Clinical trial NCT02764489: FEIBA Reconstitution Volume Reduction and Faster Infusion Study (FEIBA STAR)
Official title: A Phase 3b/4, Prospective, Multicenter, Open-label, Randomized, Crossover Study of Tolerability and Safety of FEIBA Reconstituted in Regular or 50% Reduced Volume and of Faster Infusion Rates in Patients With Hemophilia A or B With Inhibitors
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Hemophilia A or B With Inhibitors
Lead sponsor: Takeda
Sponsor class: INDUSTRY
Collaborators: name: Baxalta Innovations GmbH, now part of Shire
First posted: 2016-05-06
Enrollment: 45
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to:

* 1. To evaluate the tolerability and safety of infusing reduced volume Factor Eight Inhibitor Bypassing Activity (FEIBA) at the standard infusion rate of 2 U/kg/min
* 2. To evaluate the tolerability and safety of infusing reduced volume FEIBA at increased rates of 4 and 10 U/kg/min, in comparison to the standard rate of 2 U/kg/min at the regular volume

Detailed description: 15 JUN 2020: The temporary enrollment stop of new patients into this study due to the COVID-19 pandemic has been lifted in one or more countries/sites, and the study is now again enrolling new patients. However, some countries/sites may still have paused the enrollment of new patients due to the pandemic.

23 APRIL 2020: Enrollment of new patients into this study has been paused due to the COVID-19 situation. The duration of this pause is dependent on the leveling and control of the COVID-19 pandemic.

Eligibility criteria: Inclusion Criteria:

1. Greater than or equal to (\> or =) 18 to less than or equal to (\< or =) 65 years old at the time of screening.
2. Hemophilia A or B of any severity, with a documented \> or = 3 months history of inhibitors (\> or = 0.6 Bethesda units \[BU\]) requiring the use of bypassing agents (FEIBA or rFVIIa) prior to screening. Inhibitor level will be tested at screening if no documented history is available.
3. Hepatitis C virus (HCV) negative, either by antibody testing or polymerase chain reaction (PCR); or HCV positive with stable liver disease.
4. Human immune deficiency virus (HIV) negative; or HIV positive with stable disease and CD4 count \> or = 200 cells per cubic millimetre (cell/mm3) at screening.
5. Adequate venous access.
6. Willing and able to comply with the requirements of the protocol.
7. If a female of childbearing potential, must have a negative blood pregnancy test and agrees to employ adequate birth control measures for the duration of the study, such as: a. Abstain from sexual intercourse, b. Use a reliable method of contraception (contraception such as an intrauterine device, barrier method \[e.g., diaphragm or sponge; female condom not permitted\] with spermicide, oral contraceptive, injectable progesterone, sub dermal implant), and have their male partner use a condom
8. If female of non-childbearing potential, confirmed at screening by fulfilling 1 of the following criteria:

   1. Postmenopausal, defined as amenorrhea for at least 12 months following cessation of all exogenous hormonal treatments and with follicle-stimulating hormone levels within the laboratory-defined postmenopausal range or postmenopausal with amenorrhea for at least 24 months and on hormonal replacement therapy.
   2. Documentation of irreversible surgical sterilization by hysterectomy, bilateral oophorectomy, bilateral tubal ligation (with no subsequent pregnancy at least 1 year from bilateral tubal ligation), or bilateral salpingectomy.

Exclusion criteria:

1. Known hypersensitivity to FEIBA or any of its components.
2. Advanced liver disease (e.g., liver biopsy confirmed diagnosis of cirrhosis, portal vein hypertension, ascites, prothrombin time \[PT\] 5 seconds above upper limit of normal).
3. Planned elective surgery during participation in this study (excluding minor procedures that will not need preventative bleeding treatments, such as exchanges of peripherally inserted central catheters).
4. Platelet count less than (\<) 100,000/ microliter (μL).
5. Taking Emicizumab (Hemlibra) for bleed prevention.
6. Clinical or laboratory evidence of disseminated intravascular coagulation based on medical history.
7. Prior history or evidence of thromboembolic event: acute myocardial infarction, deep vein thrombosis, pulmonary embolism, etc.
8. Diagnosis of advanced atherosclerosis, malignancy, and/or other diseases that may increase the participant's risk of thromboembolic complications.
9. Participant is taking any immunomodulating drug (e.g., corticosteroid agents at a dose equivalent to hydrocortisone greater than (\>) 10 milligram per day (mg/day), or α-interferon) within 30 days prior to enrollment except anti-retroviral chemotherapy.
10. Herbal supplements that contain anti-platelet activity.
11. Participant has participated in another clinical study involving an investigational product (IP) or investigational device within 30 days prior to enrollment or is scheduled to participate in another clinical study involving an IP or investigational device during the course of this study.
12. Participant is a family member or employee of the investigator.
13. 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: Number of Participants With Any Treatment Emergent Adverse Event (TEAE)
timeFrame: From first dose of study drug up to 7 days after the end of infusion (up to Day 41)
measure: Number of Participants With Any Hypersensitivity Reaction
timeFrame: From first dose of study drug up to 7 days after the end of infusion (up to Day 41)
measure: Number of Participants With Any Thromboembolic Event
timeFrame: From first dose of study drug up to 7 days after the end of infusion (up to Day 41)
measure: Number of Participants With Any Infusion Site Reaction
timeFrame: From first dose of study drug up to 7 days after the end of infusion (up to Day 41)
measure: Number of Participants With AEs Leading to Study Discontinuation
timeFrame: From first dose of study drug up to 7 days after the end of infusion (up to Day 41)
measure: Number of Participants With Vital Signs Considered as AEs
timeFrame: From first dose of study drug up to 7 days after the end of infusion (up to Day 41)
measure: Number of Participants With Laboratory Assessments Considered as AEs
timeFrame: From first dose of study drug up to 7 days after the end of infusion (up to Day 41)
Secondary outcomes:
Other outcomes:
Locations:
city: Zagreb
country: Croatia
facility: University Hospital Center Zagreb
city: Skopje
country: North Macedonia
facility: PHI Institute for Transfusion Medicine of Macedonia
city: Poltava
country: Ukraine
facility: MV Sklifosovskyi Poltava Hematology
Study officials:
affiliation: Shire
name: Study Director
role: STUDY_DIRECTOR
References: