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

NCT02548143 | Completed Phase 3 Results DMC

• 1 other identifier: LFB-FVIIa-008-14
• Study Type: interventional
• Target: 12
• Locations: 6 countries
• Sites: 9

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.

Conditions

Hemophilia

Outcome Measures

Primary Outcomes (1)

• 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

  The final assessment was performed by the investigator at the study center 48 hours after the last dose of LR769 and was based upon the totality of the assessments performed on the patient at each time point. 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.

  48 (±4) hours after the last administration of LR769

Secondary Outcomes (2)

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

  24 hours after procedure completion

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

  72 hours after procedure completion

Study Arms (1)

Coagulation Factor VIIa (Recombinant)

EXPERIMENTAL

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)

Interventions

Coagulation Factor VIIa (Recombinant) BIOLOGICAL

LR769

Coagulation Factor VIIa (Recombinant)

Eligibility Criteria

• Age: 6 Months - 75 Years
• Sex: male
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Each patient must meet the following criteria to be enrolled in this study:
• be male with a diagnosis of congenital hemophilia A or B of any severity
• have one of the following:
• a positive inhibitor test Bethesda Unit (BU) ≥5 (as confirmed at screening by the institutional lab), OR
• 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
• 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
• 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)
• be scheduled for an elective surgical or other invasive procedure
• 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
• 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

You may not qualify if:

• Patients who meet any of the following criteria will be excluded from the study:
• have any coagulation disorder other than hemophilia A or B
• be immunosuppressed (ie, the patient should not be receiving systemic immunosuppressive medication; cluster of differentiation 4 (CD4) counts at screening should be \>200/µL)
• known intolerance to LR769 or any of its excipients
• currently receiving immune tolerance induction (ITI) therapy
• have a known allergy or hypersensitivity to rabbits
• have a platelet count\<100,000/µL
• 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)
• 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)
• 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
• have an active malignancy (those with non-melanoma skin cancer are allowed)
• 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)
• 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
• have active gastric or duodenal ulcer disease

Sponsors & Collaborators

• Laboratoire français de Fractionnement et de Biotechnologies: lead
• LFB USA, Inc.: collaborator

Study Sites (9)

UT Southwestern Medical Center

Dallas, Texas, 75235, United States

Location

Dr. Jose Eleuterio Gonzalez Monterrey University Hospital

Monterrey, Nuevo León, 64460, Mexico

Location

Hematology Research Center of the Russian Academy of Medical Sciences

Moscow, 125167, Russia

Location

Charlotte Maxeke Johannesburg Academic Hospital, Hemophilia Comprehensive Care

Parktown, Gauteng, 2193, South Africa

Location

Worthwhile Clinical Trials, Lakeview Hospital

Benoni, South Africa

Location

University and Polytechnic Hospital La Fe, Hemostasis and Thrombosis Unit

Valencia, 46026, Spain

Location

City Scientific-Practical center for diagnosics

Kiev, Ukraine

Location

National Specialized Children's Hospital OKHMATDYT, Centre for Hemostatic Pathology

Kyiv, Ukraine

Location

Institute of Blood Pathology and Transfusion Medicine

Lviv, Ukraine

Location

MeSH Terms

Conditions

Hemophilia A

Interventions

Factor VII

Condition Hierarchy (Ancestors)

Blood Coagulation Disorders, Inherited; Blood Coagulation Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Coagulation Protein Disorders; Hemorrhagic Disorders; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Enzyme Precursors; Enzymes and Coenzymes; Blood Coagulation Factors; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Protein Precursors; Biological Factors

Results Point of Contact

• Title: Kerry Biron, Director US Clinical Operations
• Organization: LFB USA

kerry.biron@lfb-usa.com

508.370.5166

Study Officials

• Miguel Escobar, MD

  Memorial Hermann Texas Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 9, 2015
• First Posted: September 14, 2015
• Study Start: August 25, 2016
• Primary Completion: August 6, 2017
• Study Completion: August 31, 2017
• Last Updated: February 25, 2022
• Results First Posted: September 6, 2019

Record last verified: 2022-02

Data Sharing

• IPD Sharing: Will not share

Locations

RU (1); UA (3); ME (1); ES (1); US (1); ZA (2)