Assess the Safety and Efficacy of Individually Tailored Prophylaxis With Human-cl rhFVIII in Patients With Severe Haemophilia A
- Conditions
- Severe Haemophilia A
- Interventions
- Biological: Human-cl rhFVIII
- Registration Number
- NCT01863758
- Lead Sponsor
- Octapharma
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- Male
- Target Recruitment
- 66
- 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
- Any coagulation disorder other than haemophilia A.
- Present or past FVIII inhibitor activity (> 0.6 Bethesda Unit [BU])
- Severe liver or kidney disease.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Human-cl rhFVIII Human-cl rhFVIII Up to 60-80 IU/kg of intravenous Human-cl rhFVIII was administered at an individually determined dose and dose interval.
- Primary Outcome Measures
Name Time Method Annualized Number of Bleeding Episodes (BE) in Phase II Beginning to the end of Phase II (6 months) 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
Name Time Method Dosage Per Week in Phase II Beginning to the end of Phase II (6 months) The mean dosage per week during Phase II of the study are reported.
Annualized Number of Bleeding Episodes (BE) in Phase II in Participants With ≤ 2 Treatments/Week Beginning to the end of Phase II (6 months) 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 Beginning to the end of Phase II (6 months) The median time between 2 prophylactic doses of Human-cl rhFVIII in the prophylactic treatment phase II were determined per patient
Annualized Number of Spontaneous Bleeding Episodes (BE) in Phase II Beginning to the end of Phase II (6 months) 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.
Trial Locations
- Locations (20)
University Hospital Martin, Department of Hematology and Transfusiology
🇸🇰Martin, Slovakia
Basingstoke and North Hampshire Hospital, Hemophilia, Hemostasis and Thrombosis Center
🇬🇧Basingstoke, United Kingdom
Manchester Royal Infirmary, Department of Clinical Hematology
🇬🇧Manchester, United Kingdom
Royal Hallamshire Hospital
🇬🇧Sheffield, United Kingdom
Medical University Vienna
🇦🇹Vienna, Austria
University Multiprofile Hospital for Active Treatment
🇧🇬Plovdiv, Bulgaria
Multiprofile Hospital for Active Treatment
🇧🇬Varna, Bulgaria
SRH Kurpfalzklinik Heidelberg GMBH
🇩🇪Heidelberg, Germany
University of Debrecen, Medical and Health Science Center
🇭🇺Debrecen, Hungary
Vivantes Hospital in Friedrichshain
🇩🇪Berlin, Germany
Hungarian National Healthcare Center
🇭🇺Budapest, Hungary
University Teaching Hospital in Bialystok, Teaching Department of Hematology with a Subdepartment of Vascular Diseases
🇵🇱Białystok, Poland
University Clinical Center, Teaching Department of Hematology and Transplantology
🇵🇱Gdańsk, Poland
Nicolaus Copernicus Municipal Specialist Hospital, Department of Hematology
🇵🇱Torun, Poland
Institute of Hematology and Transfusion Medicine, Depart. of Hemostatic Disorders and Internal Diseases
🇵🇱Warsaw, Poland
Louis Turcanu Emergency Clinical Children's Hospital
🇷🇴Timisoara, Romania
Sanador SRL
🇷🇴Bucharest, Romania
University Hospital Saint Cyril and Metod
🇸🇰Bratislava, Slovakia
Specialized Hospital for Active Treatment
🇧🇬Sofia, Bulgaria
Royal London Hospital, Barts and the London Hemophilia Center
🇬🇧London, United Kingdom