Clinical trial NCT02020369: Phase III Study of Coagulation FVIIa (Recombinant) in Congenital Hemophilia A or B Patients With Inhibitors
Official title: A Phase III Study on the Safety, Pharmacokinetics and Efficacy of Coagulation Factor VIIa (Recombinant) in Congenital Hemophilia A or B Patients With Inhibitors to Factor VIII or IX
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Hemophilia A With Inhibitors
Hemophilia B With Inhibitors
Lead sponsor: rEVO Biologics
Sponsor class: INDUSTRY
Collaborators: name: Laboratoire français de Fractionnement et de Biotechnologies
First posted: 2013-12-24
Enrollment: 27
Sex: MALE
Minimum age (years): 12
Maximum age (years): 75
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: The purpose of the study is to assess the safety, efficacy and pharmacokinetics of 2 separate dose regimens (75µg/kg and 225 µg/kg) of Coagulation Factor VIIa (Recombinant) for the treatment of bleeding episodes in hemophilia A or B patients with inhibitors to Factor VIII/IX

Detailed description: This was a global, multicenter, Phase III, prospective, open-label, randomized, crossover study. After obtaining informed consent and performance of screening procedures, patients who met all inclusion and exclusion criteria were randomized to one of two treatment regimens as follows:

* 75 µg/kg treatment regimen
* 225 µg/kg treatment regimen

For each treatment regimen there were two phases:

* Phase A (Initial phase)
* Phase B (Treatment phase)

The assigned treatment regimen was the dose administered in Phase A and was the starting dose in Phase B.

Eligibility criteria: Inclusion Criteria:

* be male with a diagnosis of congenital hemophilia A and/or B of any severity
* have one of the following:
* a positive inhibitor test Bethesda Unit (BU) ≥ 5 (as confirmed at screening by the institutional lab), OR
* a BU\<5 but expected to have a high anamnestic response to FVIII or FIX, as demonstrated from the subject's medical history, precluding the use of Factor VIII or IX products to treat bleedings, OR
* a BU\<5 but expected to be refractory to increased dosing of FVIII or FIX, as demonstrated from the subject's medical history, precluding the use of Factor VIII or IX products to treat bleedings
* be 12 years or older, up to and including 75 years of age (NOTE: different age restrictions may apply per local regulation and/or ethical considerations)
* have at least 3 bleeding episodes of any severity in the past 6 months be capable of understanding and willing to comply with the conditions of the protocol
* have read, understood and provided written informed consent (patient and/or parent(s)/legal guardian(s) if \<18 years of age)

Exclusion Criteria:

* have any coagulation disorder other than hemophilia A or B
* be immuno-suppressed (i.e., the patient should not be receiving systemic immunosuppressive medication, cluster of differentiation 4 (CD4) counts at screening should be \>200/µl)
* have a known allergy or hypersensitivity to rabbits
* have platelet count \<100,000/mL
* have had within one month prior to first administration of the study drug in this study a major surgical procedure (e.g. orthopedic, abdominal)
* have received an investigational drug within 30 days of the first study drug administration, or is expected to receive such drug during participation in this study
* have a clinically relevant hepatic (AST and/or alanine aminotransferase (ALT) \>3 times the upper limit of normal) and/or renal impairment (creatinine \>2 times the upper limit of normal)
* have a history of arterial and/or venous thromboembolic events (such as myocardial infarction, ischemic strokes, transient ischemic attacks, deep venous thrombosis or pulmonary embolism) within 2 years prior to first dose of study drug, or current New York Heart Association (NYHA) functional classification score of stage II -IV
* have an active malignancy (those with non-melanoma skin cancer are allowed)
* have any life-threatening disease or other disease or condition which, according to the investigator's judgment, could imply a potential hazard to the patient, interfere with the trial participation or trial outcome (e.g., a history of non-responsiveness to bypassing products).

Primary outcomes:
measure: Proportion of Successfully Treated Mild/Moderate Bleeding Episodes
timeFrame: 12 hours after first administration of study drug
Secondary outcomes:
measure: Proportion of Mild/Moderate Bleeding Episodes With Patient (Pt)-Reported "Good" or "Excellent" Responses at 12 Hours
timeFrame: at 12 hours
measure: Time to Assessment of a "Good" or "Excellent" Response of Mild/Moderate Bleeding Episodes by the Patient
timeFrame: Within 24 hours of Bleeding Episode
measure: Number of Administrations of Study Drug Per Mild/Moderate Bleeding Episode
timeFrame: Within 24 hours of Bleeding Episode
measure: Total Amount of Study Drug Administered Per Mild/Moderate Bleeding Episode
timeFrame: Through study completion
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Orthopaedic Hemophilia Treatment Center
state: California
city: Sacramento
country: United States
facility: University of California Davis Comprehensive Cancer Center
state: California
city: Aurora
country: United States
facility: University of Colorado Hemophilia and Thrombosis Center
state: Colorado
city: Chicago
country: United States
facility: Rush University Medical Center
state: Illinois
city: Minneapolis
country: United States
facility: University of Minnesota Medical Center Fairview
state: Minnesota
city: Gomel
country: Belarus
facility: Republican Research Center for Radiation Medicine and Human Ecology
city: Sofia
country: Bulgaria
facility: Specialized Hospital for Active Treatment of Hematological Diseases
city: Tbilisi
country: Georgia
facility: LTD HEMA
city: Ramat Gan
country: Israel
facility: Chaim Sheba Medical Center, Tel-hashomer hospital
city: Warsaw
country: Poland
facility: Institute of Hematology and Transfusion Medicine
city: Bucharest
country: Romania
facility: Sandor SRL
city: Kirov
country: Russian Federation
facility: Kirov Research Institute of Hematology and Blood Transfusion
city: Moscow
country: Russian Federation
facility: Hematology Research Center
city: Saint-Petersburg
country: Russian Federation
facility: City Outpatient Clinic #37
city: Kyiv
country: Ukraine
facility: Kyiv City Clinical Hospital #9
city: Lviv
country: Ukraine
facility: Institute of Blood Pathology and Transfusion Medicine of Academy of Medical Sciences of Ukraine
city: Basingstoke
country: United Kingdom
facility: Basingstoke and North Hampshire Hospital, Hemophilia, Hemostasis and Thrombosis Center
Study officials:
affiliation: Saint Eloi Hospital
name: Jean Francois Schved, MD
role: PRINCIPAL_INVESTIGATOR
References: