Immunogenicity and Safety Study of Topical Recombinant Thrombin in Surgical Hemostasis

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the safety and immune system response to recombinant thrombin when used to control bleeding in spinal and vascular surgery.

Detailed Description
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This is a Phase 3b, open-label, single-group, multisite safety and immunogenicity study of recombinant thrombin (rThrombin) in participants who are at least 18 years of age and undergoing spinal or vascular surgery. Eligible participants will receive topical rThrombin during surgery and complete a 1-month follow-up visit.

Official Title
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A Phase 3b, Open-Label, Single-Group Immunogenicity and Safety Study of Topical Recombinant Thrombin (rThrombin) in Surgical Hemostasis

Conditions
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Spinal Surgery, Vascular Surgery

Intervention / Treatment
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* Biological: rThrombin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Currently undergoing cervical, thoracic, or lumbar discectomy; corpectomy, laminectomy, lateral or interbody fusion, including both anterior and posterior approaches (not including minimally invasive procedures; arterial reconstruction; peripheral artery bypass (PAB) grafting; or arteriovenous (AV) vascular access procedures History of surgery with high likelihood of exposure to bovine thrombin within the past 3 years. Prior surgery must have been 1 of the following open procedures: open procedures involving the spine or cranium, PAB grafting, AV vascular access procedures, autologous skin grafting, or other surgical procedure accompanied by documented treatment with bovine thrombin Age of 18 years or younger at time of informed consent If female and of child-bearing potential: Negative pregnancy test result within 14 days prior to treatment Use of a medically accepted form of contraception from the time of informed consent to completion of all follow-up study visits, if sexually active male or a sexually active female of childbearing potential Signed IRB/independent ethics committee-approved informed consent document Exclusion Criteria: Currently undergoing procedures requiring cardiopulmonary bypass or involving the aortic arch Known hypersensitivity to rThrombin or any of its components Presence of medical, social, or psychosocial factors that, in the opinion of the investigator, could impact safety or compliance with study procedures Breastfeeding Receipt of treatment with any experimental agent within 30 days of study enrollment or treatment

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>rThrombin | Biological: rThrombin<br>* 1000 U/mL applied directly or in combination with absorbable gelatin sponge or powder<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Anti-recombinant Thrombin (rThrombin) Product Antibodies at Day 29 in Participants With and Without Anti-bovine Thrombin Product Antibodies at Baseline | Seropositive=with specific anti-bovine thrombin product antibodies; seronegative=without specific anti-bovine thrombin product antibodies. | At Day 29 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Death as Outcome, Serious Adverse Events, Treatment-related Adverse Events (AEs), and Treatment-emergent AEs | AE=a new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may or may not have a causal relationship with treatment. SAE=an unfavorable medical event that results in death, persistent or significant incapacity, or drug dependency or abuse; is life-threatening, or a congenital anomaly/birth defect; or requires or prolongs hospitalization. Treatment-related=possibly, probably, or certainly related to study drug. Treatment-emergent=onset on or after treatment start. Grade (Gr) 1=mild, Gr 2=moderate, Gr 3=severe, Gr 4=life threatening/disabling, Gr 5=death. | Day 1 (surgery) to Day 29 (end of study), continuously | 
| Number of Participants With Abnormal Hematology Laboratory Results of Common Terminology Criteria (CTC) Grade 2 or Higher at Baseline and Day 29 | Hemoglobin, low (g/L): Grade 2=<100 Grade 3=<80; Grade 4=<65. Platelets, low: Grade 2=<75*10^9/L; Grade 3=<50*10^9/L; Grade 4=<25*10^9/L. Leukocytes, low: Grade 2=<3.0-2.0*10^9/L; Grade 3=<2.0-1.0*10^9/L; Grade 4=<1.0*10^9/L. Lymphocytes, low: Grade 2=<0.8*10^9/L; Grade 3=<0.5*10^9/L; Grade 4=<0.2*10^9/L. Neutrophils, low: Grade 2=<1.5*10^9/L; Grade 3=<1.0*10^9/L; Grade 4=<0.5*10^9/L. Changes in hematocrit values observed were not graded for severity. | Baseline and Day 29 (end of study) | 
| Number of Participants With Elevations in Coagulation Parameters of CTC Grade 3 or Higher at Baseline and Day 29 | Activated partial thromboplastin time (aPTT) elevations: Grade 3=>2*upper limit of normal (ULN). International normalized ratio(INR)elevations: Grade 3=>2*ULN. Changes in prothrombin time were not graded for toxicity. n=Number of participants with assessments available at that visit. | Baseline and Day 29 (end of study) | 
| Number of Participants With Abnormal Laboratory Results in Median Levels of Immunoglobulin A, G, and M at Baseline or Day 29 | Abnormal laboratory findings were recorded as AEs when the investigator considered them to be clinically significant (eg, an unusual result for the surgical population or for an individual participant) or when they were associated with symptoms or required treatment or a change in patient management. | Baseline and Day 29 (end of study) | 
| Number of Participants With Clinically Significant Changes in Mean Values for Vital Signs (Temperature, Systolic Blood Pressure, Diastolic Blood Pressure, Respiration Rate, Heart Rate) at Baseline and Day 29 | Laboratory findings considered clinically significant by investigator when associated with symptoms, required specific treatment, or required a change in participant management. Clinically significant changes in vital signs were reported as adverse events. | Baseline and Day 29 (end of study) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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safety, Phase 3b, rThrombin, spine surgery, vascular surgery, hemostasis, immunogenicity