A Phase 3 Study of the Safety and Efficacy of Coagulation Factor VIIa (Recombinant) for the Prevention of Excessive Bleeding in Patients With Congenital Hemophilia A or B With Inhibitors to Factor VIII or IX Undergoing Elective Major Surgical Procedures SCOPE HIM

Study Overview
=================
Brief Summary
-----------------
This is an interventional, prospective, international, multicenter, single-arm, Phase 3, and sequential efficacy and safety study in adolescents and adults with congenital hemophilia A or B with inhibitors to factor VIII (FVIII) or factor IX (FIX) undergoing elective major surgical procedures.

Official Title
-----------------
A Phase 3 Study of the Safety and Efficacy of Coagulation Factor VIIa (Recombinant) for the Prevention of Excessive Bleeding in Patients With Congenital Hemophilia A or B With Inhibitors to Factor VIII or IX Undergoing Elective Major Surgical Procedures

Conditions
-----------------
Hemophilia

Intervention / Treatment
-----------------
* Biological: Coagulation Factor VIIa (Recombinant)


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: 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: positive inhibitor test BU ≥5 (as confirmed at screening by the institutional lab) OR an inhibitor test BU <5 (as confirmed at screening by the institutional lab) but expected to have an anamnestic response to FVIII or FIX, as demonstrated by a history of a high-responding inhibitor manifested by a previous anamnestic response, defined as a peak inhibitor titer >5 BU after re-exposure to factor concentrates, precluding the use of FVIII or FIX products to treat or prevent bleeding OR an inhibitor test BU <5 (as confirmed at screening by the institutional lab) but expected to be refractory to FVIII or FIX, as demonstrated by the patient's history of previous failure to respond to FVIII or FIX concentrates, even in the absence of a documented anamnestic response, precluding the use of FVIII or FIX products to treat or prevent bleeding episodes. be ≥12 years to ≤65 years of age on the day of informed consent be scheduled for an elective major surgical procedure as defined in the study protocol (see Table ''Definitions for the specific purpose of Study F7TG2202'') have Hb ≥ 12 g/dL be capable of understanding and willing to comply with the conditions of the protocol OR in the case of a patient under the age of legal majority, 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 or parent(s)/legal guardian(s) if the patient is minor according to local regulation) and, where applicable according to local regulation, patient's assent if the patient is minor - Exclusion Criteria: 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 (i.e. the patient should not be receiving systemic immunosuppressive medication; CD4+ cell 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 or suspected allergy or hypersensitivity to rabbits or rabbit proteins have platelet count <100,000/μL have received an investigational drug within 30 days or within 5 half-lives of that investigational drug, whichever is longer, of the planned first LR769 administration, or be expected to receive such drug during participation in this study. Patients who have received fitusiran in a clinical study may not participate in this clinical study for 6 months since the last dose and if they have an antithrombin III level not in the normal range at screening. for patients using emicizumab, have received during the last 6 months or currently receiving a maintenance dosing regimen of emicizumab different from the indicated one ± 10% of approved dose), i.e. different from 1.5 mg/kg once weekly (±10%), 3 mg/kg (±10%) every two weeks or 6 mg/kg (±10%) every four weeks for patients using emicizumab, currently be any plans, or notes in the patient's medical records that would suggest the need to increase or decrease emicizumab dosing due to antidrug antibodies (ADAs), reduced PK, or coagulation/safety-related issues (e.g. lack of response, or potential/actual thromboembolic concerns, etc) 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, DVT, or 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 study participation or study outcome (e.g. chronic, unmanaged hepatitis infection) be using aspirin, non-steroidal anti-inflammatory drugs (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 have received a FVII- or FVIIa-containing product (either plasma derived or recombinant) within 24 hours prior to administration of LR769 have a contraindication to antifibrinolytics have planned combined major surgeries at the same time be administered pharmacologic thromboprophylaxis within 5 half-lives of that medication before surgery or for the duration of treatment with LR769 -

Ages Eligible for Study
-----------------
Minimum Age: 12 Years
Maximum Age: 65 Years

Sexes Eligible for Study
-----------------
Male

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Coagulation Factor VIIa (Recombinant)<br> | Biological: Coagulation Factor VIIa (Recombinant)<br>* LR769<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| proportion of successfully at wound closure | proportion of successfully treated major procedures defined by a good or excellent global hemostatic response. | at wound closure | 
| proportion of successfully at 24 hours after surgery | proportion of successfully treated major procedures defined by a good or excellent global hemostatic response. | at 24 hours after surgical wound closure | 
| proportion of successfully at 120 hours after surgery | proportion of successfully treated major procedures defined by a good or excellent global hemostatic response. | at 120 hours after surgical wound closure |