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

NCT00851721 | Completed Phase 3 Results DMC

• 2 other identifiers: 0907012008-003855-65
• Study Type: interventional
• Target: 52
• Locations: 10 countries
• Sites: 17

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.

Conditions

Hemophilia A or B With Inhibitors; Hemophilia A; Hemophilia B

Keywords

Hemophilia A; Factor VIII Inhibitor; Factor IX Inhibitor; Hemophilia B

Outcome Measures

Primary Outcomes (1)

• Reduction in Annualized Bleeding Episode Rate (ABR) Among Participants Receiving Prophylactic Treatment as Compared to Those Treated On-demand

  Participants were Randomized to Receive 1 of the 2 Following Treatment Regimens: 1.On-Demand: FEIBA NF dose \& dosing interval as prescribed by treating physician 2.Prophylaxis: 85 ± 15 U/kg of FEIBA NF every other day during 12-month prophylactic period Annualized rate of bleeding episodes was calculated as: (Number of bleeding episodes/observed treatment period in days) \* 365.25

  12 months ± 14 days

Secondary Outcomes (42)

• Annualized Bleeding Rate by Treatment Regimen, Bleeding Etiology, and Bleed Type

  12 months ± 14 days

• Differences in Mean Transformed Annualized Bleeding Rate Between On-Demand and Prophylaxis Treatment Regimens by Bleeding Etiology, and Bleeding Type

  12 months ± 14 days

• Annualized Bleeding Rate for New Target Joints

  12 months ± 14 days

• Differences in Mean Transformed Annualized Bleeding Rate Between On-Demand and Prophylaxis Treatment Regimens: New Target Joints

  12 months ± 14 days

• Number of New Target Joints

  12 months ± 14 days

Study Arms (2)

Prophylaxis arm

EXPERIMENTAL

Biological: Factor VIII Inhibitor Bypassing Activity (nanofiltered, vapor heat-treated)

On-demand arm

ACTIVE COMPARATOR

Biological: Factor VIII Inhibitor Bypassing Activity (nanofiltered, vapor heat-treated)

Interventions

Factor VIII Inhibitor Bypassing Activity (nanofiltered, vapor heat-treated) BIOLOGICAL

85 ± 15 U/kg of FEIBA NF every other day during the 12-month prophylactic period

Also known as: FEIBA NF

Prophylaxis arm

Eligibility Criteria

• Age: 4 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Baxalta now part of Shire: lead

Study Sites (17)

Unknown Facility

Chicago, Illinois, United States

Location

Unknown Facility

Cleveland, Ohio, United States

Location

Unknown Facility

Rio de Janeiro, Rio de Janeiro, Brazil

Location

Unknown Facility

São Paulo, São Paulo, Brazil

Location

Unknown Facility

Sofia, Bulgaria

Location

Unknown Facility

Zagreb, Croatia

Location

Unknown Facility

Kanagawa, Japan

Location

Unknown Facility

Nara, Japan

Location

Unknown Facility

Wellington, New Zealand

Location

Unknown Facility

Krakow, Poland

Location

Unknown Facility

Warsaw, Poland

Location

Unknown Facility

Bucharest, Romania

Location

Unknown Facility

Timișoara, Romania

Location

Unknown Facility

Kirov, Russia

Location

Unknown Facility

Moscow, Russia

Location

Unknown Facility

Yekaterinburg, Russia

Location

Unknown Facility

Lviv, Ukraine

Location

Related Publications (1)

• 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.

  PMID: 23910578 RESULT

MeSH Terms

Conditions

Hemophilia A; Hemophilia B

Interventions

anti-inhibitor coagulant complex

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

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: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 25, 2009
• First Posted: February 26, 2009
• Study Start: March 31, 2009
• Primary Completion: October 17, 2012
• Study Completion: October 17, 2012
• Last Updated: May 19, 2021
• Results First Posted: March 14, 2014

Record last verified: 2021-04

Locations

NZ (1); RU (3); JP (2); UA (1); CR (1); BU (1); BR (2); RO (2); PL (2); US (2)