Phase 3
N=36
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
Hemophilia A or B With Inhibitors · Hemophilia A · Hemophilia B
Bottom Line
View on ClinicalTrials.gov: NCT00851721 ↗Enrolled (actual)
36
Serious AEs
36.1%
Results posted
Mar 2014
Primary outcome: Primary: Reduction in Annualized Bleeding Episode Rate (ABR) Among Participants Receiving Prophylactic Treatment as Compared to Those Treated On-demand — 28.7; 7.9 bleeds/year — p=0.0003
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 3
- Interventions
- Factor VIII Inhibitor Bypassing Activity (nanofiltered, vapor heat-treated) (Biological)
- Age
- Pediatric, Adult, Older Adult · 4+ yrs
- Sex
- All
- Sponsor
- Baxalta now part of Shire
- Primary completion
- Oct 2012
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Reduction in Annualized Bleeding Episode Rate (ABR) Among Participants Receiving Prophylactic Treatment as Compared to Those Treated On-demand |
28.7; 7.9 | 0.0003 sig |
| SECONDARY Annualized Bleeding Rate by Treatment Regimen, Bleeding Etiology, and Bleed Type |
18.9; 5.6; 4.7; 2.5; 22.9; 6.0 | — |
| SECONDARY Differences in Mean Transformed Annualized Bleeding Rate Between On-Demand and Prophylaxis Treatment Regimens by Bleeding Etiology, and Bleeding Type |
2.2; 1.0; 2.4; 0.8; 2.1; 0.8 | 0.0008 sig |
| SECONDARY Annualized Bleeding Rate for New Target Joints |
5.9; 0.0 | — |
| SECONDARY Differences in Mean Transformed Annualized Bleeding Rate Between On-Demand and Prophylaxis Treatment Regimens: New Target Joints |
1.6 | 0.0271 sig |
| SECONDARY Number of New Target Joints |
23; 7 | — |
| SECONDARY Assessment of Objective Clinical Symptoms- Visual Analog Scale (VAS): Pain in Adolescents and Adults (≥12 Years Old) |
29.0; 49.5; 10.0; 33.8; 3.0; 6.2 | — |
| SECONDARY Assessment of Clinical Symptoms - Visual Analog Scale (VAS): Pain in Pediatrics (<12 Years Old) |
27; 3; 3; 1; 12; 3 | — |
| SECONDARY Assessment of Clinical Symptoms - Range of Motion (ROM) |
15.0; 10.0; 10.0; 8.0; 20.0; 15.5 | — |
| SECONDARY Assessment of Hemostasis for Treatment of Bleeding Episodes- Overall Efficacy Rating at 6 Hours |
109; 16; 355; 106; 142; 42 | — |
| SECONDARY Assessment of Hemostasis for Treatment of Bleeding Episodes- Overall Efficacy Rating at 24 Hours |
282; 42; 280; 89; 36; 12 | — |
| SECONDARY Total Weight Adjusted Dose to Control a Bleeding Episode |
4049.7; 1524.9 | 0.0067 sig |
| SECONDARY The Number of Bleeding Episode (BE) Which Required 1, 2, 3, or ≥4 Infusions to Control Bleeding |
352; 98; 134; 41; 62; 13 | — |
| SECONDARY Abnormal Activated Partial Thromboplastin Time (aPTT) Assay Results |
67.3; 68.5; 68.0; 62.7; 68.2; 65.6 | — |
| SECONDARY Abnormal D-Dimer Assay Results |
862.0; 833.5; 690.0; 1021.5; 969.0; 1032.0 | — |
| SECONDARY Abnormal Fibrinogen Assay Results |
428.0; 422.0; NA; 402.0; 415.0; 759.0 | — |
| SECONDARY Abnormal Fibrin Degradation Products (FDP) Assay Results |
16.0; 12.0; NA; 8.0; 8.0; 8.0 | — |
| SECONDARY Abnormal Prothrombin Fragment F 1.2 Assay Results |
284.0; 308.0; 336.5; 579.0; 448.0; 430.0 | — |
| SECONDARY Abnormal Prothrombin Time Assay Results |
9.4; 9.6; 9.5; NA; NA; 12.5 | — |
| SECONDARY Abnormal Thrombin-Antithrombin III (TAT) Assay Results |
