Clinical trial NCT01174446: Pivotal Study (Pharmacokinetics, Efficacy, Safety) of BAX 326 (rFIX) in Hemophilia B Patients
Official title: Recombinant Factor IX (BAX 326): A Phase 1/3, Prospective, Controlled, Multicenter Study Evaluating Pharmacokinetics, Efficacy, Safety and Immunogenicity in Previously Treated Patients With Severe or Moderately Severe Hemophilia B
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Hemophilia B
Lead sponsor: Takeda
Sponsor class: INDUSTRY
First posted: 2010-08-03
Enrollment: 86
Sex: ALL
Minimum age (years): 12
Maximum age (years): 65
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: The purpose of this pivotal Phase 1/3 study is to determine the pharmacokinetic (PK) parameters, the hemostatic efficacy, and the safety of BAX 326, a recombinant factor IX, in previously treated patients (PTPs) with severe and moderately severe hemophilia B.


Eligibility criteria: Main Inclusion Criteria:

* Participant is 12 to 65 years old at the time of screening
* Participant and/or legal representative has/have provided signed informed consent
* Participant has severe (factor IX (FIX) level \< 1%) or moderately severe (FIX level 1-2%) hemophilia B (based on the one stage activated partial thromboplastin time (aPTT) assay), as tested at screening at the central laboratory
* Participant is previously treated with plasma-derived or recombinant FIX concentrate(s) for a minimum of 150 exposure days (EDs) (based on the participant's medical records); if a verifiable, documented history is unavailable, the participant can be enrolled if s/he has 100-150 EDs to any FIX product that are not fully documented and has participated in Study 050901 for at least 50 EDs to Immunine prior to enrollment (not valid for US and Japan).
* Participant has no evidence of a history of FIX inhibitors
* If the participant is to receive prophylactic treatment, the participant is willing to receive prophylactic treatment over a period of 6 months.
* If the participant is to receive on-demand treatment, the participant has ≥12 documented bleeding episodes requiring treatment within 12 months prior to enrollment and is willing to receive on-demand treatment for the duration of this study.

Main Exclusion Criteria:

* The participant has a history of FIX inhibitors with a titer ≥0.6 Bethesda Units (BU) (as determined by the Nijmegen modification of the Bethesda assay or the assay employed in the respective local laboratory) at any time prior to screening
* The participant has a detectable FIX inhibitor at screening, with a titer ≥0.6 BU as determined by the Nijmegen modification of the Bethesda assay in the central laboratory
* The participant's weight is \< 35 kg or \> 120 kg
* The participant has a history of allergic reaction, eg, anaphylaxis, following exposure to FIX concentrate(s)
* The participant has a known hypersensitivity to hamster proteins or recombinant furin (rFurin)
* The participant has ongoing or recent evidence of a thrombotic disease, fibrinolysis or disseminated intravascular coagulation (DIC)

Primary outcomes:
measure: Study Part 1- Area Under the Plasma Concentration Versus Time Curve From 0 to 72 Hours Per Dose
timeFrame: 72 hours
Secondary outcomes:
measure: Study Parts 1 and 3: Area Under the Plasma Concentration/Time Curve From Time 0 to Infinity Per Dose (AUC0-∞/ Dose)
timeFrame: 0-30 minutes before infusion up to 72 hours post-infusion
measure: Study Parts 1 and 3: Mean Residence Time (MRT)
timeFrame: 0-30 minutes before infusion up to 72 hours post-infusion
measure: Study Parts 1 and 3: Clearance (CL)
timeFrame: 0-30 minutes before infusion up to 72 hours post-infusion
measure: Study Parts 1 and 3: Incremental Recovery at Cmax (IR at Cmax)
timeFrame: 0-30 minutes before infusion up to 1 hour post-infusion
measure: Incremental Recovery (IR) at 30 Minutes Over Time
timeFrame: 0-30 minutes before infusion and 30 minutes post-infusion
measure: Change in Incremental Recovery (IR) at 30 Minutes Over Time
timeFrame: 0-30 minutes before infusion and 30 minutes post-infusion
measure: Study Parts 1 and 3: Half Life (T 1/2)
timeFrame: 0-30 minutes before infusion up to 72 hours post-infusion
measure: Study Parts 1 and 3: Volume of Distribution at Steady State (Vss)
timeFrame: 0-30 minutes before infusion up to 72 hours post-infusion
measure: Study Part 2: Annualized Bleed Rate (ABR) During Treatment With BAX326
timeFrame: Study Part 2 = 26 weeks ± 1 week (Note: Study Part 1 = 2-4 weeks)
measure: Bleeding Episodes Treated With 1, 2 or ≥3 Infusions of BAX326 by Bleeding Site and Cause
timeFrame: Study Part 2 = 26 weeks ± 1 week (Study Part 2 began at week 3-5)
measure: Hemostatic Efficacy at Resolution of All Bleeding Episodes (BEs) Treated With BAX326 by Bleeding Site and Cause
timeFrame: At bleed resolution throughout the study period of 22 months (Study Parts 1, 2, and 3)
measure: Total Weight-adjusted Dose Per Bleeding Episode (BEs) of All BEs Treated With BAX326 by Bleeding Site and Cause
timeFrame: Study Part 2 = 26 weeks ± 1 week (Note: Study Part 1 = 2-4 weeks)
measure: Consumption of BAX326 Per Event Per Participant
timeFrame: Study Part 2 = 26 weeks ± 1 week (Note: Study Part 1 = 2-4 weeks)
measure: Consumption of BAX326 Per Participant: Median Number of Infusions Per Month
timeFrame: Study Part 1 = 2-4 weeks, Study Part 2 = 26 weeks ± 1 week (Prophylaxis and On-Demand period), Study Part 3 = 1 week (Total = 29-31 weeks)
measure: Consumption of BAX326 Per Participant: Median Weight-adjusted Consumption Per Month
timeFrame: Study Part 1 = 2-4 weeks, Study Part 2 = 26 weeks ± 1 week (Prophylaxis and On-Demand period), Study Part 3 = 1 week (Total = 29-31 weeks)
measure: Number of Participants Who Developed Inhibitory Antibodies to Factor IX (FIX)
timeFrame: Study Part 1 = 2-4 weeks, Study Part 2 = 26 weeks ± 1 week, Study Part 3 = 1 week (Total = 29-31 weeks)
measure: Occurrence of Total Binding Antibodies of Indeterminate Specificity (Within Assay Variability)
timeFrame: Study Part 1 = 2-4 weeks, Study Part 2 = 26 weeks ± 1 week, Study Part 3 = 1 week (Total = 29-31 weeks)
measure: Occurrence of Treatment Related Total Binding Antibodies
timeFrame: Study Part 1 = 2-4 weeks, Study Part 2 = 26 weeks ± 1 week, Study Part 3 = 1 week (Total = 29-31 weeks)
measure: Number of Participants Who Experienced Severe Allergic Reactions (e.g. Anaphylaxis)
timeFrame: Study Part 1 = 2-4 weeks, Study Part 2 = 26 weeks ± 1 week, Study Part 3 = 1 week (Total = 29-31 weeks)
measure: Number of Participants Who Experienced Thrombotic Events
timeFrame: Study Part 1 = 2-4 weeks, Study Part 2 = 26 weeks ± 1 week, Study Part 3 = 1 week (Total = 29-31 weeks)
measure: Number of Participants With Clinically Significant Changes in Laboratory Parameters: Clinical Chemistry
timeFrame: Study Part 1 = 2-4 weeks, Study Part 2 = 26 weeks ± 1 week, Study Part 3 = 1 week (Total = 29-31 weeks)
measure: Number of Participants With Clinically Significant Changes in Laboratory Parameters: Hematology
timeFrame: Study Part 1 = 2-4 weeks, Study Part 2 = 26 weeks ± 1 week, Study Part 3 = 1 week (Total = 29-31 weeks)
measure: Number of Participants With Clinically Significant Changes in Laboratory Parameters: Vital Signs
timeFrame: Study Part 1 = 2-4 weeks, Study Part 2 = 26 weeks ± 1 week, Study Part 3 = 1 week (Total = 29-31 weeks)
measure: Number of Participants With Clinically Significant Changes in Laboratory Parameters: Thrombogenic Markers
timeFrame: Study Part 1 = 2-4 weeks, Study Part 2 = 26 weeks ± 1 week, Study Part 3 = 1 week (Total = 29-31 weeks)
measure: Number of Adverse Events (AEs) After BAX326 Treatment
timeFrame: Study Part 1 = 2-4 weeks, Study Part 2 = 26 weeks ± 1 week, and Study Part 3 = 1 week (Total = 29-31 weeks)
measure: Number of Participants With Adverse Events (AEs) After BAX326 Treatment
timeFrame: Study Part 1 = 2-4 weeks, Study Part 2 = 26 weeks ± 1 week, and Study Part 3 = 1 week (Total = 29-31 weeks)
measure: EuroQoL (Quality of Life)-5 Dimensions (EQ-5D) Total Index Scores
timeFrame: Baseline at either Study Part 1, or Study Part 2, and End of Study (study weeks 29-31)
measure: EuroQoL (Quality of Life)-5 Dimensions Visual Analogue Scale (EQ-5D VAS) Scores
timeFrame: Baseline at either Study Part 1, or Study Part 2, and End of Study (study weeks 29-31)
measure: General Pain Assessment Through a Visual Analog Scale (VAS)
timeFrame: Baseline at either Study Part 1, or Study Part 2, and End of Study (study weeks 29-31)
measure: Short Form (36) Health Survey (SF-36): HRQoL 'Physical Component Score' (PCS)
timeFrame: Baseline at either Study Part 1, or Study Part 2, and End of Study (study weeks 29-31)
measure: SF-36: HRQoL 'Mental Health' (MH)
timeFrame: Baseline at either Study Part 1, or Study Part 2, and End of Study (study weeks 29-31)
measure: SF-36: HRQoL Physical Functioning' (PF)
timeFrame: Baseline at either Study Part 1, or Study Part 2, and End of Study (study weeks 29-31)
measure: SF-36: HRQoL Role-Physical (RP)
timeFrame: Baseline at either Study Part 1, or Study Part 2, and End of Study (study weeks 29-31)
measure: SF-36: HRQoL Role-Emotional
timeFrame: Baseline at either Study Part 1, or Study Part 2, and End of Study (study weeks 29-31)
measure: SF-36: HRQoL Bodily Pain
timeFrame: Baseline at either Study Part 1, or Study Part 2, and End of Study (study weeks 29-31)
measure: SF-36: HRQoL Mental Health
timeFrame: Baseline at either Study Part 1, or Study Part 2, and End of Study (study weeks 29-31)
measure: SF-36: HRQoL Vitality
timeFrame: Baseline at either Study Part 1, or Study Part 2, and End of Study (study weeks 29-31)
measure: SF-36: HRQoL Social Functioning
timeFrame: Baseline at either Study Part 1, or Study Part 2, and End of Study (study weeks 29-31)
measure: SF-36: HRQoL General Health
timeFrame: Baseline at either Study Part 1, or Study Part 2, and End of Study (study weeks 29-31)
measure: Pediatric Quality of Life Questionnaire (PedsQL) Physical Health Summary Score (Ages 12-16)
timeFrame: Baseline at either Study Part 1, or Study Part 2, and End of Study (study weeks 29-31)
measure: Pediatric Quality of Life Questionnaire (PedsQL) Psychosocial Health Summary Score (Ages 12-16)
timeFrame: Baseline at either Study Part 1, or Study Part 2, and End of Study (study weeks 29-31)
measure: Pediatric Quality of Life Questionnaire (PedsQL) Total Score (Ages 12-16)
timeFrame: Baseline at either Study Part 1, or Study Part 2, and End of Study (study weeks 29-31)
measure: Health-Related Quality of Life (HRQoL) Disease-specific: Haem-A-QoL
timeFrame: Baseline at either Study Part 1, or Study Part 2, and End of Study (study weeks 29-31)
measure: Health-Related Quality of Life (HRQoL) Disease-specific: Haemo-QoL - Participants On-Demand (Ages 12-16)
timeFrame: Baseline at either Study Part 1, or Study Part 2, and End of Study (study weeks 29-31)
measure: Health Resource Use - Number of Hospitalizations
timeFrame: Study Part 1 = 2-4 weeks, Study Part 2 = 26 weeks ± 1 week, Study Part 3 = 1 week (Total = 29-31 weeks)
measure: Health Resource Use - Total Days of Hospital Stay
timeFrame: Study Part 1 = 2-4 weeks, Study Part 2 = 26 weeks ± 1 week, Study Part 3 = 1 week (Total = 29-31 weeks)
measure: Health Resource Use - Emergency Room Visits
timeFrame: Study Part 1 = 2-4 weeks, Study Part 2 = 26 weeks ± 1 week, Study Part 3 = 1 week (Total = 29-31 weeks)
measure: Health Resource Use - Unscheduled Doctor's Office Visits
timeFrame: Study Part 1 = 2-4 weeks, Study Part 2 = 26 weeks ± 1 week, Study Part 3 = 1 week (Total = 29-31 weeks)
measure: Health Resource Use - Days Lost From Work or School
timeFrame: Study Part 1 = 2-4 weeks, Study Part 2 = 26 weeks ± 1 week, Study Part 3 = 1 week (Total = 29-31 weeks)
Other outcomes:
Locations:
city: Rosario
country: Argentina
city: Brasilia
country: Brazil
city: Sao Paulo
country: Brazil
city: Sofia
country: Bulgaria
city: Santiago
country: Chile
city: Bogotá
country: Colombia
city: Cali
country: Colombia
city: Prague
country: Czechia
city: Hiroshima
country: Japan
city: Nara
country: Japan
city: Tochigi
country: Japan
city: Tokyo
country: Japan
city: Gdansk
country: Poland
city: Krakow
country: Poland
city: Lodz
country: Poland
city: Warsaw
country: Poland
city: Bucharest
country: Romania
city: Timisoara
country: Romania
city: Kirov
country: Russian Federation
city: Moscow
country: Russian Federation
city: St. Petersburg
country: Russian Federation
city: Barcelona
country: Spain
city: Malmö
country: Sweden
city: Lviv
country: Ukraine
city: London
country: United Kingdom
Study officials:
affiliation: Takeda
name: Study Director
role: STUDY_DIRECTOR
References:
citation: Windyga J, Lissitchkov T, Stasyshyn O, Mamonov V, Rusen L, Lamas JL, Oh MS, Chapman M, Fritsch S, Pavlova BG, Wong WY, Abbuehl BE. Pharmacokinetics, efficacy and safety of BAX326, a novel recombinant factor IX: a prospective, controlled, multicentre phase I/III study in previously treated patients with severe (FIX level <1%) or moderately severe (FIX level </=2%) haemophilia B. Haemophilia. 2014 Jan;20(1):15-24. doi: 10.1111/hae.12228. Epub 2013 Jul 9.