Clinical trial NCT03091751: Efficacy and Safety of AlphaNine Versus BeneFIX in Patients With Severe Hereditary Haemophilia B
Official title: Efficacy and Safety of Factor IX (FIX) Contained in AlphaNine® and Its Pharmacokinetic Comparison With BeneFIX® in Patients With Severe Hereditary Haemophilia B
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Hemophilia B
Keywords: Factor IX (FIX)
Lead sponsor: Grifols Biologicals, LLC
Sponsor class: INDUSTRY
First posted: 2017-03-27
Enrollment: 13
Sex: ALL
Minimum age (years): 12
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility 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

Primary outcomes:
measure: Mean Difference of Area Under the Curve (AUC): BeneFIX Compared to AlphaNine
timeFrame: 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.
measure: Mean Difference of In Vivo Recovery: BeneFIX Compared to AlphaNine
timeFrame: 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.
measure: Mean Difference of Terminal Half-Life: BeneFIX Compared to AlphaNine
timeFrame: 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.
measure: Mean Difference of Clearance: BeneFIX Compared to AlphaNine
timeFrame: 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.
measure: Mean Difference of Mean Residence Time (MRT): BeneFIX Compared to AlphaNine
timeFrame: 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.
Secondary outcomes:
Other outcomes:
Locations:
city: Pleven
country: Bulgaria
facility: Medical University Pleven
city: Sofia
country: Bulgaria
facility: National Center of Haematology
city: Varna
country: Bulgaria
facility: Medical University, University Hospital "Sveta Marina",
Study officials:
References: