LR769 in Congenital Hemophilia Patients With Inhibitors Undergoing Elective Surgery or Invasive Procedures
Condition: Hemophilia
MeSH terms: Hemophilia A
Intervention: Coagulation Factor VIIa (Recombinant)
Intervention description: LR769
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 12.0
Sex: Male
Minimum age: 6 Months
Maximum age: 75 Years
Healthy volunteers: No

Summary:

      The purpose of this study, PerSept 3, is to evaluate LR769 for the prevention of excessive
      bleeding and achievement of hemostasis in congenital hemophilia A or B patients who have
      inhibitors to Factor VIII or Factor IX , are aged 6 months to 75 years, inclusive; and who
      are undergoing elective surgical or other invasive procedures. Administration of LR769 will
      be performed just prior to surgery/procedure and will be repeated during and after the
      surgery/procedure to achieve and maintain adequate hemostasis as determined by the
      investigator's judgment.
    

Eligibility criteria:

        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. a positive inhibitor test Bethesda Unit (BU) ≥5 (as confirmed at screening by the
                  institutional lab), OR

               2. a BU <5 but expected to have a high anamnestic response to FVIII or FIX, as
                  demonstrated from the patient's medical history, precluding the use of FVIII or
                  FIX products to treat or prevent bleeding, OR

               3. a BU <5 but expected to be refractory to increased dosing of FVIII or FIX, as
                  demonstrated from the patient's medical history, precluding the use of FVIII or
                  FIX products to treat or prevent bleeding episodes

          3. be ≥6 months to ≤75 years of age; different age restrictions may apply per local
             regulation and ethical considerations (enrollment of children <12 years of age will
             not begin until after review of data from the PERSEPT 2 study by the DMC)

          4. be scheduled for an elective surgical or other invasive procedure

          5. be capable of understanding and willing to comply with the conditions of the protocol
             OR in the case of a patient <18 years of age, parent(s)/legal guardian(s) must be
             capable of understanding and willing to comply with the conditions of the protocol

          6. have read, understood, and provided written Informed Consent (patient and/or
             parent(s)/legal guardian(s) if the patient is <18 years of age) or Assent, if
             applicable

        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 (ie, the patient should not be receiving systemic
             immunosuppressive medication; cluster of differentiation 4 (CD4) counts at screening
             should be >200/µL)

          3. known intolerance to LR769 or any of its excipients

          4. currently receiving immune tolerance induction (ITI) therapy

          5. have a known allergy or hypersensitivity to rabbits

          6. have a platelet count<100,000/µL

          7. have received an investigational drug within 30 days of the planned first LR769
             administration , or is expected to receive such drug during participation in this
             study (with the exception of patients who are or were participating in another LR769
             study, eg, a study assessing the treatment of bleeding episodes with LR769)

          8. 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)

          9. have a history of arterial and/or venous thromboembolic events (such as myocardial
             infarction, ischemic strokes, transient ischemic attacks, deep venous thrombosis (DVT)
             or pulmonary embolism (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

         10. have an active malignancy (those with non-melanoma skin cancer are allowed)

         11. 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 trial participation or trial outcome (eg, a history of
             non-responsiveness to bypassing products)

         12. be using aspirin, NSAIDS, herbs, natural medications, or other drugs with platelet
             inhibitory properties within one week prior to surgery and for the duration of
             treatment with LR769

         13. have active gastric or duodenal ulcer disease