bleeding Episodes (BE) in Phase II
The annualized number of total BEs was calculated for each participant as follows: d*y/t, where y = the number of BEs documented in Phase II, t = the number of treatment periods in days, and d = 365.25, the number of days per year. A bleeding episode (BE) was defined as any BE whether treated or not during Phase II of the study; BEs related to surgery were not included. This study was considered as showing efficacy if the annualized number of BEs was reduced by 50% compared to the number of BEs observed in study GENA-01 where patient where severe Hemophilia A patients were treated on-demand (NCT00989196).
Secondary Outcome Measures
Annualized Number of Spontaneous Bleeding Episodes (BE) in Phase II
The annualized number of spontaneous BEs was calculated for each participant as follows: d*y/t, where y = the number of spontaneous BEs documented in Phase II, t = the number of treatment periods in days, and d = 365.25, the number of days per year. A spontaneous bleeding episode (BE) was defined as a BE whether treated or not during Phase II of the study. BEs related to surgery and BEs due to trauma or due to other causes were not included.
Annualized Number of Bleeding Episodes (BE) in Phase II in Participants With ≤ 2 Treatments/Week
The annualized number of BEs was calculated for each participant as follows: d*y/t, where y = the number of BEs documented in Phase II, t = the number of treatment periods in days, and d = 365.25, the number of days per year. A bleeding episode (BE) was defined as a BE whether treated or not during Phase II of the study. BEs related to surgery were not included.
Median Dosing Interval During Individually Tailored Prophylaxis
The median time between 2 prophylactic doses of Human-cl rhFVIII in the prophylactic treatment phase II were determined per patient
Dosage Per Week in Phase II
The mean dosage per week during Phase II of the study are reported.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01863758
Brief Title
Assess the Safety and Efficacy of Individually Tailored Prophylaxis With Human-cl rhFVIII in Patients With Severe Haemophilia A
Official Title
Prospective, Open-label, Multicenter Phase 3b Study to Assess the Safety and Efficacy of Individually Tailored Prophylaxis With Human-cl rhFVIII in Previously Treated Adult Patients With Severe Haemophilia A
Study Type
Interventional
2. Study Status
Record Verification Date
July 2017
Overall Recruitment Status
Completed
Study Start Date
August 2013 (undefined)
Primary Completion Date
January 2015 (Actual)
Study Completion Date
January 2015 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Octapharma
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
To compare the number of breakthrough bleeds under tailored prophylaxis with Human cell line recombinant factor FVIII (Human-cl rhFVIII) with the historical bleeding rate from patients who received Human-cl rhFVIII as on demand treatment.
Detailed Description
There were 3 phases in this study: (1) An initial pharmacokinetic (PK) assessment in which participants received a single infusion of 60±5 IU/kg of Human-cl rhFVIII; blood samples were collected for 72 hours following the infusion. (2) Prophylactic Treatment-Phase I during which participants received infusions of 30-40 IU/kg of human-cl rhFVIII every other day or 3x/week for 1-3 months. (3) Prophylactic Treatment-Phase II during which the dose and dosing interval were determined individually from data gathered in the initial PK assessment. The maximum dosing interval with a dose of ≤ 60-80 IU/kg that maintains a trough level of ≥ 0.01 IU/mL was determined. Participants were treated for 6 months.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Severe Haemophilia A
7. Study Design
Primary Purpose
Prevention
Study Phase
Phase 3
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
66 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Human-cl rhFVIII
Arm Type
Experimental
Arm Description
Up to 60-80 IU/kg of intravenous Human-cl rhFVIII was administered at an individually determined dose and dose interval.
Intervention Type
Biological
Intervention Name(s)
Human-cl rhFVIII
Intervention Description
Human-cl rhFVIII was provided as a freeze-dried concentrate to be reconstituted in water for injection.
Primary Outcome Measure Information:
Title
Annualized Number of Bleeding Episodes (BE) in Phase II
Description
The annualized number of total BEs was calculated for each participant as follows: d*y/t, where y = the number of BEs documented in Phase II, t = the number of treatment periods in days, and d = 365.25, the number of days per year. A bleeding episode (BE) was defined as any BE whether treated or not during Phase II of the study; BEs related to surgery were not included. This study was considered as showing efficacy if the annualized number of BEs was reduced by 50% compared to the number of BEs observed in study GENA-01 where patient where severe Hemophilia A patients were treated on-demand (NCT00989196).
