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Trial record 2 of 2 for:    LFB USA

LR769 in Congenital Hemophilia Patients With Inhibitors Undergoing Elective Surgery or Invasive Procedures (PerSept3)

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ClinicalTrials.gov Identifier: NCT02548143
Recruitment Status : Completed
First Posted : September 14, 2015
Last Update Posted : January 25, 2018
Sponsor:
Collaborator:
Laboratoire français de Fractionnement et de Biotechnologies
Information provided by (Responsible Party):
LFB USA, Inc.

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.

Condition or disease Intervention/treatment Phase
Hemophilia Biological: Coagulation Factor VIIa (Recombinant) Phase 3

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 Type : Interventional  (Clinical Trial)
Actual Enrollment : 12 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : August 25, 2016
Actual Primary Completion Date : August 6, 2017
Actual Study Completion Date : August 31, 2017

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Hemophilia

Arm Intervention/treatment
Experimental: Coagulation Factor VIIa (Recombinant)
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.
Biological: Coagulation Factor VIIa (Recombinant)
LR769




Primary Outcome Measures :
  1. Percentage of surgical or other invasive procedures with a "good" or "excellent" response to LR769 treatment as assessed by the investigator, based on the totality of the assessments performed on the patient [ Time Frame: 48 (±4) hours after the last administration of LR769 ]
    Excellent: postoperative blood loss similar to or less than expected following this type of procedure in a patient who does not have a bleeding disorder and who is undergoing the same surgical or other invasive procedure; no blood component transfusion is required Good: postoperative blood loss greater, but not substantially greater than expected, following this type of procedure in a patient who does not have a bleeding disorder and who is undergoing the same surgical or other invasive procedure, not explained by a surgical/medical issue other than hemophilia; no unexpected need for blood component transfusion


Secondary Outcome Measures :
  1. Percentages of success as defined as the combination of "good" and "excellent" responses by the investigator or designee [ Time Frame: Every 24(±2) hours after procedure completion until end of treatment and at last dose ]
    Good: postoperative blood loss greater than expected following this type of procedure in a patient who does not have a bleeding disorder and who is undergoing the same surgical or other invasive procedure, not explained by a surgical/medical issue other than hemophilia; no unexpected need for blood component transfusion Excellent: postoperative blood loss similar to or less than expected following this type of procedure in a patient who does not have a bleeding disorder and who is undergoing the same surgical or other invasive procedure; no blood component transfusion is required

  2. Percentages of "poor," "moderate," "good," and "excellent" response by the investigator or designee [ Time Frame: Every 24(±2) hours after procedure completion until end of treatment; last dose; 48(±4) hours after last administration of LR769 ]
    Poor: uncontrolled postoperative blood loss, not explained by a surgical/medical issue other than hemophilia that requires intervention (rescue therapy requirement (bypass agent or porcine FVIII), and/or increased blood component (>2 fold greater than expected) transfusion, and/or leads to hypotension or unexpected transfer to Intensive Care Unit Moderate: postoperative blood loss that is substantially greater than expected following this type of procedure in a patient who does not have a bleeding disorder and who is undergoing the same surgical or other invasive procedure, not explained by a surgical/medical issue other than hemophilia; additional blood component [within 2 fold greater than expected] transfusion is necessary

  3. Percentages of intraoperative success as defined as the combination of "good" and "excellent" responses by the surgeon /practitioner [ Time Frame: Intraoperative period ]
    Excellent: intraoperative blood loss similar to or less than expected for this type of procedure in a patient who does not have a bleeding disorder and who is undergoing the same surgical or other invasive procedure,no blood component transfusion is required Good: intraoperative blood loss that is greater than expected (but not more than 50% greater) for this type of procedure in a patient who does not have a bleeding disorder and who is undergoing the same surgical or other invasive procedure; no unexpected increased blood component transfusion requirement

  4. Percentages of "poor," "moderate," "good," and "excellent" intraoperative response by the surgeon/practitioner [ Time Frame: Intraoperative period ]
    Poor: uncontrolled intraoperative blood loss, not explained by a surgical/medical issue other than hemophilia, that requires intervention (rescue therapy requirement (bypass agent or porcine FVIII), and/or increased blood component (>2 fold greater than expected) transfusion, and/or leads to hypotension or unexpected transfer to Intensive Care Unit [ICU]) Moderate: intraoperative blood loss that is substantially greater than expected (more than 50% greater) for this type of procedure in a patient who does not have a bleeding disorder and who is undergoing the same surgical or other invasive procedure, not explained by a surgical/medical issue other than hemophilia; additional blood component (within 2 fold greater than expected) transfusion is necessary

