Clinical trial NCT02895945: BAX 802 in CHA With Inhibitors
Official title: A Phase 3, Multicenter, Open-label Study of the Efficacy and Safety of B-Domain Deleted Recombinant Porcine Factor VIII (BAX 802) in Subjects With Congenital Hemophilia A With Factor VIII Inhibitors Undergoing Surgical or Other Invasive Procedures
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Hemophilia A
Lead sponsor: Takeda
Sponsor class: INDUSTRY
Collaborators: name: Baxalta Innovations GmbH, now part of Shire
First posted: 2016-09-12
Enrollment: 8
Sex: MALE
Minimum age (years): 12
Maximum age (years): 75
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to evaluate the efficacy and safety of BAX 802 in males with congenital hemophilia A (CHA) with inhibitors who are undergoing major or minor elective surgical, dental, or other invasive procedures.


Eligibility criteria: Inclusion Criteria

1. Participant requires a major or minor elective surgical, dental or other invasive procedure
2. Participant is male and ≥ 12 to ≤ 75 years old at the time of screening
3. Participant has provided signed informed consent (and assent for adolescent participants, as applicable) in accordance with local regulatory requirements
4. Participant has severe (factor VIII (FVIII) level \< 1%) or moderately severe (FVIII level ≤ 2%) congenital hemophilia A (CHA) with inhibitors to human factor VIII (hFVIII) of ≥ 0.6 Bethesda units (BU), as tested at screening at the central laboratory
5. Participant is not currently receiving or has recently received (\< 30 days) immune tolerance induction (ITI) therapy
6. Participant has a Karnofsky performance score of ≥ 60 at screening
7. Participant is human immunodeficiency virus negative (HIV-); or HIV+ with stable disease and CD4+ count ≥ 200 cells/mm\^3 at screening
8. Participant is hepatitis C virus negative (HCV-) by antibody or polymerase chain reaction (PCR) testing; or HCV+ with chronic stable hepatitis disease. Positive serologies will be confirmed by PCR testing.
9. Participant is willing and able to comply with the requirements of the protocol.

Exclusion Criteria

1. The participant requires emergency surgery
2. Severe chronic liver dysfunction or disease (e.g., ≥ 5 × upper limit of normal \[ULN\] alanine aminotransferase \[ALT\], as confirmed by central laboratory at screening or a documented prothrombin time/international normalized ratio \[PT/INR\] \> 1.5)
3. Clinically symptomatic renal disease (serum creatinine \> 2.0 mg/dL), as confirmed by central laboratory at screening
4. Anti-porcine factor VIII (pFVIII) inhibitor \> 10 BU prior to surgery
5. Platelet count \< 100,000/μL at screening
6. Participant has another active coagulation disorder, other than hemophilia A, as per the medical history
7. Planned use of α-interferon with or without ribavirin for HCV infected patients or planned use of a protease inhibitor for HIV infected patients. Patients currently taking any of these medications for ≥ 30 days are eligible
8. Known hypersensitivity to recombinant porcine factor VIII (rpFVIII), or hamster or murine proteins
9. Participant has an ongoing or recent (within 3 months of screening) thrombo-embolic disease, fibrinolysis or disseminated intravascular coagulation (DIC)
10. Participant has been exposed to an IP within 30 days prior to enrollment or is scheduled to participate in another clinical study involving an investigational product (IP) or investigational device during the course of this study
11. Participant is unable to tolerate quantity of blood to be drawn for protocol procedures
12. Participant is a family member or employee of the Investigator.

