Clinical trial NCT00851721: 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
Official 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Hemophilia A or B With Inhibitors
Hemophilia A
Hemophilia B
Keywords: Hemophilia A
Factor VIII Inhibitor
Factor IX Inhibitor
Hemophilia B
Lead sponsor: Takeda
Sponsor class: INDUSTRY
First posted: 2009-02-26
Enrollment: 52
Sex: ALL
Minimum age (years): 4
Maximum age (years): 65
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of the study was to determine the efficacy, safety, and health-related quality of life benefits with FEIBA NF prophylactic treatment as compared with on-demand treatment.


Eligibility criteria: 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

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

Primary outcomes:
measure: Reduction in Annualized Bleeding Episode Rate (ABR) Among Participants Receiving Prophylactic Treatment as Compared to Those Treated On-demand
timeFrame: 12 months ± 14 days
Secondary outcomes:
measure: Annualized Bleeding Rate by Treatment Regimen, Bleeding Etiology, and Bleed Type
timeFrame: 12 months ± 14 days
measure: Differences in Mean Transformed Annualized Bleeding Rate Between On-Demand and Prophylaxis Treatment Regimens by Bleeding Etiology, and Bleeding Type
timeFrame: 12 months ± 14 days
measure: Annualized Bleeding Rate for New Target Joints
timeFrame: 12 months ± 14 days
measure: Differences in Mean Transformed Annualized Bleeding Rate Between On-Demand and Prophylaxis Treatment Regimens: New Target Joints
timeFrame: 12 months ± 14 days
measure: Number of New Target Joints
timeFrame: 12 months ± 14 days
measure: Assessment of Objective Clinical Symptoms- Visual Analog Scale (VAS): Pain in Adolescents and Adults (≥12 Years Old)
timeFrame: Throughout the study period, 12 months ± 14 days
measure: Assessment of Clinical Symptoms - Visual Analog Scale (VAS): Pain in Pediatrics (<12 Years Old)
timeFrame: 12 months ± 14 days
measure: Assessment of Clinical Symptoms - Range of Motion (ROM)
timeFrame: 12 months ± 14 days
measure: Assessment of Hemostasis for Treatment of Bleeding Episodes- Overall Efficacy Rating at 6 Hours
timeFrame: 6 h ± 30 min post-infusion
measure: Assessment of Hemostasis for Treatment of Bleeding Episodes- Overall Efficacy Rating at 24 Hours
timeFrame: 24 ± 1 h post-infusion
measure: Total Weight Adjusted Dose to Control a Bleeding Episode
timeFrame: 12 months ± 14 days
measure: The Number of Bleeding Episode (BE) Which Required 1, 2, 3, or ≥4 Infusions to Control Bleeding
timeFrame: 12 months ± 14 days
measure: Abnormal Activated Partial Thromboplastin Time (aPTT) Assay Results
timeFrame: Screening visit, Month 3, Month 6, Month 9, and Termination visit
measure: Abnormal D-Dimer Assay Results
timeFrame: Screening visit, Month 3, Month 6, Month 9, and Termination visit
measure: Abnormal Fibrinogen Assay Results
timeFrame: Screening visit, Month 3, Month 6, Month 9, and Termination visit
measure: Abnormal Fibrin Degradation Products (FDP) Assay Results
timeFrame: Screening visit, Month 3, Month 6, Month 9, and Termination visit
measure: Abnormal Prothrombin Fragment F 1.2 Assay Results
timeFrame: Screening visit, Month 3, Month 6, Month 9, and Termination visit
measure: Abnormal Prothrombin Time Assay Results
timeFrame: Screening visit, Month 3, Month 6, Month 9, and Termination visit
measure: Abnormal Thrombin-Antithrombin III (TAT) Assay Results
timeFrame: Screening visit, Month 3, Month 6, Month 9, and Termination visit
measure: Viral Serology From Screening Visit and Study Termination Visit: Hepatitis A, Hepatitis B, and Hepatitis C
timeFrame: 12 months ± 14 days
measure: Viral Serology From Screening Visit and Study Termination Visit: HIV-1/2 Antibody (Ab)
timeFrame: 12 months ± 14 days