  5. Intraoperative blood loss [ Time Frame: Intraoperative period ]
    Intraoperative blood loss determined by the surgeon/practitioner as compared to the surgeon/practitioner's maximum predicted blood loss

  6. Number of events requiring transfusion [ Time Frame: Between start of procedure and 48 (±4) hours after last administration of LR769 ]
    Number of events requiring transfusion after last administration of LR769

  7. Changes in hemoglobin [ Time Frame: Between start of procedure and 48 (±4) hours after last administration of LR769 ]
    Changes in hemoglobin

  8. Amount of LR769 used [ Time Frame: First dose to last dose of LR769 ]
    Total, and separated by use in hospital, at home, or for specific reasons (eg, physical therapy, or other reasons like drain or suture removal)

  9. Number and type of bleeding episodes at the surgical site [ Time Frame: Between start of procedure and 48 (±4) hours after last administration of LR769 ]
    Number and type of bleeding episodes at the surgical site

  10. Number of surgical interventions/re-explorations for bleeding episodes [ Time Frame: Between start of procedure and 48 (±4) hours after last administration of LR769 ]
    Number of surgical interventions/re-explorations for bleeding episodes


Other Outcome Measures:
  1. Analysis of adverse events (AE) and serious adverse events (SAE) [ Time Frame: First LR769 administration through 28 (±3) days after last administration of LR769 ]
    Analysis (including relationship to LR769, severity , and outcome) of adverse events (AE) and serious adverse events (SAE)

  2. Analysis of treatment-emergent thromboembolic events [ Time Frame: Start of procedure through 28 (±3) days after last administration of LR769 ]
    Analysis of treatment-emergent thromboembolic events

  3. Analysis of allergic and anaphylactic reactions [ Time Frame: Start of procedure through 28 (±3) days after last administration of LR769 ]
    Analysis of allergic and anaphylactic reactions

  4. Analysis of treatment-emergent antibodies against LR769 or host-related impurities [ Time Frame: Start of procedure through 28 (±3) days after last administration of LR769 ]
    Analysis of treatment-emergent antibodies against LR769 or host-related impurities



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   6 Months to 75 Years   (Child, Adult, Older Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02548143


Locations
United States, Texas
UT Southwestern Medical Center
Dallas, Texas, United States, 75235
Mexico
Dr. Jose Eleuterio Gonzalez Monterrey University Hospital
Monterrey, Nuevo Leon, Mexico, 64460
Russian Federation
Hematology Research Center of the Russian Academy of Medical Sciences
Moscow, Russian Federation, 125167
South Africa
Charlotte Maxeke Johannesburg Academic Hospital, Hemophilia Comprehensive Care
Parktown, Gauteng, South Africa, 2193
Worthwhile Clinical Trials, Lakeview Hospital
Benoni, South Africa
Spain
University and Polytechnic Hospital La Fe, Hemostasis and Thrombosis Unit
Valencia, Spain, 46026
Ukraine
City Scientific-Practical center for diagnosics
Kiev, Ukraine
National Specialized Children's Hospital OKHMATDYT, Centre for Hemostatic Pathology
Kyiv, Ukraine
Institute of Blood Pathology and Transfusion Medicine
Lviv, Ukraine
Sponsors and Collaborators
LFB USA, Inc.
Laboratoire français de Fractionnement et de Biotechnologies
Investigators
Principal Investigator: Miguel Escobar, MD Memorial Hermann Texas Medical Center

Responsible Party: LFB USA, Inc.
ClinicalTrials.gov Identifier: NCT02548143     History of Changes
Other Study ID Numbers: LFB-FVIIa-008-14
First Posted: September 14, 2015    Key Record Dates
Last Update Posted: January 25, 2018
Last Verified: January 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Additional relevant MeSH terms:
Hemophilia A
Blood Coagulation Disorders, Inherited
Blood Coagulation Disorders
Hematologic Diseases
Coagulation Protein Disorders
Hemorrhagic Disorders
Genetic Diseases, Inborn