Primary outcomes:
measure: Percentage of Surgeries With a "Good" or "Excellent" Response as Measured by the Global Hemostatic Efficacy Assessment (GHEA) Score
timeFrame: Day 1 up to discharge or Day 14 (whichever was earlier)
Secondary outcomes:
measure: Actual Blood Loss, Estimated Volume of Expected Average Blood Loss and Expected Maximum Blood Loss During Intra-operative, Post-operative and Peri-operative Period
timeFrame: Intra-operative: up to completion of surgery (Day 1), Post-operative: at 24 hours post-surgery, and Peri-operative: at discharge or Day 14 (whichever was earlier)
measure: Ratio of Actual Blood Loss and Estimated Volume of Expected Average Blood Loss During Intra-operative, Post-operative and Peri-operative Period
timeFrame: Intra-operative: up to completion of surgery (Day 1), Post-operative: at 24 hours post-surgery, and Peri-operative: at discharge or Day 14 (whichever was earlier)
measure: Ratio of Actual Blood Loss and Expected Maximum Blood Loss During Intra-operative, Post-operative and Peri-operative Period
timeFrame: Intra-operative: up to completion of surgery (Day 1), Post-operative: at 24 hours post-surgery, and Peri-operative: at discharge or Day 14 (whichever was earlier)
measure: Percentage of Major Surgeries With Good or Excellent Hemostatic Score
timeFrame: Day 1 up to discharge or Day 14 (whichever was earlier)
measure: Average Daily Weight-adjusted Dose of BAX 802 Per Participant During Pre-operative, Intra-operative and Post-operative Period
timeFrame: Pre-operative: before surgery, Intra-operative: up to completion of surgery (Day 1), Post-operative: from completion of surgical procedure till discharge or 14 days post surgery (whichever was earlier)
measure: Total Weight-adjusted Dose of BAX 802 Per Participant During Pre-operative, Intra-operative and Post-operative Period
timeFrame: Pre-operative: before surgery, Intra-operative: up to completion of surgery (Day 1), Post-operative: from completion of surgical procedure till discharge or 14 days post surgery (whichever was earlier)
measure: Volume of Blood Products Transfused
timeFrame: From initiation of the surgery up to discharge or Day 14 (whichever came earlier)
measure: Number of Participants With De Novo Inhibitors
timeFrame: Baseline up end of study (EOS) (up to 44 months)
measure: Number of Participants With Anamnestic Reactions
timeFrame: Baseline up to EOS (up to 44 months)
measure: Mean Change From Baseline up to EOS in Inhibitory and Binding Antibodies to pFVIII
timeFrame: Baseline up to EOS (up to 44 months)
measure: Mean Change From Baseline up to EOS in Inhibitory and Binding Antibodies to hFVIII
timeFrame: Baseline up to EOS (up to 44 months)
measure: Number of Participants With Clinically Significant Change From Baseline in Binding Antibodies to Baby Hamster Kidney (BHK) Proteins
timeFrame: Baseline up to EOS (up to 44 months)
measure: Number of Participants With Thromboembolic Events
timeFrame: Baseline up to EOS (up to 44 months)
measure: Number of Participants With Severe Allergic Reactions
timeFrame: Baseline up to EOS (up to 44 months)
measure: Number of Participants With Investigational Product (IP) Related Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs
timeFrame: Baseline up to EOS (up to 44 months)
measure: Number of Participants With Clinically Significant Change From Baseline in Vital Sign
timeFrame: Baseline up to EOS (up to 44 months)
measure: Number of Participants With Clinically Significant Change From Baseline in Clinical Laboratory Values
timeFrame: Baseline up to EOS (up to 44 months)
Other outcomes:
Locations:
city: Peoria
country: United States
facility: Bleeding and Clotting Disorders Institute
state: Illinois
city: Winston-Salem
country: United States
facility: Wake Forest University Baptist Medical Center
state: North Carolina
city: Cleveland
country: United States
facility: Case Western Reserve University
state: Ohio
city: Sofia
country: Bulgaria
facility: UMHAT 'Tsaritsa Yoanna - ISUL', EAD
city: Sofia
country: Bulgaria
facility: UMHATEM 'N.I. Pirogov', EAD
city: Montréal
country: Canada
facility: Hopital Maisonneuve-Rosemont d/b/a CIUSSS de l'Est-de-l'Île-de-Montréal
state: Quebec
city: Bonn
country: Germany
facility: Universitaetsklinikum Bonn AoeR
city: Leipzig
country: Germany
facility: Zentrum für Hämostaseologie, Universitätsklinikum Leipzig AöR
city: Castelfranco Veneto
country: Italy
facility: Presidio Ospedaliero di Castelfranco Veneto
state: Treviso
city: Firenze
country: Italy
facility: Azienda Ospedaliera Universitaria Careggi
city: Milano
country: Italy
facility: Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico
city: Padova
country: Italy
facility: Azienda Ospedaliera di Padova
city: Utrecht
country: Netherlands
facility: UMC Utrecht
city: Oslo
country: Norway
facility: Oslo Universitetssykehus - Rikshospitalet
city: Warszawa
country: Poland
facility: Instytut Hematologii i Transfuzjologii-1-1Y7-1347
city: Kirov
country: Russian Federation
facility: FSBI of Science "Kirov Scientific and Research Institute of Hematology and Blood Transfusion of FMBA.
city: Johannesburg
country: South Africa
facility: Bleeding Disorders Unit and Clinical Haematology Service at Charlotte Maxeke JHB Academic Hospital
city: Valencia
country: Spain
facility: Hospital Universitari i Politecnic La Fe
state: Comunidad Valenciana
city: La Coruña
country: Spain
facility: Complejo Hospitalario Universitario A Coruña
city: Madrid
country: Spain
facility: Hospital Universitario La Paz
city: Ankara
country: Turkey
facility: Ankara University Medical Faculty
city: Izmir
country: Turkey
facility: Ege University Medical Faculty
city: Izmir
country: Turkey
facility: Ege University Medical Faculty
city: Kocaeli
country: Turkey
facility: Kocaeli University Medical Faculty
Study officials:
affiliation: Shire
name: Study Director
role: STUDY_DIRECTOR
References: