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 Information
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
Administrative Informations
NCT ID
NCT02548143
Organization ID
LFB-FVIIa-008-14
Responsible Party
Sponsor
Study Sponsor
Laboratoire français de Fractionnement et de Biotechnologies
Collaborators
LFB USA, Inc.
Study Sponsor
Miguel Escobar, MD, Principal Investigator, Memorial Hermann Texas Medical Center
Verification Date
February 2022