Hemophilia B
Conditions
Keywords
Factor IX (FIX)
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.
Interventions
DRUGBeneFIX
BeneFIX is a recombinant FIX that contains nonacog alfa, reconstituted in solvent and administered as a single dose of 65-75 IU/kg.
Sponsors
Grifols Biologicals, LLC
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
12 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * 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
Exclusion criteria
* 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 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 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). |
Countries
Bulgaria
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| BeneFIX BeneFIX is a recombinant FIX provided in a vial containing 100 IU/mL lyophilized nonacog alfa accompanied with solvent for reconstitution and injection.
BeneFIX: BeneFIX is a recombinant FIX that contains nonacog alfa, reconstituted in solvent and administered as a single dose of 65-75 IU/kg. | 22 |
| Total | 22 |
Baseline characteristics
| Characteristic | BeneFIX |
|---|---|
| Age, Categorical <=18 years | 1 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 21 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 22 Participants |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 22 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 22 |
| other Total, other adverse events | 0 / 22 |
| serious Total, serious adverse events | 0 / 22 |
Outcome results
Primary
Mean Difference of Area Under the Curve (AUC): BeneFIX Compared to AlphaNine
BeneFIX pharmacokinetic parameter of area under the curve (AUC 0-inf) was assessed and compared to the AlphaNine pharmacokinetic parameter (PK2 study).
Time frame: 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.
Population: Thirteen subjects with 2 prior pharmacokinetic assessments with AlphaNine (PK1, PK2) had a third PK assessment with BeneFIX (PK3). Nine subjects had PK3 analysis with BeneFIX as part of a previous study. In total, 22 subjects treated with BeneFIX (PK3) were analyzed jointly and compared to 25 subjects treated with AlphaNine (PK2).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| BeneFIX | Mean Difference of Area Under the Curve (AUC): BeneFIX Compared to AlphaNine | 10.41 IU x hour/dL | Standard Deviation 563.081 |
p-value: 0.7795% CI: [-224.88, 245.7]t-test, 1 sided
Primary
Mean Difference of Clearance: BeneFIX Compared to AlphaNine
BeneFIX pharmacokinetic parameter of clearance was assessed and compared to the AlphaNine pharmacokinetic parameter (PK2 Study).
Time frame: 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.
Population: Thirteen subjects with 2 prior pharmacokinetic assessments with AlphaNine (PK1, PK2) had a third PK assessment with BeneFIX (PK3). Nine subjects had PK3 analysis with BeneFIX as part of a previous study. In total, 22 subjects treated with BeneFIX (PK3) were analyzed jointly and compared to 25 subjects treated with AlphaNine (PK2).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| BeneFIX | Mean Difference of Clearance: BeneFIX Compared to AlphaNine | -0.0058 mL/min x kg | Standard Deviation 0.0145 |
p-value: 0.1695% CI: [-0.0119, 0.0003]t-test, 1 sided
Primary
Mean Difference of In Vivo Recovery: BeneFIX Compared to AlphaNine
BeneFIX pharmacokinetic parameter of in vivo recovery was assessed and compared to the AlphaNine pharmacokinetic parameter (PK2 Study).
Time frame: 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.
Population: Thirteen subjects with 2 prior pharmacokinetic assessments with AlphaNine (PK1, PK2) had a third PK assessment with BeneFIX (PK3). Nine subjects had PK3 analysis with BeneFIX as part of a previous study. In total, 22 subjects treated with BeneFIX (PK3) were analyzed jointly and compared to 25 subjects treated with AlphaNine (PK2).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| BeneFIX | Mean Difference of In Vivo Recovery: BeneFIX Compared to AlphaNine | 0.3068 kg/dL | Standard Deviation 0.37505 |
p-value: 0.00295% CI: [0.1501, 0.4635]t-test, 1 sided
Primary
Mean Difference of Mean Residence Time (MRT): BeneFIX Compared to AlphaNine
BeneFIX pharmacokinetic parameter of mean residence time (MRT 0-inf) was assessed and compared to the AlphaNine pharmacokinetic parameter (PK2 Study).
Time frame: 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.
Population: Thirteen subjects with 2 prior pharmacokinetic assessments with AlphaNine (PK1, PK2) had a third PK assessment with BeneFIX (PK3). Nine subjects had PK3 analysis with BeneFIX as part of a previous study. In total, 22 subjects treated with BeneFIX (PK3) were analyzed jointly and compared to 25 subjects treated with AlphaNine (PK2).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| BeneFIX | Mean Difference of Mean Residence Time (MRT): BeneFIX Compared to AlphaNine | -7.609 hours | Standard Deviation 13.7121 |
p-value: 0.0295% CI: [-13.344, -1.879]t-test, 1 sided
Primary
Mean Difference of Terminal Half-Life: BeneFIX Compared to AlphaNine
BeneFIX pharmacokinetic parameter of terminal half-life was assessed and compared to the AlphaNine pharmacokinetic parameter (PK2 Study).
Time frame: 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.
Population: Thirteen subjects with 2 prior pharmacokinetic assessments with AlphaNine (PK1, PK2) had a third PK assessment with BeneFIX (PK3). Nine subjects had PK3 analysis with BeneFIX as part of a previous study. In total, 22 subjects treated with BeneFIX (PK3) were analyzed jointly and compared to 25 subjects treated with AlphaNine (PK2).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| BeneFIX | Mean Difference of Terminal Half-Life: BeneFIX Compared to AlphaNine | -3.3 hours | Standard Deviation 13.48 |
p-value: 0.395% CI: [-8.9, 2.3]t-test, 1 sided