Efficacy and Safety of AlphaNine Versus BeneFIX in Patients With Severe Hereditary Haemophilia B
- Registration Number
- NCT03091751
- Lead Sponsor
- Grifols Biologicals, LLC
- Brief Summary
The goal of this non-randomized, multi-center study in subjects with severe hereditary haemophilia B was to determine and compare the pharmacokinetic and safety profiles of BeneFIX in subjects having had 2 prior pharmacokinetic assessments with AlphaNine.
- Detailed Description
Two pharmacokinetic assessments (studies) were carried out in the same subjects during a previous clinical trial. The first pharmacokinetic study (PK1) was performed after a single dose of AlphaNine. The second pharmacokinetic study (PK2) was performed following 26 Weeks of AlphaNine treatment after PK1. To compare AlphaNine with BeneFIX, a third pharmacokinetic study (PK3) (current study) was performed after a single dose of BeneFIX administered following a 7- to 15-day wash-out period.
The main objective of the PK3 study was to assess the pharmacokinetic profile of BeneFIX and compare to the pharmacokinetic profile of AlphaNine from the PK2 study.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 13
- Participated in the previous study "Efficacy and safety of factor IX (FIX) contained in Alphananine in patients with severe hereditary haemophilia B":
- Congenital deficiency in Factor IX (FIX)
- FIX residual activity of ≤2% of normal
- Had required FIX-containing products in the past and in clinical records that were collected data to assess a reliable estimation of at least 150 treatment exposure days to previous products
- Was able to receive treatment for more than 10 days for a 6-month period
Key
- Received a dose of FIX in the 7 days prior to the infusion
- FIX inhibitor level of >0.5 Bethesda units (BU) or clinically relevant presence in the past (≥5 BU)
- Active bleeding at the moment of infusion
- Had a known allergic reaction to any BeneFIX component
- Exhibited symptoms of any intercurrent infection (ie, fever, chills, nausea) at the time of the first infusion
- Had any disease that might affect the distribution or metabolism of FIX and which could affect interpretation of the study (such as non-controlled diabetes mellitus)
- Had non-controlled arterial hypertension
- Had abnormal renal function (creatinine >1.5 mg/dL)
- Had documented liver cirrhosis or any hepatic disorder with alanine aminotransferase (ALT) levels 2.5x upper limit of normal (ULN )
- Prevision to be concomitantly treated with other FIX-containing products
- Had conditions that might affect subject compliance (survival-limiting [in 2 year time] diseases, alcohol or other drug abuse, etc.)
- Unable to provide a storage plasma sample before the first dose of BeneFIX
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description BeneFIX BeneFIX BeneFIX is a recombinant FIX provided in a vial containing 100 IU/mL lyophilized nonacog alfa accompanied with solvent for reconstitution and injection.
- Primary Outcome Measures
Name Time Method Mean Difference of In Vivo Recovery: BeneFIX Compared to AlphaNine Baseline (prior to the infusion), and at 15 and 30 minutes, 1, 3, 6, 9, 24, 48, 72, and 74 hours following a single dose infusion of BeneFIX administered following a 7 to 15 day wash-out period. BeneFIX pharmacokinetic parameter of in vivo recovery was assessed and compared to the AlphaNine pharmacokinetic parameter (PK2 Study).
Mean Difference of Area Under the Curve (AUC): BeneFIX Compared to AlphaNine Baseline (prior to the infusion), and at 15 and 30 minutes, 1, 3, 6, 9, 24, 48, 72, and 74 hours following a single dose infusion of BeneFIX administered following a 7 to 15 day wash-out period. BeneFIX pharmacokinetic parameter of area under the curve (AUC 0-inf) was assessed and compared to the AlphaNine pharmacokinetic parameter (PK2 study).
Mean Difference of Terminal Half-Life: BeneFIX Compared to AlphaNine Baseline (prior to the infusion), and at 15 and 30 minutes, 1, 3, 6, 9, 24, 48, 72, and 74 hours following a single dose infusion of BeneFIX administered following a 7 to 15 day wash-out period. BeneFIX pharmacokinetic parameter of terminal half-life was assessed and compared to the AlphaNine pharmacokinetic parameter (PK2 Study).
Mean Difference of Clearance: BeneFIX Compared to AlphaNine Baseline (prior to the infusion), and at 15 and 30 minutes, 1, 3, 6, 9, 24, 48, 72, and 74 hours following a single dose infusion of BeneFIX administered following a 7 to 15 day wash-out period. BeneFIX pharmacokinetic parameter of clearance was assessed and compared to the AlphaNine pharmacokinetic parameter (PK2 Study).
Mean Difference of Mean Residence Time (MRT): BeneFIX Compared to AlphaNine Baseline (prior to the infusion), and at 15 and 30 minutes, 1, 3, 6, 9, 24, 48, 72, and 74 hours following a single dose infusion of BeneFIX administered following a 7 to 15 day wash-out period. BeneFIX pharmacokinetic parameter of mean residence time (MRT 0-inf) was assessed and compared to the AlphaNine pharmacokinetic parameter (PK2 Study).
- Secondary Outcome Measures
Name Time Method
Trial Locations
- Locations (3)
Medical University Pleven
🇧🇬Pleven, Bulgaria
National Center of Haematology
🇧🇬Sofia, Bulgaria
Medical University, University Hospital "Sveta Marina",
🇧🇬Varna, Bulgaria