BAX 326 Pediatric Study

Hemophilia B Clinical Trial

Official title:

BAX 326 (Recombinant Factor IX): A Phase 2/3 Prospective, Uncontrolled, Multicenter Study Evaluating Pharmacokinetics, Efficacy, Safety, and Immunogenicity in Previously Treated Pediatric Patients With Severe (FIX Level < 1%) or Moderately Severe (FIX Level 1-2%) Hemophilia B

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01488994
• Other study ID #: 251101
• Secondary ID: 2011-002437-19
• Status: Completed
• Phase: Phase 2/Phase 3
• Start date: December 20, 2011
• Est. completion date: May 14, 2013

Study information

• Verified date: April 2021
• Source: Takeda
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to assess BAX 326 pharmacokinetic parameters, to evaluate its hemostatic efficacy, safety, immunogenicity, and changes in health-related quality of life in pediatric patients.

Description:

The secondary outcome measure: Area Under the Plasma Concentration Versus Time Curve From 0 to 72 Hours (h) Post-infusion analysis was not done due to the different time-points for the last PK blood sample, AUC0-72 h was redundant and only total AUC was included in the PK analysis.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 23
• Est. completion date: May 14, 2013
• Est. primary completion date: May 14, 2013
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 12 Years

Eligibility

Main Inclusion Criteria:

• Participant and/or legal representative has/have voluntarily provided signed informed consent
• Participant has severe (FIX level < 1%) or moderately severe (FIX level = 2%) hemophilia B
• Participant is < 12 years old at the time of screening
• Participant has no evidence of a history of FIX inhibitors (based on the participant's medical records)
• Participant is immunocompetent as evidenced by a CD4 count = 200 cells/mm^3

Main Exclusion Criteria:

• Participant has a detectable FIX inhibitor at screening, with a titer = 0.6 Bethesda Unit (BU)
• Participant has a history of allergic reaction, e.g. anaphylaxis, following exposure to FIX concentrate(s)
• Participant has evidence of an ongoing or recent thrombotic disease
• Participant has an inherited or acquired hemostatic defect other than hemophilia B

Related Conditions & MeSH terms

• Hemophilia A
• Hemophilia B

Intervention

Biological:
• BAX326
All participants underwent a pharmacokinetic evaluation with BAX326 (recombinant Factor IX) followed by twice weekly prophylactic treatment for 6 months or for at least 50 exposure days, whichever occurred last.

Locations

Country	Name	City	State
India	LNJP Maulana Azad Medical College & Associated Hospitals	New Delhi
Poland	University Pediatric Hospital	Krakow
Poland	Stanislaw Popowski Provincial Specialist Pediatric Hospital	Olsztyn
Poland	Professor Tadeusz Sokolowski Independent Public Teaching Hospital of the Pomeranian Medical University in Szczecin	Szczecin
Romania	S.C. Sanador SRL	Bucharest
Romania	Louis Turcanu Emergency Children's Hospital	Timisoara
Russian Federation	Regional Clinical Hospital	Ekaterinburg
Russian Federation	Pediatric Regional Clinical Hospital, Hematology Department	Krasnodar
Russian Federation	Republican Center for Hemophilia Treatment	St. Petersburg
Ukraine	State Institution "Institute of Blood Pathology and Transfusion Medicine of the Academy of Medical Sciences of Ukraine"	Lviv
United Kingdom	Manchester Children´s Hospital	Manchester

Sponsors (1)

Lead Sponsor	Collaborator
Baxalta now part of Shire

Countries where clinical trial is conducted

India,  Poland,  Romania,  Russian Federation,  Ukraine,  United Kingdom, 

References & Publications (1)

