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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT00851721




Registration number
NCT00851721
Ethics application status
Date submitted
25/02/2009
Date registered
26/02/2009
Date last updated
19/05/2021

Titles & IDs
Public title
Efficacy and Safety Study of Prophylactic Versus On-Demand Treatment With Feiba NF in Subjects With Hemophilia A or B and a High Titer Inhibitor
Scientific title
FEIBA NF: A Prospective, Open-label, Randomized, Parallel Study to Evaluate the Efficacy and Safety of Prophylactic Versus On-Demand Treatment in Subjects With Hemophilia A or B and a High Titer Inhibitor
Secondary ID [1] 0 0
2008-003855-65
Secondary ID [2] 0 0
090701
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Hemophilia A or B With Inhibitors 0 0
Hemophilia A 0 0
Hemophilia B 0 0
Condition category
Condition code
Blood 0 0 0 0
Clotting disorders
Human Genetics and Inherited Disorders 0 0 0 0
Other human genetics and inherited disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Other - Factor VIII Inhibitor Bypassing Activity (nanofiltered, vapor heat-treated)
Treatment: Other - Factor VIII Inhibitor Bypassing Activity (nanofiltered, vapor heat-treated)

Experimental: Prophylaxis arm -

Active comparator: On-demand arm -


Treatment: Other: Factor VIII Inhibitor Bypassing Activity (nanofiltered, vapor heat-treated)
85 ± 15 U/kg of FEIBA NF every other day during the 12-month prophylactic period

Treatment: Other: Factor VIII Inhibitor Bypassing Activity (nanofiltered, vapor heat-treated)
FEIBA NF dose and dosing interval as prescribed by the treating physician

