LR769 in Congenital Hemophilia Patients With Inhibitors Undergoing Elective Surgery or Invasive Procedures

Brief Title

LR769 in Congenital Hemophilia Patients With Inhibitors Undergoing Elective Surgery or Invasive Procedures

Official Title

Phase 3 Study of Safety and Efficacy of Coagulation Factor VIIa (Recombinant) for Prevention of Excessive Bleeding in Congenital Hemophilia A/B Patients With Inhibitors to Factor VIII/IX Undergoing Elective Surgery/Other Invasive Procedures

Brief 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.
    

Detailed Description

      This study is an international, multicenter, single-arm, Phase 3 study. Patients aged 6
      months to 75 years, inclusive, who have congenital hemophilia A or B with inhibitors to
      Factor VIII or Factor IX and who are scheduled for an elective surgical or other invasive
      procedure will be enrolled. Both major and minor surgical or other invasive procedures are
      allowed in the study.

      Initial Treatment: Regardless of procedure, patients who meet all eligibility criteria will
      receive an initial intravenous (IV) bolus dose of LR769 within ≤2 minutes before the surgical
      incision or start of the invasive procedure. For a minor elective surgery or other minor
      invasive procedure, a dose of 75 μg/kg will be used as the initial dose; for a major elective
      surgery or other major invasive procedure, a dose of 200 μg/kg of LR769 will be used as the
      initial dose. For both minor and major procedures, administration will be repeated no more
      frequently than every 2 hours (±5 minutes) at a dose of 75 μg/kg during and after surgery or
      invasive procedure.

      Treatment for Major Surgical Procedures: The initial dose of LR769 will be followed by
      repeated administration of 75 µg/kg of LR769 every 2 hours (±5 minutes) for the first 48
      hours after completion of the procedure. The minimum duration of LR769 treatment for major
      procedures will be 5 days and dosing frequency will be followed according to the guidelines
      specified in the protocol.

      Treatment for Minor Surgical or Other Invasive Procedures: The initial dose of LR769 will be
      followed by repeated administration of 75 µg/kg of LR769 every 2 hours (±5 minutes) for the
      first 48 hours. The minimum duration of LR769 infusion for minor procedures will be 2 days,
      except for certain procedures that may not require this duration of treatment to achieve
      hemostasis as noted in the protocol. Dosing frequency will be according to the guidelines
      specified in protocol for minor surgical or other invasive procedures.
    

Study Phase

Phase 3

Study Type

Interventional

Primary Outcome

Percentage of Surgical or Other Invasive Procedures Defined as "Good" or "Excellent" Response to LR769 Treatment as Assessed by the Investigator, Based on the Totality of the Assessments Performed on the Patient

Secondary Outcome

 Percentages of Success as Defined as the Combination of "Good" and "Excellent" Responses by the Investigator or Designee

Condition

Hemophilia

Intervention

Coagulation Factor VIIa (Recombinant)

Study Arms / Comparison Groups

 Coagulation Factor VIIa (Recombinant)

Description:  A dose of 75 μg/kg (minor surgery or invasive procedure) or 200 μg/kg (major surgery or major invasive procedure) of LR769 will be administered as an initial intravenous (IV) bolus dose of LR769 within ≤2 minutes before the surgical incision or start of the invasive procedure. For both minor and major procedures, the initial dose will be followed by repeated administration of 75 µg/kg of LR769 every 2 hours (±5 minutes) for the first 48 hours after completion of the procedure and then as per the dosing schedules in the protocol for major or minor surgeries or invasive procedures. The minimum duration of LR769 treatment for major procedures will be 5 days, and for minor procedures 2 days except for certain procedures that may not require this duration of treatment.

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Status

Biological

Estimated Enrollment

12

Start Date

August 25, 2016

Completion Date

August 31, 2017

Primary Completion Date

August 6, 2017

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
      

Gender

Male

Ages

6 Months - 75 Years

Accepts Healthy Volunteers

No

Contacts

Miguel Escobar, MD, , 

Location Countries

Mexico

Location Countries

Mexico

NCT ID

NCT02548143

Organization ID

LFB-FVIIa-008-14

Responsible Party

Sponsor

Study Sponsor

LFB USA, Inc.

Collaborators

 Laboratoire français de Fractionnement et de Biotechnologies

Study Sponsor

Miguel Escobar, MD, Principal Investigator, Memorial Hermann Texas Medical Center

Verification Date

May 2020