Urasinski T, Stasyshyn O, Andreeva T, Rusen L, Perina FG, Oh MS, Chapman M, Pavlova BG, Valenta-Singer B, Abbuehl BE. Recombinant factor IX (BAX326) in previously treated paediatric patients with haemophilia B: a prospective clinical trial. Haemophilia. 2 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Adverse Events (AEs) Possibly or Probably Related to BAX326		Throughout study period (approximately 17 months)
Secondary	Pharmacokinetics (PK): Total Area Under the Plasma Concentration Versus Time Curve From 0 to 72 Hours Post-infusion Per Dose (AUC 0-72h/Dose)		Within 30 mins pre-infusion and 4 post-infusion timepoints
Secondary	Pharmacokinetics (PK): Total Area Under the Plasma Concentration Versus Time Curve From 0 to Infinity Post-infusion Per Dose (Total AUC/Dose)		Within 30 mins pre-infusion and 4 post-infusion timepoints. Refer to Population Description below for more details.
Secondary	Pharmacokinetics (PK): Mean Residence Time (MRT)	Computed as total area under the first moment curve (total AUMC) divided by the total area under the concentration versus time curve (total AUC)	Within 30 mins pre-infusion and 4 post-infusion timepoints. Refer to Population Description below for more details.
Secondary	Pharmacokinetics (PK): Factor IX (FIX) Clearance (CL)	Computed as the dose divided by total Area under the curve (AUC)	Within 30 mins pre-infusion and 4 post-infusion timepoints. Refer to Population Description below for more details.
Secondary	Pharmacokinetics (PK): Incremental Recovery (IR)	The rise in FIX activity in IU/dL per unit dose administered in IU/kg. Calculated as follows: (FIX activity at post-infusion minus FIX activity at pre-infusion) divided by weight-adjusted dose	Within 30 mins pre-infusion and 30 mins post-infusion
Secondary	Pharmacokinetics (PK): Elimination Phase Half-life (T 1/2)	Calculated as log_e2/?, where ? is the regression slope in the terminal phase of the least absolute deviations regression model	Within 30 mins pre-infusion and 4 post-infusion timepoints. Refer to Population Description below for more details.
Secondary	Pharmacokinetics (PK): Volume of Distribution at Steady State (Vss)	Computed as Clearance (CL) * Mean residence time (MRT)	Within 30 mins pre-infusion and 4 post-infusion timepoints. Refer to Population Description below for more details.
Secondary	Pharmacokinetics (PK): Incremental Recovery (IR) Over Time	IR calculated as follows: (FIX activity at post-infusion minus FIX activity at pre-infusion) divided by weight-adjusted dose. IR is determined at baseline (PK analysis), Week 5, Week 13 and Week 26 timepoints. Number of participants contributing data (N) for this outcome measure is included in the category title in the order: pediatric participants > 6 years of age; pediatric participants 6 to <12 years of age; pharmacokinetic Full Analysis Set (PKFAS).	Within 30 mins pre-infusion and 30 mins post-infusion at baseline, Week 5, Week 13 and Week 26.
Secondary	Hemostatic Efficacy: Treatment of Bleeding Episodes: Number of Infusions Per Bleeding Episode		Throughout study period (approximately 17 months)
Secondary	Hemostatic Efficacy: Treatment of Bleeding Episodes: Overall Hemostatic Efficacy Rating at Resolution of Bleed	Rating Scale for Treatment of bleeding episodes (4-point ordinal scale): - Excellent: Full relief of pain and cessation of objective signs of bleeding (eg, swelling, tenderness, and decreased range of motion in the case of musculoskeletal hemorrhage) after a single infusion. No additional infusion required for the control of bleeding. Administration of further infusions to maintain hemostasis did not affect this scoring. - Good: Definite pain relief and/or improvement in signs of bleeding after a single infusion. Possibly requires more than 1 infusion for complete resolution. - Fair: Probable and/or slight relief of pain and slight improvement in signs of bleeding after single infusion. Required more than 1 infusion for complete resolution. - None: No improvement or condition worsens.	Throughout study period (approximately 17 months)
Secondary	Hemostatic Efficacy: Prophylaxis: Annualized Bleeding Rate (ABR)	The annualized bleeding rate (ABR) during prophylaxis was calculated only for participants who had adequate treatment time for bleeding rate assessment (i.e., more than 3 months of prophylaxis treatment). The observation period for prophylaxis was to be the time between the first and the last prophylactic infusions. The treatment period for surgery was to be excluded from the bleed rate calculation. ABR calculated as (Number of bleeding episodes/observed treatment period in days) * 365.25.	Throughout study period (approximately 17 months)
Secondary	Consumption of BAX326: Number of Infusions Per Month		Throughout study period (approximately 17 months)
Secondary	Consumption of BAX326: Number of Infusions Per Year		Throughout study period (approximately 17 months)
Secondary	Consumption of BAX326: Weight-adjusted Consumption Per Month		Throughout study period (approximately 17 months)
Secondary	Consumption of BAX326: Weight-adjusted Consumption Per Year (Annualized)		Throughout study period (approximately 17 months)