Intervention code [1] 0 0
Treatment: Other
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Reduction in Annualized Bleeding Episode Rate (ABR) Among Participants Receiving Prophylactic Treatment as Compared to Those Treated On-demand
Timepoint [1] 0 0
12 months ± 14 days
Secondary outcome [1] 0 0
Annualized Bleeding Rate by Treatment Regimen, Bleeding Etiology, and Bleed Type
Timepoint [1] 0 0
12 months ± 14 days
Secondary outcome [2] 0 0
Differences in Mean Transformed Annualized Bleeding Rate Between On-Demand and Prophylaxis Treatment Regimens by Bleeding Etiology, and Bleeding Type
Timepoint [2] 0 0
12 months ± 14 days
Secondary outcome [3] 0 0
Annualized Bleeding Rate for New Target Joints
Timepoint [3] 0 0
12 months ± 14 days
Secondary outcome [4] 0 0
Differences in Mean Transformed Annualized Bleeding Rate Between On-Demand and Prophylaxis Treatment Regimens: New Target Joints
Timepoint [4] 0 0
12 months ± 14 days
Secondary outcome [5] 0 0
Number of New Target Joints
Timepoint [5] 0 0
12 months ± 14 days
Secondary outcome [6] 0 0
Assessment of Objective Clinical Symptoms- Visual Analog Scale (VAS): Pain in Adolescents and Adults (=12 Years Old)
Timepoint [6] 0 0
Throughout the study period, 12 months ± 14 days
Secondary outcome [7] 0 0
Assessment of Clinical Symptoms - Visual Analog Scale (VAS): Pain in Pediatrics (<12 Years Old)
Timepoint [7] 0 0
12 months ± 14 days
Secondary outcome [8] 0 0
Assessment of Clinical Symptoms - Range of Motion (ROM)
Timepoint [8] 0 0
12 months ± 14 days
Secondary outcome [9] 0 0
Assessment of Hemostasis for Treatment of Bleeding Episodes- Overall Efficacy Rating at 6 Hours
Timepoint [9] 0 0
6 h ± 30 min post-infusion
Secondary outcome [10] 0 0
Assessment of Hemostasis for Treatment of Bleeding Episodes- Overall Efficacy Rating at 24 Hours
Timepoint [10] 0 0
24 ± 1 h post-infusion
Secondary outcome [11] 0 0
Total Weight Adjusted Dose to Control a Bleeding Episode
Timepoint [11] 0 0
12 months ± 14 days
Secondary outcome [12] 0 0
The Number of Bleeding Episode (BE) Which Required 1, 2, 3, or =4 Infusions to Control Bleeding
Timepoint [12] 0 0
12 months ± 14 days
Secondary outcome [13] 0 0
Abnormal Activated Partial Thromboplastin Time (aPTT) Assay Results
Timepoint [13] 0 0
Screening visit, Month 3, Month 6, Month 9, and Termination visit
Secondary outcome [14] 0 0
Abnormal D-Dimer Assay Results
Timepoint [14] 0 0
Screening visit, Month 3, Month 6, Month 9, and Termination visit
Secondary outcome [15] 0 0
Abnormal Fibrinogen Assay Results
Timepoint [15] 0 0
Screening visit, Month 3, Month 6, Month 9, and Termination visit
Secondary outcome [16] 0 0
Abnormal Fibrin Degradation Products (FDP) Assay Results
Timepoint [16] 0 0
Screening visit, Month 3, Month 6, Month 9, and Termination visit
Secondary outcome [17] 0 0
Abnormal Prothrombin Fragment F 1.2 Assay Results
Timepoint [17] 0 0
Screening visit, Month 3, Month 6, Month 9, and Termination visit
Secondary outcome [18] 0 0
Abnormal Prothrombin Time Assay Results
Timepoint [18] 0 0
Screening visit, Month 3, Month 6, Month 9, and Termination visit
Secondary outcome [19] 0 0
Abnormal Thrombin-Antithrombin III (TAT) Assay Results
Timepoint [19] 0 0
Screening visit, Month 3, Month 6, Month 9, and Termination visit
Secondary outcome [20] 0 0
Viral Serology From Screening Visit and Study Termination Visit: Hepatitis A, Hepatitis B, and Hepatitis C
Timepoint [20] 0 0
12 months ± 14 days
Secondary outcome [21] 0 0
Viral Serology From Screening Visit and Study Termination Visit: HIV-1/2 Antibody (Ab)
Timepoint [21] 0 0
12 months ± 14 days
Secondary outcome [22] 0 0
Viral Serology From Screening Visit and Study Termination Visit: Parvovirus B19 IgG Antibody [IV]
Timepoint [22] 0 0
12 months ± 14 days
Secondary outcome [23] 0 0
Viral Serology From Screening Visit and Study Termination Visit: Parvovirus B19 IgM Antibody [IV]
Timepoint [23] 0 0
12 months ± 14 days
Secondary outcome [24] 0 0
Rate of Related Adverse Events (AEs) Per Year
Timepoint [24] 0 0
12 months ± 14 days
Secondary outcome [25] 0 0
Rate of Related Adverse Events (AEs) During or Within 1 Hour of Infusion Per Year
Timepoint [25] 0 0
12 months ± 14 days
Secondary outcome [26] 0 0
Number of Related Thromboembolic Adverse Events (AEs)
Timepoint [26] 0 0
12 months ± 14 days
Secondary outcome [27] 0 0
Absolute Changes in Inhibitor Titer of Hemophilia A Participants With Shifts in Factor VIII (FVIII) Inhibitor Titer Levels
Timepoint [27] 0 0
12 months ± 14 days
Secondary outcome [28] 0 0
Absolute Changes in Inhibitor Titer of Hemophilia B Participants With Shifts in Factor IX (FIX) Inhibitor Titer Levels
Timepoint [28] 0 0
12 months ± 14 days
Secondary outcome [29] 0 0
Pharmacoeconomics: Annual Days Lost Due to Bleeding (Work or School)
Timepoint [29] 0 0
12 months ± 14 days
Secondary outcome [30] 0 0
Pharmacoeconomics: Annual Number of Hospitalizations for Bleeding
Timepoint [30] 0 0
12 months ± 14 days
Secondary outcome [31] 0 0
Pharmacoeconomics: Annual Number of Hospitalizations for Indwelling Line
Timepoint [31] 0 0
12 months ± 14 days
Secondary outcome [32] 0 0
Pharmacoeconomics: Annual Number of Emergency Room Visits
Timepoint [32] 0 0
12 months ± 14 days
Secondary outcome [33] 0 0
Pharmacoeconomics: Annual Number of Physician's Office Visits
Timepoint [33] 0 0
12 months ± 14 days
Secondary outcome [34] 0 0
Pharmacoeconomics: Annual Total Length of Hospitalization for Bleeding
Timepoint [34] 0 0
12 months ± 14 days
Secondary outcome [35] 0 0
Pharmacoeconomics: Annual Total Length of Hospitalization for Indwelling Line
Timepoint [35] 0 0
12 months ± 14 days
Secondary outcome [36] 0 0
Pharmacoeconomics: Annual Total Number of Days Lost (Work or School)
Timepoint [36] 0 0
12 months ± 14 days
Secondary outcome [37] 0 0
Health-Related Quality of Life (HRQoL): EuroQoL (Quality of Life)-5 Dimensions (EQ-5D) Index Scores
Timepoint [37] 0 0
12 months ± 14 days
Secondary outcome [38] 0 0
Hemophilia-specific Quality of Life Questionnaire for Adults (Haem-A-QoL) = 16 Years Old
Timepoint [38] 0 0
12 months ± 14 days
Secondary outcome [39] 0 0
Hemophilia-specific Quality of Life Questionnaire for Children and Adolescents < 16 Years Old (Haemo-QoL) - Parent's Evaluation
Timepoint [39] 0 0
12 months ± 14 days
Secondary outcome [40] 0 0
Hemophilia-specific Quality of Life Questionnaire for Children and Adolescents < 16 Years Old (Haemo-QoL) - Child's Evaluation
Timepoint [40] 0 0
12 months ± 14 days
Secondary outcome [41] 0 0
Health-Related Quality of Life (HRQoL) - General Pain Assessment Using a Visual Analogue Scale (VAS) in Adults and Adolescents =12 Years Old
Timepoint [41] 0 0
Baseline, 6 months and 12 months ± 14 days
Secondary outcome [42] 0 0
Health-Related Quality of Life (HRQoL) - General Pain Assessment Using a Visual Analogue Scale (VAS) in Pediatrics <12 Years Old
Timepoint [42] 0 0
Baseline, 6 months and 12 months ± 14 days