Time Frame
Beginning to the end of Phase II (6 months)
Secondary Outcome Measure Information:
Title
Annualized Number of Spontaneous Bleeding Episodes (BE) in Phase II
Description
The annualized number of spontaneous BEs was calculated for each participant as follows: d*y/t, where y = the number of spontaneous BEs documented in Phase II, t = the number of treatment periods in days, and d = 365.25, the number of days per year. A spontaneous bleeding episode (BE) was defined as a BE whether treated or not during Phase II of the study. BEs related to surgery and BEs due to trauma or due to other causes were not included.
Time Frame
Beginning to the end of Phase II (6 months)
Title
Annualized Number of Bleeding Episodes (BE) in Phase II in Participants With ≤ 2 Treatments/Week
Description
The annualized number of BEs was calculated for each participant as follows: d*y/t, where y = the number of BEs documented in Phase II, t = the number of treatment periods in days, and d = 365.25, the number of days per year. A bleeding episode (BE) was defined as a BE whether treated or not during Phase II of the study. BEs related to surgery were not included.
Time Frame
Beginning to the end of Phase II (6 months)
Title
Median Dosing Interval During Individually Tailored Prophylaxis
Description
The median time between 2 prophylactic doses of Human-cl rhFVIII in the prophylactic treatment phase II were determined per patient
Time Frame
Beginning to the end of Phase II (6 months)
Title
Dosage Per Week in Phase II
Description
The mean dosage per week during Phase II of the study are reported.
Time Frame
Beginning to the end of Phase II (6 months)
10. Eligibility
Sex
Male
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Severe haemophilia A (FVIII:C < 1%) according to medical history.
Male patients ≥ 18 years old.
Previous treatment with a FVIII concentrate (regular prophylaxis with good compliance or on-demand treatment) for at least 150 exposure days (EDs).
Good documentation regarding dosing and bleeding frequency in the 6 months preceding study start.
Immunocompetence (CD4+ count > 200/microliter).
HIV-negative, if positive, viral load < 200 particles/microliter or < 400,000 copies/mL.
Freely given written informed consent
Exclusion Criteria:
Any coagulation disorder other than haemophilia A.
Present or past FVIII inhibitor activity (> 0.6 Bethesda Unit [BU])
Severe liver or kidney disease.
Facility Information:
Facility Name
Medical University Vienna
City
Vienna
Country
Austria
Facility Name
University Multiprofile Hospital for Active Treatment
City
Plovdiv
Country
Bulgaria
Facility Name
Specialized Hospital for Active Treatment
City
Sofia
Country
Bulgaria
Facility Name
Multiprofile Hospital for Active Treatment
City
Varna
Country
Bulgaria
Facility Name
Vivantes Hospital in Friedrichshain
City
Berlin
Country
Germany
Facility Name
SRH Kurpfalzklinik Heidelberg GMBH
City
Heidelberg
Country
Germany
Facility Name
Hungarian National Healthcare Center
City
Budapest
Country
Hungary
Facility Name
University of Debrecen, Medical and Health Science Center
City
Debrecen
Country
Hungary
Facility Name
University Teaching Hospital in Bialystok, Teaching Department of Hematology with a Subdepartment of Vascular Diseases
City
Białystok
Country
Poland
Facility Name
University Clinical Center, Teaching Department of Hematology and Transplantology
City
Gdańsk
Country
Poland
Facility Name
Nicolaus Copernicus Municipal Specialist Hospital, Department of Hematology
City
Torun
Country
Poland
Facility Name
Institute of Hematology and Transfusion Medicine, Depart. of Hemostatic Disorders and Internal Diseases
City
Warsaw
Country
Poland
Facility Name
Sanador SRL
City
Bucharest
Country
Romania
Facility Name
Louis Turcanu Emergency Clinical Children's Hospital
City
Timisoara
Country
Romania
Facility Name
University Hospital Saint Cyril and Metod
City
Bratislava
Country
Slovakia
Facility Name
University Hospital Martin, Department of Hematology and Transfusiology
City
Martin
Country
Slovakia
Facility Name
Basingstoke and North Hampshire Hospital, Hemophilia, Hemostasis and Thrombosis Center
City
Basingstoke
Country
United Kingdom
Facility Name
Royal London Hospital, Barts and the London Hemophilia Center
City
London
Country
United Kingdom
Facility Name
Manchester Royal Infirmary, Department of Clinical Hematology
City
Manchester
Country
United Kingdom
Facility Name
Royal Hallamshire Hospital
City
Sheffield
Country
United Kingdom
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Assess the Safety and Efficacy of Individually Tailored Prophylaxis With Human-cl rhFVIII in Patients With Severe Haemophilia A
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