5.1; 5.6; 4.7; 12.3; 7.9; 5.6 | — |
| SECONDARY Viral Serology From Screening Visit and Study Termination Visit: Hepatitis A, Hepatitis B, and Hepatitis C |
1; 0; 8; 11; 8; 4 | — |
| SECONDARY Viral Serology From Screening Visit and Study Termination Visit: HIV-1/2 Antibody (Ab) |
0; 0; 18; 16; 1; 1 | — |
| SECONDARY Viral Serology From Screening Visit and Study Termination Visit: Parvovirus B19 IgG Antibody [IV] |
3; 1; 14; 13; 0; 2 | — |
| SECONDARY Viral Serology From Screening Visit and Study Termination Visit: Parvovirus B19 IgM Antibody [IV] |
0; 0; 1; 0; 17; 16 | — |
| SECONDARY Rate of Related Adverse Events (AEs) Per Year |
0.000; 0.000 | — |
| SECONDARY Rate of Related Adverse Events (AEs) During or Within 1 Hour of Infusion Per Year |
0.000; 0.000 | — |
| SECONDARY Number of Related Thromboembolic Adverse Events (AEs) |
0; 0 | — |
| SECONDARY Absolute Changes in Inhibitor Titer of Hemophilia A Participants With Shifts in Factor VIII (FVIII) Inhibitor Titer Levels |
12.1; 4.0; 2.0; NA; 12.9; 5.3 | — |
| SECONDARY Absolute Changes in Inhibitor Titer of Hemophilia B Participants With Shifts in Factor IX (FIX) Inhibitor Titer Levels |
3.2; NA; NA; NA; NA; NA | — |
| SECONDARY Pharmacoeconomics: Annual Days Lost Due to Bleeding (Work or School) |
16.4; 8.8 | — |
| SECONDARY Pharmacoeconomics: Annual Number of Hospitalizations for Bleeding |
0.6; 0.6 | — |
| SECONDARY Pharmacoeconomics: Annual Number of Hospitalizations for Indwelling Line |
0.1; 0.1 | — |
| SECONDARY Pharmacoeconomics: Annual Number of Emergency Room Visits |
0.4; 0.4 | — |
| SECONDARY Pharmacoeconomics: Annual Number of Physician's Office Visits |
2.2; 2.6 | — |
| SECONDARY Pharmacoeconomics: Annual Total Length of Hospitalization for Bleeding |
5.0; 5.3 | — |
| SECONDARY Pharmacoeconomics: Annual Total Length of Hospitalization for Indwelling Line |
0.7; 0.7 | — |
| SECONDARY Pharmacoeconomics: Annual Total Number of Days Lost (Work or School) |
17.4; 15.4 | — |
| SECONDARY Health-Related Quality of Life (HRQoL): EuroQoL (Quality of Life)-5 Dimensions (EQ-5D) Index Scores |
0.627; 0.620; 0.621; 0.729; 0.605; 0.700 | — |
| SECONDARY Hemophilia-specific Quality of Life Questionnaire for Adults (Haem-A-QoL) ≥ 16 Years Old |
35.0; 26.0; 25.0; 18.9; 25.6; 23.7 | — |
| SECONDARY Hemophilia-specific Quality of Life Questionnaire for Children and Adolescents < 16 Years Old (Haemo-QoL) - Parent's Evaluation |
25.9; 39.3; 25.6; 36.6; 21.4; 28.6 | — |
| SECONDARY Hemophilia-specific Quality of Life Questionnaire for Children and Adolescents < 16 Years Old (Haemo-QoL) - Child's Evaluation |
33.0; 44.6; 21.4; 37.5; 25.0; 32.9 | — |
| SECONDARY Health-Related Quality of Life (HRQoL) - General Pain Assessment Using a Visual Analogue Scale (VAS) in Adults and Adolescents ≥12 Years Old |
35.2; 55.5; 36.6; 32.7; 32.4; 29.8 | — |
| SECONDARY Health-Related Quality of Life (HRQoL) - General Pain Assessment Using a Visual Analogue Scale (VAS) in Pediatrics <12 Years Old |
1; 0; 0; 1; 1; 0 | — |
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
Data sourced from ClinicalTrials.gov (NCT00851721). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.