Hemophilia
Conditions
Brief summary
This is an interventional, prospective, international, multicenter, single-arm, Phase 3, and sequential efficacy and safety study in adolescents and adults with congenital hemophilia A or B with inhibitors to factor VIII (FVIII) or factor IX (FIX) undergoing elective major surgical procedures.
Interventions
BIOLOGICALCoagulation Factor VIIa (Recombinant)
Eptacog Beta (activated) (EB)
Sponsors
Laboratoire français de Fractionnement et de Biotechnologies
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
12 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
Each patient must meet the following criteria to be enrolled in this study: 1. be male with a diagnosis of congenital hemophilia A or B of any severity 2. have one of the following: 1. current positive inhibitor test BU ≥5 (as confirmed at screening by the institutional lab) or history of high-responding inhibitors (BU ≥5) not further successfully treated by Immune Tolerance Induction OR 2. a condition precluding the use of FVIII or FIX products to treat or prevent bleeding such as a previous anamnestic response after exposure to factor concentrates or a previous failure to respond to FVIII or FIX concentrates 3. be ≥12 years to ≤65 years of age on the day of informed consent 4. be scheduled for an elective major surgical procedure as defined in the study protocol (see Table ''Definitions for the specific purpose of Study F7TG2202'') 5. have Hb ≥ 12 g/dL 6. be capable of understanding and willing to comply with the conditions of the protocol OR in the case of a patient under the age of legal majority, parent(s)/legal guardian(s) must be capable of understanding and willing to comply with the conditions of the protocol 7. have read, understood, and provided written informed consent (patient or parent(s)/legal guardian(s) if the patient is minor according to local regulation) and, where applicable according to local regulation, patient's assent if the patient is minor
Exclusion criteria
Patients who meet any of the following criteria will be excluded from the study. 1. have any coagulation disorder other than hemophilia A or B 2. be immunosuppressed (i.e. the patient should not be receiving systemic immunosuppressive medication; CD4+ cell counts at screening should be \>200/μL) 3. known intolerance to EB or any of its excipients 4. currently receiving immune tolerance induction (ITI) therapy 5. have a known or suspected allergy or hypersensitivity to rabbits or rabbit proteins 6. have platelet count \<100,000/μL 7. have received an investigational drug within 30 days or within 5 half-lives of that investigational drug, whichever is longer, of the planned first EB administration, or be expected to receive such drug during participation in this study. Patients who have received fitusiran in a clinical study may not participate in this clinical study for 6 months since the last dose and if they have an antithrombin III level not in the normal range at screening. 8. for patients using emicizumab, have received during the last 6 months or currently receiving a maintenance dosing regimen of emicizumab different from the indicated one ± 10% of approved dose), i.e. different from 1.5 mg/kg once weekly (±10%), 3 mg/kg (±10%) every two weeks or 6 mg/kg (±10%) every four weeks 9. for patients using emicizumab, currently be any plans, or notes in the patient's medical records that would suggest the need to increase or decrease emicizumab dosing due to antidrug antibodies (ADAs), reduced PK, or coagulation/safety-related issues (e.g. lack of response, or potential/actual thromboembolic concerns, etc) 10. have a clinically relevant hepatic (aspartate aminotransferase \[AST\] and/or alanine aminotransferase \[ALT\] \>3 times the upper limit of normal \[ULN\]) and/or renal impairment (creatinine \>2 times the ULN) 11. have a history of arterial and/or venous thromboembolic events (such as myocardial infarction, ischemic strokes, transient ischemic attacks, DVT, or PE) within 2 years prior to the planned first dose of LR769, uncontrolled arrhythmia, or current New York Heart Association (NYHA) functional classification score of stages II - IV 12. have an active malignancy (those with non-melanoma skin cancer are allowed) 13. 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, or interfere with the study participation or study outcome (e.g. chronic, unmanaged hepatitis infection) 14. be using aspirin, non-steroidal anti-inflammatory drugs (NSAIDS), herbs, natural medications, or other drugs with platelet inhibitory properties within one week prior to surgery and for the duration of treatment with EB 15. have active gastric or duodenal ulcer disease 16. have received a FVII- or FVIIa-containing product (either plasma derived or recombinant) within 24 hours prior to administration of EB 17. have a contraindication to antifibrinolytics 18. have planned combined major surgeries at the same time or have already been enrolled and treated for a previous elective major surgery in the same SCOPE HIM study 19. be administered pharmacologic thromboprophylaxis within 5 half-lives of that medication before surgery or for the duration of treatment with EB -
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Eptacog Beta (Activated) (EB) Effectiveness Based on Protocol's Aggregate Score | From surgical wound closure until 120 hours after surgical wound closure | Successfully treated major procedures defined by a good or excellent global hemostatic response, based on an aggregate score from 3 timepoints (intra-operative, 24h post-operative, 120h post-operative), each individual score depending on comparison between actual and preliminary-communicated expected blood loss and transfusions for a similar patient without bleeding disorder undergoing the same surgical procedure, but also on the use or not of IMP extra-doses or of rescue therapy. |
Countries
Malaysia, Mexico, South Africa, Thailand, Turkey (Türkiye), United States
Contacts
PRINCIPAL_INVESTIGATORMiguel ESCOBAR, MD
The University of Texas Health Science Center, Houston
Participant flow
Recruitment details
Male patients, aged ≥12 years to ≤65 years, with hemophilia A or B with positive inhibitor test BU ≥5 (current or past if not further successfully treated by ITI), or a condition precluding the use of FVIII or FIX products to treat/prevent bleeding, and scheduled to undergo an elective major surgery, were to be enrolled. Major surgeries were those that usually required ≥5 days of factor replacement in this population and typically involved entry into a body cavity or similarly complex procedures
Pre-assignment details
During the screening period, the surgeons had to communicate at least 3 working days before the date of the planned surgery, its expected characteristics including blood loss and transfusion predictions for approval by an enrollment committee comprising an expert surgeon competent in the surgery in patients with hemophilia.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 2 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 1 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 1 Participants |
| Region of Enrollment South Africa | 1 participants |
| Region of Enrollment United States | 1 participants |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 2 |
| other Total, other adverse events | 2 / 2 |
| serious Total, serious adverse events | 0 / 2 |
Outcome results
None listed