Pivotal Study (Pharmacokinetics, Efficacy, Safety) of BAX 326 (rFIX) in Hemophilia B Patients

NCT01174446 | Completed Phase 3 Results DMC

• 2 other identifiers: 2509012009-016720-31
• Study Type: interventional
• Target: 86
• Locations: 14 countries
• Sites: 25

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.

Conditions

Hemophilia B

Outcome Measures

Primary Outcomes (1)

• Study Part 1- Area Under the Plasma Concentration Versus Time Curve From 0 to 72 Hours Per Dose

  Computed using the linear trapezoidal method. The concentration at 72 hours was interpolated from the two nearest sampling time points or extrapolated using the last quantifiable concentration and the terminal rate constant λz. λz was estimated from the slope of natural log-linear fitting to latter quantifiable concentrations, with largest adjusted R\^2.

  72 hours

Secondary Outcomes (49)

• Study Parts 1 and 3: Area Under the Plasma Concentration/Time Curve From Time 0 to Infinity Per Dose (AUC0-∞/ Dose)

  0-30 minutes before infusion up to 72 hours post-infusion

• Study Parts 1 and 3: Mean Residence Time (MRT)

  0-30 minutes before infusion up to 72 hours post-infusion

• Study Parts 1 and 3: Clearance (CL)

  0-30 minutes before infusion up to 72 hours post-infusion

• Study Parts 1 and 3: Incremental Recovery at Cmax (IR at Cmax)

  0-30 minutes before infusion up to 1 hour post-infusion

• Incremental Recovery (IR) at 30 Minutes Over Time

  0-30 minutes before infusion and 30 minutes post-infusion

Study Arms (2)

BAX 326

EXPERIMENTAL

Recombinant factor IX (rFIX)

Biological: BAX 326

BeneFIX

ACTIVE COMPARATOR

Recombinant Factor IX (rFIX)

Biological: BeneFIX

Interventions

BAX 326 BIOLOGICAL

* Study Part 1: Pharmacokinetic (PK) Crossover with BAX326 and BeneFIX * Study Part 2: Open-label evaluation of prophylaxis and on-demand BAX326 only * Study Part 3: Open-label repeat of PK evaluation (repeat Study Part 1) with BAX326 only and same study participants as Study Part 1

Also known as: Recombinant factor IX (rFIX), RIXUBIS

BAX 326

BeneFIX BIOLOGICAL

* Study Part 1: Pharmacokinetic (PK) Crossover with BAX326 and BeneFIX. * BeneFIX only used in Part 1 of this study. * Study Part 2 and 3 only utilized BAX326

Also known as: Recombinant factor IX (rFIX)

BeneFIX

Eligibility Criteria

• Age: 12 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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)

Sponsors & Collaborators

• Baxalta now part of Shire: lead

Study Sites (25)

Unknown Facility

Rosario, Argentina

Location

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Brasília, Brazil

Location

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São Paulo, Brazil

Location

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Sofia, Bulgaria

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Santiago, Chile

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Bogotá, Colombia

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Cali, Colombia

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Prague, Czechia

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Hiroshima, Japan

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Nara, Japan

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Tochigi, Japan

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Tokyo, Japan

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Gdansk, Poland

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Krakow, Poland

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Lodz, Poland

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Warsaw, Poland

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Bucharest, Romania

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Timișoara, Romania

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Kirov, Russia

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Moscow, Russia

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Saint Petersburg, Russia

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Barcelona, Spain

Location

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Malmo, Sweden

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Lviv, Ukraine

Location

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London, United Kingdom

Location

Related Publications (1)

• 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.

  PMID: 23834666 RESULT

MeSH Terms

Conditions

Hemophilia B

Interventions

Factor IX

Condition Hierarchy (Ancestors)

Blood Coagulation Disorders, Inherited; Blood Coagulation Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Coagulation Protein Disorders; Hemorrhagic Disorders; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Genetic Diseases, X-Linked

Intervention Hierarchy (Ancestors)

Enzyme Precursors; Enzymes and Coenzymes; Blood Coagulation Factors; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Protein Precursors; Biological Factors

Results Point of Contact

• Title: Study Director
• Organization: Shire

ClinicalTransparency@shire.com

+1 866 842 5335

Study Officials

• Study Director

  Takeda

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 2, 2010
• First Posted: August 3, 2010
• Study Start: July 29, 2010
• Primary Completion: May 3, 2012
• Study Completion: May 3, 2012
• Last Updated: May 20, 2021
• Results First Posted: November 25, 2013

Record last verified: 2021-04

Locations

PL (4); RU (3); UA (1); BU (1); ES (1); RO (2); AR (1); BR (2); CO (2); JP (4); SE (1); GB (1); CL (1); CZ (1)