Eligibility
Key inclusion criteria
* Signed and dated informed consent form by the participant or the participant's legally authorized representative
* The participant is = 4 to = 65 years of age
* The participant has a Karnofsky performance score of = 60
* Hemophilia A and B of any severity, with documented history of high-titer inhibitor (> 5 Bethesda unit (BU)) for at least 12 months; or, if inhibitor titer is = 5 BU, and the participant is refractory with increased dosing of either factor VIII (FVIII) or factor IX (FIX), as demonstrated from the participant's medical history
* Currently being treated on an on-demand basis for treatment of bleeding episodes
* Adequate venous access, with or without central venous device
* = 12 bleeding episodes requiring treatment with by-passing agents in the past 12 months, based on medical history
* Competent in-home treatment and infusion therapy
* Currently using bypassing agents (activated prothrombin complex concentrate (APCC) or recombinant activated factor VII (rFVIIa)) for treatment of bleeding episodes
* HCV-, either by antibody testing or polymerase chain reaction (PCR); or HCV+ with stable hepatic disease
* HIV-, or HIV+ with stable disease and CD4 count > 200 cells/mm3 at screening
* Female participant of childbearing potential, presents with a negative serum pregnancy test, and agrees to employ adequate birth control measures for the duration of the study
Minimum age
4 Years
Maximum age
65 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Currently receiving immune tolerance induction (ITI)
* Currently on regular prophylactic therapy to prevent bleeding episodes
* Clinically symptomatic liver disease (e.g. diagnosis of cirrhosis [confirmed by liver biopsy], portal vein hypertension, ascites, prothrombin time (PT) 5 seconds above upper limit of normal)
* Platelet count < 100,000/ml
* Planned elective surgery during participation in this study
* Participant is currently participating in another clinical study and has received an investigational product or device within 30 days prior to study entry
* Planned use of pegylated or non-pegylated alpha-interferon with or without ribavirin for HCV infected participants or planned use of a protease inhibitor for HIV infected participants. Participants currently taking any of these medications for a 30-day course are eligible.
* Clinically significant increase in D-dimer levels from historical baseline and/or associated with chronic liver disease or clinically evident thromboembolic event
* Known hypersensitivity to anti-inhibitor coagulant complexes (AICCs)
* Currently treated with a systemic immunomodulating drug
* Prior history of thromboembolic event: acute myocardial infarction, deep vein thrombosis, or pulmonary embolism
* Diagnosis of advanced atherosclerosis, malignancy and/or other diseases that may increase the participant's risk of thromboembolic complications
* Clinically significant medical, psychiatric, or cognitive illness, or recreational drug/alcohol use that, in the opinion of the investigator, would affect participant safety or compliance

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Illinois
Country [2] 0 0
United States of America
State/province [2] 0 0
Ohio
Country [3] 0 0
Brazil
State/province [3] 0 0
RJ
Country [4] 0 0
Brazil
State/province [4] 0 0
SP
Country [5] 0 0
Bulgaria
State/province [5] 0 0
Sofia
Country [6] 0 0
Croatia
State/province [6] 0 0
Zagreb
Country [7] 0 0
Japan
State/province [7] 0 0
Kanagawa
Country [8] 0 0
Japan
State/province [8] 0 0
Nara
Country [9] 0 0
New Zealand
State/province [9] 0 0
Wellington
Country [10] 0 0
Poland
State/province [10] 0 0
Krakow
Country [11] 0 0
Poland
State/province [11] 0 0
Warsaw
Country [12] 0 0
Romania
State/province [12] 0 0
Bucharest
Country [13] 0 0
Romania
State/province [13] 0 0
Timisoara
Country [14] 0 0
Russian Federation
State/province [14] 0 0
Ekaterinburg
Country [15] 0 0
Russian Federation
State/province [15] 0 0
Kirov
Country [16] 0 0
Russian Federation
State/province [16] 0 0
Moscow
Country [17] 0 0
Ukraine
State/province [17] 0 0
Lviv

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Baxalta now part of Shire
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Study Director
Address 0 0
Takeda
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

TypeCitations or Other Details
Journal Antunes SV, Tangada S, Stasyshyn O, Mamonov V, Phi... [More Details]