Efficacy and Safety of AlphaNine Versus BeneFIX in Patients With Severe Hereditary Haemophilia B

Efficacy and Safety of Factor IX (FIX) Contained in AlphaNine® and Its Pharmacokinetic Comparison With BeneFIX® in Patients With Severe Hereditary Haemophilia B

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.

Study Overview

• Status: Completed
• Conditions: Hemophilia B
• Intervention / Treatment: Drug: BeneFIX

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.

• Study Type: Interventional
• Enrollment (Actual): 13
• Phase: Phase 2

Contacts and Locations

Study Locations

• Bulgaria
  • Pleven, Bulgaria, 5800
    • Medical University Pleven
  • Sofia, Bulgaria, 1000
    • National Center of Haematology
  • Varna, Bulgaria, 9010
    • Medical University, University Hospital "Sveta Marina",

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years and older (ADULT, OLDER_ADULT, CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: BeneFIX; BeneFIX is a recombinant FIX provided in a vial containing 100 IU/mL lyophilized nonacog alfa accompanied with solvent for reconstitution and injection.	Drug: BeneFIX; BeneFIX is a recombinant FIX that contains nonacog alfa, reconstituted in solvent and administered as a single dose of 65-75 IU/kg.; Other Names: recombinant coagulation factor IX

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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).	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.
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).	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.
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).	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.
Mean Difference of Clearance: BeneFIX Compared to AlphaNine	BeneFIX pharmacokinetic parameter of clearance was assessed and compared to the AlphaNine pharmacokinetic parameter (PK2 Study).	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.
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).	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.

Collaborators and Investigators

• Sponsor: Grifols Biologicals, LLC

Study record dates

Study Major Dates

• Study Start (ACTUAL): August 1, 2005
• Primary Completion (ACTUAL): October 1, 2009
• Study Completion (ACTUAL): October 1, 2009

Study Registration Dates

• First Submitted: March 16, 2017
• First Submitted That Met QC Criteria: March 21, 2017
• First Posted (ACTUAL): March 27, 2017

Study Record Updates

• Last Update Posted (ACTUAL): July 25, 2017
• Last Update Submitted That Met QC Criteria: June 26, 2017
• Last Verified: June 1, 2017

More Information

Terms related to this study

• Keywords: Factor IX (FIX)
• Additional Relevant MeSH Terms: Hematologic Diseases; Blood Coagulation Disorders, Inherited; Coagulation Protein Disorders; Hemorrhagic Disorders; Genetic Diseases, Inborn; Genetic Diseases, X-Linked; Blood Coagulation Disorders; Hemophilia A; Hemophilia B
• Other Study ID Numbers: IG-404-1

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• product manufactured in and exported from the U.S.: Yes