measure: Viral Serology From Screening Visit and Study Termination Visit: Parvovirus B19 IgG Antibody [IV]
timeFrame: 12 months ± 14 days
measure: Viral Serology From Screening Visit and Study Termination Visit: Parvovirus B19 IgM Antibody [IV]
timeFrame: 12 months ± 14 days
measure: Rate of Related Adverse Events (AEs) Per Year
timeFrame: 12 months ± 14 days
measure: Rate of Related Adverse Events (AEs) During or Within 1 Hour of Infusion Per Year
timeFrame: 12 months ± 14 days
measure: Number of Related Thromboembolic Adverse Events (AEs)
timeFrame: 12 months ± 14 days
measure: Absolute Changes in Inhibitor Titer of Hemophilia A Participants With Shifts in Factor VIII (FVIII) Inhibitor Titer Levels
timeFrame: 12 months ± 14 days
measure: Absolute Changes in Inhibitor Titer of Hemophilia B Participants With Shifts in Factor IX (FIX) Inhibitor Titer Levels
timeFrame: 12 months ± 14 days
measure: Pharmacoeconomics: Annual Days Lost Due to Bleeding (Work or School)
timeFrame: 12 months ± 14 days
measure: Pharmacoeconomics: Annual Number of Hospitalizations for Bleeding
timeFrame: 12 months ± 14 days
measure: Pharmacoeconomics: Annual Number of Hospitalizations for Indwelling Line
timeFrame: 12 months ± 14 days
measure: Pharmacoeconomics: Annual Number of Emergency Room Visits
timeFrame: 12 months ± 14 days
measure: Pharmacoeconomics: Annual Number of Physician's Office Visits
timeFrame: 12 months ± 14 days
measure: Pharmacoeconomics: Annual Total Length of Hospitalization for Bleeding
timeFrame: 12 months ± 14 days
measure: Pharmacoeconomics: Annual Total Length of Hospitalization for Indwelling Line
timeFrame: 12 months ± 14 days
measure: Pharmacoeconomics: Annual Total Number of Days Lost (Work or School)
timeFrame: 12 months ± 14 days
measure: Health-Related Quality of Life (HRQoL): EuroQoL (Quality of Life)-5 Dimensions (EQ-5D) Index Scores
timeFrame: 12 months ± 14 days
measure: Hemophilia-specific Quality of Life Questionnaire for Adults (Haem-A-QoL) ≥ 16 Years Old
timeFrame: 12 months ± 14 days
measure: Hemophilia-specific Quality of Life Questionnaire for Children and Adolescents < 16 Years Old (Haemo-QoL) - Parent's Evaluation
timeFrame: 12 months ± 14 days
measure: Hemophilia-specific Quality of Life Questionnaire for Children and Adolescents < 16 Years Old (Haemo-QoL) - Child's Evaluation
timeFrame: 12 months ± 14 days
measure: Health-Related Quality of Life (HRQoL) - General Pain Assessment Using a Visual Analogue Scale (VAS) in Adults and Adolescents ≥12 Years Old
timeFrame: Baseline, 6 months and 12 months ± 14 days
measure: Health-Related Quality of Life (HRQoL) - General Pain Assessment Using a Visual Analogue Scale (VAS) in Pediatrics <12 Years Old
timeFrame: Baseline, 6 months and 12 months ± 14 days
Other outcomes:
Locations:
city: Chicago
country: United States
state: Illinois
city: Cleveland
country: United States
state: Ohio
city: Rio de Janeiro
country: Brazil
state: RJ
city: Sao Paulo
country: Brazil
state: SP
city: Sofia
country: Bulgaria
city: Zagreb
country: Croatia
city: Kanagawa
country: Japan
city: Nara
country: Japan
city: Wellington
country: New Zealand
city: Krakow
country: Poland
city: Warsaw
country: Poland
city: Bucharest
country: Romania
city: Timisoara
country: Romania
city: Ekaterinburg
country: Russian Federation
city: Kirov
country: Russian Federation
city: Moscow
country: Russian Federation
city: Lviv
country: Ukraine
Study officials:
affiliation: Takeda
name: Study Director
role: STUDY_DIRECTOR
References:
citation: Antunes SV, Tangada S, Stasyshyn O, Mamonov V, Phillips J, Guzman-Becerra N, Grigorian A, Ewenstein B, Wong WY. Randomized comparison of prophylaxis and on-demand regimens with FEIBA NF in the treatment of haemophilia A and B with inhibitors. Haemophilia. 2014 Jan;20(1):65-72. doi: 10.1111/hae.12246. Epub 2013 Aug 1.