Secondary	Consumption of BAX326: Weight-adjusted Consumption Per Event	Event includes prophylactic infusions of study product and infusions of study product for treatment of bleeding episodes (BEs).	Throughout study period (approximately 17 months)
Secondary	Safety and Immunogenicity: Number of Participants Who Developed Inhibitory Antibodies to Factor IX (FIX)		Throughout study period (approximately 17 months)
Secondary	Safety and Immunogenicity: Number of Participants Who Developed Total Binding Antibodies to Factor IX (FIX)	If more than 2-dilution increase as compared to pre-study level at screening and titers verified for specificity in the confirmatory assay. AB=antibodies in category for outcome measure data.	Throughout study period (approximately 17 months)
Secondary	Safety: Number of Participants With Severe Allergic Reactions, e.g. Anaphylaxis		Throughout study period (approximately 17 months)
Secondary	Safety: Number of Participants With Thrombotic Events		Throughout study period (approximately 17 months)
Secondary	Safety: Number of Participants With Clinically Significant Changes in Routine Laboratory Parameters (Haematology and Clinical Chemistry), and Vital Signs	Categories consist of Clinically Significant (CS) changes in haemaotology parameters, clinical chemistry parameters and vital signs. Abbreviations in categories; Clin=clinical; params=parameters	Throughout study period (approximately 17 months)
Secondary	Safety: Number of Participants Who Developed Antibodies to Chinese Hamster Ovary (CHO) Proteins and Recombinant Furin (rFurin)	If more than 2-dilution increase as compared to pre-study level at screening and titers verified for specificity in the confirmatory assay.	Throughout study period (approximately 17 months)
Secondary	Health-related Quality of Life (HRQoL): PedsQL™ Change From Baseline in Total Score	For this study, the PedsQL™ questionnaires for participants 2 to 7 years of age (parent-proxy versions for age groups 2-4 years and 5-7 years) and PedsQL™ Child version for participants 8 to 12 years of age were used. The Peds-QL is a generic Health-Related Quality of Life (HR QoL) instrument designed specifically for a pediatric population. It captures the following domains: general health/activities, feelings/emotional, social functioning, school functioning. A 5-point score is used for each domain: from 0 (never) to 4 (almost always). Items are reversed scored and linearly transformed to a 0-100 scale as follows: 0=100, 1=75, 2=50, 3=25, 4=0 so that higher scores indicate better quality of life (QoL). The total score is the mean (average) of all scores from the 4 domains. The change from baseline in total score is reported- a positive score indicates a better QoL compared to baseline and a negative score indicates a poorer QoL compared to baseline.	Baseline and 6 months
Secondary	Health-related Quality of Life (HRQoL): Haemo-QoL, Change From Baseline in Total Score	The Haemo-QoL is a quality of life (QoL) assessment instrument for children and adolescents with haemophilia. As a hemophilia-specific instrument, this measure assesses very specific aspects of dealing with hemophilia. For the Haemo-QoL, higher scores indicate a worse quality of life. Scores on a scale range between 0 and 100.	Baseline and 6 months
Secondary	Health Resource Use: Number of Hospitalizations	The number of hospitalizations per participant. Number of participants contributing data (N) for this outcome measure is included in the category title in the order: pediatric participants < 6 years of age; pediatric participants 6 to <12 years of age; Full Analysis Set.	Baseline (Pharmacokinetic [PK] assessment), Week 5, Week 13 and Week 26
Secondary	Health Resource Use: Length of Hospitalization	The length of hospitalization per participant. Number of participants contributing data (N) for this outcome measure is included in the category title in the order: pediatric participants < 6 years of age; pediatric participants 6 to <12 years of age; Full Analysis Set.	Baseline (Pharmacokinetic [PK] assessment), Week 5, Week 13 and Week 26
Secondary	Health Resource Use: Unscheduled Doctor's Office Visits	The number of unscheduled doctor's Office visits per participant. Number of participants contributing data (N) for this outcome measure is included in the category title in the order: pediatric participants < 6 years of age; pediatric participants 6 to <12 years of age; Full Analysis Set.	Baseline (Pharmacokinetic [PK] assessment), Week 5, Week 13 and Week 26
Secondary	Health Resource Use: Emergency Room Visits	The number of Emergency Room visits per participant. Number of participants contributing data (N) for this outcome measure is included in the category title in the order: pediatric participants < 6 years of age; pediatric participants 6 to <12 years of age; Full Analysis Set.	Baseline (Pharmacokinetic [PK] assessment), Week 5, Week 13 and Week 26
Secondary	Health Resource Use: Days Lost From School	The number of days lost from school per participant. Number of participants contributing data (N) for this outcome measure is included in the category title in the order: pediatric participants < 6 years of age; pediatric participants 6 to <12 years of age; Full Analysis Set.	Baseline (Pharmacokinetic [PK] assessment), Week 5, Week 13 and Week 26